Cancer Therapy Advisor January/February 2017 Issue

JANUARY/FEBRUARY 2017 | VOL 3, ISSUE 3

CancerTherapyAdvisor.com

CancerTherapyAdvisor

A20 FEATURE

Watson: A Promising Tool or a Glorified Search Engine?

FEATURING Cancer Therapy Regimens and Oncology Drug Monographs from

Watson is receiving attention as a tool that many hope will be useful for oncologists, though it may be limited by an inability to intelligently interpret clinical trials.

1 Bone Cancer 3 Brain Cancer 5 Breast Cancer 12 Endocrine Cancer

A9 LATEST NEWS

 16 Gastrointestinal Cancer 26 Genitourinary Cancer

Headlines in oncology research, including hematologic malignancies and pediatric cancers A18 IN THE CLINIC JANUARY/FEBRUARY 2017 | VOL 3, ISSUE 3

Hyperthermic Intraperitoneal Chemotherapy in Colorectal Cancer With Peritoneal Carcinomatosis

35 Gynecologic Cancer 37 Head and Neck Cancer

 39 Hematologic Cancer  63 Lung Cancer  81 Sarcoma 84 Skin Cancer 89 Associated Hematological

A22 VIEWPOINT

Developing microRNA Biomarkers To Detect and Treat Prostate Cancer

A24 EXPERT PERSPECTIVE Seven States Approve Some Form of Marijuana Initiative

Disorders



Regimen included

A6 FEATURED PRODUCT

A26 REGIMEN & MONOGRAPH INDEX

Drug Descriptions of Evomela and Lartruvo

A8 IN THE PIPELINE

-103 CANCER THERAPY REGIMENS & 1 DRUG MONOGRAPHS Highlighted topics () contain both treatment regimens and drug monographs.

The Latest on Oncology Drugs

A9 LATEST NEWS Headlines in Oncology Research and Practice

A18 IN THE CLINIC Hyperthermic Intraperitoneal Chemotherapy in Colorectal Cancer With Peritoneal Carcinomatosis C. ANDREW KISTLER, MD, PharmD, RPh

A20

A22

3 Brain Cancer 5 Breast Cancer 12 Endocrine Cancer

 16 Gastrointestinal Cancer

26 Genitourinary Cancer

FEATURE

35 Gynecologic Cancer

Watson: A Promising Tool or a Glorified Search Engine?

37 Head and Neck Cancer

NICOLAI WOHNS, MD

 39 Hematologic Cancer

 63 Lung Cancer

 81 Sarcoma

VIEWPOINT Developing microRNA Biomarkers To Detect and Treat Prostate Cancer BRYANT FURLOW

A24

1 Bone Cancer

84 Skin Cancer 89 Associated Hematological Disorders

EXPERT PERSPECTIVE Seven States Approve Some Form of Marijuana Initiative JASON HOFFMAN, PharmD, RPh

104 ALPHABETICAL INDEX 110 MANUFACTURERS INDEX

Cancer Therapy Advisor (ISSN 2375-558X), January/February 2017, Volume 3, Number 3. Published 6 times annually by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales, Editorial and Subscription information call (646) 638-6000 (M–F, 9am–5pm, ET). Standard Postage paid at Orem, UT. Postmaster: Send changes of address to Cancer Therapy Advisor, c/o Direct Medical Data, 10255 W. Higgins Rd., Suite 280, Rosemont, IL 60018.

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EDITORIAL & BUSINESS STAFF

EDITORIAL ADVISORY BOARD

Managing Editor, Haymarket Oncology

Barbara Ann Burtness, MD

Lauren Burke

Yale Cancer Center  New Haven, CT

Oncology Editor

Steven J. Cohen, MD

Jonathan Goodman, MPhil

Thomas Jefferson University Hospital  Philadelphia, PA

Oncology Writer

E. David Crawford, MD

Jason Hoffman, PharmD, RPh

Senior Manager, Drug Information

University of Colorado, Denver  Aurora, CO

Anissa Lee, RPh

Isabel Cunningham, MD

Group Art Director, Medical Communications

Columbia University College of Physicians & Surgery  New York, NY

Jennifer Dvoretz

Don S. Dizon, MD, FACP

Assistant Art Director

Massachusetts General Hospital Cancer Center  Boston, MA

Holly Morrison

Jeffrey M. Farma, MD

Production Manager

Fox Chase Cancer Center  Philadelphia, PA

Brian Wask (646) 638-6066

Neal D. Shore, MD, FACS

Circulation Manager

Atlantic Urology Clinics  Myrtle Beach, SC

Paul Silver

Vice President, Sales & Business Development Scott Bugni (917) 882-0658; scott.bugni@haymarketmedia.com

Account Manager

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Manager, Multi-Channel Business Development Marc A. DiBartolomeo (609) 417-0628; marc.dibartolomeo@haymarketmedia.com

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HAYMARKET MEDIA INC.

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Chief Executive Officer

Contact the Editor:

Lee Maniscalco

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CancerTherapyAdvisor.com | JANUARY/FEBRUARY 2017 | CANCER THERAPY ADVISOR A5

FEATURED PRODUCT

Evomela

Rx

Company: Spectrum Pharmacologic class: Alkylating agent Active ingredients: Melphalan HCl 50 mg/vial; lyophilized pwd; for IV infusion after reconstitution.

Indications: High-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation in patients with multiple myeloma. Palliative treatment of multiple myeloma when oral therapy is not appropriate.

Pharmacology: Melphalan is an alkylating agent of the bischloroethylamine type. Like other bifunctional alkylating agents, it is active against both resting and rapidly dividing tumor cells.

Clinical trials: An open-label, single-arm, non-randomized trial of Evomela was conducted in 61 patients who had symptomatic multiple myeloma and at least 2x106 CD34+ cells/kg cryopreserved stem cells available.

Evomela was administered at 100 mg/ m2/day by IV infusion for 2 consecutive days prior to autologous stem cell transplantation (ASCT).

The objective of the trial was to determine the overall safety and toxicity profile of Evomela 200 mg/m2 in patients with multiple myeloma undergoing ASCT. Efficacy was evaluated by the International Myeloma Working Group response criteria comparing the disease response immediately prior to ASCT to the disease response assessed at 90 to 100 days post-transplant. Also, successful myeloablation and time to engraftment were evaluated.

The overall response rate (partial or better) improved from 79% pre-ASCT to 95% at 90 to 100 days post-transplant. There was also an increase in

the number of patients with a stringent complete response from 0 patients pre-ASCT to 16% at 90 to 100 days post-transplant. Myeloablation, neutrophil engraftment, and platelet engraftment were achieved by all patients.

A randomized trial compared prednisone + IV melphalan vs prednisone + oral melphalan in the treatment of multiple myeloma (295 patients). Overall response rates at week 22 were comparable (38% vs 44%, respectively; P > .2).

Conclusions as to the relative activity of the 2 formulations, response duration and survival after week 22, could not be made due to changes in trial design.

For more clinical trial data, see full labeling.

Adults: Give prophylactic antiemetics.

Conditioning treatment: Give by IV infusion over 30 minutes. 100 mg/m2 daily for 2 consecutive days (days -3 and -2) prior to transplantation (day 0). If patient weighs more than 130% of ideal body weight, use adjusted ideal body weight. Palliative treatment: Give

by IV infusion over 15–20 minutes. 16 mg/m2 as a single infusion at 2-week intervals for 4 doses, then at 4-week intervals after recovery from toxicity.

Renal impairment (BUN ≥ 30mg/dL):

A6 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

consider up to 50% dose reduction for palliative treatment.

Children: Not established.

Warnings/Precautions: Prior irradiation or chemotherapy. Severe bone marrow suppression. Monitor CBCs during treatment; provide supportive care for infections, anemia, thrombocytopenia until adequate recovery. GI toxicity: provide supportive care. Monitor LFTs. Renal impairment. Embryo-fetal toxicity: use effective contraception during and after treatment. Pregnancy, nursing mothers: not recommended.

Interactions: Caution with cyclosporine, BCNU, nalidixic acid.

Adverse reactions: Decreased neutrophil, WBC, lymphocyte, and platelet counts, diarrhea, nausea, fatigue, hypokalemia, anemia, vomiting; hypersensitivity reactions, hepatic disorders, secondary malignancies, infertility.

How supplied: Single-dose vial (20mL)—1 For more information call (888) 292-9617 or visit www.Evomela.com.

FEATURED PRODUCT

Lartruvo

Rx

Company: Eli Lilly Pharmacologic class: PDGFR-alpha inhibitor Active ingredients: Olaratumab 500 mg/50 mL; soln for IV infusion; preservative-free.

Indication: In combination with doxorubicin, for the treatment of adults with soft tissue sarcoma with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery.

Pharmacology: Olaratumab is a human IgG1 antibody that binds PDGFR-alpha, a receptor involved in cell growth, chemotaxis, and mesenchymal stem cell differentiation. The receptor has also been detected on some tumor and stromal cells, including sarcomas, where signaling can contribute to cancer cell proliferation, metastasis, and maintenance of the tumor microenvironment.

Clinical trials: The efficacy of Lartruvo was seen in Trial 1, an open-label, randomized, active-controlled study (133 patients). Patients were randomized (1:1) to receive Lartruvo in combination with doxorubicin or doxorubicin alone. Lartruvo 15 mg/kg was given as an IV infusion on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity. All patients received doxorubicin 75 mg/m2 as an IV infusion on day 1 of each 21-day cycle for a maximum of 8 cycles and were permitted to receive dexrazoxane prior to doxorubicin in cycles 5 to 8.

The efficacy outcome measures were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) as assessed by an investigator and by independent review.

Patients in the Lartruvo plus doxorubicin group had a significant improvement in OS as compared to the doxorubicin alone group (26.5 months vs 14.7 months, hazard ratio [HR] 0.52, 95% CI: 0.34, 0.79; P < .05). Patients in the Lartruvo plus doxorubicin group had a longer PFS as compared to the doxorubicin alone group (8.2 months vs 4.4 months, HR 0.74, 95% CI: 0.46, 1.19). Also, patients in the Lartruvo plus doxorubicin group had a higher ORR (complete response + partial response) as compared to the doxorubicin alone group (18.2% vs 7.5%).

For more clinical trial data, see full labeling.

for signs/symptoms of infusion-related reactions during and post-infusion.

Permanently discontinue for grade 3/4 infusion-related reactions; interrupt for grade 1/2 infusion-related reactions; resume at 50% of initial rate after resolution. If neutropenic fever/infection or grade 4 neutropenia lasts longer than 1 week, discontinue until ANC ≥ 1,000μL then permanently reduce dose to 12 mg/kg. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for 3 months after last dose. Pregnancy.

Nursing mothers: not recommended (during and for 3 months after last dose).

Adults: Premedicate with IV diphenhydramine and IV dexamethasone prior to infusion on day 1 of cycle 1. Give with doxorubicin for the first 8 cycles: refer to doxorubicin PI for dosing and modifications. Give by IV infusion over 60 minutes. 15 mg/kg on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Adverse reactions: With doxorubicin: nausea, fatigue, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, headache, anxiety, dry eyes, lymphopenia, neutropenia, thrombocytopenia, hyperglycemia, elevated aPTT, hypokalemia, hypophosphatemia, increased alkaline phosphatase.

Children: Not established.

How supplied: Single-dose vial—1

Warnings/Precautions: Have resuscitative equipment available. Monitor

For more information call (800) 545-5979 or visit www.Lartruvo.com.

CancerTherapyAdvisor.com | JANUARY/FEBRUARY 2017 | CANCER THERAPY ADVISOR A7

IN THE PIPELINE FDA Accepts Biologics License Application for Proposed Biosimilar Trastuzumab

FDA Grants Priority Review sBLA for Pembrolizumab + Chemo for NSCLC

T h e U. S . Fo o d a n d D r u g Administration (FDA) has accepted Mylan’s Biologics License Application (BLA) for MYL-1401O, a proposed biosimilar to branded trastuzumab (Herceptin), a human epidermal growth factor receptor 2 (HER2)/neu receptor antagonist indicated for the treatment of HER2-overexpressing breast cancer and metastatic gastric or gastroesophageal junction adenocarcinoma.

The BLA submission is based on findings from the multicenter, double-blind, phase 3 HERITAGE trial (ClinicalTrials. gov Identifier: NCT02472964), which evaluated the efficacy and safety of MYL1401O plus paclitaxel or docetaxel compared with trastuzumab plus a taxane in 458 treatment-naive women with ERBB2 (HER2)-positive metastatic breast cancer.

Results of the study showed that 69.6% (95% CI, 63.62-75.51) of patients who received the proposed biosimilar achieved a response by week 24 compared with 64.0% (95% CI, 57.81-70.26) of those given trastuzumab.

There was no statistically significant difference in progression-free survival, time to tumor progression, or overall survival between the 2 treatment arms at week 48.

The safety profiles of the 2 agents were similar, with the most frequently reported adverse events being neutropenia, peripheral neuropathy, and diarrhea.

The FDA is expected to take action

by September 2017. If approved, MYL14010 could be the first biosimilar trastuzumab in the United States.

T h e U. S . Fo o d a n d D r u g Administration (FDA) has granted Priority Review to Merck’s supplemental Biologics License Application (sBLA) for pembrolizumab (Keytruda) in combination with chemotherapy for the first-line treatment of metastatic or advanced non-squamous non-small cell lung cancer (NSCLC) regardless of PD-L1 expression and with no EGFR or ALK genomic tumor aberrations.

Th is sBL A subm ission, wh ich seeks accelerated approval for pembrolizumab at a fixed dose of 200 mg administered intravenously in combination with pemetrexed 500 mg/m 2 and carboplatin AUC 5 mg/mL/min every 3 weeks for 4 cycles, is based on findings from part 2, cohort G of the KEYNOTE-021 trial (ClinicalTrials. gov Identifier: NCT02039674).

The study, which was presented at the European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen, showed that the addition of pembrolizumab to pemetrexed and carboplatin significantly reduced the risk of progression by 47% compared with pemetrexed plus carboplatin alone (hazard ratio, 0.53; 95% CI, 0.31-0.91; P = .0102). Median progression-free survival was 13.0 months with pembrolizumab in contrast with 8.9 months in the control group.

Under t he F DA’s Accelerated Approval program, the FDA set a target action date of May 10, 2017, for the sBLA. Pembrolizumab is approved for the first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression (tumor

For more information call (724) 514-1800 or visit Mylan.com.

A8 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

proport ion score [ TPS] of 50% or greater), with no EGFR or ALK genomic tumor aberrations, as well as for patients with metastatic NSCLC whose tumors express PD-L1 (TPS of 1% or more), with disease progression on or after platinum-containing chemotherapy.

For more information call (908) 7404000 or visit Merck.com.

Bristol-Myers Squibb and Janssen Announce Nivolumab/Daratumumab Collaboration Bristol-Myers Squibb and Janssen Biotech are collaborating to test whether combining nivolumab and daratumumab will have synergistic clinical effects, according to a press release.

A phase 1 study (ClinicalTrials.gov Identifier: NCT01592370) of nivolumab in multiple myeloma will now include daratumumab in 1 of its study arms; more studies of the combination—in particular for solid tumors such as non-small cell lung cancer, colorectal cancer, triple-negative breast cancer, head and neck cancer, and pancreatic cancer—will commence in 2017.

Nivolumab is a PD-1 immune checkpoint inhibitor with several indications, including metastatic melanoma and nonsmall cell lung cancer. Daratumumab is a CD38-directed cytolytic antibody indicated for some previously treated patients with multiple myeloma.

The combination may be effective for a variety of cancers, though it is not specified how the drugs will work synergistically.

For more information visit BMS.com or Janssen.com.

LATEST NEWS

Melanomas of the female genital tract have unique molecular features that may be targetable using precision medicine, according to an article published in Cancer.

Only 1407 melanomas of the vulvar or vaginal regions were reported to the Surveillance, Epidemiology, and End Results (SEER) database between 1973 and 2010, though these diseases have a poor prognosis in contrast with cutaneous melanoma. For this literature-based paper, the authors compared molecular analyses of melanomas of the female genital tract with those of non-gynecologic melanomas to determine targeted treatment options for these rare cancers.

Of all cases reviewed from a sample of molecular profiles taken between 2009 and 2015, 51 melanomas of the genital tract and 2253 non-gynecologic melanomas were included.

BRAF mutations were more common in genital tract cancers than non-gynecologic (26% vs 8.3%); KIT mutation was also most common among genital tract cancers.

PD-1 and PD-L1 expression was common in female genital tract melanomas; PI3KCA mutations were rare.

BRAF-mutant female genital tract cancers were likely to express TUBB3, which is associated with taxane resistance.

In genital tract melanomas without KIT mutations, ERCC1 expression tended to be higher and O-6-methylguanine-DNA methyltransferase (MGMT) expression tended to be lower, suggesting resistance to platinum agents and sensitivity to alkylating agents.

MK-2206 Not Superior to Everolimus for Renal Cell Carcinoma Allosteric inhibition of AKT with MK-2206 is not superior to everolimus for the treatment of patients with advanced renal cell carcinoma (RCC) refractory to anti-vascular endothelial growth factor (VEGF) therapy, according to a study published in the Annals of Oncology.

Upregulation of the phosphoinositide-3 phosphate kinase (PI3K) pathway is associated with worse outcomes for patients with advanced RCC. Researchers hypothesized that inhibiting AKT in patients refractory to anti-VEGF therapy would eliminate key drivers of tumor growth and cancer pathway signaling, prolonging progression-free survival.

Researchers enrolled 43 patients with metastatic or

unresectable RCC refractory to anti-VEGF treatment. In this open-label, phase 2 study (ClinicalTrials.gov Identifier: NCT01239342), participants were randomly assigned 2:1 to receive MK-2206, a selective allosteric inhibitor of AKT, or everolimus.

Results of the first futility analysis showed that median progression-free survival was 3.68 months with MK-2206 compared with 5.98 months with everolimus, leading to study closure.

Researchers observed 1 complete response and 3 partial responses in the MK-2206 treatment arm vs no complete or partial responses in the everolimus arm, though progressive disease was the best response in 44.8% of patients treated with MK-2206 and 14.3% of those given everolimus.

Treatment with MK-2206 was associated with a significantly higher incidence of rash and pruritus than everolimus. About 38% of patients in the experimental arm required dose reduction vs 21.4% of everolimus-treated patients.

MK-2206 is being studied in a variety of solid tumors and hematologic malignancies, including in the I-SPY 2 adaptive clinical trial for breast cancer.

FDA Grants Priority Review to Regorafenib for Liver Cancer The U.S. Food and Drug Administration (FDA) has granted priority review status to the supplemental New Drug Application (sNDA) submitted by Bayer for regorafenib (Stivarga) as second-line systemic therapy of patients with advanced hepatocellular carcinoma (HCC), according to a press release from Bayer.

The sNDA is based on findings from the ongoing, international, phase 3 RESOURCE trial (ClinicalTrials.gov Identifier: NCT01774344), which evaluated the efficacy and safety of regorafenib compared with placebo in 573 patients with HCC whose disease had progressed during treatment with sorafenib.

The study, which was presented during the European Society of Medical Oncology (ESMO) 18th World Congress on Gastrointestinal Cancer in Barcelona, showed that patients receiving regorafenib had a 38% reduced risk of death compared with those given placebo and best supportive care (hazard ratio [HR], 0.62; 95% CI, 0.50-0.78; P < .001); median overall survival was 10.6 months and 7.8 months, respectively.

Second-line treatment with regorafenib reduced the risk of progression or death by 54% (HR, 0.46; 95% CI, 0.37-0.56; P < .001) and time to disease progression by 56% (HR, 0.44; 95% CI, 0.36-0.55; P < .001) compared with placebo.

Regorafenib is indicated for the treatment of patients with

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Š CNRI / SCIENCE SOURCE

Gynecologic Melanoma: Genetics and Targetable Mutations

LATEST NEWS

Chemotherapy in Lung Cancer: Evaluating Timing for Adjuvant Treatment Timing of adjuvant chemotherapy after a patient undergoes resection for non–small cell lung cancer (NSCLC) may be a factor of overall survival, according to an article published in JAMA Oncology.

Adjuvant chemotherapy is standard for patients with lymph node metastases, tumors of at least 4 cm, or extensive invasion locally. There is, however, no consensus on the best time to administer this therapy; researchers therefore consulted the National Cancer Database to determine the optimal time of therapy administration.

Of 1,039,990 patients with NSCLC identified through the database, 31,474 were categorized into 4 groups after exclusion: 3359 patients who received adjuvant therapy fewer than 39 days post-resection, 5137 patients treated 39 to 56 days post-resection, 3977 patients treated more than 56 days post-resection, and 19,001 patients who did not receive adjuvant therapy.

No significant survival differences were seen when patients were treated up to 4 months after surgery; the authors noted, however, that “a small but significant difference in survival exists based on when chemotherapy is given but is not able to be appreciated within this data set.”

Some sociodemographic factors were associated with a delay in receipt of adjuvant treatment, including advanced age, not having medical insurance, and low education; this finding illustrates a need for physician awareness of a patient’s socioeconomic status to ensure receipt of timely treatment.

Effect of Sorafenib on OS Dependent on Viral Status The effect of sorafenib on overall survival may depend on the hepatitis status of patients with advanced hepatocellular carcinoma (HCC), according to a study in the Journal of Clinical Oncology.

Findings from the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial led to sorafenib becoming the standard of care for patients with advanced unresectable HCC. To assess the unclear relationship between disease etiology and survival, researchers conducted a meta-analysis of 3 large

prospective randomized trials that included sorafenib as the control arm. Investigators analyzed data from 3256 patients, 50% of whom received sorafenib.

Patients who were both hepatitis B virus (HBV) negative and hepatitis C virus (HCV) positive had a lower risk of death than patients with other viral statuses (log [hazard ratio], −0.27; 95% CI, −0.46-−0.06).

Among patients who were HBV negative and HCV positive, median overall survival for those treated with sorafenib was 12.6 months compared with 10.2 months for patients treated with other agents, which included brivanib, sunitinib, and linifanib.

Patients with other hepatitis statuses, such as HBV positive and HCV negative, did not have any improvement in overall survival attributable to sorafenib.

The authors hypothesize that HCV proteins modulate the expression of microRNAs, influencing the sensitivity of HCC cells to sorafenib.

Second Opinions for Breast Cancer Treatment: Factors and Effects Education, genetic testing, and interest in one’s treatment are all factors influencing whether a patient seeks a second opinion for breast cancer treatment, according to an article published in JAMA Oncology.

The availability of many treatment regimens for breast cancer, as well as the ever-increasing list of genetic biomarkers for which oncologists test, can make medical decision-making difficult for patients, leading to second consultations. It is unclear, however, which factors influence patients to seek a second opinion, and whether second opinions tend to influence treatment decision-making.

For this survey-based study, researchers identified 3880 patients with stage I or II breast cancer identified through the Surveillance, Epidemiology, and End Results (SEER) registries of Georgia and Los Angeles County, 1901 of which were included in the sample.

Nearly 10% (168) of patients solicited a second opinion; factors associated with solicitation included being college educated, frequently using online support groups, and a preference for making one’s own treatment decisions. Patients who had a variant of unknown significance result on germline genetic tests were 3 times as likely to seek a second opinion.

Second opinions did not, however, appear to increase the likelihood of chemotherapy receipt.

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© THINKSTOCK

metastatic colorectal cancer, as well as for locally advanced, unresectable, or metastatic gastrointestinal stromal tumor previously treated with imatinib and sunitinib.

Chemo-free Induction Efficacious in Younger Patients With Mantle Cell Lymphoma

Higher Idarubicin Dose During Consolidation Improves Leukemia-free Survival in AML

Chemotherapy-free induction with ibrutinib and rituximab is efficacious and well-tolerated among young patients with newly diagnosed mantle cell lymphoma, according to preliminary findings presented at the A merican Societ y of Hematology (ASH) 58th Annual Meeting and Exposition.

“Frontline therapy is the most important therapy for mantle cell lymphoma,” said principal investigator Michael Wang, MD, of the department of stem cell transplantation and cellular therapy at The University of Texas MD Anderson Cancer Center in Houston. “Frontline therapy could kill all MCL cells at the first strike, eliminate any change for secondary resistance, cause long-term remissions, and, if ideally optimized, become a shortcut to cure MCL.” To evaluate chemotherapy-free induction among young and fit patients, researchers enrolled 50 patients aged 65 years or younger with newly diagnosed mantle cell lymphoma. In part 1, patients received ibrutinib plus rituximab induction therapy until best response, followed by a shortened course of intense chemoimmunotherapy in part 2.

Patients then received intense consolidation therapy consisting of rituximab plus cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD), alternating every 28 days with rituximab plus high-dose methotrexate and cytarabine.

If in complete remission after initial ibrutinib and rituximab treatment, patients received 4 additional treatments of intense chemoimmunotherapy. If patients had a partial response or progression, and were responding to intensive chemoimmunotherapy, they received 2 cycles of chemoimmunotherapy.

All of the 45 evaluable patients achieved a response in part 1, including complete remissions in 73% and partial remissions in 27%. Thirty-three patients have completed both part 1 and part 2.

Toxicity after intensive chemoimmunotherapy in shortened cycles was improved compared with historical controls, though longer follow-up is needed to fully understand the safety of this approach.

“This is the first time for chemotherapy-free therapy to achieve an overall response rate of 100%; it is unprecedented efficacy at frontline in young patients with mantle cell lymphoma,” Dr Wang concluded.

A higher dose of idarubicin during consolidation therapy improves leukemia-free survival without increasing non-hematologic toxicity among adults with acute myeloid leukemia (AML), according to a study presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition.

In an effort to evaluate whether an increased idarubicin dose during consolidation therapy improves outcomes for adults with AML, researchers enrolled 293 patients with AML who achieved complete remission after 1 or 2 cycles of intensive induction therapy consisting of idarubicin, cytarabine, and etoposide. Participants were randomly assigned 1:1 to receive 2 cycles of consolidation therapy with cytarabine, etoposide, and idarubicin for either 2 or 3 days (standard and intensive arms, respectively).

After a median follow-up of 5.3 years, results showed that the higher dose of idarubicin was associated with 26% reduced risk of the disease recurring (hazard ratio, 0.74; 95% CI, 0.550.99; P = .045). The 3-year leukemia-free survival rate was 47% (95% CI, 40-56) with 3 days of idarubicin vs 35% (95% CI, 28-44) with 2 days.

“Idarubicin intensification improved leukemia-free survival,” said Andrew Wei, MBBS, PhD, of the Alfred Hospital in Melbourne, Australia. “Idarubicin intensification also improved leukemia-free survival censored for hematopoietic stem cell transplantation.”

Final analyses showed that there was no significant difference in 3-year overall survival between the 2 arms (hazard ratio, 0.75; 95% CI, 0.54-1.05; P = .092). The 3-year overall survival rates were 61% with intensive idarubicin vs 50% with standard dose.

“Idarubicin intensification significantly prolongs marrow suppression during consolidation,” added Dr Wei. The median durations of grades 3 to 4 neutropenia and thrombocytopenia were significantly longer in the intensive idarubicin arm, but there were no significant differences in grade 3 to 4 non-hematological toxicities between the treatment arms.

“Although intensive consolidation increased myelotoxicity, there was no evidence of increased cardiac complications,” said Dr Wei. “Larger patient numbers are needed to determine the benefit of anthracycline intensification within genetic subgroups,” Dr Wei concluded.

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© THINKSTOCK

LATEST NEWS | HEMATOLOGIC MALIGNANCIES

HEMATOLOGIC MALIGNANCIES

After cessation of imatinib therapy in patients with chronic myeloid leukemia (CML), there were no differences in molecular relapse-free survival (MRFS) between patients with prior 4.5 log reduction but detectable disease and those with undetectable disease, according to a study presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition.

“Several studies have shown that in a proportion of patients with deep molecular response, treatment can be successfully stopped,” said Markus Pfirrmann, PhD, of the Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Ludwig-Maximilians-Universität München in Germany.

Because duration of MR4 was a prognostic factor associated with MRFS after tyrosine kinase inhibitor discontinuation in the EURO-SKI trial and depth of response is suspected to influence MRFS, researchers investigated the impact on MRFS of deep molecular response status at treatment cessation.

Investigators analyzed data from 357 participants of EUROSKI, of whom 33 (9%) were “MR4 only” (status A), 125 (35%) had “MR4.5, detectable disease” (status B), and 199 patients (56%) had “MR4.5, undetectable disease” (status C).

Results showed that 61% (95% CI, 42-77) of status A (MR4) patients were still in at least major molecular response at 6 months compared with 58% (95% CI, 53-63) of status B or C (MR4.5) patients (odds ratio, 1.11; 95% CI, 0.54-2.32).

To reduce bias, researchers conducted a propensity score-matching analysis by matching 119 status B patients with 119 status C patients, which continued to show a non-significant difference in MRFS between the 2 groups.

Nilotinib Discontinuation Following Deep Molecular Response Some patients with chronic myeloid leukemia (CML) who have maintained deep molecular responses for at least 2 years can safely discontinue nilotinib, though relapse may occur even after more than 10 years of sustained deep molecular response, according to a study presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition.

To examine the safety and efficacy of nilotinib discontinuation and to identify predictive factors for successful

discontinuation of nilotinib, researchers designed the Stop Nilotinib (NILSt) trial, a single-arm, phase 2 study.

Investigators enrolled 114 patients with CML in chronic phase who achieved MR4.5 by treatment with imatinib or nilotinib and were treated with nilotinib for a further 2 years. Patients who maintained MR4.5 during those 2 years were eligible for discontinuation of nilotinib. Those who lost MR4.5 restarted nilotinib therapy.

The treatment-free remission rate 1 year after discontinuation of nilotinib was 62.2% (90% CI, 53.0-70.8).

Thirty-six patients experienced loss of MR4.5, with most occurring within 6 months of nilotinib discontinuation, though 34 of those achieved a second MR4.5 within a median of 2.2 months (95% CI, 1.5-2.6) Age, sex, Sokal score, Hasford score, EUTOS score, history of interferon-alpha therapy, total duration of imatinib or nilotinib therapy, time to MR4.5, or trough concentrations of nilotinib in sera did not predict the likelihood of maintaining MR4.5 at 1 year after discontinuation.

DVd Superior to Vd Regardless of Prior Lines of Therapy in Myeloma Daratumumab plus bortezomib and dexamethasone (DVd) is superior to bortezomib plus dexamethasone (Vd) regardless of the number of prior lines of therapy, cytogenetic risk, or time since last therapy in patients with relapsed/refractory multiple myeloma, according to an updated analysis of the pivotal CASTOR study presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition.

Daratumumab is a first-in-class CD38-blocking monoclonal antibody that demonstrated activity in combination with bortezomib and dexamethasone in contrast with Vd alone in a pre-specified interim analysis of the phase 3 CASTOR trial of patients with relapsed/refractory multiple myeloma (hazard ratio, 0.39). The U.S. Food and Drug Administration approved the combination for this indication in November 2016.

To identify the patient population who derive the most benefit from this regimen, researchers conducted subgroup analyses with respect to prior lines of therapy and cytogenetic status after additional follow-up.

At a median follow-up of 13.0 months, an additional 7% of patients receiving DVd achieved a complete response or better with longer follow-up.

Subgroup analyses demonstrated that the daratumumab combination improves outcomes regardless of cytogenetic risk.

No new safety signals were observed with longer follow-up.

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No Impact of Detectable Disease on MRFS After Imatinib Cessation in CML

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LATEST NEWS | PEDIATRIC CANCER

Among patients with wild-type gastrointestinal stromal tumors (GISTs), there was no improvement in event-free survival with more extensive or serial resections, suggesting that resections for this disease be restricted to the initial procedure, according to a study published in the Journal of Clinical Oncology.

Wild-type GISTs, which lack KIT or PDGFRA mutations, are unique subtypes of GIST that are most common among children. There are, however, limited studies evaluating the impact of staging variables and resections on clinical outcome.

To determine the effect of staging variables, extent of resection, and repeat resection of tumors on event-free survival, researchers analyzed data from 76 patients with wild-type GIST who underwent resection for their disease. All patients were treated at a wild-type GIST clinic that was established by the National Cancer Institute in 2008.

At a median follow-up of 4.1 years, the overall event-free survival was 72.6% at 1 year, 57.6% at 2 years, 23.7% at 5 years, and 16.3% at 10 years postoperatively.

Patients with metastatic disease (adjusted hazard ratio [aHR], 2.3; 95% CI, 1.0-5.1; P = .04) and those with greater than 5 mitoses per 50 high-power fields (aHR, 2.5; 95% CI, 1.1-6.0; P = .03) had about a 2 times higher risk of disease progression or recurrence.

There was no significant impact of negative microscopic resection margins (aHR, 0.9; 95% CI, 0.4-2.2; P = .86) or type of gastric resection (P = .67) on event-free survival.

Repeated resection following the initial resection was significantly associated with reduced postoperative event-free survival (P < .01).

These findings suggest that disease progression or recurrence may be more closely related to tumor biology than surgical management. The authors concluded that subsequent resections after the initial procedure for wild-type GISTs be performed only to eliminate symptoms such as obstruction or bleeding.

Lower-intensity Intensification Therapy in Childhood ALL Pediatric patients with acute lymphoblastic lymphoma (ALL) at standard risk for relapse do not benefit from lower-intensity, delayed intensification therapy, according to a study

presented during the plenary session of the American Society of Hematology (ASH) 58th Annual Meeting and Exposition.

To evaluate the efficacy of reduced treatment burden in this group of patients with best treatment response and the lowest risk of relapse, researchers randomly assigned 1164 pediatric patients with ALL to receive protocol III or standard protocol II for delayed re-intensification. Protocol III is shorter than protocol II by 20 days, and includes 50% lower doses of vincristine, doxorubicin, and cyclophosphamide, and a 30% lower dose of dexamethasone vs standard therapy.

“Only the most favorable patients selected by excellent minimal residual disease response were randomized aiming at a reduction in cumulative doses,” said investigator Martin Schrappe, MD, of the department of general pediatrics, ALLBFM Study Group at the Christian-Albrechts University Kiel and University Medical Center Schleswig-Holstein in Germany.

After a median follow-up of 8.6 years, results showed that 90.7% of patients who received protocol III were event-free at 5 years compared with 94.7% of those given protocol II. The cumulative incidence of relapse at 5 years was 14.3% in the protocol III group and 1.2% in the protocol II group (P = .02), though there was no significant difference in overall survival between the 2 arms.

“In B-precursor ALL, we observed 50% more relapses in less-intensively treated patients,” Dr Schrappe added.

The 8-year cumulative incidence of secondary malignancies was 1.3% with protocol III and 0.68% with protocol II, while the rate of grade 3 to 4 infections was similar between the groups.

Sentinel Lymph Node Biopsy Recommended for Patients With Sarcoma Sentinel lymph node biopsies (SLNB) are more reliable position-emission tomography/computed tomography (PET-CT) for assessing lymph node metastases among young patients with sarcoma, according to a study published in Cancer.

Identifying nodal metastases in this patient group is important for determining treatment. Researchers enrolled 28 young patients, which included pediatric patients through young adults, to determine whether SLNB with single-photon emission computed tomography/computed tomography (SPECTCT) is a more effective test than PET-CT. Three of the 7 patients with nodal metastases identified by SLNB tested normal with PET-CT scans. An image developed by a PET-CT scan that indicated nodal metastases was only 29% likely to be correct.

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© THINKSTOCK

Resections for Wild-type GISTs Should Be Restricted to Initial Procedures

PEDIATRIC CANCER

Dabrafenib Shows Promising Activity in BRAF+ Low-grade Gliomas Targeted therapy with dabrafenib is active and well-tolerated among patients with relapsed or refractory BRAF V600-positive pediatric low-grade glioma, according to a presentation at ESMO 2016 Congress.

Approximately 15% to 20% of children with low-grade glioma harbor BRAF V600 mutations, and these patients have historically worse survival and lower objective response rates to first- and second-line chemotherapy relative to patients with BRAF V600 wild-type disease. Researchers evaluated the activity of targeted BRAF inhibition with dabrafenib among pediatric patients with recurrent or progressive disease.

For the open-label, phase 1/2a study, investigators enrolled 32 patients aged 2 to 17 years with BRAF V600-mutant relapsed or refractory low-grade glioma. Overall, 24 patients received the recommended phase 2 dose of second-line dabrafenib.

The overall response rate was 41% per independent review, which included 2 complete responses and 11 partial responses.

Median duration response was 11 months; 8 responses were ongoing at the time of analysis.

The confirmed overall response rate per investigator assessment was 72% (95% CI, 53-86), which included 1 complete response and 2 partial responses.

FDA Approves Blinatumomab for Pediatric B-cell Precursor ALL The U.S. Food and Drug Administration (FDA) granted accelerated approval to blinatumomab (Blincyto) for the treatment of pediatric patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Approval of this supplemental Biologics License Application is based on findings from Study â&#x20AC;&#x2DC;205, an open-label, multicenter, single-arm trial, which assessed the efficacy and safety of blinatumomab among 93 children with relapsed or refractory B-cell precursor ALL.

In May 2016, it was reported that the trial met its phase 2 primary end point of complete remission within the first 2 cycles of immunotherapy.

Continued approval may be contingent upon verification of clinical benefit in additional studies.

The most common grade 3 or worse treatment-related adverse events with the recommended dose were anemia, neutropenia, febrile neutropenia, thrombocytopenia, and hypokalemia.

Clinicians should be aware that blinatumomab may cause life-threatening or fatal cytokine release syndrome, and neurological toxicities that may be severe, life-threatening, or fatal.

Childhood CML Survival Worst for Children Under 5 Years Old Although the development of kinase inhibitors coincides with revolutionized clinical outcomes in pediatric patients with chronic myeloid leukemia (CML), age disparities in survival remain substantial, according to a study published in the European Journal of Cancer.

The use of molecular therapies has improved therapeutic outcomes in adult patients with CML. Researchers therefore evaluated trends in survival and geographic disparities among children with CML prior to and after the introduction of kinase inhibitors in the United States and Southeastern Europe.

Investigators analyzed data from 369 patients aged 0 to 14 years with CML, as well as patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Patients were included in 14 Southeastern European cancer registries and the Surveillance, Epidemiology, and End Results (SEER) database.

Among children with CML, 2-year survival ranged from 81% to 89% in the post-kinase inhibitor era compared with 49% to 66% in the pre-kinase inhibitor period, suggesting a 63% reduction in the risk of death with the introduction of targeted therapies (hazard ratio [HR], 0.37; 95% CI, 0.23-0.60).

Subgroup analyses showed that children aged younger than 5 years had a 3 times higher risk of death than those aged 10 to 14 years (HR, 3.03; 95% CI, 1.85-4.94), and patients living in Southeastern Europe had a 56% higher death risk than those treated in the United States (HR, 1.56; 95% CI, 1.01-2.42).

Age appeared to be a significant predictor of CML survival regardless of geographic area and period of kinase inhibitor administration. For example, among patients younger than 5 years, risk of death was 2.7 times higher than older children in the pre-kinase inhibitor period (HR, 2.71; 95% CI, 1.534.79) and 3.4 times higher in the era after the introduction of kinase inhibitors (HR, 3.38; 95% CI, 1.29-8.85).

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The authors conclude that SLNB is superior to PET-CT for determining whether a young patient with sarcoma has nodal metastases. No patient who underwent SLNB had any biopsy-related infections.

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IN THE CLINIC | BY C. ANDREW KISTLER, MD, PharmD, RPh

Hyperthermic Intraperitoneal Chemotherapy in Colorectal Cancer With Peritoneal Carcinomatosis CRS and HIPEC appear to have promising data when used in the optimal patient population.

C

Š SCOTT CAMAZINE & SUE TRAINOR / SCIENCE SOURCE

olorectal cancer (CRC) is the third most common cancer diagnosed in the United States.1 Unfortunately, up to 20% of new CRC cases have metastases at the time of diagnosis. The most common sites of metastatic disease in CRC are the liver, lung, and peritoneum. Close to 5% of patients with CRC will present with peritoneal carcinomatosis (PC), and have an average 6-month survival if not treated.2 Even when these patients are treated with systemic chemotherapy, survival outcomes are worse in contrast with those patients with distant metastases (12.7 vs 17.6 months).

Overall, stage IV patients with CRC and PC have limited treatment options and worse survival.

One treatment modality that is accumulating data for patients with CRC and PC is hyperthermia intraperitoneal chemotherapy (HIPEC) combined with cytoreduction surgery (CRS). One of

One of the many challenges of treating PC in stage IV CRC is drug delivery.

Metastases in the liver caused by colon adenocarcinoma.

A18 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

the many challenges of treating PC in stage IV CRC patients is drug delivery.

It is often difficult to attain adequate drug levels within the peritoneum. If chemotherapy doses are subsequently increased in attempts to raise drug concentrations, the patient is exposed to more systemic side effects. HIPEC aims to deliver chemotherapy directly to the peritoneum, which can increase local drug concentrations, as well as reduce the total systemic exposure from the chemotherapy.

HIPEC is typically preceded by CRS. CRS assists in removing as much peritoneal disease as possible, so that HIPEC can have the best local exposure possible. The patient must be thoroughly evaluated for CRS, as many patients may not be candidates for surgery. Potential contraindications to CRS include extensive intra-abdominal lymph node metastases and extensive small bowel involvement. In addition to PC, many patients with prior intra-abdominal surgical history may have adhesions that can be cleared to help increase chemotherapy exposure.

HIPEC can be administered directly into the peritoneal cavity after CRS. There are at least 3 prognostic scales to consider using when evaluating a patient for CRS and HIPEC, which include the colorectal peritoneal (COREP) score, prognostic score (PS), and peritoneal surface disease severity score (PSDS).3 Although there is no consensus on which prognostic score is the best to use, much of the recent data support the COREP score.

As CRS and HIPEC are still accumulating data, there are a limited number of clinical trials off which to base regimens. One study showed a median overall survival of 19.2 months in patients treated with CRS and HIPEC.4 The overall survival was increased to approximately 32 months when there

IN THE CLINIC was complete CRS. Another study demonstrated an overall median survival advantage when comparing CRS and HIPEC (22.3 months) to palliative surgery combined with systemic chemotherapy (12.6 months).5 A systematic review reported improved medial survival—33 vs 12.5 months—and 5-year survival—40% vs 13%—when comparing CRS and HIPEC to palliative surgery and systemic chemotherapy.6 The same chemotherapy that is used in the intravenous form is not always used for HIPEC. The ideal agents for HIPEC have advantageous pharmacokinetic profiles that will have limited systemic absorption and an increased effect with heat. Mitomycin C and 5-fluorouracil have both been used for HIPEC. CRS and HIPEC do appear to have

promising data when used in the optimal patient population. It is important, when considering CRS and HIPEC, that a patient reviews an institution’s experience with this collaborative treatment approach. ■

intraperitoneal chemotherapy. Ann Surg

Oncol. 2013;20(13):4183-9.

4. Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer:

References

a multi-institutional study. J Clin Oncol.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30.

2. Spiliotis J, Halkia E, de Bree E. Treatment of peritoneal surface malignancies with hyperthermic intraperitoneal chemotherapy-current perspectives. Curr Oncol.

2016;23(3):e266-75.

2004;22:3284-92.

5. Chua TC, Esquivel J, Pelz JO, Morris DL. Summary of current therapeutic options for peritoneal metastases from colorectal cancer. J Surg Oncol. 2013;107:566-73.

6. Verwaal VJ, van Ruth S, de Bree E, et al.

Randomized trial of cytoreduction and

3. Cashin PH, Graf W, Nygren P, Mahteme

hyperthermic intraperitoneal chemotherapy

H. Comparison of prognostic scores

versus systemic chemotherapy and palliative

for patients with colorectal cancer

surgery in patients with peritoneal carcino-

peritoneal metastases treated with

matosis of colorectal cancer. J Clin Oncol.

cytoreductive surgery and hyperthermic

2003;21:3737-43.

CRS/HIPEC Contrasted With Palliative Surgery/Systemic Chemotherapy Cytoreduction surgery (CRS) and hyperthermia intraperitoneal chemotherapy (HIPEC) is a treatment combination being used increasingly frequently for patients with colorectal cancer with peritoneal carcinomatosis. Below is a breakdown of the advantages and disadvantages of CRS and HIPEC contrasted with those of palliative surgery and systemic chemotherapy.

▶ CRS/HIPEC

▶ Palliative

• HIPEC post-CRS is directed to the peritoneum to reduce systemic-level side effects.

• Overall survival may range from 20 to 63 months (median 33). Five-year overall survival may range between 17% and 51% (median 40%).1 • Prognostic scales (eg, COREP) should be considered before treatment.

• Grade 3 to 4 adverse events include leukopenia, gastrointestinal fistula, and hemorrhage.2

Surgery/ Systemic Chemo • Overall survival may range from 5 to 24 months (median 12.5). Five-year overall survival may range from 13% and 22% (median 13%).1 • Patient is exposed to systemic-wide effects of chemotherapy.

• More patients can undergo this treatment than CRS/HIPEC.

References 1. Chua TC, Esquivel J, Pelz JO, Morris DL. Summary of current therapeutic options for peritoneal metastases from colorectal cancer. J Surg Oncol.

2013;107:566-73.

2. Verwaal VJ, van Ruth S, de Bree E, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21:3737-43.

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FEATURE

Watson: A Promising Tool or a Glorified Search Engine?

Watson, hoped to be a useful tool for clinicians, is limited by an inability to interpret clinical trials.

BY NICOLAI WOHNS, MD Dr Wohns is a senior resident in internal medicine at Boston Medical Center. His interests lie at the intersection of medicine and philosophy. He studied medicine at The Pennsylvania State University College of Medicine, philosophy at University College London, and mathematics at Northwestern University.

find phrases in its database that are associated with the question. The more algorithms that find the same answer, the more likely Watson is to be correct.

This simplicity belies the sophisticated technology responsible for its power, composed of advanced natural language processing, knowledge representation, and machine learning capabilities.2 In 2011, Watson also broke out on the health care scene, when IBM partnered with Columbia University in New York and the University of Maryland in College Park to identify the best way to exploit its clinical decision-making technology.3 In October 2016, IBM and Quest Diagnostics, a genomic sequencing and oncology diagnostics company, in collaboration with Memorial Sloan Kettering Cancer Center (MSKCC) in

New York, New York, and the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, launched Watson Genomics, promising to revolutionize personalized cancer care.

Researchers at IBM believe that oncology can uniquely benefit from the powers of Watson, with specific promises to make treatment recommendations and connect patients with ongoing clinical trials. Its procedure goes as follows: first, Quest will sequence the genome of the tumor.

Watson Genomics then takes this product and compares the specific genetic mutations in the tumor to those at its disposal. This now includes not only the medical literature available publicly, but also MSKCC’s and the Broad Institute’s databases.4 There are, however, several obstacles

Oncologists are trying to use Watson to identify targeted treatment options.

A20 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

© JARED LAZARUS / FEATURE PHOTO SERVICE FOR IBM

T

he power of big data and cognitive computing technology is lost on no one. Its areas of application range from the analysis of biochemical networks to management consulting and the Twitter-sphere.

IBM’s Watson is 1 of the most conspicuous players in the arena. It is an advanced question-answering computer system that is perhaps most famous for winning the quiz show Jeopardy in 2011.1 Watson works by taking questions formed in simple English, parsing them into keywords and phrases, and then applying hundreds of language analysis algorithms simultaneously to

© JARED LAZARUS / FEATURE PHOTO SERVICE FOR IBM

FEATURE that may prevent contributions by Watson to clinical care.

Clinical trials are carefully designed to expose 1 or many variables to establish causal links in oncology. But there are confounding variables and hidden biases that complicate the studied phenomena, though researchers take many steps to limit their influence.

They publish research protocols and statistical goals before the research is undertaken. They randomize subjects and gather and compare ethnographic and clinical information. Even with these techniques, however, there remain elements that pervert the validity of a trial. “Controlling” for certain variables exists on a spectrum, not in a binary fashion where they are either “controlled for” or “not controlled for.” There are unforeseen factors and inherent biases in design and implementation that influence study outcomes. It is unclear whether considerations of external validity, or the extent to which a study bears on a given patient or population, also pose a problem for Watson.

It may even compound the problem by perpetuating a study’s biases into its final report, giving it a patina of objectivity it lacks in reality.

Watson’s greatest and most impressive advantage is its ability to swiftly analyze the vast corpus of oncology literature.

Physicians and patients alike dream of a computing system that can aggregate information about every cancer that has been sampled and, by accessing the world’s databases and analyzing outcome data, deliver new and life-saving insights into novel therapies for any given patient.

Watson is not, however, the realization of this dream: it does not crunch the raw data to arrive at new conclusions. Watson can only search what has already been studied to bring it to bear on a posed question, establishing

statistical relationships between fragments of information based on available literature. It cannot evaluate the raw data behind the literature and therefore cannot arrive at novel conclusions about, say, a specific genetic mutation.

All in all, it is a sophisticated but superficial search engine.

Suppose we send a blood sample of a patient with chronic lymphocytic leukemia (CLL) for analysis with next-generation sequencing, a parallel sequencing approach that is routinely employed. This provides a tremendous amount of molecular profiling data, creating millions of snippets of sequenced DNA that are then recom-

There are inherent biases in design and implementation that influence study outcomes. posed by computerized algorithms. Of the many genetic alterations identified with this technology, there will be a handful associated with specific therapeutic considerations. Let’s say that 1 in particular, the CARD11 gene, is associated with resistance to ibrutinib, a monoclonal antibody that is the standard of care for relapsed or refractory CLL with 11q deletion. Watson’s algorithms may not identify that the patient’s leukemia would be resistant to ibrutinib, which would be a mistake, because CARD11 mutations have been studied only in large B-cell lymphoma, not extensively in CLL. It is possible that Watson’s impressive array of algorithmic systems can be adjusted to analyze the unfiltered data in MSKCC’s and the Broad Institute’s databases. Its most reliable service,

however, may simply be to identify promising references to be reviewed by the researcher and clinician.

IBM recently announced a new partnership with Illumina, a competing sequencing company to Quest.

Physicians using Illumina’s service will now be among those who benefit from Watson’s analysis. This is simply an expansion of Watson’s domain, however, not a change in tactic or a technological upgrade. Although Watson’s capabilities are essentially search functions—albeit ones that are extremely powerful—Watson is poised to further expand its influence in personalized cancer care, doubtlessly helping many physicians and patients in the process.

Systems of artificial intelligence, like Watson, have the ability to learn from their past analyses. They can correct prior misalignments to optimize found matches and maximize statistical relevance. It will, however, require a large amount of input and constant feedback from researchers and physicians to train machine learning models. It remains to be seen how patient data will be used for this purpose. ■ References 1. Ferrucci DA. Introduction to “This is Watson”.

IBM J Res Dev. 2012;56:1-15. doi: 10.1147/ JRD.2012.2184356 2. Thompson C. What is I.B.M.’s Watson? The

New York Times Magazine website. http:// www.nytimes.com/2010/06/20/magazine/ 20Computer-t.html. Updated June 16, 2010.

Accessed November 2016.

3. Wakeman N. IBM’s Watson heads to medical school. Washington Technology website. https://washingtontechnology.com/articles/2011/02/17/ibm-watson-next-steps. aspx. Updated February 17, 2011. Accessed November 2016.

4. IBM Watson for Genomics. IBM website. http://www.ibm.com/watson/health/oncology/genomics/. Accessed November 2016.

CancerTherapyAdvisor.com | JANUARY/FEBRUARY 2017 | CANCER THERAPY ADVISOR A21

VIEWPOINT | BRYANT FURLOW

Developing microRNA Biomarkers To Detect and Treat Prostate Cancer Short, noncoding regulatory stretches of microRNA hold promise as prostate cancer biomarkers.

W

orldwide, prostate cancer is the most common malignancy diagnosed in men.

Early detection is a challenge, however, as prostate-specific antigen (PSA) tests remain controversial and imprecise, contributing to overtreatment. While prognostic and treatment outcome– predicting molecular biomarkers are available for other cancer types, similar tools have proven elusive for prostate cancer. Several research teams around the world are now developing biomarker microRNAs (miRNAs)—small bits of non–protein coding RNA involved in gene regulation and typically containing fewer than 25 nucleotides.1,2 miRNAs are dysregulated in different cancer types, including prostate cancers. miRNAs can be extracted from tissues, blood, serum, plasma, or urine; their short sequence length renders them less fragile and more persistent in tissues and biofluids than longer nucleic acid sequences, which tend to fragment, noted Olorunseun O. Ogunwobi, MD, PhD, an associate professor at Hunter College of the City University of New York.

Structural stability in tissues and biofluids implies improved reproducibility in testing, Dr Ogunwobi noted. These molecules are promising targets for the development of both prognostic biomarkers and drugs.

“Understanding their roles in cancers such as their differential expression in

the different stages of cancer may result in the discovery of prognostic biomarkers as well as possible therapeutic targets,” he told Cancer Therapy Advisor.

“The 8q24 human chromosomal region contains the long non–protein coding gene locus, PVT1. The PVT1 gene locus is dysregulated in prostate cancer. The PVT1 gene locus encodes 6 miRNAs: miR-1204, miR-1205, miR-1206, miR1207-3p, miR-1207-5p, and miR-1208.”

These molecules are promising targets for the development of both prognostic biomarkers and drugs.

Dr Ogunwobi’s laboratory has been working to understand the role of the PVT1 locus and its miRNAs in prostate cancer. They discovered that miR1207-3p, in particular, is “significantly underexpressed” in prostate cancer cell lines compared with normal prostate epithelial cells. Its increased expression inhibits prostate tumor cell proliferation and migration and induces apoptosis.

There is also early evidence that miR-1207-3p underexpression might be involved in the development of prostate cancer and tumor progression.

A22 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

“For reasons still unclear, the incidence of prostate cancer is highest among men of African ancestry (moAA),” Dr Ogunwobi said.

Early detection could help to reduce the United States’ racial disparity in prostate cancer mortality, he noted. He hopes that miR-1207-3p will prove to be the right tool for that job.

“Our study demonstrated that 2 of the 3 prostate cancer cell lines from moAA have the least expression of miR-12073p, and that overall, the prostate cancer cell lines from moAA have less miR1207-3p expression than cell lines from Caucasian males,” he said. “Also, miR1207-3p expression is comparable in both indolent and aggressive cellular models of prostate cancer derived from moAA, suggesting that loss of miR1207-3p may already be present in early prostate cancer.”

The team’s recent study on miR-12073p’s potential as a prognostic biomarker found, among other things, that its expression in prostate tumor tissue is lower among patients of African ancestry than European ancestry.

Dr Ogunwobi believes that his lab’s work thus far shows that miRNA-12073p is a promising biomarker candidate for aggressive prostate cancer. They are now analyzing its expression in normal prostate tissue and benign prostate enlargement—as well as in prostate tumor tissue from a large cohort of patients that includes moAA. ■ References 1. Fabris L, Ceder Y, Chinnaiyan AM, et al. The potential of microRNAs as prostate cancer biomarkers. Eur Urol. 2016;70(2):312-22. doi: 10.1016/j.eururo.2015.12.054 2. Das DK, Osborne JR, Lin HY, Park JY, Ogunwobi OO. miR-1207-3p is a novel prognostic biomarker of prostate cancer. Translat

Oncol. 2016;9(3):236-241. doi: 10.1016/j. tranon.2016.04.005

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EXPERT PERSPECTIVE | JASON HOFFMAN, PharmD, RPh

Seven States Approve Some Form of Marijuana Initiative Cancer Therapy Advisor spoke with Judith A. Paice, PhD, RN, to better understand how clinicians are reacting to these legalizations and how she responds to patients asking about cannabis use.

A

rkansas, California, Florida, M a i n e , M a s s a c hu s e t t s , Nevada, and North Dakota approved some form of marijuana initiative on Election Day in 2016, potentially reducing barriers for patients with cancer hoping to use marijuana to relieve symptoms of pain or to increase appetite as an alternative to approved medications.

On November 8, 2016, voters in California, Maine, Massachusetts, and Nevada approved initiatives for the legalization of marijuana, while people in Arkansas, Florida, and North Dakota voted to approve marijuana for medical usage. Voters in Montana also approved an initiative to repeal a 3-patient limit for medical marijuana providers.

The American Society of Clinical Oncology (ASCO) does not have a position on the legalization of marijuana, though the psychoactive drug is listed as a potential adjuvant analgesic and as a possible management strategy for refractory pain conditions in the ASCO clinical practice guideline for the management of chronic pain in survivors of adult cancer.

“As of this writing, 23 states and the District of Columbia allow for medical cannabis, although it is illegal on the federal level. Currently, there is insufficient evidence to recommend medical cannabis for the first-line management of chronic pain in cancer survivors,” the ASCO guideline states. “Evidence suggests it is worthy of consideration as an adjuvant analgesic or in the management of refractory pain conditions.

There is also insufficient evidence to recommend 1 particular preparation of cannabis over another, and the U.S. Food and Drug Administration has not approved any drug product containing or derived from botanical marijuana.”1 Based on intermediate quality of evidence, ASCO recommends that clinicians follow specific state regulations that allow access to medical cannabis or cannabinoids for patients with chronic pain.

Cancer Therapy Advisor spoke with guideline author Judith A. Paice, PhD, RN, a professor of medicine at Northwestern University Feinberg School of Medicine and an oncology nurse at Lurie Comprehensive Cancer Center in Chicago, Illinois, to better understand how oncology clinicians are

reacting to these legalizations and how she responds to patients asking about cannabis use.

Cancer Therapy Advisor: How often do patients ask about marijuana use and for what reason are they asking?

DR PAICE: Patients frequently ask about the use of marijuana or cannabis. One reason they are asking is that they have unrelieved symptoms. They might have adverse effects to the medications that we are providing to treat their pain or other symptoms. For example, because opioids cause constipation, people are looking for alternatives to traditional medicine. Because there has been so much media attention to the cannabinoids, people think that they must be really quite effective.

Cancer Therapy Advisor: How do you counsel patients asking about cannabis use?

DR PAICE: The 2 most important points that I counsel patients about are the 3 the types of cannabis that exist and the different routes of administration. The 3 different types of cannabis are our body’s own endogenous cannabinoids, the phytocannabinoids (which is what most people are doing when they are smoking cannabis) and synthetic cannabinoids like dronabinol (Marinol).

The reason it’s so important to talk about those 3 types is because patients may be listening to reports that are not specific as to the type studied.

There are more data about synthetic cannabinoids, but there are a few studies about the phytocannabinoids for nerve pain, particularly in cancer and

The reason it’s so important to talk about the 3 types [of cannabis that exist] is because patients may be listening to reports that are not specific as to the type studied.

A24 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

EXPERT PERSPECTIVE in HIV. The reason that there are not many studies about the phytocannabinoids is because up until recently, the National Institutes of Health (NIH) was not awarding many grants.

The different routes of administration are also important for patients to understand. Cannabis can be inhaled via a joint or vaporizer, which may limit the amount of harsh chemicals that might be inhaled. The ingested route includes eating food substances that contain cannabis oil, and there are oils that can be applied topically at the site of pain. We really have data only about inhaled forms with respect to analgesic efficacy, but the challenge about oils is that we have no data on those.

We do have a bit of knowledge about the onset, which has important implications for patients. When you smoke or inhale, you get blood levels in 2 to 5 minutes, but when you ingest it, the bioavailability is delayed and the onset can be 2 to 6 hours. This has been causing

some difficulties in states where cannabis is legal recreationally where tourists are consuming more cannabis because they are not feeling immediate effects.

Cancer Therapy Advisor: Do you think that the approval of these ballot initiatives is a positive step toward increased access to cannabis fo r patients seeking additional symptom relief?

DR PAICE: There are insufficient data on the use of medical cannabis in patients with cancer. We would like to see more data about both the benefits and the potential harms. In all of the studies conducted in patients with cancer pain, they were studying patients who were already taking opioids, and as a result, we do not know whether cannabis should be used in the firstline setting. â&#x2013;

Cancer Therapy Advisor: Anecdotally, w h a t a r e p a t i e n t s u s i n g phyto c a n n a b i n o i d s a n d s y n t h e t i c cannabinoids for, and do they think these agents have been helpful?

DR PAICE: Dron abi nol i s now approved by the U.S. Food and Drug Administration for the use of AIDSrelated anorexia. I do find for some patients that dronabinol can be useful for improving appetite, and I certainly see that with the phytocannabinoids too.

The benefits that patients report from using phytocannabinoids include pain control, improved appetite, anxiolysis, and improved sleep. Those are the most common uses that I hear anecdotally from patients. Some patients tell me taking a few puffs before bedtime helps to relax and reduce pain.

Reference 1. Paice JA, Portenoy R, Lacchetti C, et al. Management of chronic pain in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline.

J Clin Oncol. 2016;34(27):3325-45.

Approval of Medical Cannabis by State1 WA

NH

1998

MT

2004

OR

VT

ND

2016

1998

ME

2013

1999

2004

MN

2014

NY

2014

MI

2008

MA

2012

RI CT 2006 NJ 2012

2010

NV

2000

DE MD 2012

IL

2013

CO

CA

2014

2000

1996

DC

2010

AZ

2010

NM

2007

AR

2016

Medical cannabis approvals AK

1998

FL

New approvals as of November 8, 2016

2016

HI

2000

Reference 1. Wilkie G, Sakr B, Rizack T. Medical marijuana use in oncology: a review. JAMA Oncol. 2016 Mar 17. doi: 10.1001/jamaoncol.2016.0155 [Epub ahead of print]

CancerTherapyAdvisor.com | JANUARY/FEBRUARY 2017 | CANCER THERAPY ADVISOR A25

REGIMEN & MONOGRAPH INDEX CANCER THERAPY REGIMENS & DRUG MONOGRAPHS 1

Bone Cancer

3 Brain Cancer 5 Breast Cancer 12 Endocrine Cancer 16 Gastrointestinal Cancer

 Colon Cancer

 Hepatocellular Carcinoma

26 Genitourinary Cancer 35 Gynecologic Cancer 37 Head and Neck Cancer 39 Hematologic Cancer  Non-Hodgkin Lymphoma: Diffuse Large B-cell Lymphoma

63 Lung Cancer

 Non-small Cell Lung Cancer

 Small Cell Lung Cancer

81 Sarcoma

 Soft Tissue Sarcoma

84 Skin Cancer 89 Associated Hematological Disorders To view the complete collection of cancer treatment regimens for all cancer types visit CancerTherapyAdvisor.com/TreatmentRegimens.

To view the complete collection of drug monographs visit CancerTherapyAdvisor.com/DrugMonographs.

A26 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

IMPORTANT INFORMATION FOR ALL READERS CANCER THERAPY ADVISOR (CTA) is an up-to-date guide to commonly prescribed pharmaceuticals, as well as certain OTC products. It has been produced to provide an easily accessible reminder of basic information useful to review when prescribing medications, such as specific indications for use, dosage, and a checklist of precautions, interactions, and adverse drug reactions. Reference should always be made to each drug being coadmin­ is­tered. The information it contains is intended solely for use by the medical profession. IT IS NOT INTENDED FOR LAY READERS. This reference has been assembled and edited by an experienced staff of pharmacists uti­ liz­ing information available from FDA-approved labeling.

Distinctions have not necessarily been made between those reactions that are well-documented and/or clinically significant, and those that carry only a theoretical risk. A renowned board of consulting medical specialists has also independently reviewed the product references.

However, although every effort is made to assure accuracy, the information in CTA is not necessarily reviewed by the supplier of a particular drug. If any questions arise about information in CTA, the physician should verify it against labeling or by contacting the company marketing the drug. The publisher and editors do not warrant or guarantee any of the products described or the information describing them. THE PUBLISHER AND EDITORS DO NOT ASSUME, AND HEREBY EXPRESSLY DISCLAIM ANY LIABILITY WHATSOEVER FOR ANY ERRORS OR OMISSIONS IN SUCH INFORMATION OR FOR ANY USE OF ANY OF THE PRODUCTS LISTED. No prescription drug should be used except on the advice of, and as directed by, a physician. The training and experience of a physician are essential to forming any opinion on the appropriateness of a specific drug for a specific patient. The information in this publication is not by itself sufficient for a lay person—or even a physician—to evaluate the risks and benefits of taking any particular drug.

In reaching professional judgments on whether to prescribe a pharmaceutical, which to prescribe, and under what regimen, the physician should thoroughly understand the options available for any clinical application, the potential effectiveness of each product, and the associated risks and side effects. This knowledge should be considered in light of the special circumstances of the patient, for each patient is unique. No single reference can substitute for medical training and experience. The physician must be familiar with the full product labeling, provided by the manufacturer or distributor of the drug, of every product he or she prescribes, as well as the relevant medical literature.

Certain additional qualifications are important in using this book. First, CTA has been deliberately kept concise, with a standardized format, so that it could be a convenient reference tool. This means that lengthy and detailed explanations about certain aspects of drugs commonly found in labeling are omitted or condensed.

Second, by revising and reprinting quarterly, CTA should be one of the most up-to-date guides to prescription drugs now available in print. Only the current issue should be used.

The prescribing decision is ultimately the responsibility of the physician. CTA is offered to assist physicians in this area. © 2017 Haymarket Media, Inc.

DRUG MONOGRAPHS

BONE CANCER HALAVEN Eisai

℞

Non-taxane microtubule dynamics inhibitor.

Eribulin mesylate 0.5mg/mL, soln for IV inj.

Indications: Treatment of unresectable or metastatic liposarcoma in patients who have received prior anthracycline-containing regimen.

Adults: Give by IV inj over 2–5mins. 1.4mg/m² on Days 1 and 8 of a 21-day cycle. Mild hepatic impairment (Child-Pugh A) or moderate-to-severe renal impairment (CrCl 15–49mL/min): 1.1mg/m² on Days 1 and 8 of a 21-day cycle. Moderate hepatic impairment (Child-Pugh B): 0.7mg/m² on Days 1 and 8 of a 21-day cycle. Hold dose for ANC <1000/mm³, platelets <75000/mm³, or grade 3 or 4 non-hematological toxicities. Delay or reduce dose according to toxicities; see full labeling. Do not re-escalate dose after it is reduced.

Children: <18yrs: not established.

Warnings/Precautions: Monitor CBCs prior to each dose; increase frequency of monitoring if grade 3 or 4 cytopenias develop, delay and reduce subsequent doses if febrile neutropenia or grade 4 neutropenia lasting >7 days develops.

Monitor for peripheral neuropathy; withhold dose if grade 3 or 4 peripheral neuropathy develops until resolution to grade 2 or less. Congenital long QT syndrome: avoid. CHF, bradyarrhythmias, electrolyte abnormalities: monitor ECG for prolonged QT interval. Correct electrolyte abnormalities (K+, Mg+) before treatment; monitor. Severe hepatic impairment (Child-Pugh C): insufficient data. Pregnancy. Use effective contraception during treatment and for ≥2 weeks (females) or 3.5 months (male partners) after final dose. Nursing mothers: not recommended (during and for 2 weeks after final dose).

Interactions: Caution with other drugs that prolong QT interval (eg, Class IA and III antiarrhythmics); monitor.

Adverse reactions: Neutropenia, anemia, asthenia/fatigue, alopecia, peripheral neuropathy, nausea, constipation, abdominal pain, pyrexia, hypokalemia, hypocalcemia; febrile neutropenia, possible QT prolongation, elevated liver enzymes.

Note: Do not mix with dextrose-containing solutions. Do not administer in same line as other drugs or fluids.

How supplied: Single-use vial (2mL)—1

LARTRUVO Lilly

℞

PDGFR-alpha inhibitor. Olaratumab 500mg/50mL; soln for IV infusion; preservativefree.

Indications: In combination with doxorubicin, for the treatment of adults with soft tissue

sarcoma with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery.

Adults: Premedicate with IV diphenhydramine and IV dexamethasone prior to infusion on Day 1 of cycle 1. Give with doxorubicin for the first 8 cycles: refer to doxorubicin PI for dosing and modifications. Give by IV infusion over 60mins.

15mg/kg on Days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.

Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Have resuscitative equipment available. Monitor for signs/symptoms of infusion-related reactions during and postinfusion. Permanently discontinue for Grade 3/4 infusion-related reactions; interrupt for Grade 1/2 infusion-related reactions; resume at 50% of initial rate after resolution. If neutropenic fever/infection or Grade 4 neutropenia lasts >1 week, discontinue until ANC ≥1,000μL then permanently reduce dose to 12mg/kg. Embryofetal toxicity. Females of reproductive potential should use effective contraception during and for 3 months after last dose. Pregnancy. Nursing mothers: not recommended (during and for 3 months after last dose).

Adverse reactions: With doxorubicin: nausea, fatigue, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, headache, anxiety, dry eyes, lymphopenia, neutropenia, thrombocytopenia, hyperglycemia, elevated aPTT, hypokalemia, hypophosphatemia, increased alkaline phosphatase.

How supplied: Single-dose vial—1

Methotrexate injection

℞

Bedford

Folic acid antagonist. Methotrexate 25mg/mL; soln for IV, IM, intra-arterial, or intrathecal administration after dilution; preservative-free. ℞ Also: Methotrexate for injection Methotrexate 1g/vial; pwd for IV, IM, intra-arterial, or intrathecal administration after dilution; preservative-free.

Indications: Non-metastatic osteosarcoma in patients who have undergone surgical resection or amputation for the primary tumor (high-dose therapy with leucovorin rescue).

Adults: Initially 12g/m2 IV infusion over 4 hours; may be increased to 15g/m2; see literature for leucovorin rescue dosing with high-dose methotrexate.

Children: See literature.

Contraindications: Pregnancy (Cat. X). Nursing mothers.

Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Discontinue if malignant lymphomas occur. Obtain baseline and monitor CBCs with differential, platelet counts, chest X-ray, and hepatic, renal and pulmonary function. During therapy monitor hematology monthly, renal and hepatic function every 1–2 months, more often if increasing dose or predisposed to toxicity (eg, dehydration).

Discontinue immediately if blood counts drop significantly. Rule out pregnancy in women of childbearing potential; use effective contraception during therapy and for at least 1 ovulatory cycle afterwards for women and for at least 3 months afterwards for men. Interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur. Hepatic or renal impairment. Obesity.

Diabetes. Peptic ulcer. Ulcerative colitis. Infection.

Dehydration. Folate deficiency. Ascites, pleural effusions: evacuate fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated.

Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin, sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, non-absorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy.

Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin).

Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, StevensJohnson syndrome).

How supplied: Soln (2mL, 4mL, 8mL, 10mL)—10 (single-use vials); pwd (1 gram)—1 (single-use vial)

VOTRIENT GlaxoSmithKline

℞

Tyrosine kinase inhibitor. Pazopanib 200mg; tabs.

Indications: Advanced soft tissue sarcoma in patients who have received prior chemotherapy.

Limitation of use: not for treating adipocytic soft tissue sarcoma or gastrointestinal stromal tumors.

Adults: Take on an empty stomach. Swallow whole.

800mg once daily. Dose adjustments: see full

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DRUG MONOGRAPHS

BONE CANCER labeling. Hepatic impairment: moderate: 200mg once daily; severe: not recommended. Concomitant strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir, clarithromycin): avoid and consider alternate drug; if warranted, reduce dose of pazopanib to 400mg; may reduce further if toxicity occurs. Concomitant strong CYP3A4 inducers (eg, rifampin): avoid and consider alternate drug.

Children: Not established.

Warnings/Precautions: Not indicated for use in combination with other cancer agents. Risk of severe and fatal hepatotoxicity (esp. ≥65yrs old).

Monitor liver tests before starting and at Weeks 3, 5, 7, and 9, thereafter at Months 3 and 4, then periodically. If ALT between 3xULN and 8xULN continue therapy with weekly monitoring until ALT returns to Grade 1 or baseline. If ALT >8xULN interrupt therapy until ALT returns to Grade 1 or baseline; may consider reintroducing at a reduced dose, measure liver tests weekly for 8 weeks; if ALT>3xULN recurs, permanently discontinue.

Permanently discontinue if ALT>3xULN and bilirubin >2xULN. Gilbert’s syndrome (see full labeling). History of QT prolongation. Cardiac dysfunction risk (including previous anthracycline exposure): evaluate LVEF at baseline and periodically; monitor for CHF. Monitor ECG, electrolytes (eg, calcium, magnesium, potassium), thyroid function. History of hemoptysis, cerebral, or clinically significant GI hemorrhage in the past 6 months: not recommended. Risk of arterial thrombotic events (within previous 6 months: not recommended). Monitor for VTE, PE, infection, proteinuria (reduce dose if 24-hour urine protein ≥3g), thrombotic microangiopathy, interstitial lung disease (ILD)/pneumonitis, GI perforation or fistula.

Monitor BP and manage hypertension promptly.

Discontinue if severe and persistent hypertension (despite antihypertensives and dose reduction), if repeat episodes of proteinuria (despite dose reductions), thrombotic microangiopathy, serious infection, ILD or pneumonitis occurs. Stop therapy at least 7 days before surgery; discontinue in patients with wound dehiscence. Females of reproductive potential must use effective contraception during therapy and for ≥2 weeks after last dose. Pregnancy (Cat.D). Nursing mothers: not recommended.

Interactions: See Adult dosing: Potentiated by strong CYP3A4 inhibitors, grapefruit juice. Avoid concomitant strong Pgp or BCRP inhibitors.

Antagonized by strong CYP3A4 inducers.

Concomitant drugs with narrow therapeutic windows metabolized by CYP3A4, CYP2D6, or CYP2C8: not recommended. Increased risk of ALT elevations with concomitant simvastatin; caution and monitor closely; follow dosing guidelines or consider alternatives to pazopanib, or discontinuing simvastatin if develops. Avoid concomitant drugs that raise gastric pH (eg, PPIs, H2-blockers). Separate antacids by several hours. Caution with concomitant drugs that prolong QT interval (eg, antiarrhythmics).

Adverse reactions: Diarrhea, hypertension, hair color changes, nausea, anorexia, vomiting,

fatigue, decreased weight, decreased appetite, tumor pain, musculoskeletal pain, headache, dysgeusia, dyspnea, skin hypopigmentation; hepatotoxicity, QT prolongation, hemorrhagic events, arterial thrombotic events (eg, MI, angina, ischemic stroke, TIA), venous thrombotic events (eg, VTE, PE), GI perforation or fistula, ILD/pneumonitis, impaired wound healing, hypothyroidism, proteinuria, infection, reversible posterior leukoencephalopathy syndrome (discontinue if occurs).

How supplied: Tabs—120

XGEVA Amgen

℞

Osteoclast inhibitor (RANKL inhibitor).

Denosumab 120mg/vial (70mg/mL); soln for SC inj; preservative-free.

Indications: Treatment of adults and skeletallymature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.

Adults: Give by SC inj into upper arm, upper thigh, or abdomen. 120mg once every 4 weeks with additional 120mg doses on Days 8 and 15 of the 1st month of therapy.

Children: Not established (interferes with bone growth and dentition).

Contraindications: Pre-existing hypocalcemia.

Warnings/Precautions: Correct hypocalcemia before starting; ensure adequate daily calcium, magnesium, and Vit.D intake, esp. in renal impairment (CrCl <30mL/min). Monitor calcium (esp. 1st weeks of initiating), phosphorus, magnesium levels and Vit.D intake in susceptible patients (eg, severe renal impairment, receiving dialysis). Risk of osteonecrosis of the jaw (ONJ) in diabetes, gingival infections. Perform oral exam and preventive dentistry before and regularly during therapy. Maintain good oral hygiene. Avoid invasive dental procedures during treatment; consider temporary discontinuation if procedure is necessary.

Evaluate for atypical fractures if thigh/groin pain develops; consider withholding therapy until risk/benefit assessment. Monitor for hypercalcemia after treatment discontinuation in patients with growing skeletons. Embryo-fetal toxicity. Pregnancy (Cat.D); use highly effective contraception during therapy, and for at least 5 months after last dose.

Nursing mothers: not recommended (may impair mammary gland development/lactation).

Interactions: Concomitant other denosumabcontaining products (eg, Prolia): not recommended.

Concomitant drugs that can lower calcium levels; monitor. Increased risk of ONJ with concomitant corticosteroids, chemotherapy, angiogenesis inhibitors or duration of denosumab exposure.

Adverse reactions: Fatigue, asthenia, hypophosphatemia, nausea, arthralgia, headache, back pain, pain in extremity, dyspnea, decreased appetite, peripheral edema, vomiting, anemia, constipation, diarrhea; ONJ, hypocalcemia (may be fatal), hypersensitivity reactions (discontinue if occur).

How supplied: Single-use vial (1.7mL)—1

YONDELIS Janssen

℞

Alkylating agent. Trabectedin 1mg; per vial; lyophilized pwd for IV infusion after reconstitution and dilution; contains sucrose.

Indications: Treatment of unresectable or metastatic liposarcoma or leiomyosarcoma in patients who have received prior anthracyclinecontaining regimen.

Adults: Give by IV infusion over 24hrs.

1.5mg/m2 every 21 days until disease progression or unacceptable toxicity. Moderate hepatic impairment: 0.9mg/m2 every 21 days.

Premedicate 30 mins prior to each dose with IV dexamethasone 20mg. Delay, reduce, or permanently discontinue dose according to severity of adverse reactions: see full labeling.

Do not increase dose in subsequent cycles once reduced.

Children: <18yrs: not established.

Warnings/Precautions: Assess neutrophil count prior to each dose and periodically during the cycle; withhold if <1,500 cells/μL on day of dosing; permanently reduce dose if lifethreatening or prolonged, severe neutropenia occurs in prior cycle. Assess CPK levels prior to each dose; withhold if serum CPK >2.5XULN; permanently discontinue if rhabdomyolysis occurs. Assess LFTs prior to each dose and as indicated based on pre-existing hepatic impairment; interrupt, reduce, or permanently discontinue dose based on severity/duration.

Assess LVEF by echocardiogram or MUGA scan prior to initiation and every 2–3 months thereafter until discontinued; withhold if LVEF below LLN; permanently discontinue if symptomatic cardiomyopathy occurs or persistent LV dysfunction not recover to LLN within 3 weeks. Severe hepatic impairment: not recommended. Embryo-fetal toxicity.

Pregnancy; use effective contraception during and for 2 months (females) or 5 months (males) after final dose. Nursing mothers: not recommended.

Interactions: Avoid concomitant strong CYP3A inhibitors (eg, oral ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, indinavir, lopinavir, ritonavir, boceprevir, nelfinavir, saquinavir, telaprevir, nefazodone, conivaptan), grapefruit or grapefruit juice; if short-term use (<14 days) necessary, give inhibitor 1 week after infusion and discontinue the day prior to next infusion. Avoid concomitant strong CYP3A inducers (eg, rifampin, phenobarbital, St. John’s wort).

Adverse reactions: Nausea, fatigue, vomiting, constipation, decreased appetite, diarrhea, peripheral edema, dyspnea, headache, neutropenia, increased ALT, thrombocytopenia, anemia, increased AST and CPK; anaphylaxis, neutropenic sepsis, rhabdomyolysis, hepatotoxicity, cardiomyopathy, extravasation resulting in tissue necrosis, infertility.

How supplied: Single-dose vial—1

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DRUG MONOGRAPHS

BRAIN CANCER AFINITOR Novartis

℞

mTOR kinase inhibitor. Everolimus 2.5mg, 5mg, 7.5mg, 10mg; tabs. ℞ Also: AFINITOR DISPERZ Everolimus 2mg, 3mg, 5mg; tabs for oral susp.

Indications: In adults and children with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected.

Adults and Children: <1yr: not recommended.

Swallow tabs whole with water or use Disperz tabs administered as a suspension only. Take at the same time each day either consistently with or without food. Prepare suspension using 5mL of water in an oral syringe or 25mL of water in a drinking glass; max 10mg dose per syringe or glass. ≥1yrs: initially 4.5mg/m2 once daily. Do not combine the 2 dosage forms to achieve the desired total dose. Use therapeutic drug monitoring to guide subsequent dosing.

Adjust dose at 2 week intervals as needed to achieve and maintain trough concentrations of 5–15ng/mL (see full labeling). Severe hepatic impairment: initiate at 2.5mg/m2 once daily.

Concomitant strong CYP3A4/PgP inhibitors: avoid; moderate CYP3A4/PgP inhibitors: initiate at 2.5mg/m2 once daily, if CYP3A4/PgP inhibitor discontinued, after 2–3 days, return to dose used prior to initiating moderate inhibitor.

Concomitant strong CYP3A4 inducers: avoid, if required, then initiate at 9mg/m2 once daily; if discontinued, then return to dose used prior to initiating strong inducer. Continue therapy until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions, or others: see full labeling.

Contraindications: Allergy to other rapamycin derivatives.

Warnings/Precautions: Monitor for new or worsening respiratory symptoms. Increased risk of infections; some may be severe or fatal; monitor and treat promptly if occur. Pre-existing invasive fungal infections: treat before starting.

Monitor for signs of wound-related complications.

Peri-surgical period. Hepatic impairment (see Adult dose). Monitor CBCs, renal function, lipids, and blood glucose prior to starting and periodically thereafter. Avoid close contact with those who have received live vaccines. Pediatrics: complete childhood vaccination series according to ACIP guidelines prior to initiation. Elderly.

Females of reproductive potential must use effective contraception during therapy and for 8 weeks after treatment. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Avoid live vaccines. Potentiated by strong CYP3A4/PgP inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole), grapefruit or grapefruit juice; avoid. Caution with moderate CYP3A4/PgP inhibitors (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem); reduce everolimus dose if used. Antagonized by strong CYP3A4/PgP inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital), St. John’s Wort; avoid.

Adverse reactions: Pneumonitis (interrupt, reduce dose and/or manage with corticosteroids; if severe, discontinue; may reintroduce daily dose at approx. 50% lower than previously administered), infections (discontinue if invasive systemic fungal infection develops), stomatitis (treat with non-alcoholic, non-peroxide mouthwash), diarrhea, nausea, abdominal pain, rash, fatigue, edema, fever, asthenia, cough, headache, decreased appetite; increased serum creatinine, blood glucose, lipids; decreased hemoglobin, platelets, neutrophils, serum phosphate; proteinuria, renal failure, others (see full labeling).

How supplied: Tabs, Disperz—28 (4 blister cards × 7 tabs)

AVASTIN Genentech

℞

Angiogenesis inhibitor. Bevacizumab 100mg, 400mg; per vial; soln for IV infusion after dilution; preservative-free.

Indications: Glioblastoma, as a single agent for patients with progressive disease following prior therapy.

Adults: Give by IV infusion. Infuse 1st dose over 90 mins; if tolerated, infuse 2nd dose over 60 mins, and subsequent doses over 30 mins.

10mg/kg every 2 weeks.

Children: Not established.

Warnings/Precautions: Risk of GI perforations, surgery and wound healing complications, and hemorrhage. Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). Do not administer if recent history of hemoptysis of ≥ ½-teaspoon of red blood. Permanently discontinue if GI perforation, tracheoesophageal fistula, any grade 4 fistula, or grade 4 venous thromboembolic event. Discontinue if fistula involving internal organ, wound healing complications, hemorrhage, severe arterial thromboembolic event (ATE), hypertensive

crisis or encephalopathy, posterior reversible encephalopathy syndrome, or nephrotic syndrome occurs; suspend therapy if severe hypertension, moderate-to-severe proteinuria (resume when <2g/24hrs), or severe infusion reaction occurs. Avoid in ovarian cancer if evidence of recto-sigmoid involvement by pelvic exam, bowel involvement on CT scan, or symptoms of bowel obstruction. History of arterial thromboembolism. Diabetes. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis; if ≥2+, do further assessment with a 24-hour urine collection.

Elderly. Increased risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy: may cause fetal harm; use effective contraception during and for 6 months after last dose. Nursing mothers: not recommended.

Adverse reactions: Epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation and fistulae, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial or venous thromboembolic events, posterior reversible encephalopathy syndrome, infusion reactions, ovarian failure, neutropenia, and infection.

How supplied: Single-use vial—1

TEMODAR Merck

℞

Alkylating agent. Temozolomide 5mg, 20mg, 100mg, 140mg, 180mg, 250mg; caps. ℞ Also: TEMODAR INJECTION Temozolomide 100mg; per vial; lyophilized pwd for IV infusion after reconstitution; contains mannitol.

Indications: Newly diagnosed glioblastoma multiforme. Refractory anaplastic astrocytoma.

Adults: See full labeling for monitoring and dose adjustment guidelines. IV: Infuse over 90 mins. Oral caps: Swallow whole with water; take on empty stomach at bedtime to reduce nausea, pretreat with antiemetics.

Glioma: Concomitant phase, for newly diagnosed: 75mg/m2 daily for 42 days with focal radiotherapy; Maintenance phase, Cycle 1: 150mg/m2 once daily for 5 consecutive days, then 23 days off; for Cycles 2 through 6: increase to 200mg/m2 once daily for 5 consecutive days if tolerated, then 23 days off.

Anaplastic astrocytoma: 150mg/m2 once daily for 5 consecutive days per 28-day treatment

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DRUG MONOGRAPHS

BRAIN CANCER cycle; increase dose in subsequent cycles to 200mg/m2 for 5 consecutive days if tolerated; continue until disease progression, discontinue if minimum dose not tolerated.

Children: Not established.

Contraindications: Hypersensitivity to dacarbazine.

Warnings/Precautions: Myelosuppression (higher risk in women or elderly, esp. in 1st cycle). Do not begin therapy unless hematology (ANC and platelets) is acceptable. Do CBC prior to treatment initiation and on Day 22 of each cycle or within 48 hours of that day; repeat weekly until recovery if ANC or platelets fall below acceptable limits. Perform LFTs at baseline, midway through Cycle 1, prior to each subsequent cycle, and 2–4wks after last dose.

Screen for HBV infection prior to initiation.

Monitor for signs of hepatitis or HBV reactivation during and several months after treatment; discontinue if occurs. Glioblastoma: monitor for and provide prophylaxis against P. carinii pneumonia (PCP). Severe renal or hepatic impairment. Avoid inhalation, and skin/mucous membrane contact, of capsule contents. Elderly.

Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Concomitant carbamazepine, phenytoin, sulfamethoxazole/trimethoprim may complicate myelosuppression assessment. May be potentiated by valproic acid.

Adverse reactions: Alopecia, fatigue, nausea, vomiting, anorexia, constipation, headache, convulsions, rash, hemiparesis, diarrhea,

asthenia, fever, dizziness, abnormal coordination, viral infection, amnesia, insomnia, edema; myelosuppression (may be dose-limiting; see full labeling), hepatotoxicity (may be fatal).

How supplied: Caps 5mg, 20mg, 100mg, 140mg 180mg—5, 14; 250mg—5; Single-use vials—1

UNITUXIN United Therapeutics

℞

GD2-binding monoclonal antibody. Dinutuximab 3.5mg/mL; soln for IV infusion after dilution; preservative-free.

Indications: In combination with granulocytemacrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2) and 13-cis-retinoic acid (RA), for the treatment of children with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy.

Adults: Not applicable.

Children: Confirm adequate hematologic, respiratory, hepatic, and renal function prior to each course. Hydrate and premedicate with antihistamines, analgesics (eg, IV opioids), and antipyretics prior to each dose: see full labeling. Give via IV infusion over 10–20 hours for 4 consecutive days; max 5 cycles. Initial rate: 0.875mg/m2/hr for 30mins; may gradually increase as tolerated up to max 1.75mg/m2/hr.

Cycles 1, 3, and 5 (24-day cycle): 17.5mg/m2/day on Days 4–7. Cycles 2 and 4 (32-day cycle): 17.5mg/m2/day on Days 8–11. Dose modifications: see full labeling.

Warnings/Precautions: Risk of serious infusion reactions; monitor during and at least 4 hours after completion of each infusion; interrupt or discontinue if severe or prolonged infusion reactions occur. Have resuscitative medications and equipment available. Risk of neuropathy. Permanently discontinue if lifethreatening infusion reactions, Grade 3 pain unresponsive to max supportive measures, Grade 4 sensory neuropathy or Grade 3 sensory neuropathy that interferes with daily activities for more than 2 weeks, Grade 2 peripheral motor neuropathy, recurrent signs of eye disorders or vision loss, signs of atypical hemolytic uremic syndrome occurs. Interrupt or discontinue if severe capillary leak syndrome, symptomatic hypotension, systolic BP less than lower limit of normal for age or decreased by >15% compared to baseline develops. Monitor for systemic infection; temporarily discontinue until resolves.

Monitor BP, peripheral blood counts during therapy, and serum electrolytes daily. Renal or hepatic impairment. Pregnancy; avoid. Use effective contraception during therapy and for at least 2 months after last dose. Nursing mothers: not recommended.

Adverse reactions: Pain, pyrexia, infusion reactions, hypotension, hyponatremia, hypokalemia, hypocalcemia, hypoalbuminemia, increased ALT/AST, vomiting, diarrhea, capillary leak syndrome, urticaria, infections, bone marrow suppression (eg, thrombocytopenia, anemia, neutropenia, lymphopenia).

How supplied: Single-use vial (5mL)—1

LIVER FUNCTION ASSESSMENT Child-Pugh Score is used to assess residual liver function and injury severity in cirrhosis patients.

CHILD-PUGH SCORES Criteria

1 point

2 points

3 points

Total serum bilirubin (mg/dL)

<2

2–3

>3

Serum albumin (g/dL)

>3.5

2.8–3.5

<2.8

INR

<1.70

1.71–2.20

>2.20

Ascites

No ascites

Ascites controlled

Ascites not controlled

Encephalopathy

No encephalopathy

Encephalopathy controlled

Encephalopathy not controlled

Class A

Class B

Class C

Points

5–6

7–9

10–15

Life expectancy

15–20 years

Candidate for liver transplant

1–3 years

Perioperative mortality

10%

30%

82%

INTERPRETATION OF CHILD-PUGH SCORES

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DRUG MONOGRAPHS

BREAST CANCER ABRAXANE Celgene

℞

Taxane antimicrotubule. Paclitaxel [bound to albumin (human)] 100mg/vial; pwd for IV infusion after reconstitution; solvent-free.

Indications: Treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy (prior therapy should have included an anthracycline unless clinically contraindicated).

Adults: Do not treat if neutrophil count <1,500 cells/mm3 or platelets <100,000 cells/mm3.

260mg/m2 by IV infusion over 30 mins every 3 weeks.

If severe neutropenia (neutrophil <500 cells/mm3 for ≥1week) or severe sensory neuropathy occurs: reduce subsequent doses to 220mg/m2; reduce to 180mg/m2 if severe neutropenia or sensory neuropathy recurs. If grade 3 sensory neuropathy occurs, suspend use until resolution to grade 1 or 2; reduce subsequent doses. Hepatic impairment: see full labeling. Avoid extravasation.

Children: Not evaluated.

Contraindications: Baseline neutrophil count <1,500 cells/mm3. Prior severe hypersensitivity reaction (do not rechallenge).

Warnings/Precautions: Do not substitute for, or with, other paclitaxel products (due to formulation differences). Do frequent complete blood cell counts. Hepatic impairment (total bilirubin >5XULN or AST >10XULN): not recommended. Monitor for sensory neuropathy, sepsis, or pneumonitis. Renal dysfunction. Contains human albumin; remote risk of viral transmission. Use appropriate contraception (men and women). Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: May potentiate or be potentiated

by CYP2C8 and/or CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin, efavirenz, nevirapine) and/or inhibitors (eg, ketoconazole, other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, nelfinavir).

Adverse reactions: Bone marrow suppression (eg, neutropenia, anemia), infections, alopecia, sensory neuropathy (may require dose reduction or interruption), peripheral neuropathy, GI upset, mucositis, fatigue/asthenia, myalgia/arthralgia, abnormal ECG; alkaline phosphatase or AST elevation; dyspnea, edema, hypotension, rash (may be serious); rare: thrombotic events.

How supplied: Single-use vial—1

AFINITOR Novartis mTOR kinase inhibitor. Everolimus 2.5mg, 5mg, 7.5mg, 10mg; tabs.

Indications: Postmenopausal women with advanced hormone receptor-positive, HER2-

℞

negative breast cancer (advanced HR+ BC) in combination with exemestane after failure of treatment with letrozole or anastrozole.

Adults: Swallow tabs whole with water. Take at the same time each day either consistently with or without food. 10mg once daily. Mild hepatic impairment (Child-Pugh class A): 7.5mg daily, may reduce to 5mg if not tolerated. Moderate hepatic impairment (Child-Pugh class B): 5mg daily, may be reduce to 2.5mg if not tolerated. Severe hepatic impairment (Child-Pugh class C): max 2.5mg daily if benefits outweigh risk. Concomitant moderate CYP3A4/PgP inhibitors: reduce to 2.5mg once daily; may consider increasing to 5mg if tolerated. If moderate inhibitor is discontinued, allow 2–3 days washout period before increasing everolimus dose; return to dose used prior to initiating the moderate inhibitor. Concomitant strong CYP3A4/PgP inducers: consider doubling the daily dose by increments of 5mg or less. If strong inducer is discontinued, consider washout period of 3–5 days before returning to the dose used prior to initiating the strong inducer.

Continue therapy until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions, or others: see full labeling.

Children: Not recommended.

Contraindications: Allergy to other rapamycin derivatives.

Warnings/Precautions: Monitor for new or worsening respiratory symptoms. Increased risk of infections; some may be severe or fatal; monitor and treat promptly if occur. Pre-existing invasive fungal infections: treat before starting.

Monitor for signs of wound-related complications.

Peri-surgical period. Hepatic impairment (see Adult dose). Monitor CBCs, renal function, lipids, and blood glucose prior to starting and periodically thereafter. Avoid close contact with those who have received live vaccines. Pediatrics: complete childhood vaccination series according to ACIP guidelines prior to initiation. Elderly.

Females of reproductive potential must use effective contraception during therapy and for 8 weeks after treatment. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Avoid live vaccines. Potentiated by strong CYP3A4/PgP inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole), grapefruit or grapefruit juice; avoid. Caution with moderate CYP3A4/PgP inhibitors (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem); reduce everolimus dose if used. Antagonized by strong CYP3A4/PgP inducers (eg, phenytoin,

carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital), St. John’s Wort; avoid.

Adverse reactions: Pneumonitis (interrupt, reduce dose and/or manage with corticosteroids; if severe, discontinue; may reintroduce daily dose at approx.

50% lower than previously administered), infections (discontinue if invasive systemic fungal infection develops), stomatitis (treat with non-alcoholic, non-peroxide mouthwash), diarrhea, nausea, abdominal pain, rash, fatigue, edema, fever, asthenia, cough, headache, decreased appetite; increased serum creatinine, blood glucose, lipids; decreased hemoglobin, platelets, neutrophils, serum phosphate; proteinuria, renal failure, others (see full labeling).

How supplied: Tabs—28 (4 blister cards × 7 tabs)

ARIMIDEX AstraZeneca

℞

Aromatase inhibitor. Anastrozole 1mg; tabs.

Indications: In postmenopausal women: adjuvant treatment of hormone receptor-positive early breast cancer; first-line treatment of hormone receptor-positive or unknown locally advanced or metastatic breast cancer; advanced breast cancer with disease progression after tamoxifen therapy.

Adults: 1mg once daily. Advanced disease: continue until tumor progression.

Children: Not applicable.

Contraindications: Women who are or may become pregnant. Pregnancy (Cat.X).

Warnings/Precautions: Pre-existing ischemic heart disease. Severe hepatic impairment.

Monitor bone mineral density, cholesterol.

Nursing mothers: not recommended.

Interactions: Antagonized by tamoxifen, estrogens; do not give concomitantly.

Adverse reactions: Hot flashes, asthenia, arthritis, pain, arthralgia, pharyngitis, hypertension, depression, nausea, vomiting, rash, osteoporosis, fractures, back pain, insomnia, headache, peripheral edema, lymphedema, dyspnea, dizziness, paresthesia, vaginal bleeding, cough, hypercholesterolemia.

How supplied: Tabs—30

AROMASIN Pfizer

℞

Aromatase inactivator. Exemestane 25mg; tabs.

Indications: In postmenopausal women: adjuvant treatment of estrogen-receptor positive early breast cancer after 2–3yrs of tamoxifen therapy to complete a total of 5yrs of hormonal therapy; advanced breast cancer with disease progression after tamoxifen therapy.

Adults: Give after a meal. 25mg once daily.

Concomitant strong CYP3A4 inducers (see Interactions): 50mg once daily.

Children: Not established.

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DRUG MONOGRAPHS

BREAST CANCER Warnings/Precautions: Not for treatment in premenopausal women. Osteoporosis; assess bone mineral density (BMD) at start of treatment.

Monitor all patients for BMD loss and treat as appropriate. Perform routine assessment of Vit. D levels prior to initiation; supplement if deficient. Hepatic or renal impairment. Embryofetal toxicity. Pregnancy. Females of reproductive potential: should undergo pregnancy testing within 7 days prior to initiation; use effective contraception during and for 1 month after final dose. Nursing mothers: not recommended (during and for 1 month after final dose).

Interactions: Antagonized by strong CYP3A4 inducers (eg, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort).

Adverse reactions: Hot flashes, fatigue, arthralgia, headache, insomnia, increased sweating, nausea, increased appetite; reductions in BMD. How supplied: Tabs—30

DELATESTRYL Endo

CIII

Androgen. Testosterone enanthate 200mg/mL; IM inj; in sesame oil; contains chlorobutanol.

Indications: Testosterone replacement therapy in adult males with congenital or acquired primary hypogonadism or hypogonadotropic hypogonadism. To stimulate puberty in males with delayed puberty. Limitations of use: not established in men with age-related hypogonadism.

Adults: Give by deep IM inj into gluteal muscle.

200–400mg once every 2–4 weeks. Max 400mg/month. Monitor closely.

Children: Not established.

Contraindications: Male breast or prostate cancer. Pregnancy (Cat.X).

Warnings/Precautions: Discontinue if jaundice, abnormal liver function, hypercalcemia, or edema occurs. Monitor liver function, hemoglobin, hematocrit, cholesterol, urine, serum calcium.

Preexisting cardiac, hepatic, or renal dysfunction.

History of MI or coronary artery disease. Monitor for venous thromboembolism; discontinue if suspected.

Elderly. Nursing mothers: not recommended.

Interactions: May potentiate oral anticoagulants, oxyphenbutazone. May alter insulin requirements.

Increased risk of edema with ACTH, corticosteroids. May affect thyroid levels.

Adverse reactions: Amenorrhea, menstrual irregularities, inhibition of gonadotropin secretion, virilization; others: inj site reactions, peliosis hepatis, edema, hepatic carcinoma, nausea, jaundice, hirsutism, acne, polycythemia, headache, anxiety, depression, paresthesia, altered libido, fluid and electrolyte disturbances, suppression of clotting factors, increased serum cholesterol.

How supplied: Multidose vial (5mL)—1

ESTRACE Allergan Estrogen. Estradiol 0.5mg, 1mg, 2mg+; scored tabs; +contains tartrazine.

Indications: Palliative treatment of metastatic breast cancer in select patients (see literature).

℞

Adults: 10mg 3 times daily for at least 3 months.

Children: Not applicable.

Contraindications: Thrombophlebitis.

Thromboembolic disorders. Cerebrovascular disorders. Abnormal undiagnosed genital bleeding. Estrogen-depended neoplasias. Liver dysfunction or disease. Pregnancy (Cat. X).

Warnings/Precautions: Asthma (2mg tabs).

Hepatic dysfunction. Conditions aggravated by fluid retention. Cardiovascular disorders, arterial vascular disease, and risks factors (eg, hypertension, diabetes, obesity, SLE). Familial hyperlipoprotenemia. Monitor BP. Discontinue if jaundice occurs and before prolonged immobilization (eg, surgery). Nursing mothers.

Adverse reactions: See literature. GI upset, headache, hypertension, edema, hypercalcemia, gallbladder or thromboembolic disease, gynecomastia, impotence, impaired glucose tolerance.

How supplied: Tabs—100

EVISTA Lilly

℞

Selective estrogen receptor modulator (SERM).

Raloxifene HCl 60mg; tabs.

Indications: Reduction in risk of invasive breast cancer in postmenopausal women: with osteoporosis and/or at high risk for invasive breast cancer.

Adults: 60mg once daily.

Children: Not recommended.

Contraindications: Active or history of venous thromboembolic events. Nursing mothers.

Pregnancy (Cat.X). Women who may become pregnant.

Warnings/Precautions: Not for use in premenopausal women. Concomitant systemic estrogen therapy: not recommended. Discontinue 72 hours before, and during prolonged immobilization; resume when fully ambulatory. Coronary heart disease or risk of coronary event (increased risk of death due to stroke). Hepatic dysfunction. Moderate to severe renal impairment.

Interactions: May antagonize warfarin; monitor.

Avoid concomitant cholestyramine, other anion exchange resins. Caution with other highly proteinbound drugs (eg, diazepam, diazoxide, lidocaine).

Adverse reactions: Hot flashes, leg cramps, peripheral edema, flu syndrome, arthralgia, sweating; rare: venous thromboembolic events.

How supplied: Tabs—30, 100, 2000

FASLODEX AstraZeneca

℞

Estrogen receptor antagonist. Fulvestrant 50mg/mL; soln for IM inj.

Indications: Hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. In combination with palbociclib: HR-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in women with disease progression after endocrine therapy.

Adults: Give by IM inj slowly (1–2 mins/injection).

500mg (as two 5mL injections, one in each buttock) on Days 1, 15, 29, then once per month thereafter. For combination therapy: give with palbociclib 125mg daily with food for 21 days, followed by 7 days off; in pre/perimenopausal women: also treat with LHRH agonists. Moderate hepatic impairment: 250mg (as one 5mL injection) on Days 1, 15, 29, then once per month thereafter. Other dose modification: see full labeling.

Children: Not established.

Warnings/Precautions: Bleeding diatheses, thrombocytopenia, or anticoagulant use.

Moderate-to-severe hepatic impairment. When administering at the dorsogluteal inj site due to proximity of the sciatic nerve. Embryo-fetal toxicity. Pregnancy: do testing within 7 days prior to initiating; use effective contraception during therapy and for 1 year after last dose. Nursing mothers: not recommended (during therapy and for 1 year after last dose).

Interactions: May interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels.

Adverse reactions: Inj site pain (including sciatica, neuralgia, neuropathic pain, peripheral neuropathy), nausea, vomiting, bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flash, anorexia, asthenia, musculoskeletal pain, cough, dyspnea, constipation; increased hepatic enzymes, hypersensitivity reactions.

How supplied: Prefilled syringe kit (2 × 5mL)—1

FEMARA Novartis

℞

Aromatase inhibitor. Letrozole 2.5mg; tabs.

Indications: In postmenopausal women: Adjuvant treatment of hormone receptor positive early breast cancer; Extended adjuvant treatment of early breast cancer after 5 years of adjuvant tamoxifen therapy; First-line treatment of hormone receptor positive or unknown, locally advanced or metastatic breast cancer; Treatment of advanced breast cancer with disease progression following antiestrogen therapy.

Adults: 2.5mg once daily. Continue until tumor progression is evident. Adjuvant or extended adjuvant therapy: treat for at least 24 months (see literature). Severe hepatic impairment or cirrhosis: 2.5mg every other day.

Children: Not applicable.

Contraindications: Women of premenopausal endocrine status. Pregnancy (Cat.X).

Warnings/Precautions: Severe renal or hepatic impairment. Monitor bone mineral density, serum cholesterol. Nursing mothers.

Adverse reactions: Pain (bone, musculoskeletal, and others), hot flashes, arthralgia, flushing, asthenia, edema, headache, dizziness, hypercholesterolemia, sweating increased, GI upset, fatigue, dyspnea, cough, insomnia, hypertension, alopecia, anorexia, weight

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DRUG MONOGRAPHS

BREAST CANCER changes, hypercalcemia, pleural effusion, vertigo; thromboembolic or cardio- or cerebrovascular events (rare).

How supplied: Tabs—30

Fluorouracil (various)

℞

Antimetabolite. Fluorouracil 50mg/mL; soln for IV inj.

Indications: Palliative management of carcinoma of the breast.

Adults: Give by IV inj. 12mg/kg once daily for 4 successive days; max 800mg/day. If no toxicity is observed, 6mg/kg are given on the 6th, 8th, 10th, and 12th days unless toxicity occurs.

Maintenance therapy: repeat dosage of 1st course every 30 days after the last day of the previous course of treatment; or give a maintenance dose of 10–15mg/kg per week as a single dose; max: 1g/week. Poor risk patients: see literature for dose adjustments.

Children: Not recommended.

Contraindications: Poor nutritional state.

Depressed bone marrow function. Potentially serious infections.

Warnings/Precautions: Narrow margin of safety; monitor for toxicity. Consider hospitalization for 1st course. History of high-dose pelvic irradiation.

Previous use of alkylating agents. Widespread involvement of bone marrow by metastatic tumors. Renal or hepatic impairment. Discontinue if signs of toxicity appear (eg, stomatitis, esophagopharyngitis, leukopenia, intractable vomiting, diarrhea, GI ulceration or bleeding, thrombocytopenia, hemorrhage). Monitor WBCs with differential before each dose. Avoid extravasation. Pregnancy (Cat.D); avoid use.

Nursing mothers: not recommended.

Interactions: Potentiated by leucovorin.

Adverse reactions: Stomatitis, esophagopharyngitis, GI upset, anorexia, leukopenia, alopecia, dermatitis, hand-foot syndrome; others.

Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase).

How supplied: Contact supplier.

HALAVEN Eisai Non-taxane microtubule dynamics inhibitor.

Eribulin mesylate 0.5mg/mL, soln for IV inj.

Indications: Treatment of metastatic breast cancer in patients who have previously received at least two chemotherapeutic regimens for metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.

℞

Adults: Give by IV inj over 2–5mins. 1.4mg/m² on Days 1 and 8 of a 21-day cycle. Mild hepatic impairment (Child-Pugh A) or moderate-to-severe renal impairment (CrCl 15–49mL/min): 1.1mg/m² on Days 1 and 8 of a 21-day cycle. Moderate hepatic impairment (Child-Pugh B): 0.7mg/m² on Days 1 and 8 of a 21-day cycle. Hold dose for ANC <1000/mm³, platelets <75000/mm³, or grade 3 or 4 non-hematological toxicities.

Delay or reduce dose according to toxicities; see full labeling. Do not re-escalate dose after it is reduced.

Children: <18yrs: not established.

Warnings/Precautions: Monitor CBCs prior to each dose; increase frequency of monitoring if grade 3 or 4 cytopenias develop, delay and reduce subsequent doses if febrile neutropenia or grade 4 neutropenia lasting >7 days develops. Monitor for peripheral neuropathy; withhold dose if grade 3 or 4 peripheral neuropathy develops until resolution to grade 2 or less. Congenital long QT syndrome: avoid. CHF, bradyarrhythmias, electrolyte abnormalities: monitor ECG for prolonged QT interval. Correct electrolyte abnormalities (K+, Mg+) before treatment; monitor. Severe hepatic impairment (Child-Pugh C): insufficient data.

Pregnancy. Use effective contraception during treatment and for ≥2 weeks (females) or 3.5 months (male partners) after final dose. Nursing mothers: not recommended (during and for 2 weeks after final dose).

Interactions: Caution with other drugs that prolong QT interval (eg, Class IA and III antiarrhythmics); monitor.

Adverse reactions: Neutropenia, anemia, asthenia/fatigue, alopecia, peripheral neuropathy, nausea, constipation, abdominal pain, pyrexia, hypokalemia, hypocalcemia; febrile neutropenia, possible QT prolongation, elevated liver enzymes.

Note: Do not mix with dextrose-containing solutions. Do not administer in same line as other drugs or fluids.

How supplied: Single-use vial (2mL)—1

HERCEPTIN Genentech

℞

Human epidermal growth factor receptor (HER2) inhibitor. Trastuzumab 440mg/vial; lyophilized pwd for IV infusion after reconstitution and dilution; preservative-free.

Indications: HER2-overexpressing metastatic breast cancer as a single agent in patients who have received one or more chemotherapy regimens; or in combination with paclitaxel in patients who have not received chemotherapy.

Adjuvant treatment in HER2-overexpressing, node-positive or node-negative breast cancer

(as a single agent following multi-modality anthracycline based therapy; in combination with doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; or in combination with docetaxel and carboplatin).

Adults: Do not substitute for or with adotrastuzumab emtansine. Give as IV infusion.

Initially 4mg/kg over 90 mins, followed by 2mg/kg over 30 mins weekly; administer until tumor progression. Adjuvant treatment (administer trastuzumab weekly for 52 weeks; therapy >52 weeks: not recommended); In combination therapy: with doxorubicin and cyclophosphamide, followed by either paclitaxel or docetaxel; or with docetaxel/carboplatin: initially 4mg/kg over 90 mins, followed by 2mg/kg over 30 mins once weekly for the 1st 12 weeks (concurrently w. paclitaxel or docetaxel) or 1st 18 weeks (concurrently w. docetaxel/carboplatin).

One week after the last trastuzumab weekly dose, give trastuzumab 6mg/kg over 30–90 mins every 3 weeks. Following multi-modality anthracycline based therapy: initially 8mg/kg over 90 mins, then 6mg/kg over 30–90 mins every 3 weeks.

Infusion reactions or cardiomyopathy: see full labeling.

Children: Not established.

Warnings/Precautions: Increased risk of cardiomyopathy. Conduct cardiac assessment (eg, history, physical exam, LVEF) at baseline, every 3 months during and after therapy or every 6 months for ≥2yrs after therapy (if adjuvant); repeat LVEF at 4 week intervals if dose is withheld due to significant left ventricular cardiac dysfunction. Interrupt therapy if dyspnea or significant hypotension occurs; consider discontinuing permanently if severe infusion reactions, CHF, pulmonary toxicity, or significant left ventricular myocardial dysfunction develops. Symptomatic intrinsic lung disease. Extensive tumor involvement of the lungs. Test for HER2 protein overexpression and HER2 gene amplification using FDAapproved tests for specific tumor type (breast or gastric/gastroesophageal adenocarcinoma).

Embryo-fetal toxicity (eg, oligohydramnios): exclude pregnancy status before initiation.

Pregnancy: avoid; use effective contraception during and for 7 months after therapy. Nursing mothers.

Interactions: Increased cardiomyopathy with anthracycline-containing chemotherapy.

Increased toxicity with other myelosuppressives.

Adverse reactions: Fever, diarrhea, nausea, chills, infections, increased cough, headache, CHF, insomnia, fatigue, dyspnea, rash, neutropenia, anemia, thrombocytopenia,

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DRUG MONOGRAPHS

BREAST CANCER stomatitis, mucosal inflammation, weight loss, nasopharyngitis, dysgeusia, myalgia, thrombosis/embolism; severe infusion reactions, febrile neutropenia/exacerbation of chemotherapy-induced neutropenia, pulmonary toxicity (eg, interstitial pneumonitis), cardiomyopathy (eg, left ventricular myocardial dysfunction).

Note: Enroll pregnant women with breast cancer who are using trastuzumab in the MotHER-the Herceptin Pregnancy Registry (800) 690-6720.

Testing considerations: HER2 protein overexpression How supplied: Vial—1 (w. diluent)

carbamazepine, enzalutamide, St. John’s wort) or moderate CYP3A inducers (eg, modafinil). May potentiate midazolam or other CYP3A substrates with narrow therapeutic index (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus, tacrolimus); reduce dose of these drugs.

Adverse reactions: Neutropenia, leukopenia, infections, fatigue, anemia, nausea, stomatitis, headache, alopecia, diarrhea, thrombocytopenia, constipation, decreased appetite, vomiting, rash, asthenia, peripheral neuropathy, epistaxis; pulmonary embolism.

How supplied: Caps—21

IBRANCE Pfizer

IXEMPRA Bristol-Myers Squibb

℞

Kinase inhibitor. Palbociclib 75mg, 100mg, 125mg; capsules.

Indications: Treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with letrozole as initial endocrine based therapy in postmenopausal women, or fulvestrant in women with disease progression following endocrine therapy.

Adults: Swallow whole. Take with food. 125mg once daily for 21 days followed by 7 days off to complete a 28-day cycle, in combination with letrozole 2.5mg once daily continuously throughout the 28-day cycle or with fulvestrant 500mg on Days 1, 15, 29, and once monthly thereafter. In the combination fulvestrant therapy: should treat with LHRH agonists according to clinical practice standards. Dose modification for adverse reactions: First reduction: 100mg/day; Second dose reduction: 75mg/day; discontinue if <75mg/day required. Dose modification for hematologic or non-hematologic toxicities: see full labeling. Concomitant strong CYP3A inhibitors: avoid and consider alternative drug; if use necessary, reduce palbociclib dose to 75mg/day.

Children: Not studied.

Warnings/Precautions: Monitor CBCs prior to initiation and at start of each cycle, as well as Day 14 of first 2 cycles, and as clinically indicated. Interrupt, reduce dose, or delay starting treatment cycles if Grade 3 or 4 neutropenia develops. Monitor for infections, pulmonary embolism; treat appropriately if develop.

Moderate or severe hepatic impairment. Severe renal impairment. Pregnancy: avoid. Use effective contraception during therapy and for at least 3 weeks (females) or 3 months (males) after last dose. Nursing mothers: not recommended (during and for 3 weeks after last dose).

Interactions: Avoid concomitant strong CYP3A inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole), grapefruit or grapefruit juice; if unavoidable, reduce dose (see Adults). Avoid concomitant strong CYP3A inducers (eg, phenytoin, rifampin,

℞

Epothilone microtubule inhibitor. Ixabepilone 15mg/vial, 45mg/vial; pwd for IV infusion after constitution and dilution; diluent contains alcohol, polyoxyethylated castor oil.

Indications: Metastatic or locally advanced breast cancer: In combination with capecitabine after failure of an anthracycline and a taxane; and as monotherapy after failure of an anthracycline, a taxane, and capecitabine.

Adults: Pretreat with both H1 and H2 blockers 1hr before infusion; and with steroid if previous hypersensitivity reaction occurred. 40mg/m2

by IV infusion over 3hrs, once every 3wks. Use max body surface area (BSA) of 2.2m2 to calculate dose if BSA >2.2m2. Moderate hepatic impairment (as monotherapy): initially 20mg/m2 per dose; max 30mg/m2 per dose (see literature).

Neuropathy, myelosuppression, concomitant strong CYP3A4 inhibitors: reduce dose.

Concomitant strong CYP3A4 inducers: consider gradual dose increases. See literature.

Children: Not recommended.

Contraindications: Baseline neutrophils <1500cells/mm3 or platelets <100,000cells/mm3.

AST or ALT >2.5XULN or bilirubin >1XULN (in combination with capecitabine).

Warnings/Precautions: Monitor CBC and liver function at baseline, then periodically. Hepatic impairment (ALT or AST >10XULN or bilirubin >3XULN: not recommended; ALT or AST >5XULN: limited data, use caution). Diabetes. Neuropathy.

Cardiac disease (discontinue if cardiac ischemia or cardiac dysfunction occurs). Monitor for signs/symptoms of neuropathy, neutropenia.

Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Potentiated by strong CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, certain macrolides, nefazodone, grapefruit juice); avoid. Caution with mild or moderate CYP3A4 inhibitors; consider alternative agents. Antagonized by strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, dexamethasone, phenobarbital); avoid.

Avoid St. John’s wort.

Adverse reactions: Peripheral sensory neuropathy, fatigue, asthenia, myalgia, arthralgia, alopecia, GI upset, stomatitis,

mucositis, musculoskeletal pain, palmarplantar erythrodysesthesia syndrome, anorexia, abdominal pain, nail disorder, constipation; myelosuppression (neutropenia, leukopenia, anemia, thrombocytopenia); hypersensitivity reactions; others.

How supplied: Kit—1 vial (w. diluent)

KADCYLA Genentech

℞

HER2-targeted antibody-drug conjugate. Adotrastuzumab emtansine 100mg, 160mg; per vial; powder; for IV infusion after reconstitution.

Indications: Treatment in patients with HER2positive (+), metastatic breast cancer (MBC) who previously received trastuzumab and a taxane, separately or in combination. Patients should have either: received prior therapy for metastatic disease or developed disease recurrence during or within 6 months of completing adjuvant therapy.

Adults: Give by IV infusion only over 90 minutes 3.6mg/kg max every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

Subsequent infusions may be given over 30 minutes if previously tolerated. Monitor closely for possible SC infiltration during infusion. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Do not substitute for or with trastuzumab. Hepatotoxicity; monitor serum transaminases and bilirubin prior to starting and to each dose; reduce dose or discontinue if occurs. Permanently discontinue if serum transaminases >3XULN and with total bilirubin >2XULN. Risk of left ventricular dysfunction. Assess LVEF prior to initiation and every 3 months during treatment; interrupt and discontinue as appropriate.

Embryo-fetal toxicity: verify pregnancy status prior to initiation. Permanently discontinue if interstitial lung disease or pneumonitis occurs.

Monitor for signs/symptoms of extravasation, infusion-related or hypersensitivity reactions; if significant, slow or interrupt infusion; discontinue if life-threatening. Monitor platelets at baseline and prior to each dose; if platelets <50,000/mm3, delay dose until recovery to ≥75,000/mm3; if platelets <25,000/mm3, delay until recovery to ≥75,000/mm3 and reduce dose.

If thrombocytopenia occurs <100,000/mm3 and concomitant anticoagulants, monitor closely.

Monitor for neurotoxicity; withhold temporarily if Grade 3 or 4 peripheral neuropathy occurs.

Test for HER2 protein overexpression or gene amplification using FDA-approved tests by labs with demonstrated proficiency. Pregnancy: avoid. Use effective contraception during therapy and for 7 months (females) or 4 months (males) after last dose. Nursing mothers: not recommended (during and for 7 months after last dose).

Interactions: Avoid concomitant strong CYP3A4 inhibitors (eg, azole antifungals, clarithromycin, atazanavir, indinavir, ritonavir,

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DRUG MONOGRAPHS

BREAST CANCER nefazodone, nelfinavir, saquinavir, telithromycin); if unavoidable, consider delaying therapy. Caution with concomitant anticoagulation or antiplatelet therapy; monitor closely.

Adverse reactions: Fatigue, nausea, musculoskeletal pain, hemorrhage, thrombocytopenia, headache; increased transaminases, constipation, epistaxis, oligohydramnios (do fetal testing if occurs), infertility.

Note: Enroll pregnant women who were exposed to Kadcyla in the MotHER Pregnancy Registry (800) 690-6720.

How supplied: Single-use vial—1

PERJETA Genentech

℞

Human epidermal growth factor receptor (HER2) dimerization inhibitor. Pertuzumab 420mg/14mL (30mg/mL); soln for IV infusion; preservativefree.

Indications: In combination with trastuzumab and docetaxel: to treat patients with HER2positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease; for the neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either >2cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer.

Limitations of use: not established as part of a doxorubicin-containing regimen. Not established in administration for >6 cycles for early breast cancer.

Adults: In combination with trastuzumab and docetaxel: initially 840mg IV over 60 minutes, followed every 3 weeks thereafter by a dose of 420mg IV over 30–60 minutes. Pertuzumab should be withheld or discontinued if trastuzumab is withheld or discontinued. If docetaxel is discontinued, treatment with pertuzumab and trastuzumab may continue. Neoadjuvant treatment: give every 3 weeks for 3 to 6 cycles as part of one of the treatment regimens for early breast cancer: see full labeling. Dose modification (missed dose, LVEF, or infusion reactions): see full labeling.

Children: Not established.

Warnings/Precautions: Risk of embryo-fetal toxicity; verify pregnancy status prior to initiation.

Pretreatment LVEF value of ≤50%, history of CHF, decreases in LVEF to <50% during prior trastuzumab therapy, uncontrolled hypertension, recent MI, serious cardiac arrythmia requiring treatment or a cumulative prior anthracycline exposure to >360mg/m2 of doxorubicin or its equivalent: not studied. Assess LVEF at baseline

and at regular intervals (eg, every 3 months in metastatic setting, and every 6 weeks in the neoadjuvant setting) during treatment; if LVEF is <45%, or is 45% to 49% with a ≥10% absolute decrease below the pretreatment value, withhold (pertuzumab + trastuzumab) and repeat LVEF within 3 weeks; discontinue if LVEF has not improved. Monitor for signs/symptoms of infusion reactions; slow or interrupt infusion and treat if occurs; discontinue if severe. Test and confirm for HER2 protein overexpression using FDA-approved tests by labs with demonstrated proficiency. Pregnancy (Cat.D); use adequate contraception during and at least 7 months after therapy. Nursing mothers: not recommended.

Adverse reactions: Diarrhea, alopecia, neutropenia, nausea, fatigue, rash, peripheral neuropathy; hypersensitivity (monitor), decreases in LVEF; pregnant women: possible oligohydramnios (monitor).

Note: Encourage women who are exposed to Perjeta during pregnancy to enroll in the MotHER Pregnancy Registry: (800) 690-6720.

How supplied: Single-use vial—1

PREMARIN Pfizer

℞

Estrogen. Conjugated estrogens 0.3mg, 0.45mg, 0.625mg, 0.9mg, 1.25mg; tabs.

Indications: Treatment of breast cancer (for palliation only) in appropriately selected women and men with metastatic disease.

Adults: 10mg 3 times daily for at least 3 months.

Children: Not applicable.

Contraindications: Known, suspected, or history of breast cancer, except in appropriately selected patients being treated for metastatic disease. Known or suspected estrogen-dependent neoplasia. Undiagnosed abnormal genital bleeding. Pulmonary embolism/DVT (active or history of). Arterial thromboembolism (eg, stroke, MI; active or history of). Liver dysfunction or disease. Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders. Known or suspected pregnancy (Cat.X).

Warnings/Precautions: Not for prevention of cardiovascular disease. Use for shortest duration consistent with treatment goals and risks. Reevaluate periodically. Patients with an intact uterus should almost always receive a progestin with systemic estrogens to avoid endometrial hyperplasia. Discontinue if cardiovascular events occur or are suspected; if jaundice occurs; and during immobilization or at least 4–6 weeks before surgery associated

with thromboembolism. Hepatic dysfunction.

Conditions aggravated by fluid retention.

Gallbladder disease. Bone disease associated with hypercalcemia. Hereditary angioedema. Do initial complete physical and repeat annually (include BP, mammogram, PAP smear). Adolescents.

Nursing mothers: not recommended.

Adverse reactions: See literature. Increased risk of cardiovascular events, estrogen-dependent carcinoma, gallbladder disease, thromboembolic disorders, hepatic tumors. GI upset, breakthrough bleeding, edema, weight changes, mastodynia, hypertension, depression, anaphylactic reactions, angioedema, intolerance to contact lenses.

How supplied: Tabs 0.3mg, 0.625mg, 1.25mg— 100, 1000; 0.45mg, 0.9mg—100

SOLTAMOX ORAL

℞

SOLUTION DARA BioSciences

Antiestrogen. Tamoxifen (as citrate) 10mg/5mL; licorice and aniseed flavors; sugar-free; contains alcohol.

Indications: Treatment of metastatic breast cancer in men and women. Axillary node-positive breast cancer in postmenopausal women after surgery + irradiation. Axillary node-negative breast cancer in women after surgery + irradiation.

Reduction in risk of invasive breast cancer in women with ductal carcinoma in situ (DCIS) after surgery + radiation. Reduction in breast cancer incidence in high-risk women.

Adults: Treatment: 20–40mg/day; give doses >20mg in divided doses (AM and PM). Reduction of incidence in high-risk women or DCIS: 20mg once daily for 5 years.

Children: Not recommended.

Contraindications: For reduction in incidence in high-risk women and women with DCIS: concomitant coumarin anticoagulants, history of deep vein thrombosis or pulmonary embolism.

Warnings/Precautions: See literature. Do gynecological exam at least annually. DCIS and risk reduction: consider increased risk of uterine cancer (endometrial adenocarcinoma, uterine sarcoma), stroke and pulmonary embolism. Women with advanced disease: discontinue if severe hypercalcemia occurs.

Monitor blood, lipids, liver function, for thromboembolism symptoms (eg, leg swelling, unexplained shortness of breath), and for uterine changes/cancer (eg, pelvic pain or pressure); promptly investigate any abnormal vaginal bleeding. Breast cancer treatment: history of thromboembolic events. Pregnancy (Cat.D); avoid. Premenopausal: use effective non-hormonal contraception during and within

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DRUG MONOGRAPHS

BREAST CANCER 2 months of discontinuing therapy; begin therapy during menses or, if irregular menses, obtain (–) B-hCG pregnancy test first. Nursing mothers: not recommended.

Interactions: See Contraindications. May potentiate oral anticoagulants; if co-administered, monitor PT. Concomitant anastrozole: not recommended. Antagonizes letrozole. Plasma levels reduced by CYP3A4 inducers (eg, rifampin, aminoglutethimide). Cytotoxic drugs increase risk of thrombotic events. Potentiated by bromocriptine.

Adverse reactions: Hot flashes, vaginal discharge, altered menses, oligomenorrhea, nausea, cough, edema, fatigue, abdominal cramps, bone and tumor pain (in advanced disease), local disease flare, hypercalcemia, thrombotic events, ovarian cysts, uterine fibroids or cancer (endometrial adenocarcinoma, uterine sarcoma), endometrial or visual changes, liver abnormalities, hypertriglyceridemia, blood dyscrasias, hair loss.

How supplied: Soln—150mL

Tamoxifen (various)

℞

Antiestrogen. Tamoxifen (as citrate) 10mg, 20mg; tabs.

Indications: Treatment of metastatic breast cancer in men and women. Axillary node-positive breast cancer in postmenopausal women after surgery + irradiation. Axillary node-negative breast cancer in women after surgery + irradiation.

Reduction in risk of invasive breast cancer in women with ductal carcinoma in situ (DCIS) after surgery + radiation. Reduction in breast cancer incidence in high-risk women.

Adults: Treatment: 20–40mg/day; give doses >20mg in divided doses (AM and PM). Reduction of incidence in high-risk women or DCIS: 20mg once daily for 5 years.

Children: McCune-Albright Syndrome, precocious puberty: see literature.

Contraindications: For risk reduction: concomitant coumarin anticoagulants, history of deep vein thrombosis or pulmonary embolism, planned pregnancy. Pregnancy (Cat.D). Nursing mothers.

Warnings/Precautions: See literature. Do gynecological exam at least annually. DCIS and risk reduction: consider increased risk of uterine cancer (endometrial adenocarcinoma, uterine sarcoma) and thrombotic events. Women with advanced disease: discontinue if severe hypercalcemia occurs. Monitor blood, lipids, liver function, for thromboembolism symptoms (eg, leg swelling, unexplained shortness of breath), and for uterine changes/cancer (eg, pelvic pain or pressure); promptly investigate any abnormal vaginal bleeding. Breast cancer treatment: history of thromboembolic events. Premenopausal: use effective non-hormonal contraception during and within 2 months of discontinuing therapy; begin therapy during menses or, if irregular menses, obtain (–) B-hCG pregnancy test first.

Interactions: May potentiate oral anticoagulants (see Contraindications). Antagonizes anastrozole

(avoid concomitant use); letrozole. Plasma levels reduced by CYP3A4 inducers (eg, rifampin).

Cytotoxic drugs increase risk of thrombotic events. Potentiated by bromocriptine.

Adverse reactions: Hot flashes, vaginal discharge, altered menses, rash, headache, nausea, cough, edema, fatigue, abdominal cramps, bone and tumor pain (in advanced disease), local disease flare, hypercalcemia, thrombotic events, ovarian cysts, uterine fibroids or cancer (endometrial adenocarcinoma, uterine sarcoma), endometrial or visual changes, jaundice, hypertriglyceridemia, blood dyscrasias, hair loss.

How supplied: Contact supplier.

TREXALL Teva

drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin).

Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, Stevens-Johnson syndrome).

How supplied: Tabs—30; soln (2mL, 4mL, 8mL, 10mL)—10 (single-use vials); pwd (1 gram)—1 (single-use vial)

TYKERB GlaxoSmithKline ℞

Folic acid antagonist. Methotrexate sodium 5mg, 7.5mg, 10mg, 15mg; scored tabs. ℞ Also: Methotrexate injection Bedford Methotrexate 25mg/mL; soln for IV, IM, intraarterial, or intrathecal administration after dilution; preservative-free. ℞ Also: Methotrexate for injection Bedford Methotrexate 1g/vial; pwd for IV, IM, intra-arterial, or intrathecal administration after dilution; preservative-free.

Indications: Breast cancer.

Adults: See literature.

Children: Not established.

Contraindications: Pregnancy (Cat. X). Nursing mothers.

Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Discontinue if malignant lymphomas occur. Obtain baseline and monitor CBCs with differential, platelet counts, chest X-ray, and hepatic, renal and pulmonary function. During therapy monitor hematology monthly, renal and hepatic function every 1–2 months, more often if increasing dose or predisposed to toxicity (eg, dehydration).

Discontinue immediately if blood counts drop significantly. Rule out pregnancy in women of childbearing potential; use effective contraception during therapy and for at least 1 ovulatory cycle afterwards for women and for at least 3 months afterwards for men. Interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur. Hepatic or renal impairment.

Obesity. Diabetes. Peptic ulcer. Ulcerative colitis. Infection. Dehydration. Folate deficiency.

Ascites, pleural effusions: evacuate fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated.

Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin, sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, nonabsorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy. Caution with other hepatotoxic

℞

Tyrosine kinase inhibitor. Lapatinib 250mg; tabs.

Indications: In combination with capecitabine, for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Limitation of use: patients should have disease progression on trastuzumab before initiating Tykerb in combination with capecitabine. In combination with letrozole for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer that overexpresses HER2 for whom hormonal therapy is indicated.

Adults: Take 1hr before or 1hr after a meal (capecitabine should be taken with food or within 30mins after food). HER2 metastatic breast cancer: 1250mg (5 tabs) once daily on Days 1–21 continuously in combination with capecitabine 2000mg/m2/day (administered orally in 2 doses approx. 12hrs apart) on Days 1–14 in a repeating 21 day cycle; continue until disease progression or unacceptable toxicity occurs. After recovery from left ventricular ejection fraction (LVEF) decrease: 1000mg/day.

Severe hepatic dysfunction (Child-Pugh Class C): 750mg/day (no clinical data for this dose adjustment). Concomitant potent CYP3A4 inducers: may titrate up to 4500mg/day (no clinical data for this dose adjustment). Hormone receptor positive, HER2 positive metastatic breast cancer: 1500mg (6 tabs) once daily continuously in combination with letrozole 2.5mg once daily.

After recovery from LVEF decrease: 1250mg/day.

Severe hepatic dysfunction: 1000mg/day (no clinical data for this dose adjustment).

Concomitant potent CYP3A4 inducers: may titrate up to 5500mg/day (no clinical data for this dose adjustment). For both: Concomitant potent CYP3A4 inhibitors: 500mg/day (no clinical data for this dose adjustment). Interrupt if diarrhea is NCI CTC grade 3, or grade 1 or 2 with complicating features develop; may restart at lower dose (reduced from 1250mg/day to 1000mg/day or from 1500mg/day to 1250mg/day) when resolves ≤ grade 1; permanently discontinue if diarrhea is grade 4. Other toxicities: discontinue if ≥grade 2 NCI CTC toxicity occurs; may restart at 1250mg/day if toxicity improves to grade

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DRUG MONOGRAPHS

BREAST CANCER 1; if recurs, may restart at 1000mg/day (with capecitabine); 1250mg/day (w. letrozole).

Children: Not established.

Warnings/Precautions: Confirm normal LVEF before starting. Discontinue if ≥grade 2 decrease in LVEF occurs, or if LVEF falls below institution’s lower limit of normal; may restart after at least 2 weeks at reduced dose if asymptomatic and LVEF recovers. Conditions that impair left ventricular function, or risk factors for QT prolongation (eg, hypokalemia, hypomagnesemia, congenital long QT syndrome, concomitant antiarrhythmics, cumulative high dose anthracyclines); correct electrolyte disturbances before starting. Monitor for interstitial lung disease or pneumonitis; discontinue if pulmonary symptoms ≥grade 3 (NCI CTCAE).

Monitor liver function tests before, every 4–6 weeks during therapy and as indicated; discontinue if hepatotoxicity occurs; do not retreat. Severe hepatic impairment: consider dose reduction.

Diarrhea: promptly treat with anti-diarrheal agents; if severe, may require fluids, electrolytes, antibiotics and therapy interruption/discontinuation. Monitor ECG. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended.

Interactions: Avoid potent CYP3A4 inhibitors (eg, ketoconazole), grapefruit; reduce dose if unavoidable. Avoid potent CYP3A4 inducers (eg, carbamazepine); slowly titrate dose up if unavoidable. May affect drugs that are affected by p-glycoprotein, CYP2C8, CYP3A4.

Adverse reactions: Diarrhea (may be severe), nausea, vomiting, hand/foot syndrome, rash, fatigue; decreased LVEF, QT prolongation, interstitial lung disease, pneumonitis, hepatotoxicity (may be fatal).

Testing considerations: HER2 protein overexpression How supplied: Tabs—150

XELODA Genentech

℞

Fluoropyrimidine. Capecitabine (prodrug of 5-fluorouracil) 150mg, 500mg; tabs.

Indications: Metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or resistant to paclitaxel when further anthracycline therapy is not indicated (eg, prior cumulative doses of 400mg/m2 of doxorubicin or its equivalents). With docetaxel for metastatic breast cancer after failure of prior anthracycline-containing regimen.

Adults: See full labeling. Give cyclically (2 weeks on, 1 week off). Swallow whole. Take with water within 30 minutes after AM & PM meals. ≥18yrs: 1250mg/m2 twice daily. Combination therapy: give with docetaxel 75mg/m2 IV infused over 1 hour every 3 weeks. Interrupt, adjust dose, and/or treat symptoms if toxicity occurs (eg, hyperbilirubinemia, diarrhea, nausea, vomiting, hand-and-foot syndrome, stomatitis) (see full labeling); do not increase dose afterwards. Renal impairment

(CrCl 51–80mL/min): monitor carefully; (CrCl 30–50mL/min): reduce capecitabine dose to 75% of starting dose (ie, 950mg/m2 twice daily).

Children: <18yrs: not established.

Contraindications: Severe renal impairment (CrCl <30mL/min).

Warnings/Precautions: Hepatic or renal dysfunction. Monitor and correct dehydration at initiation. Coronary artery disease. Interrupt therapy if severe diarrhea occurs; give antidiarrheals until resolves or reduces to Grade 1. Dihydropyrimidine dehydrogenase deficiency. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Increased anticoagulant effect with warfarin; monitor PT/INR frequently.

Potentiated by leucovorin. Monitor phenytoin and other CYP2C9 substrates.

Adverse reactions: Diarrhea, hand-andfoot syndrome, nausea, vomiting, abdominal pain, fatigue/weakness, hyperbilirubinemia; lymphopenia, necrotizing enterocolitis, stomatitis, dermatitis, anorexia, cardiotoxicity, blood dyscrasias, paresthesias, eye irritation, edema, myalgia, dehydration, alopecia; severe mucocutaneous reactions (eg, SJS, TEN); permanently discontinue if occurs.

Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase) How supplied: Tabs 150mg—60; 500mg—120

DOSAGES FOR THE ELDERLY Special caution is advised when prescribing drugs for elderly patients. Keep the following points in mind when prescribing drugs for patients of approximately 60 years or older:

1. Renal Function: Glomerular filtration rate, renal tubular secretion and blood flow tend to decrease with advancing age, while the incidence of renal pathology increases.

2. Drug Sensitivity: Elderly patients may show unusual sensitivity or paradoxical reactions to a number of drugs. Refer to the complete prescribing information.

3. Drug Distribution: The ratio of fat to lean body weight may increase in the elderly, which affects the volume of distribution of fat-soluble drugs. Plasma albumin concentrations may be decreased in the elderly. This potentiates plasma-protein bound drugs and increases the potential for drug interactions caused by plasma-protein displacement.

4. Polypharmacy: It is important to determine the patient’s current medication use, including nonprescription products, before adding any medication to determine any possible interactions.

5. Hepatic Function: Reduced function of metabolic enzymes in the liver may occur in the elderly.

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DRUG MONOGRAPHS

ENDOCRINE CANCER ABRAXANE Celgene

℞

Taxane antimicrotubule. Paclitaxel [bound to albumin (human)] 100mg/vial; pwd for IV infusion after reconstitution; solvent-free.

Indications: First-line treatment of metastatic adenocarcinoma of the pancreas, in combination with gemcitabine.

Adults: Do not treat if neutrophil count <1,500 cells/mm3 or platelets <100,000 cells/mm3.

125mg/m2 IV over 30–40 mins on Days 1, 8, and 15 of each 28-day cycle. Moderate to severe hepatic impairment (total bilirubin >1.5): not recommended. Dose reductions for hematologic and neurologic adverse reactions: see full labeling. Avoid extravasation.

Children: Not evaluated.

Contraindications: Baseline neutrophil count <1,500 cells/mm3. Prior severe hypersensitivity reaction (do not rechallenge).

Warnings/Precautions: Do not substitute for, or with, other paclitaxel products (due to formulation differences). Do frequent complete blood cell counts. Hepatic impairment (total bilirubin >5XULN or AST >10XULN): not recommended. Monitor for sensory neuropathy, sepsis, or pneumonitis. Renal dysfunction.

Contains human albumin; remote risk of viral transmission. Use appropriate contraception (men and women). Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: May potentiate or be potentiated

by CYP2C8 and/or CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin, efavirenz, nevirapine) and/or inhibitors (eg, ketoconazole, other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, nelfinavir).

Adverse reactions: Bone marrow suppression (eg, neutropenia, anemia), infections, alopecia, sensory neuropathy (may require dose reduction or interruption), peripheral neuropathy, GI upset, mucositis, fatigue/asthenia, myalgia/arthralgia, abnormal ECG; alkaline phosphatase or AST elevation; dyspnea, edema, hypotension, rash (may be serious); rare: thrombotic events.

How supplied: Single-use vial—1

AFINITOR Novartis

℞

mTOR kinase inhibitor. Everolimus 2.5mg, 5mg, 7.5mg, 10mg; tabs.

Indications: In adults with progressive neuroendocrine tumors of pancreatic origin (PNET) or progressive, well-differentiated, nonfunctional neuroendocrine tumors (NET) of gastrointestinal or lung origin with unresectable, locally advanced or metastatic disease. Not for treating functional carcinoid tumors.

Adults: Swallow tabs whole with water. Take at the same time each day either consistently with or without food. 10mg once daily. Mild hepatic impairment (Child-Pugh class A): 7.5mg daily, may reduce to 5mg if not tolerated. Moderate

hepatic impairment (Child-Pugh class B): 5mg daily, may be reduce to 2.5mg if not tolerated.

Severe hepatic impairment (Child-Pugh class C): max 2.5mg daily if benefits outweigh risk.

Concomitant moderate CYP3A4/PgP inhibitors: reduce to 2.5mg once daily; may consider increasing to 5mg if tolerated. If moderate inhibitor is discontinued, allow 2–3 days washout period before increasing everolimus dose; return to dose used prior to initiating the moderate inhibitor. Concomitant strong CYP3A4/PgP inducers: consider doubling the daily dose by increments of 5mg or less. If strong inducer is discontinued, consider washout period of 3–5 days before returning to the dose used prior to initiating the strong inducer. Continue therapy until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions, or others: see full labeling.

Children: Not recommended.

Contraindications: Allergy to other rapamycin derivatives.

Warnings/Precautions: Monitor for new or worsening respiratory symptoms. Increased risk of infections; some may be severe or fatal; monitor and treat promptly if occur. Pre-existing invasive fungal infections: treat before starting.

Monitor for signs of wound-related complications.

Peri-surgical period. Hepatic impairment (see Adult dose). Monitor CBCs, renal function, lipids, and blood glucose prior to starting and periodically thereafter. Avoid close contact with those who have received live vaccines. Pediatrics: complete childhood vaccination series according to ACIP guidelines prior to initiation. Elderly.

Females of reproductive potential must use effective contraception during therapy and for 8 weeks after treatment. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Avoid live vaccines. Potentiated by strong CYP3A4/PgP inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole), grapefruit or grapefruit juice; avoid. Caution with moderate CYP3A4/PgP inhibitors (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem); reduce everolimus dose if used. Antagonized by strong CYP3A4/PgP inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital), St. John’s Wort; avoid.

Adverse reactions: Pneumonitis (interrupt, reduce dose and/or manage with corticosteroids; if severe, discontinue; may reintroduce daily dose at approx. 50% lower than previously administered), infections (discontinue if invasive systemic fungal infection develops), stomatitis (treat with non-alcoholic, non-peroxide mouthwash), diarrhea, nausea, abdominal pain, rash, fatigue, edema, fever, asthenia, cough, headache, decreased appetite; increased serum creatinine, blood glucose, lipids; decreased hemoglobin, platelets, neutrophils, serum

phosphate; proteinuria, renal failure, others (see full labeling).

How supplied: Tabs—28 (4 blister cards × 7 tabs)

CAPRELSA AstraZeneca

℞

Kinase inhibitor. Vandetanib 100mg, 300mg, tabs.

Indications: Symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.

Adults: Do not crush tabs. May disperse tabs in 2oz noncarbonated water for oral or NGT administration; avoid contact of dispersion with skin, mucous membranes. 300mg once daily.

Renal impairment (CrCl<50mL/min): initially 200mg once daily. Dose adjustments for adverse reactions: see full labeling. Do not take a missed dose within 12hrs of the next dose.

Children: Not established.

Contraindications: Congenital long QT syndrome.

Warnings/Precautions: Hypocalcemia, hypokalemia, hypomagnesemia, QTcF interval >450msec, history of torsades de pointes, bradyarrhythmias, uncompensated heart failure, recent hemoptysis: not recommended.

Ventricular arrhythmias. Recent MI. Monitor electrolytes (esp. K+, Ca++, Mg++), TSH, and ECG for QT prolongation at baseline, 2–4 weeks and 8–12 weeks after starting, then every 3 months, and after dose reductions or dose interruptions >2 weeks; reduce dose as needed. Correct electrolyte disturbances before starting. Maintain serum K+ at least 4mEq/mL. Hepatic impairment (Child-Pugh B or C): not recommended. Interrupt therapy and follow-up if acute or worsening pulmonary symptoms, QTcF >500msec, or CTCAE Grade ≥3 toxicity occurs. Monitor for heart failure; consider discontinuing if occurs. Discontinue if confirmed interstitial lung disease, severe ischemic cerebrovascular event, hemorrhage, uncontrolled hypertension, or posterior leukoencephalopathy symptoms (RPLS) occur.

Avoid sun, UV light. Elderly. Pregnancy (Cat. D) (may cause fetal harm; use appropriate effective contraception during and for 4 months after stopping therapy), nursing mothers: not recommended.

Interactions: Avoid strong CYP3A4 inducers (eg, rifampicin, St. John’s Wort). Avoid other drugs that can prolong QT interval (eg, amiodarone, disopyramide, procainamide, sotalol, dofetilide, chloroquine, clarithromycin, dolasetron, granisetron, haloperidol, pimozide, methadone, moxifloxacin).

Potentiates OCT2 transporters (eg, metformin), digoxin; monitor.

Adverse reactions: Diarrhea/colitis (suspend if severe), rash, acneiform dermatitis, nausea, hypertension, headache, upper respiratory tract infections, decreased appetite, abdominal pain, hypocalcemia, hypoglycemia, increased ALT; QT prolongation, torsades de pointes, sudden death, severe skin reactions (eg,

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DRUG MONOGRAPHS

ENDOCRINE CANCER toxic epidermal necrolysis, Stevens-Johnson syndrome; permanently discontinue if occurs), photosensitivity.

Note: Prescribers and pharmacies must enroll in the Caprelsa REMS program by calling (800) 236-9933 or visit www.caprelsarems.com.

How supplied: Tabs—30

COMETRIQ Exelixis

℞

Kinase inhibitor. Cabozantinib 20mg, 80mg; caps.

Indications: Treatment of progressive, metastatic medullary thyroid cancer (MTC).

Adults: Not interchangeable with cabozantinib tabs. Swallow whole. 140mg daily. Do not eat at least 2 hours before or 1 hour after dose. Continue until disease progression or unacceptable toxicity.

Withhold for Grade 4 hematologic adverse reactions, ≥Grade 3 non-hematologic reactions or intolerable Grade 2 reactions. Upon improvement to Grade 1 or to baseline, reduce dose as follows: previously on 140mg daily, resume at 100mg daily; previously on 100mg daily, resume at 60mg daily; previously on 60mg daily, resume at 60mg if tolerated, otherwise discontinue.

Mild-to-moderate hepatic impairment: initially 80mg daily. Concomitant strong CYP3A4 inhibitors: reduce daily dose by 40mg; resume dose used prior to starting inhibitor 2–3 days after discontinuation of inhibitor. Concomitant strong CYP3A4 inducers: increase daily dose by 40mg; resume dose used prior to starting inducer 2–3 days after discontinuation of inducer. Max daily dose: 180mg.

Children: Not studied.

Warnings/Precautions: Permanently discontinue if the following occurs: GI or non-GI perforation/fistula formation, severe hemorrhage, serious arterial thromboembolic events (eg, MI, cerebral infarction), nephrotic syndrome, malignant hypertension, hypertensive crisis, persistent uncontrolled hypertension despite optimal medical management, osteonecrosis of the jaw, reversible posterior leukoencephalopathy syndrome. Recent history of hemorrhage, hemoptysis: avoid. Stop treatment at least 28 days prior to scheduled surgery (including invasive dental procedures); withhold dose if dehiscence or wound healing complications require medical intervention. Severe hepatic impairment: not recommended. Severe renal impairment. Monitor for bleeding, hypertension, proteinuria (measure urine protein regularly).

Pregnancy. Females of reproductive potential should use effective contraception during and for 4 months after final dose. Nursing mothers: not recommended.

Interactions: Avoid concomitant strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole, grapefruit or grapefruit juice) and strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s Wort): see Adult dose. May be potentiated by MRP2 inhibitors (eg, abacavir, adefovir, cidofovir, furosemide, lamivudine, nevirapine, ritonavir, probenecid, saquinavir, tenofovir); monitor for increased toxicity.

Adverse reactions: Diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome, decreased weight/appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, constipation, increased AST, ALT, alkaline phosphatase, lymphopenia, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, hyperbilirubinemia.

How supplied: 140mg daily-dose carton—4 blister cards (each: 7x80mg and 21x20mg caps); 100mg daily-dose carton—4 blister cards (each: 7x80mg and 7x20mg caps); 60mg daily-dose carton—4 blister cards (each: 21x20mg caps)

Fluorouracil (various)

℞

Antimetabolite. Fluorouracil 50mg/mL; soln for IV inj.

Indications: Palliative management of carcinoma of the pancreas.

Adults: Give by IV inj. 12mg/kg once daily for 4 successive days; max 800mg/day. If no toxicity is observed, 6mg/kg are given on the 6th, 8th, 10th, and 12th days unless toxicity occurs.

Maintenance therapy: repeat dosage of 1st course every 30 days after the last day of the previous course of treatment; or give a maintenance dose of 10–15mg/kg per week as a single dose; max: 1g/week. Poor risk patients: see literature for dose adjustments.

Children: Not recommended.

Contraindications: Poor nutritional state.

Depressed bone marrow function. Potentially serious infections.

Warnings/Precautions: Narrow margin of safety; monitor for toxicity. Consider hospitalization for 1st course. History of highdose pelvic irradiation. Previous use of alkylating agents. Widespread involvement of bone marrow by metastatic tumors. Renal or hepatic impairment. Discontinue if signs of toxicity appear (eg, stomatitis, esophagopharyngitis, leukopenia, intractable vomiting, diarrhea,

GI ulceration or bleeding, thrombocytopenia, hemorrhage). Monitor WBCs with differential before each dose. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended.

Interactions: Potentiated by leucovorin.

Adverse reactions: Stomatitis, esophagopharyngitis, GI upset, anorexia, leukopenia, alopecia, dermatitis, hand-foot syndrome; others.

Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase).

How supplied: Contact supplier.

LENVIMA Eisai

℞

Kinase inhibitor. Lenvatinib 4mg, 10mg; capsules.

Indications: Treatment of locally recurrent or metastatic, progressive, radioactive iodinerefractory differentiated thyroid cancer.

Adults: Swallow whole or may dissolve capsule contents into liquid. 24mg once daily until disease progression or unacceptable toxicity occurs.

Severe renal impairment (CrCl <30mL/min) or severe hepatic impairment (Child-Pugh C): 14mg once daily. Dose modifications for adverse reactions or lab abnormalities: see full labeling.

Children: Not established.

Warnings/Precautions: Control blood pressure prior to treatment; monitor after 1 week, every 2 weeks for the first 2 months, and then at least monthly thereafter during therapy.

Discontinue if life-threatening hypertension, Grade 4 cardiac dysfunction or hemorrhage, arterial thrombotic event, hepatic failure, nephrotic syndrome, GI perforation or lifethreatening fistula, or severe and persistent neurologic symptoms occur. Withhold if Grade 3 hypertension persists despite therapy, Grade 3 cardiac dysfunction or hemorrhage, ≥Grade 3 liver impairment or QT prolongation >500ms, Grade 3 or 4 renal failure/impairment, ≥2g of proteinuria/24hrs, or reversible posterior leukoencephalopathy syndrome (RPLS) occurs.

Monitor for signs/symptoms of cardiac decompensation. Monitor liver function prior to treatment, every 2 weeks for the first 2 months, then at least monthly during treatment. Monitor for proteinuria prior to, and periodically during treatment. Monitor for dehydration and treat if diarrhea develops; interrupt if Grade 3 or 4 and permanently discontinue if Grade 4 diarrhea persists despite therapy. Hypovolemia. Congenital long QT syndrome, CHF, bradyarrhythmias, or those taking Class Ia or III antiarrhythmic drugs; monitor ECGs. Monitor and correct electrolyte

Access Cancer Therapy Advisor treatment regimens in a user-friendly format.

CancerTherapyAdvisor.com/TreatmentRegimens.

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DRUG MONOGRAPHS

ENDOCRINE CANCER abnormalities. Monitor blood calcium levels at least monthly; replace as needed during treatment. Monitor thyroid function prior to initiation and at least monthly thereafter; treat hypothyroidism as needed. ESRD. Embryofetal toxicity. Pregnancy: avoid. Use effective contraception during and for at least 2 weeks after treatment completion. Nursing mothers: not recommended.

Adverse reactions: Hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, weight decreased, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, dysphonia.

How supplied: Blister cards—6

NEXAVAR Bayer and Onyx

toxic epidermal necrolysis), fatigue, weight loss, diarrhea, anorexia, abdominal pain, hypertension, hemorrhage, electrolyte abnormalities; druginduced hepatitis, QT prolongation.

How supplied: Tabs—120

ONIVYDE Merrimack

℞

Multikinase inhibitor. Sorafenib 200mg; tabs.

Indications: Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment.

Adults: Take on an empty stomach. 400mg twice daily. If toxicity occurs, may reduce dose to 400mg and 200mg 12hrs apart (either dose can come first); if second reduction is required, may reduce dose to 200mg twice daily; if third reduction is required, may reduce to 200mg once daily (see full labeling). Concomitant strong CYP3A4 inducers: consider increasing dose, monitor for toxicity.

Children: Not established.

Contraindications: Concomitant carboplatin/paclitaxel in patients with squamous cell lung cancer.

Warnings/Precautions: Avoid in congenital long QT syndrome. Monitor patients with CHF, bradyarrhythmias, drugs known to prolong the QT interval, electrolyte abnormalities. Discontinue if severe dermatologic toxicity, hypertension, GI perforation, hemorrhage, cardiac ischemia, MI occurs. Suspend therapy before major surgery.

Monitor BP weekly during the first 6 weeks and thereafter. Monitor hepatic function regularly; discontinue if transaminases significantly elevated. Severe hepatic impairment (Child-Pugh C) or on dialysis. Monitor TSH levels monthly and adjust thyroid therapy. Use effective contraception during and for 2 weeks after stopping treatment.

Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: See Contraindications. Avoid strong CYP3A4 inducers (eg, St. John’s Wort, dexamethasone, phenytoin, carbamazepine, rifabutin, rifampin, phenobarbital) and neomycin; may decrease sorafenib levels. May potentiate warfarin (monitor PT & INR), other drugs metabolized by UGT1A1 or UGT1A9 pathway, or substrates of CYP2B6, CYP2C8, CYP2C9, P-gp.

Concomitant Class Ia and III antiarrhythmics; may prolong QT interval.

Adverse reactions: Dermatologic toxicity (eg, rash, hand-foot skin reaction, alopecia, pruritus, dry skin, Stevens-Johnson syndrome,

pyrexia; neutropenic fever or sepsis, dehydration, septic shock, pneumonia, acute renal failure, thrombocytopenia.

How supplied: Single-dose vial—1

SOMATULINE DEPOT Ipsen ℞

Topoisomerase inhibitor. Irinotecan 43mg/10mL; liposomal dispersion for IV infusion after dilution.

Indications: In combination with fluorouracil and leucovorin, for treatment of metastatic adenocarcincoma of the pancreas after disease progression following gemcitabine-based therapy.

Limitations of use: as a single agent, not for the treatment of metastatic adenocarcinoma of the pancreas.

Adults: Do not substitute for other irinotecan HCl-containing drugs. Give by IV infusion over 90 mins prior to fluorouracil and leucovorin.

70mg/m2 every 2 weeks. If homozygous UGT1A1*28 allele: initially 50mg/m2; may increase to 70mg/m2 as tolerated in subsequent cycles.

If serum bilirubin >ULN: no dose recommended.

Premedicate with corticosteroid and antiemetic 30 mins prior to infusion. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Severe and lifethreatening neutropenia, neutropenic sepsis, diarrhea can occur. Monitor CBCs on Days 1 and 8 of every cycle and more frequently if indicated; withhold if ANC <1500/mm3 or neutropenic fever occurs; reduce dose in subsequent cycles for Grade 3–4 neutropenia or neutropenic fever after recovery. Bowel obstruction: do not administer. Withhold for Grade 2–4 diarrhea; initiate loperamide if late onset or atropine IV/SC (unless contraindicated) if early onset; resume at reduced dose after recovery to Grade 1.

Withhold if new or progressive dyspnea, cough, and fever occurs, pending evaluation; discontinue if interstitial lung disease confirmed. Permanently discontinue if severe hypersensitivity reaction occurs. Females of reproductive potential should use effective contraception during therapy and for 1 month after final dose; males should use condoms during and for 4 months after final dose. Pregnancy. Nursing mothers: not recommended (during therapy and for 1 month after final dose).

Interactions: Avoid concomitant strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, rifabutin, rifapentine, phenobarbital, St. John’s wort) if possible; substitute non-enzyme inducing therapies at least 2 weeks before initiating irinotecan. Avoid concomitant strong CYP3A4 (eg, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) or UGT1A1 inhibitors (eg, atazanavir, gemfibrozil, indinavir) if possible; discontinue CYP3A inhibitors at least 1 week before initiating irinotecan.

Adverse reactions: Diarrhea, fatigue/asthenia, vomiting, nausea, decreased appetite, stomatitis,

℞

Somatostatin analogue. Lanreotide 60mg, 90mg, 120mg; prolonged-release soln for SC inj.

Indications: Treatment of unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival.

Adults: Give by deep SC inj into the superior external quadrant of the buttock. Rotate inj site.

120mg every 4 weeks.

Children: Not established.

Warnings/Precautions: Diabetes.

Hypothyroidism. Cardiovascular disease. Hepatic or severe renal impairment. Monitor thyroid function, gallbladder, glucose. Pregnancy (Cat.C).

Nursing mothers: not recommended.

Interactions: Potentiates bromocriptine, CYP450 substrates (eg, quinidine, terfenadine), bradycardia-inducing drugs (eg, β-blockers); adjust doses. Antagonizes cyclosporine; adjust dose. May need to adjust antidiabetic agents.

Adverse reactions: Diarrhea, cholelithiasis, abdominal pain, nausea, inj site reactions; gallbladder sludge, gallstones, hyperglycemia, hypoglycemia, sinus bradycardia, hypertension, anemia; rare: hypothyroidism.

How supplied: Single-use pre-filled syringe—1

SUTENT Pfizer

℞

Multikinase inhibitor. Sunitinib (as malate) 12.5mg, 25mg, 37.5mg, 50mg; gelatin caps.

Indications: Progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in patients with unresectable locally advanced or metastatic disease.

Adults: 37.5mg once daily continuously without a scheduled off-treatment period. May adjust dose in increments or decrements of 12.5mg.

Concomitant strong CYP3A4 inhibitors (see Interactions): may reduce dose to 25mg daily.

Concomitant strong CYP3A4 inducers (see Interactions): may increase to max 62.5mg daily.

Children: Not established.

Warnings/Precautions: Hepatotoxicity; may be severe or fatal. Monitor liver function tests before starting, during each cycle of treatment and as clinically needed; interrupt if Grade 3 or 4 hepatic adverse events occur and discontinue if no resolution; if severe liver function changes or signs/symptoms of failure, do not restart.

Cardiovascular events: monitor for CHF during therapy, and LVEF at baseline and periodically; interrupt or reduce dose if LVEF <50% and >20% below baseline; discontinue if CHF occurs. History of QT prolongation or proarrythmic conditions (eg, bradycardia, electrolyte disturbances); perform periodic ECG, monitor electrolytes. Monitor

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DRUG MONOGRAPHS

ENDOCRINE CANCER BP. Suspend therapy if severe hypertension, seizures, or pancreatitis develops. Obtain CBCs, platelets, serum chemistries at start of each cycle. Concomitant exposure to risk factors (eg, IV bisphosphonates therapy or dental disease) may increase the risk of osteonecrosis of the jaw; avoid or consider preventive dentistry prior to treatment. Risk of tumor lysis syndrome: monitor closely in RCC and GIST patients with high tumor burden. Monitor for thyroid dysfunction; obtain baseline levels prior to treatment. Monitor blood glucose levels during and after treatment discontinuation. Monitor for proteinuria; perform baseline and periodic urinalyses; interrupt and reduce dose if 24-hr urine protein ≥3g; discontinue if nephrotic syndrome or repeat urine protein ≥3g persists. Undergoing major surgery. Stress (monitor for adrenal insufficiency).

Discontinue if severe cutaneous reactions (eg, erythema multiforme, SJS, TEN) develop; do not restart if diagnosis suspected. ESRD on dialysis.

Severe hepatic impairment. Pregnancy (Cat.D; avoid). Nursing mothers: not recommended.

Interactions: May be potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), grapefruit; consider reducing dose or use alternate drug. May be antagonized by CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital); consider increasing dose or use alternate drug. Concomitant St. John’s wort: not recommended. Caution with concomitant antiarrhythmics.

Adverse reactions: Fatigue, asthenia, fever, diarrhea, nausea, vomiting, mucositis/stomatitis, dyspepsia, abdominal pain, constipation, hypertension, peripheral edema, rash, handfoot syndrome, skin discoloration, dry skin, hair color changes, altered taste, headache, back pain, arthralgia, extremity pain, cough, dyspnea, anorexia, bleeding; hepatotoxicity, left ventricular dysfunction, QT prolongation, osteonecrosis of the jaw, tumor lysis syndrome, thyroid dysfunction, impaired wound healing, hypoglycemia, thrombotic microangiopathy (discontinue if develops), proteinuria, necrotizing fasciitis (discontinue if occurs), others (see full labeling).

How supplied: Caps—28

TARCEVA Astellas and Genentech

℞

Kinase inhibitor. Erlotinib (as HCl) 25mg, 100mg, 150mg; tabs.

Indications: In combination with gemcitabine: first-line treatment of locally

advanced, unresectable or metastatic pancreatic cancer.

Adults: Take on empty stomach. 100mg once daily + gemcitabine (see full labeling). Use until disease progression or unacceptable toxicity occurs. Diarrhea unresponsive to loperamide, severe skin reactions, strong CYP3A4 inhibitors (see Interactions), hepatic impairment: reduce in 50mg decrements. Concomitant CYP3A4 inducers (see Interactions): increase in 50mg increments at 2-week intervals; max 450mg (see full labeling). Concurrent cigarette smoking: increase in 50mg increments at 2-week intervals; max 300mg (see full labeling); upon cessation, reduce to 150mg or 100mg daily.

Children: Not established.

Warnings/Precautions: Discontinue if interstitial lung disease, severe hepatic toxicity, GI perforation, severe bullous, blistering or exfoliating skin conditions, or corneal perforation or severe ulceration occurs. Withhold or consider discontinuing therapy if severe renal failure due to dehydration, or acute/worsening ocular disorders occur. Monitor LFTs periodically; withhold in patients without history of hepatic impairment for total bilirubin >3XULN or transaminases >5XULN, or in patients with history of hepatic impairment or biliary obstruction for doubling of bilirubin or tripling of transaminases over baseline. Discontinue if abnormal LFTs do not improve or resolve within 3 weeks. Withhold for persistent severe diarrhea unresponsive to loperamide, severe rash, or grade 3–4 keratitis. Monitor renal function, serum electrolytes, pulmonary function, INR, prothrombin time. History of peptic ulcers or diverticular disease. Pregnancy (Cat.D); use effective contraception during therapy and at least 2 weeks after the last dose. Nursing mothers: not recommended.

Interactions: Potentiated by CYP3A4 inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, grapefruit) and CYP1A2 inhibitors (eg, ciprofloxacin); avoid if possible. Plasma levels decreased by CYP3A4 inducers (eg, rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, St. John’s wort), proton pump inhibitors or H2 blockers (take erlotinib 10hrs after and at least 2hrs before next dose), and smoking; avoid if possible. Increased risk of GI perforation with concomitant anti-angiogenic agents, steroids, NSAIDs, taxane-based chemotherapy. Monitor for bleeding with oral anticoagulants, NSAIDs. Adverse reactions: Rash, diarrhea, nausea, vomiting, anorexia, fatigue, elevated LFTs,

unexplained pulmonary symptoms (eg, dyspnea, cough, fever; discontinue and follow-up if occurs), stomatitis, infection; rare: GI perforation (may be fatal), ocular disorders (eg, conjunctivitis, keratitis, corneal ulceration/perforation), MI/ischemia, hemolytic anemia, cerebrovascular accidents, interstitial lung disease; hepatic or renal failure and hepatorenal syndrome (may be fatal); bullous, blistering and exfoliative skin conditions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis).

Testing considerations: K-RAS mutation analysis, EGFR amplification analysis How supplied: Tabs—30

GENERIC NAME The active ingredients and strengths are listed under the name of each dosage form. If the product contains tartrazine, alcohol, flavors, or is alcohol-, sugar-, or dye-free, it is noted. Abbreviations are used to describe the dosage form and its formulation, e.g.: tabs = tablets caps = capsules e-c = enteric coated sust rel = sustained-release ext rel = extended-release

BRAND NAME The main name under which the product and all other dosage forms in the monograph are marketed.

LEGAL CATEGORY Federal schedule. The laws governing the prescribing/dispensing of products vary from state to state.

Take advantage of our free online medical calculators at CancerTherapyAdvisor.com/MedicalCalculators.

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CANCER TREATMENT REGIMEN

GASTROINTESTINAL CANCER Colon Cancer Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team.

Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly.

The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Advanced or Metastatic Disease1 Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

mFOLFOX6

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Days 1–3: 5-FU 400mg/m2 IV bolus on day 1, then 1,200mg/m2/day × 2 days (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks.

mFOLFOX6 + Bevacizumab3,5ab

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Days 1–3: 5-FU 400mg/m2 IV bolus on day 1, then 1,200mg/m2/day × 2 days (total 2,400mg/m2 over 46–48 hours) IV continuous infusion Day 1: Bevacizumab 5mg/kg IV. Repeat cycle every 2 weeks.

mFOLFOX6 + Panitumumab (KRAS/NRAS WT gene only)3,6ab

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Days 1–3: 5-FU 400mg/m2 IV bolus on day 1, then 1,200mg/m2/day × 2 days (total 2,400mg/m2 over 46–48 hours) IV continuous infusion Day 1: Panitumumab 6mg/kg IV over 60 minutes.

Repeat cycle every 2 weeks.

FOLFOX + Cetuximab (KRAS/NRAS WT gene only)3,7ab

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Days 1–3: 5-FU 400mg/m2 IV bolus on day 1, then 1,200mg/m2/day × 2 days (total 2,400mg/m2 over 46–48 hours) IV continuous infusion.

Repeat cycle every 2 weeks, plus Cetuximab 400mg/m2 IV over 2 hours for the first infusion, then 250mg/m2 IV over 60 minutes weekly.

OR Day 1: Cetuximab 500mg/m2 IV over 2 hours every 2 weeks.

CapeOX2c

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours Days 1–14: Capecitabine 850–1,000mg/m2 orally twice daily Day 1: Bevacizumab 7.5mg/kg IV. Repeat cycle every 3 weeks.

CapeOX + Bevacizumab2,8c

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours Days 1–14: Capecitabine 850–1,000mg/m2 orally twice daily.

Repeat cycle every 3 weeks.

FOLFIRI9ab

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes Day 1: Leucovorin 400mg/m2 IV infusion to match duration of irinotecan infusion Days 1–3: 5-FU 400mg/m2 IV bolus day 1, then 1,200mg/m2/day × 2 days (total 2,400mg/m2 over 46–48 hours) continuous infusion.

Repeat cycle every 2 weeks.

FOLFIRI + Bevacizumab9,10ab

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes Day 1: Leucovorin 400mg/m2 IV infusion to match duration of irinotecan infusion Days 1–3: 5-FU 400mg/m2 IV bolus day 1, then 1,200mg/m2/day × 2 days (total 2,400mg/m2 over 46–48 hours) IV continuous infusion Day 1: Bevacizumab 5mg/kg IV. Repeat cycle every 2 weeks.

2-4ab

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CANCER TREATMENT REGIMEN

GASTROINTESTINAL CANCER Advanced or Metastatic Disease1 (continued) REGIMEN

DOSING

FOLFIRI + Cetuximab (KRAS/NRAS WT gene only)9,10,12ab

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes Day 1: Leucovorin 400mg/m2 IV infusion to match duration of irinotecan infusion Days 1–3: 5-FU 400mg/m2 IV bolus day 1, then 1,200mg/m2/day × 2 days (total 2,400mg/m2 over 46–48 hours) IV continuous infusion, plus Days 1 and 8: Cetuximab 400mg/m2 IV over 2 hours first infusion, then 250mg/m2 IV over 60 minutes.

OR Day 1: Cetuximab 500mg/m2 IV over 2 hours.

Repeat cycle every 2 weeks

FOLFIRI + Panitumumab (KRAS/NRAS WT gene only)9,13a

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes Day 1: Leucovorin 400mg/m2 IV infusion to match duration of irinotecan infusion Days 1–3: 5-FU 400mg/m2 IV bolus day 1, then 1,200mg/m2/day × 2 days (total 2,400mg/m2 over 46–48 hours) IV continuous infusion Day 1: Panitumumab 6mg/kg IV over 60 minutes.

Repeat cycle every 2 weeks.

FOLFIRI + ziv-aflibercept14ab

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes Day 1: Leucovorin 400mg/m2 IV infusion to match duration of irinotecan infusion Days 1–3: 5-FU 400mg/m2 IV bolus day 1, then 1,200mg/m2/day × 2 days (total 2,400mg/m2 over 46–48 hours) continuous infusion Day 1: Ziv-aflibercept 4mg/kg IV over 1 hour.

Repeat cycle every 2 weeks.

FOLFIRI + Ramucirumab15ab

Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes Day 1: Leucovorin 400mg/m2 IV infusion to match duration of irinotecan infusion Days 1–3: 5-FU 400mg/m2 IV bolus day 1, then 1,200mg/m2/day × 2 day (total 2,400mg/m2 over 46–48 hours) IV continuous infusion Day 1: Ramucirumab 8mg/kg IV over 60 minutes.

Repeat cycle every 2 weeks.

Capecitabine16

Days 1–14: Capecitabine 850–1,250mg/m2 orally twice daily.

Repeat cycle every 3 weeks.

Capecitabine + Bevacizumab8,16

Day 1: Bevacizumab 7.5mg/kg IV Days 1–14: Capecitabine 850–1,250mg/m2 orally twice daily.

Repeat cycle every 3 weeks.

Bolus or infusional 5-FU/leucovorin Days 1, 8, 15, 22, 29, and 36: Leucovorin 500mg/m2 IV over 2 hours Roswell Park regimen17 Days 1, 8, 15, 22, 29, and 36: 5-FU 500mg/m2 IV bolus 1 hour after start of leucovorin.

Repeat cycle every 8 weeks.

Simplified biweekly infusional 5-FU/LV (sLV5FU2)9ab

Day 1: Leucovorin 400mg/m2 IV over 2 hours Days 1–3: 5-FU bolus 400mg/m2 and then 1,200mg/m2/day × 2 days (total 2,400mg/m2 over 46–48 hours) continuous infusion.

Repeat cycle every 2 weeks.

Weekly infusional LV5FU218,19

Day 1: Leucovorin 20mg/m2 IV over 2 hours Day 1: 5-FU 500mg/m2 IV bolus injection 1 hour after the start of leucovorin Day 1: 5-FU 2,600mg/m2 by 24-hour infusion plus leucovorin 500mg/m2 IV. Repeat cycle every week.

IROX20

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, followed by irinotecan 200mg/m2 IV over 30–90 minutes.

Repeat cycle every 3 weeks.

FOLFOXIRI  bevacizumab21,22

Day 1: Irinotecan 165mg/m2 IV + oxaliplatin 85mg/m2 IV Day 1: Leucovorin 400mg/m2 IV Days 1–3: Fluorouracil 1,600mg/m2/day × 2 days (total 3,200mg/m2 over 48 hours) continuous infusion starting on day 1,  Day 1: Bevacizumab 5mg/kg IV. Repeat cycle every 2 weeks.

Irinotecan23,24

Days 1 and 8: Irinotecan 125mg/m2 IV over 30–90 minutes.

Repeat cycle every 3 weeks.

OR Day 1: Irinotecan 300–350mg/m2 IV over 30–90 minutes.

Repeat cycle every 3 weeks.

OR Day 1: Irinotecan 180mg/m2 IV over 30–90 minutes.

Repeat cycle every 2 weeks. continued

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CANCER TREATMENT REGIMEN

GASTROINTESTINAL CANCER Colon Cancer Treatment Regimens Advanced or Metastatic Disease1 (continued) REGIMEN

DOSING

Cetuximab (KRAS/NRAS WT gene only) + irinotecan12,25

Cetuximab 400mg/m2 first infusion, then 250mg/m2 IV weekly OR cetuximab 500mg/m2 IV every 2 weeks,  Irinotecan 300–350mg/m2 IV every 3 weeks OR irinotecan 180mg/m2 IV every 2 weeks OR irinotecan 125mg/m2 on days 1 and 8 and repeat every 3 weeks.

Cetuximab (KRAS/NRAS WT gene only)12,23

Day 1: Cetuximab 400mg/m2 first infusion, then 250mg/m2 IV weekly OR 500mg/m2 IV over 2 hours.

Repeat cycle every 2 weeks.

Panitumumab (KRAS/NRAS WT gene only)26

Panitumumab 6mg/kg IV over 60 minutes every 2 weeks.

Regorafenib27

Days 1–21: Regorafenib 160mg orally daily.

Repeat cycle every 28 days.

Trifluridine + tipiracil28

Days 1–5 and 8–12: Trifluridine + tipiracil 35mg/m2 up to a maximum dose of 80mg/dose (based on the trifluridine component) orally twice daily.

Repeat cycle every 28 days.

Adjuvant Chemotherapy Regimens Principals of Adjuvant Therapy1 FOLFOX is superior to 5-FU/leucovorin for patients with stage III colon cancer.29,30 Capecitabine/oxaliplatin is superior to bolus 5-FU/ leucovorin for patients with stage III colon cancer. FLOX is an alternative to FOLFOX or CapeOx but FOLFOX or CapeOx is preferred.31 Capecitabine appears to be equivalent to bolus 5-FU/leucovorin in patients with stage III colon cancer.32 A survival benefit has not been demonstrated for the addition of oxaliplatin to 5-FU/leucovorin in stage II colon cancer.33 FOLFOX is reasonable for high-risk stage II patients and is not indicated for good- or average-risk patients with stage II colon cancer.

A benefit for the addition of oxaliplatin to 5-FU/leucovorin in patients age 70 and older has not been proven.33 Bevacizumab, cetuximab, panitumumab, irinotecan, ziv-aflibercept, ramucirumab, regorafenib, or trifluridine + tipiracil should not be used in the adjuvant setting for patients with stage II or III colon cancer outside the setting of a clinical trial. mFOLFOX634-36ab

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Days 1–3: 5-FU 400mg/m2 IV bolus on day 1, then 1,200mg/m2/day × 2 days (total 2,400mg/m2 over 46–48 hours) continuous infusion.

Repeat cycle every 2 weeks.

FLOX37

5-FU 500mg/m2 IV bolus weekly × 6 + leucovorin 500mg/m2 IV weekly × 6, each 8-week cycle × 3 with oxaliplatin 85mg/m2 IV administered on weeks 1, 3, and 5 of each 8-week cycle × 3.

Capecitabine38

Days 1–14: Capecitabine 1,250mg/m2 orally twice daily.

Repeat cycle every 3 weeks for 24 weeks.

CapeOx39,40

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours Days 1–14: Capecitabine 1,000mg/m2 orally twice daily.

Repeat cycle every 3 weeks for 24 weeks.

5-FU/leucovorin41,42ab

Leucovorin 500mg/m2 given as a 2-hour infusion and repeated weekly × 6 weeks, plus 5-FU 500mg/m2 given IV bolus 1 hour after the start of leucovorin and repeated weekly × 6 weeks.

Repeat cycle every 8 weeks for 4 cycles.

OR Simplified biweekly infusional 5-FU/LV (sLV5FU2) Leucovorin 400mg/m2 IV over 2 hours on day 1, followed by 5-FU bolus 400mg/m2 and then 1,200mg/m2/day × 2 days (total 2,400mg/m2 over 46-48 hours) continuous infusion.

Repeat cycle every 2 weeks.

Leucovorin 400mg/m2 is the equivalent of levoleucovorin 200mg/m2.

NCCN recommends limiting chemotherapy orders to 24-hour units (i.e., 1,200mg/m2/day NOT 2,400mg/m2 over 48 hours) to minimize medication errors. c The majority of safety and efficacy data for this regimen have been developed in Europe, where a capecitabine starting dose of 1,000mg/m2 twice daily for 14 days, repeated every 21 days, is standard. Evidence suggests that North American patients may experience greater toxicity with capecitabine (as well as with other fluoropyrimidines) than European patients, and may require a lower dose of capecitabine. The relative efficacy of CapeOx with lower starting doses of capecitabine has not been addressed in large-scale randomized trials. a

b

18 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

CANCER TREATMENT REGIMEN

GASTROINTESTINAL CANCER References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.2.2016. Available at: http://www.nccn.org.

Accessed October 26, 2016.

2. deGramont A, Figer A, Seymour M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in ­advanced rectal cancer. J Clin Oncol.

2000;18:2938–2947.

3. Cheeseman SL, Joel SP, Chester JD, et al. A “modified d ­ eGramont” regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. Br J Cancer.

2002;87:393–399. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12177775.

4. Maindrault-Goebel F, deGramont A, Louvet C, et al. Evaluation of o­ xaliplatin dose intensity in bimonthly leucovorin and 48-hour 5-fluorouracil continuous infusion regimens (FOLFOX) in ­pretreated metastatic colorectal cancer. Ann Oncol. 2000;11:1477–1483.

5. Emmanouilides C, Sfakiotaki G, Androulakis N, et al. Front-line bevacizumab in combination with oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) in patients with metastatic colorectal cancer: a multicenter phase II study. BMC Cancer. 2007;7:91.

6. Douillard JY, Siena S, Cassidy J, et al. Randomized, phase Ill trial of panitumumab with infusional fluorouracil, leucovorin, and ­oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010;28: 4697–4705.

7. Venook AP, Niedzwiecki D, Lenz H-J, et al. CALGB/SWOG 80405: Phase III trial of irinotecan/5-FU/leucovorin (­FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab or cetuximab for patients with KRAS wild-type untreated metastatic adenocarcinoma of the colon or rectum [­abstract]. ASCO Meeting Abstracts 2014;32:LBA3.

8. Saltz LB, Clarke S, Diaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase Ill study. J Clin Oncol. 2008;26:2013–2019. Available at: http:// www.ncbi.nlm.nih.gov/pubmed/18421054.

9. Andre T, Louvet C, Maindrault-Goebel F, et al. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. Eur J Cancer. 1999;35(9):1343–1347.

10. Fuchs CS, Marshall J, Mitchell E, et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol. 2007;25: 4779– 4786. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17947725.

11. Cunningham D, Humblet Y, Siena 5, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N EngI J Med. 2004;351:337–345.

12. Martin-Martorell P, Rosellô S, Rodriguez-Braun E, et al. Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial. Br J Cancer. 2008;99:455–458.

13. Peeters M, Price TJ, Cervantes A, et al. Randomized phase Ill study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol.

2010;28:4706–4713. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20921462.

14. Van Cutsem E, Tabernero J, Lakomy R, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatinbased regimen. J Clin Oncol. 2012;30:3499–3506. Available at: http://www.ncbi. nlm.nih.gov/pubmed/22949147.

15. Tabernero J, Yoshino T, Cohn AL, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomized, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015;16:499–508.

16. Van Cutsem E, Twelves C, Cassidy J, et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in ­patients with metastatic colorectal cancer: results of a large phase Ill study. J Clin Oncol. 2001;19:4097–4106.

17. Wolmark N. Rockette H, Fisher B, et al. The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Protocol C-03. J Clin Oncol. 1993;11:1879–1887.

18. Jäger E, Heike M, Bernhard H, et al. Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in ­advanced colorectal cancer: results of a randomized multicenter trial. J Clin Oncol. 1996;14:2274–2279.

19. Douillard JY, Cunningham D, Roth AD, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre ­randomized trial. The Lancet. 2000;355:1041–1047.

20. Haller DG, Rothenberg ML, Wong AO, et al. Oxaliplatin plus i­ rinotecan compared with irinotecan alone as second-line treatment after single agent fluoropyrimidine therapy for ­metastatic colorectal carcinoma. J Clin Oncol. 2008;26:4544–4550.

21. Falcone A, Ricci S, Brunetti I, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal ­cancer: The Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007;25(13):1670–1676.

22. Loupakis F, Cremolini C, Masi G, et al. FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic colorectal cancer (MCRC): results of the phase III randomized TRIBE trial. J Clin Oncol. 2013;31(Suppl 4) Abstract 336.

23. Cunningham D, Pyrhonen S, James R, et al. Randomized trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. The Lancet. 1998;352:1413–1418.

24. Fuchs CS, Moore MR, Harker G, et al. Phase Ill comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer. J Clin Oncol.

2003;21:807–814.

25. Van Cutsem E, Tejpar S, Vanbeckevoort D, et al. Intrapatient cetuximab dose escalation in metastatic colorectal cancer according to the grade of early skin reactions: the randomized EVEREST study. J Clin Oncol. 2012;30:2861–2868.

Available at: http://www.ncbi.nlm.nih.gov/pubmed/22753904.

26. Van Custem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-­refractory metastatic colorectal cancer. J Clin Oncol. 2007;25:1658–1664.

27. Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381:303–312. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23177514.

28. Mayer RJ, Van Cutsem E, Falcone A, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer (RECOURSE). N Engl J Med. 2015;372:1909-1919.

29. Andre T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350:2343–51.

30. Andre T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trail. J Clin Oncol. 2009;27:3109–16. Epub 2009 May 18.

31. Kuebler JP, Wieand HS, O’Connell MJ, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007;25:2198–2204.

32. Twelves C, Wong A, Nowacki MP, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005; 352(26):2696–704.

33. Tournigand C, André T, Bonnetain F, et al. Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly (between ages 70 and 75 years) with colon cancer: a subgroup analyses of the Multicenter International Study of oxaliplatin, fluorouracil, and leucovorin in the adjuvant treatment of colon cancer trial. J Clin Oncol. 2012;published online ahead of print on August 20, 2012.

34. Andre T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N EngI J Med. 2004;350:2343–2351.

35. Cheeseman SL, Joel SP, Chester JD, et al. A “modified d ­ eGramont” regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. Br J Cancer.

2002;87:393–399. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12177775.

36. Maindrault-Goebel F, deGramont A, Louvet C, et al. Evaluation of oxaliplatin dose intensity in bimonthly leucovorin and 48-hour 5-fluorouracil continuous infusion regimens (FOLFOX) in pretreated metastatic colorectal cancer. Ann Oncol. 2000; 11:1477–1483.

37. Kuebler JP, Wieand HS, O’Connell MJ, et al. Oxaliplatin c­ ombined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon ­cancer: r­ esults from NSABP C-07. J Clin Oncol. 2007:25:2198–2204.

38. Twelves C, Wong A, Nowacki MP, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Eng J Med. 2005;352:2696–2704.

39. Schmoll HJ, Cartwright T, Tabernero J, et al. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. J Clin Oncol. 2007;25:102–109.

40. Hailer DG, Tabernero J, Maroun J, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer.

J Clin Oncol. 2011;29:1465–1471. Available at: http://www.ncbi.nlm.nih.gov/ pubmed/21383294.

41. Haller DG, Catalano PJ, Macdonald JS Mayer RJ. Phase III study of fluorouracil, leucovorin and levamisole in high risk stage II and III colon cancer: final report of Intergroup 0089. J Clin Oncol. 2005:23:8671–8678.

42. Andre T, Louvet C, Maindrault-Goebel F, et al. CPT-11 (­irinotecan) addition to bimonthly, high-dose leucovorin and bolus and c­ ontinuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. Eur J Cancer. 1999;35(9):1343–1347.

(Revised 11/2016) © 2017 by Haymarket Media, Inc.

CancerTherapyAdvisor.com | JANUARY/FEBRUARY 2017 | CANCER THERAPY ADVISOR 19

CANCER TREATMENT REGIMEN

GASTROINTESTINAL CANCER Hepatocellular Carcinoma Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team.

Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly.

The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Unresectable Hepatocellular Carcinoma (not candidates for transplant)1 Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

Sorafenib 2,3

Sorafenib 400mg orally twice daily without food for Child-Pugh Class A (category 1) or Child-Pugh Class B.

Chemotherapya

Preferred in the context of a clinical trial.

Metastatic Hepatocellular Carcinoma1 Sorafenib2

Sorafenib 400mg orally twice daily without food.

General treatment notes: • Sorafenib is the standard of care for unresectable and metastatic hepatocellular carcinoma in patients with Child-Pugh score A (Category 1) recommendation or Child-Pugh score B.1-2 • Treatment should continue until the patient is no longer clinically benefiting from therapy or until unacceptable toxicity occurs.

• Treatment interruption and/or dose reduction may be needed to manage suspected adverse drug reactions.

• Available safety data are limited for Child-Pugh Class B or Class C patients and dosing is uncertain.

• Use with extreme caution in patients with elevated bilirubin levels. The impact of sorafenib on patients potentially eligible for transplant is unknown.4 a

There are limited data supporting the use of systemic chemotherapy and/or radiotherapy, and their use in the context of a clinical trial is preferred.

References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™. Hepatobiliary. v 1.2016. Available at: http://www.nccn.org/ professionals/physician_gls/pdf/hepatobiliary.pdf. Accessed May 3, 2016.

2. Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34.

3. Nexavar [prescribing information]. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2013.

4. Miller AA, Murry DJ, Owzar K, et al. Phase I and pharmacokinetic study of sorafenib in patients with hepatic or renal dysfunction: CALGB 60301. J Clin Oncol. 2009; 27:1800–1805.

(Revised 6/2016) © 2017 by Haymarket Media, Inc.

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20 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

DRUG MONOGRAPHS

GASTROINTESTINAL CANCER AVASTIN Genentech

℞

Angiogenesis inhibitor. Bevacizumab 100mg, 400mg; per vial; soln for IV infusion after dilution; preservative-free.

Indications: Metastatic colorectal carcinoma, in combination with 5-FU-based chemotherapy for first- or second-line treatment; or in combination with fluoropyrimidine-irinotecanor fluoropyrimidine-oxaliplatin-based therapy for second-line treatment in patients who have progressed on a first-line Avastin-containing regimen. Limitation of use: not for adjuvant treatment of colon cancer.

Adults: Give by IV infusion. Infuse 1st dose over 90 mins; if tolerated, infuse 2nd dose over 60 mins, and subsequent doses over 30 mins.

5mg/kg (when used with bolus-IFL) or 10mg/kg (when used with FOLFOX-4) once every 2 weeks until disease progression detected; 5mg/kg every 2 weeks or 7.5mg/kg every 3 weeks (when used with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based therapy).

Children: Not established.

Warnings/Precautions: Risk of GI perforations, surgery and wound healing complications, and hemorrhage. Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). Do not administer if recent history of hemoptysis of ≥ ½-teaspoon of red blood.

Permanently discontinue if GI perforation, tracheoesophageal fistula, any grade 4 fistula, or grade 4 venous thromboembolic event.

Discontinue if fistula involving internal organ, wound healing complications, hemorrhage, severe arterial thromboembolic event (ATE), hypertensive crisis or encephalopathy, posterior reversible encephalopathy syndrome, or nephrotic syndrome occurs; suspend therapy if severe hypertension, moderate-to-severe proteinuria (resume when <2g/24hrs), or severe infusion reaction occurs. Avoid in ovarian cancer if evidence of recto-sigmoid involvement by pelvic exam, bowel involvement on CT scan, or symptoms of bowel obstruction. History of arterial thromboembolism. Diabetes. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis; if ≥2+, do further assessment with a 24-hour urine collection. Elderly. Increased risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy: may cause fetal harm; use effective contraception during and for 6 months after last dose. Nursing mothers: not recommended.

Adverse reactions: Epistaxis, headache, hypertension, rhinitis, proteinuria, taste

alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation and fistulae, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial or venous thromboembolic events, posterior reversible encephalopathy syndrome, infusion reactions, ovarian failure, neutropenia, and infection.

How supplied: Single-use vial—1

CYRAMZA Lilly

℞

Human IgG1 monoclonal antibody. Ramucirumab 10mg/mL; per vial; soln for IV infusion after dilution; preservative-free.

Indications: As a single agent, or in combination with paclitaxel, for treatment of advanced or metastatic, gastric or gastro-esophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinumcontaining chemotherapy. In combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil), for the treatment of metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.

Adults: Give by IV infusion over 60 mins.

Premedicate with IV histamine H1-antagonist (eg, diphenhydramine) prior to each infusion; or with dexamethasone and acetaminophen in those who have experienced Grade 1 or 2 infusion reaction. Gastric cancer: 8mg/kg every 2 weeks.

When given in combination: administer prior to paclitaxel. mCRC: 8mg/kg every 2 weeks prior to FOLFIRI. Continue until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Increased risk of hemorrhage; permanently discontinue if severe bleeding occurs. Control hypertension prior to initiating. Monitor blood pressure every 2 weeks or more frequently as indicated; if severe hypertension develops, temporarily suspend until medically controlled. Monitor for infusion-related reactions during therapy. Have emergency resuscitative equipment available.

Permanently discontinue if severe arterial thromboembolic events, severe uncontrolled hypertension (despite antihypertensives), hypertensive crisis or encephalopathy, Grade 3 or 4 infusion-related reactions, urine protein >3g/24hrs, nephrotic syndrome, or GI perforation occurs. Impaired wound healing: withhold Cyramza prior to surgery. Clinical deterioration in patients with Child-Pugh B or C cirrhosis

(eg, new or worsening encephalopathy, ascites, hepatorenal syndrome). Discontinue if reversible posterior leukoencephalopathy syndrome develops. Monitor proteinuria by urine dipstick and/or urinary protein creatinine ratio. Monitor thyroid function. Pregnancy: avoid. Use effective contraception during therapy and for ≥3 months after last ramucirumab dose. Nursing mothers: not recommended.

Adverse reactions: Hypertension, diarrhea, headache, fatigue, asthenia, hyponatremia, anemia, intestinal obstruction, neutropenia, epistaxis, stomatitis/mucosal inflammation, rash, decreased appetite; arterial thromboembolic events, proteinuria, GI perforation, infusionrelated reactions.

How supplied: Single-dose vial (10mL, 50mL)—1

ELOXATIN Sanofi Aventis

℞

Alkylating agent (organoplatinum complex).

Oxaliplatin 5mg/mL; soln for IV infusion after dilution; preservative-free.

Indications: Adjuvant treatment for Stage III colon cancer in patients who have undergone complete resection of the primary tumor (in combination with infusional 5-FU/LV). Treatment of advanced colorectal cancer (in combination with infusional 5-FU/LV).

Adults: See full labeling. Premedicate with antiemetics. Give by IV infusion every two weeks for a total of 6 months (12 cycles) for adjuvant use or until disease progression or unacceptable toxicity for advanced disease. Day 1: 85mg/m2 + leucovorin, followed by 5-FU. Day 2: Leucovorin followed by 5-FU. Severe renal impairment: initially 65mg/m2. Neuropathy, other toxicities: see full labeling for dose adjustments.

Children: Not established.

Contraindications: Known allergy to other platinum compounds.

Warnings/Precautions: Monitor for allergic reactions; discontinue if occurs; do not rechallenge. Have epinephrine, corticosteroids, antihistamines available during infusion. Monitor for neuropathy; reduce dose or discontinue if needed. Severe neutropenia: delay therapy until neutrophils ≥1.5 × 109/L; withhold for sepsis or septic shock; reduce dose after recovery. Monitor WBCs with differential, hemogloblin, platelets, blood chemistries (including ALT, AST, bilirubin, creatinine) before each cycle. Discontinue if interstitial lung disease or pulmonary fibrosis is suspected. Patients with CHF, bradyarrhythmias, concomitant drugs known to prolong the QT interval, and electrolyte abnormalities: monitor ECG. Correct hypokalemia or hypomagnesemia

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CancerTherapyAdvisor.com | JANUARY/FEBRUARY 2017 | CANCER THERAPY ADVISOR 21

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER prior to initiation; monitor periodically during therapy. Congenital long QT syndrome; avoid.

Renal impairment. Avoid extravasation.

Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended.

Interactions: Caution with concomitant nephrotoxic agents. Monitor oral anticoagulants.

Adverse reactions: Peripheral sensory neuropathy, neutropenia, thrombocytopenia, anemia, GI upset, increased liver enzymes, fatigue, stomatitis; allergic reactions, pulmonary fibrosis (may be fatal), hepatotoxicity, QT prolongation, ventricular arrhythmias, rhabdomyolysis (may be fatal; discontinue if occurs).

Testing considerations: ERCC1 overexpression How supplied: Single-use vials (50mg, 100mg)—1

ERBITUX Bristol-Myers Squibb

℞

Epidermal growth factor receptor blocker.

Cetuximab 100mg/vial, 200mg/vial; soln for IV infusion; preservative-free.

Indications: K-Ras (wild-type), EGFR-expressing metastatic colorectal cancer: for use in combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) for first-line treatment, or in combination with irinotecan (if refractory to irinotecan-based chemotherapy), or as a single agent (after failure of both irinotecan- and oxaliplatin-based regimens or if irinotecan-intolerant). Limitation of use: not indicated for Ras mutant colorectal cancer that harbor somatic mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) or when Ras mutation test results are unknown.

Adults: Pretreat with H1 blocker. Give by IV infusion (use filter); max rate: 10mg/min. Initial dose: 400mg/m2 once over 2hrs; then 250mg/m2 once weekly over 1 hour until disease progression or unacceptable toxicity. Complete administration 1hr prior to FOLFIRI. Permanently reduce infusion rate by 50% if Grade 1 or 2 and non-serious Grade 3 infusion reaction occurs; permanently discontinue if Grade 3 or 4 serious reaction occurs. Monitor patient during and for 1hr postinfusion. Skin toxicity: see full labeling.

Children: Not established.

Warnings/Precautions: Confirm EGFR expression status and absence of Ras mutation for colorectal cancer prior to initiation. Discontinue if severe infusion reactions or interstitial lung disease occur. Monitor for infusion reactions, cardiopulmonary arrest, pulmonary toxicity, dermatologic toxicities/infection; avoid sun, UV light. Additive cutaneous reactions with irradiation. Cardiovascular diseases (w. irradiation or platinum-based therapy with 5-FU). Monitor electrolytes (eg, magnesium, potassium, calcium) during and after cetuximab therapy. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Increased mucositis (Grade 3–4), radiation recall syndrome, acneiform rash, cardiac events, and electrolyte disturbances with radiation and cisplatin.

Adverse reactions: Cutaneous reactions (pruritus, nail changes), acneform rash, headache, diarrhea, infection, asthenia, mucositis, weight loss, xerostomia, dehydration, electrolyte abnormalities; infusion reactions (may be severe: eg, bronchospasm, dyspnea), interstitial lung disease, cardiopulmonary arrest, hypomagnesemia, fever, sepsis, kidney failure, pulmonary embolus; others (see full labeling).

Testing considerations: EGFR amplification analysis, K-RAS mutation analysis, B-RAF mutation analysis.

How supplied: Single-use vials—1

Fluorouracil (various)

℞

Antimetabolite. Fluorouracil 50mg/mL; soln for IV inj.

Indications: Palliative management of carcinoma of the colon, rectum, and stomach.

Adults: Give by IV inj. 12mg/kg once daily for 4 successive days; max 800mg/day. If no toxicity is observed, 6mg/kg are given on the 6th, 8th, 10th, and 12th days unless toxicity occurs.

Maintenance therapy: repeat dosage of 1st course every 30 days after the last day of the previous course of treatment; or give a maintenance dose of 10–15mg/kg per week as a single dose; max: 1g/week. Poor risk patients: see literature for dose adjustments.

Children: Not recommended.

Contraindications: Poor nutritional state.

Depressed bone marrow function. Potentially serious infections.

Warnings/Precautions: Narrow margin of safety; monitor for toxicity. Consider hospitalization for 1st course. History of highdose pelvic irradiation. Previous use of alkylating agents. Widespread involvement of bone marrow by metastatic tumors. Renal or hepatic impairment. Discontinue if signs of toxicity appear (eg, stomatitis, esophagopharyngitis, leukopenia, intractable vomiting, diarrhea, GI ulceration or bleeding, thrombocytopenia, hemorrhage). Monitor WBCs with differential before each dose. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended.

Interactions: Potentiated by leucovorin.

Adverse reactions: Stomatitis, esophagopharyngitis, GI upset, anorexia, leukopenia, alopecia, dermatitis, hand-foot syndrome; others.

Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase).

How supplied: Contact supplier.

FUSILEV Spectrum

℞

Folate analogue. Levoleucovorin (as calcium pentahydrate) 50mg/vial; pwd for IV inj after reconstitution; contains mannitol 50mg/vial; 175mg/17.5mL; soln for IV inj; preservative-free.

Indications: Palliative treatment of advanced metastatic colorectal cancer in combination with 5-fluorouracil (5-FU).

Adults: Administer levoleucovorin and 5-FU separately to avoid precipitate formation.

Regimen 1: give levoleucovorin at 100mg/m2 by slow IV inj over a minimum of 3 minutes, followed by 5-FU at 370mg/m2 by IV inj.

Regimen 2: give levoleucovorin at 10mg/m2 by IV inj, followed by 5-FU at 425mg/m2 by IV inj.

Both: Treat daily for 5 days. Five-day treatment course may be repeated at 4 week (28 days) intervals for 2 courses, and then repeated at 4–5 week (28–35 days) intervals provided that patient recovered completely from toxic effects from prior treatment course. Dose adjustments for subsequent treatment course: see literature.

Children: Not recommended.

Warnings/Precautions: Not for treating pernicious anemia and megaloblastic anemia.

Elderly. Debilitated. Pregnancy (Cat.C). Nursing mothers.

Interactions: Potentiates 5-fluorouracil toxicity. Antagonizes TMP/SMZ. Antagonizes anticonvulsants (eg, phenobarbital, primidone, phenytoin). May be affected by drugs that affect MTX elimination.

Adverse reactions: Stomatitis, nausea, diarrhea.

How supplied: Single-use vial (pwd, soln)—1

GLEEVEC Novartis

℞

Kinase inhibitor. Imatinib (as mesylate) 100mg, 400mg; scored tabs.

Indications: Kit (CD117) (+) unresectable and/or metastatic malignant GI stromal tumors (GIST).

Adjuvant treatment of adults following complete gross resection of Kit (CD117) (+) GIST. Adults: Take with food and water. May disperse tab in water or apple juice and take promptly. ≥18yrs: GIST: 400mg once daily; up to 800mg daily (given as 400mg twice daily) may be considered if clinically indicated. Adjuvant GIST treatment: 400mg once daily; 36 months of treatment recommended (see full labeling).

If severe non-hematologic reactions develop: interrupt dose; resume at a lower dose in hepatic dysfunction. Severe hepatic impairment: reduce dose by 25%. Renal or hematologic reactions: see full labeling. Avoid concomitant strong CYP3A4 inducers (eg, rifampin): if needed, increase imatinib dose by at least 50%.

Children: Not recommended.

Warnings/Precautions: Hepatic or renal impairment. Monitor weight and for fluid retention regularly; CBCs weekly for 1st month, bi-weekly for 2nd month, then periodically (eg, every 2–3 months); liver function at baseline then monthly or as needed; GI symptoms at baseline. Cardiovascular disease or risk factors; monitor. Immunosuppression and potential toxicities (liver, kidney, cardiac) from long-term use. Monitor for tumor lysis syndrome; correct

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER clinically significant dehydration and treat high uric acid levels before initiating therapy.

Monitor growth in children. Possible cardiogenic shock/LV dysfunction in conditions with high eosinophil levels (eg, HES/CEL, MDS/MPD, ASM); consider concomitant systemic steroid prophylaxis (1–2mg/kg) for 1 or 2 wks if abnormal ECG or serum troponin. Monitor TSH levels in thyroidectomy patients undergoing levothyroxine replacement. Pregnancy (Cat.D); avoid. Use highly effective contraception during treatment.

Nursing mothers: not recommended.

Interactions: Avoid grapefruit juice. Potentiated

by CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, nefazodone, clarithromycin, telithromycin). Antagonized by strong CYP3A4 inducers (eg, dexamethasone, fosphenytoin, phenytoin, phenobarbital, carbamazepine, oxcarbamazepine, primidone, St. John’s wort, rifampin, rifabutin, rifampicin); consider alternatives. May potentiate drugs metabolized

by CYP3A4 (eg, benzodiazepines, dihydropyridine calcium channel blockers, cyclosporine, ergots, alfentanil, fentanyl, pimozide, quinidine, certain statins, sirolimus, tacrolimus), CYP2D6, or CYP2C9 (use heparin instead of warfarin).

Adverse reactions: Edema (may be severe), nausea, vomiting, musculoskeletal pain, diarrhea, muscle cramps, rash (may be severe; eg, erythema multiforme, Stevens-Johnson syndrome), fatigue, abdominal pain, dizziness, blurred vision, somnolence, fever, headache, cough, arthralgia/myalgia, dyspnea, hypokalemia, night sweats, anorexia, pruritus, hemorrhage, anemia, neutropenia, thrombocytopenia, weight gain, renal or hepatotoxicity, immunosuppression, hypothyroidism; rare: severe CHF, LV dysfunction.

How supplied: 100mg—90; 400mg—30

HERCEPTIN Genentech

℞

Human epidermal growth factor receptor (HER2) inhibitor. Trastuzumab 440mg/vial; lyophilized pwd for IV infusion after reconstitution and dilution; preservative-free.

Indications: HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, in combination with cisplatin and capecitabine or 5-fluorouracil, in patients who have not received prior treatment.

Adults: Do not substitute for or with adotrastuzumab emtasine. Give as IV infusion. Initially 8mg/kg over 90 mins, followed by 6mg/kg over 30–90 mins every 3 weeks until disease progression. Infusion reactions or cardiomyopathy: see full labeling.

Children: Not established.

Warnings/Precautions: Increased risk of cardiomyopathy. Conduct cardiac assessment (eg, history, physical exam, LVEF) at baseline, every 3 months during and after therapy or every 6 months for ≥2yrs after therapy (if adjuvant); repeat LVEF at 4 week intervals if dose is withheld due to significant left ventricular cardiac dysfunction. Interrupt therapy if dyspnea or significant hypotension occurs; consider discontinuing permanently if severe infusion reactions, CHF, pulmonary toxicity, or significant left ventricular myocardial dysfunction develops. Symptomatic intrinsic lung disease.

Extensive tumor involvement of the lungs. Test for HER2 protein overexpression and HER2 gene amplification using FDA-approved tests for specific tumor type (breast or gastric/gastroesophageal adenocarcinoma). Embryo-fetal toxicity (eg, oligohydramnios): exclude pregnancy status before initiation. Pregnancy: avoid; use effective contraception during and for 7 months after therapy. Nursing mothers.

Interactions: Increased cardiomyopathy with anthracycline-containing chemotherapy.

Increased toxicity with other myelosuppressives.

Adverse reactions: Diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, dysgeusia, infections; severe infusion reactions, febrile neutropenia/exacerbation of chemotherapyinduced neutropenia, pulmonary toxicity (eg, interstitial pneumonitis), cardiomyopathy (eg, left ventricular myocardial dysfunction); pregnant women: possible oligohydramnios (monitor).

Testing considerations: HER2 protein overexpression How supplied: Vial—1 (w. diluent)

Leucovorin Teva

℞

Folic acid derivative. Leucovorin calcium 100mg/vial, 350mg/vial; lyophilized pwd for IV or IM inj after reconstitution; preservative-free.

Indications: Palliative treatment of advanced colorectal cancer in combination with 5-fluorouracil.

Adults: Max IV infusion rate: 160mg/min.

200mg/m2 by slow IV inj over a minimum of 3 minutes, followed by 5-fluorouracil (370mg/m2); or 20mg/m2 IV followed by 5-fluorouracil (425mg/m2); both regimens: daily for 5 days, may be repeated at 4-week intervals for 2 courses and then repeated at 4–5 week intervals (if completely recovered from toxic effects of previous course).

Children: See literature.

Contraindications: Pernicious anemia and other megaloblastic anemias due to Vit. B12 deficiency.

Warnings/Precautions: Do not administer intrathecally. CNS metastases. Monitor CBCs with differential, platelets, electrolytes, liver function tests prior to each treatment, then periodically.

Elderly. Debilitated. Pregnancy (Cat.C). Nursing mothers.

Interactions: Potentiates toxicity of 5-fluorouracil; use lower 5-fluorouracil dose.

May antagonize phenobarbital, phenytoin, and primidone. Caution with trimethoprimsulfamethoxazole.

Adverse reactions: Leukopenia, thrombocytopenia, infection, GI upset, stomatitis, constipation, lethargy, malaise, fatigue, alopecia, dermatitis, anorexia; seizures, syncope.

How supplied: Single-use vials—1

LONSURF Taiho Oncology

℞

Antineoplastic thymidine-based nucleoside analog + thymidine phosphorylase inhibitor. Trifluridine, tipiracil; 15mg/6.14mg, 20mg/8.19mg; tabs.

Indications: Treatment of metastatic colorectal cancer in patients previously treated with fluoropyrimidine-, oxaliplatin- and irinotecanbased chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

Adults: Take within 1 hour after completion of AM & PM meals. Initially 35mg/m2 twice daily on Days 1–5 and 8–12 of each 28-day cycle until disease progression or unacceptable toxicity; max 80mg per dose (based on trifluridine component). Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Obtain CBC prior to and on Day 15 of each cycle, and as clinically indicated. Do not initiate cycle until ANC ≥1,500/mm3 or febrile neutropenia is resolved, platelets ≥75,000/mm3 or Grade 3/4 nonhematological adverse reactions resolved to Grade 0/1. Withhold dose if ANC <500/mm3 or febrile neutropenia, platelets <50,000/mm3, or Grade 3/4 non-hematological adverse reactions occur; upon recovery, resume at a reduced dose (see full labeling). Moderate or severe hepatic impairment: not studied. Moderate renal impairment: may require dose modification; severe (CrCl <30mL/min) or ESRD: not studied.

Elderly. Pregnancy. Females of reproductive potential must use effective contraception during treatment; males must use condoms during and for ≥3 months after final dose. Nursing mothers:

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER not recommended (during treatment and for 1 day after final dose).

Adverse reactions: Anemia, neutropenia, asthenia/fatigue, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, abdominal pain, pyrexia.

How supplied: Tabs—20, 40, 60

NEXAVAR Bayer and Onyx

℞

Multikinase inhibitor. Sorafenib 200mg; tabs.

Indications: Unresectable hepatocellular carcinoma.

Adults: Take on an empty stomach. 400mg twice daily. If toxicity occurs, may reduce dose to 400mg once daily; if further dose reduction required, may reduce dose to 400mg every other day (see full labeling). Concomitant strong CYP3A4 inducers: consider increasing dose, monitor for toxicity.

Children: Not established.

Contraindications: Concomitant carboplatin/paclitaxel in patients with squamous cell lung cancer.

Warnings/Precautions: Avoid in congenital long QT syndrome. Monitor patients with CHF, bradyarrhythmias, drugs known to prolong the QT interval, electrolyte abnormalities. Discontinue if severe dermatologic toxicity, hypertension, GI perforation, hemorrhage, cardiac ischemia, MI occurs. Suspend therapy before major surgery.

Monitor BP weekly during the first 6 weeks and thereafter. Monitor hepatic function regularly; discontinue if transaminases significantly elevated.

Severe hepatic impairment (Child-Pugh C) or on dialysis. Use effective contraception during and for 2 weeks after stopping treatment. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: See Contraindications. Avoid strong CYP3A4 inducers (eg, St. John’s Wort, dexamethasone, phenytoin, carbamazepine, rifabutin, rifampin, phenobarbital) and neomycin; may decrease sorafenib levels. May potentiate warfarin (monitor PT & INR), other drugs metabolized by UGT1A1 or UGT1A9 pathway, or substrates of CYP2B6, CYP2C8, CYP2C9, P-gp.

Concomitant Class Ia and III antiarrhythmics; may prolong QT interval.

Adverse reactions: Dermatologic toxicity (eg, rash, hand-foot skin reaction, alopecia, pruritus, dry skin, Stevens-Johnson syndrome, toxic epidermal necrolysis), fatigue, weight loss, diarrhea, anorexia, abdominal pain, hypertension, hemorrhage, electrolyte abnormalities; druginduced hepatitis, QT prolongation.

How supplied: Tabs—120

STIVARGA Bayer

℞

Kinase inhibitor. Regorafenib 40mg; tabs.

Indications: Treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild type, an

anti-EGFR therapy. Treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate or sunitinib malate.

Adults: Swallow whole with water after a lowfat meal (contains <600 calories and <30% fat). 160mg once daily for the first 21 days of each 28-day cycle; until disease progression or unacceptable toxicity. Dose modifications: see full prescribing information.

Children: <18yrs: not established.

Warnings/Precautions: Risk of severe liver injury (may be fatal). Obtain LFTs before starting and at least every 2 weeks during first 2 months of treatment; interrupt and reduce or discontinue if persistent hepatotoxicity or hepatocellular necrosis occurs. Severe hepatic impairment: not recommended. Increased risk of hemorrhage; permanently discontinue if severe or lifethreatening. Interrupt and reduce or permanently discontinue if dermatological toxicity occurs (eg, hand-foot skin reaction [a.k.a. palmar-plantar erythrodysesthesia], rash). Ensure BP is controlled before starting; monitor weekly for the first 6 weeks then every cycle or as clinically indicated; withhold if severe or uncontrolled. Myocardial ischemia/infarction: withhold if new or acute onset develops; resume when resolved. Discontinue if reversible posterior leukoencephalopathy syndrome (RPLS) or GI perforation/fistula develops. Wound healing complications: stop treatment at least 2 weeks before surgery; discontinue if wound dehiscence occurs. Asian patients (monitor). Embryo-fetal toxicity. Females and males of reproductive potential should use effective contraception during treatment and up to 2 months after completion. Pregnancy. Nursing mothers: not recommended (during and for 2 weeks after final dose).

Interactions: Potentiated by strong CYP3A4 inhibitors (eg, clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, voriconazole); avoid. Antagonized by strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital, St. John’s Wort); avoid. Potentiates BCRP substrates (eg, methotrexate, fluvastatin, atorvastatin); monitor closely for related toxicity.

Monitor INR levels with concomitant warfarin.

Adverse reactions: Asthenia/fatigue, decreased appetite and food intake, hand-foot skin reaction, diarrhea, mucositis, weight loss, infection, hypertension, dysphonia, GI and abdominal pain, rash, fever, nausea; hepatotoxicity, hemorrhage, GI perforation, cardiac ischemia/infarction, RPLS. How supplied: Tabs—84 (3 × 28)

SUTENT Pfizer

℞

Multikinase inhibitor. Sunitinib (as malate) 12.5mg, 25mg, 37.5mg, 50mg; gelatin caps.

Indications: Gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate.

Adults: 50mg once daily for 4 weeks, then 2 weeks off (see full labeling). May adjust dose in increments or decrements of 12.5mg.

Concomitant strong CYP3A4 inhibitors (see Interactions): may reduce dose to 37.5mg daily.

Concomitant strong CYP3A4 inducers (see Interactions): may increase to max 87.5mg daily.

Children: Not established.

Warnings/Precautions: Hepatotoxicity; may be severe or fatal. Monitor liver function tests before starting, during each cycle of treatment and as clinically needed; interrupt if Grade 3 or 4 hepatic adverse events occur and discontinue if no resolution; if severe liver function changes or signs/symptoms of failure, do not restart.

Cardiovascular events: monitor for CHF during therapy, and LVEF at baseline and periodically; interrupt or reduce dose if LVEF <50% and >20% below baseline; discontinue if CHF occurs.

History of QT prolongation or proarrythmic conditions (eg, bradycardia, electrolyte disturbances); perform periodic ECG, monitor electrolytes. Monitor BP. Suspend therapy if severe hypertension, seizures, or pancreatitis develops. Obtain CBCs, platelets, serum chemistries at start of each cycle. Concomitant exposure to risk factors (eg, IV bisphosphonates therapy or dental disease) may increase the risk of osteonecrosis of the jaw; avoid or consider preventive dentistry prior to treatment. Risk of tumor lysis syndrome: monitor closely in RCC and GIST patients with high tumor burden. Monitor for thyroid dysfunction; obtain baseline levels prior to treatment. Monitor blood glucose levels during and after treatment discontinuation.

Monitor for proteinuria; perform baseline and periodic urinalyses; interrupt and reduce dose if 24-hr urine protein ≥3g; discontinue if nephrotic syndrome or repeat urine protein ≥3g persists.

Undergoing major surgery. Stress (monitor for adrenal insufficiency). Discontinue if severe cutaneous reactions (eg, erythema multiforme, SJS, TEN) develop; do not restart if diagnosis suspected. ESRD on dialysis. Severe hepatic impairment. Pregnancy (Cat.D; avoid). Nursing mothers: not recommended.

Interactions: May be potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), grapefruit; consider reducing dose or use alternate drug. May be antagonized by CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital); consider increasing dose or use alternate drug. Concomitant St. John’s wort: not recommended. Caution with concomitant antiarrhythmics.

Adverse reactions: Fatigue, asthenia, fever, diarrhea, nausea, vomiting, mucositis/stomatitis, dyspepsia, abdominal pain, constipation, hypertension, peripheral edema, rash, handfoot syndrome, skin discoloration, dry skin, hair color changes, altered taste, headache, back

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER pain, arthralgia, extremity pain, cough, dyspnea, anorexia, bleeding; hepatotoxicity, left ventricular dysfunction, QT prolongation, osteonecrosis of the jaw, tumor lysis syndrome, thyroid dysfunction, impaired wound healing, hypoglycemia, thrombotic microangiopathy (discontinue if develops), proteinuria, necrotizing fasciitis (discontinue if occurs), others (see full labeling).

How supplied: Caps—28

VECTIBIX Amgen

℞

Human epidermal growth factor receptor (EGFR) inhibitor. Panitumumab 20mg/mL; soln for IV infusion after dilution; preservative-free.

Indications: First-line treatment of wild-type KRAS metastatic colorectal carcinoma (mCRC) in combination with FOLFOX, or as monotherapy following disease progression after prior fluoropyrimidine-, oxaliplatin-, and irinotecancontaining chemotherapy as determined by an FDA-approved test. Limitation of use: not for treating KRAS-mutant mCRC or for whom KRAS mutation status is unknown.

Adults: 6mg/kg by IV infusion over 60 mins once every 14 days. If 1st infusion is tolerated, give subsequent infusions over 30–60 mins.

Doses >1000mg: infuse over 90 mins. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Confirm absence of a KRAS mutation using an FDA-approved test prior to initiation. Withhold or discontinue therapy for dermatologic or soft tissue toxicity associated with severe inflammatory or infectious complications; monitor. Discontinue if severe infusion reactions develop. Interrupt therapy if acute onset or worsening of pulmonary symptoms; discontinue if interstitial lung disease (ILD) is confirmed.

Limit sun exposure. Monitor electrolytes (eg, magnesium, calcium) prior to initiation, during, and for 8 weeks after completing therapy.

Monitor for ocular toxicities (eg, keratitis); interrupt or discontinue if occur. May impair fertility in women; use effective contraception during treatment and for 6 months following last dose. Pregnancy (Cat.C). Nursing mothers: not recommended; discontinue during therapy and for 2 months after last dose.

Interactions: Concomitant bevacizumab and chemotherapy: increased mortality and toxicity may occur.

Adverse reactions: Skin rash, paronychia, fatigue, nausea, diarrhea; hypomagnesemia, hypocalcemia, hypokalemia, dermatologic toxicities with possible infection (may be fatal), infusion reactions, immunogenicity, ILD,

pulmonary fibrosis, keratitis, photosensitivity, possible acute renal failure w. chemotherapy.

Testing considerations: EGFR amplification analysis, K-RAS mutation analysis.

How supplied: Single-use vial (5mL, 10mL, 20mL)—1

XELODA Genentech

ZALTRAP Sanofi US and Regeneron

℞

Fluoropyrimidine. Capecitabine (prodrug of 5-fluorouracil) 150mg, 500mg; tabs.

Indications: First-line treatment of metastatic colorectal carcinoma when fluoropyrimidine therapy alone is preferred. Adjuvant treatment of Dukes’ C colon cancer after complete resection of the primary tumor when fluoropyrimidine therapy alone is preferred.

Adults: See full labeling. Give cyclically (2 weeks on, 1 week off). Swallow whole. Take with water within 30 minutes after AM & PM meals. ≥18yrs: 1250mg/m2 twice daily. Continue for a total of 8 cycles. Interrupt, adjust dose, and/or treat symptoms if toxicity occurs (eg, hyperbilirubinemia, diarrhea, nausea, vomiting, hand-and-foot syndrome, stomatitis) (see full labeling); do not increase dose afterwards.

Renal impairment (CrCl 51–80mL/min): monitor carefully; (CrCl 30–50mL/min): reduce capecitabine dose to 75% of starting dose (ie, 950mg/m2 twice daily).

Children: <18yrs: not established.

Contraindications: Severe renal impairment (CrCl <30mL/min).

Warnings/Precautions: Hepatic or renal dysfunction. Monitor and correct dehydration at initiation. Coronary artery disease. Interrupt therapy if severe diarrhea occurs; give antidiarrheals until resolves or reduces to Grade 1. Dihydropyrimidine dehydrogenase deficiency. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Increased anticoagulant effect with warfarin; monitor PT/INR frequently.

Potentiated by leucovorin. Monitor phenytoin and other CYP2C9 substrates.

Adverse reactions: Diarrhea, hand-andfoot syndrome, nausea, vomiting, abdominal pain, fatigue/weakness, hyperbilirubinemia; lymphopenia, necrotizing enterocolitis, stomatitis, dermatitis, anorexia, cardiotoxicity, blood dyscrasias, paresthesias, eye irritation, edema, myalgia, dehydration, alopecia; severe mucocutaneous reactions (eg, SJS, TEN); permanently discontinue if occurs.

Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase) How supplied: Tabs 150mg—60; 500mg—120

℞

Fusion protein. Ziv-aflibercept 25mg/mL; soln for IV infusion after dilution; preservativefree.

Indications: In combination with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) for patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen.

Adults: Start ziv-aflibercept prior to any component of the FOLFIRI regimen on treatment day. Give 4mg/kg as an IV infusion over 1hr every 2 weeks; continue until disease progression or unacceptable toxicity. For recurrent or severe hypertension, suspend until controlled. Upon resumption, permanently reduce to 2mg/kg. For recurrent proteinuria, suspend until proteinuria <2g per 24hrs, then permanently reduce to 2mg/kg.

Children: Not established.

Warnings/Precautions: Increased risk of hemorrhage; monitor for signs/symptoms. Do not start in patients with severe hemorrhage; discontinue if develops. Monitor for GI perforation, fistula formation, compromised wound healing; discontinue if occurs.

Suspend therapy at least 4 weeks prior to elective surgery; do not resume for at least 4 weeks following major surgery and until wound is fully healed. Monitor BP every 2 weeks and treat appropriately if hypertension occurs; temporarily suspend until controlled; discontinue if hypertensive crisis/encephalopathy occurs. Discontinue if arterial thromboembolic events (eg, transient ischemic attack, cerebrovascular accident, angina pectoris) occur. Monitor for proteinuria; suspend if proteinuria ≥2g per 24hrs; discontinue if nephrotic syndrome or thrombotic microangiopathy occurs. Monitor CBC with differential at baseline and prior to start of each cycle; delay until neutrophils ≥1.5x109/L. Risk of severe diarrhea and dehydration esp. in elderly (monitor). Discontinue if reversible posterior leukoencephalopathy syndrome occurs.

Pregnancy (Cat. C). Use effective contraception during and up to 3 months after the last dose.

Nursing mothers: not recommended.

Adverse reactions: Leukopenia, diarrhea, neutropenia, proteinuria, AST/ALT increased, stomatitis, fatigue, thrombocytopenia, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, headache.

How supplied: Single-use vials (100mg/4mL)—1, 3; (200mg/8mL)—1

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DRUG MONOGRAPHS

GENITOURINARY CANCER AFINITOR Novartis

℞

mTOR kinase inhibitor. Everolimus 2.5mg, 5mg, 7.5mg, 10mg; tabs.

Indications: In adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. In adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery.

Adults: Swallow tabs whole with water. Take at the same time each day either consistently with or without food. 10mg once daily. Mild hepatic impairment (Child-Pugh class A): 7.5mg daily, may reduce to 5mg if not tolerated. Moderate hepatic impairment (Child-Pugh class B): 5mg daily, may be reduce to 2.5mg if not tolerated.

Severe hepatic impairment (Child-Pugh class C): max 2.5mg daily if benefits outweigh risk.

Concomitant moderate CYP3A4/PgP inhibitors: reduce to 2.5mg once daily; may consider increasing to 5mg if tolerated. If moderate inhibitor is discontinued, allow 2–3 days washout period before increasing everolimus dose; return to dose used prior to initiating the moderate inhibitor. Concomitant strong CYP3A4/PgP inducers: consider doubling the daily dose by increments of 5mg or less.

If strong inducer is discontinued, consider washout period of 3–5 days before returning to the dose used prior to initiating the strong inducer. Continue therapy until disease progression or unacceptable toxicity occurs.

Dose modifications for adverse reactions, or others: see full labeling.

Children: Not recommended.

Contraindications: Allergy to other rapamycin derivatives.

Warnings/Precautions: Monitor for new or worsening respiratory symptoms. Increased risk of infections; some may be severe or fatal; monitor and treat promptly if occur.

Pre-existing invasive fungal infections: treat before starting. Monitor for signs of woundrelated complications. Peri-surgical period.

Hepatic impairment (see Adult dose). Monitor CBCs, renal function, lipids, and blood glucose prior to starting and periodically thereafter.

Avoid close contact with those who have received live vaccines. Pediatrics: complete childhood vaccination series according to ACIP guidelines prior to initiation. Elderly. Females of reproductive potential must use effective contraception during therapy and for 8 weeks after treatment. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Avoid live vaccines. Potentiated by strong CYP3A4/PgP inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole), grapefruit or grapefruit juice; avoid. Caution with moderate CYP3A4/PgP inhibitors (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem); reduce

everolimus dose if used. Antagonized by strong CYP3A4/PgP inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital), St. John’s Wort; avoid.

Adverse reactions: Pneumonitis (interrupt, reduce dose and/or manage with corticosteroids; if severe, discontinue; may reintroduce daily dose at approx. 50% lower than previously administered), infections (discontinue if invasive systemic fungal infection develops), stomatitis (treat with non-alcoholic, non-peroxide mouthwash), diarrhea, nausea, abdominal pain, rash, fatigue, edema, fever, asthenia, cough, headache, decreased appetite; increased serum creatinine, blood glucose, lipids; decreased hemoglobin, platelets, neutrophils, serum phosphate; proteinuria, renal failure, others (see full labeling).

How supplied: Tabs—28 (4 blister cards × 7 tabs)

AVASTIN Genentech

℞

Angiogenesis inhibitor. Bevacizumab 100mg, 400mg; per vial; soln for IV infusion after dilution; preservative-free.

Indications: Metastatic renal cell carcinoma (mRCC) in combination with interferon alfa.

Adults: Give by IV infusion. Infuse 1st dose over 90 mins; if tolerated, infuse 2nd dose over 60 mins, and subsequent doses over 30 mins.

10mg/kg every 2 weeks with interferon alfa.

Children: Not established.

Warnings/Precautions: Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). History of hemoptysis of ≥ ½-teaspoon of red blood: do not administer.

Discontinue if GI perforation, non-GI fistula formation, wound healing complications, serious hemorrhage, severe arterial or Grade 4 venous thromboembolic events, hypertensive crisis, nephrotic syndrome, or posterior reversible encephalopathy syndrome occurs; suspend therapy if severe hypertension, moderate to severe proteinuria (resume when <2g/24hrs), or severe infusion reaction occurs. Cardiovascular disease. Diabetes. Monitor BP every 2–3 weeks.

Monitor proteinuria by dipstick urine analysis.

Elderly. Increased risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy (Cat.C). Nursing mothers: not recommended.

Adverse reactions: Epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial or venous thromboembolic events, posterior reversible encephalopathy syndrome, infusion reactions, ovarian failure.

How supplied: Single-use vial—1

CABOMETYX Exelixis

℞

Kinase inhibitor. Cabozantinib 20mg, 40mg, 60mg; tabs.

Indications: Treatment of advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy.

Adults: Do not substitute with cabozantinib caps. Swallow whole. 60mg daily. Do not eat at least 2 hours before or 1 hour after dose. Continue until disease progression or unacceptable toxicity. Stop treatment at least 28 days prior to scheduled surgery (including dental). Withhold for Grade 4 adverse reactions, Grade 3 or intolerable Grade 2 adverse reactions that are unmanageable with dose reduction or supportive care. Upon improvement to Grade 1 or to baseline, reduce dose as follows: previously on 60mg daily, resume at 40mg daily; previously on 40mg daily, resume at 20mg daily; previously on 20mg daily, resume at 20mg if tolerated, otherwise discontinue.

Concomitant a strong CYP3A4 inhibitor: reduce daily dose by 20mg; resume dose used prior to starting inhibitor 2–3 days after discontinuation of inhibitor. Concomitant a strong CYP3A4 inducer: increase daily dose by 20mg; resume dose used prior to starting inducer 2–3 days after discontinuation of inducer. Max daily dose: 80mg. Mild or moderate hepatic impairment: initially 40mg once daily.

Children: Not studied.

Warnings/Precautions: Permanently discontinue if the following occurs: unmanageable GI perforation/fistula, severe hemorrhage, serious arterial thromboembolic events (eg, MI, cerebral infarction), hypertensive crisis or severe hypertension despite optimal medical management, nephrotic syndrome, reversible posterior leukoencephalopathy syndrome. Recent history or risk of severe hemorrhage: do not administer. Monitor for GI perforations/fistulas. Monitor BP regularly; withhold for hypertension inadequately controlled with medical management; resume at reduced dose when resolved. Withhold therapy if intolerable Grade 2 diarrhea, unmanageable Grade 3/4 diarrhea, or intolerable Grade 2/3 palmar-plantar erythrodysesthesia syndrome (PPES) develops until improvement to Grade 1; resume at reduced dose. Severe hepatic impairment: not recommended. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for 4 months after final dose. Pregnancy. Nursing mothers: not recommended (during and for 4 months after final dose).

Interactions: Avoid concomitant strong CYP3A4 inhibitors (eg, boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit or grapefruit juice) and strong CYP3A4 inducers (eg, rifampin, phenytoin,

26 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

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DRUG MONOGRAPHS

GENITOURINARY CANCER carbamazepine, phenobarbital, rifabutin, rifapentine, St. John’s Wort); if unavoidable, see Adult dose.

Adverse reactions: Diarrhea, fatigue, nausea, decreased appetite, PPES, hypertension, vomiting, weight decreased, constipation, lab abnormalities.

How supplied: Tabs—30

CASODEX AstraZeneca

if jaundice occurs and before prolonged immobilization (eg, surgery).

Adverse reactions: See literature. GI upset, headache, hypertension, edema, hypercalcemia, gallbladder or thromboembolic disease, gynecomastia, impotence, impaired glucose tolerance.

How supplied: Multi-dose vials (5mL)—1 ℞

Antiandrogen. Bicalutamide 50mg; tabs.

Indications: In combination with luteinizing hormone-releasing hormone (LHRH) analogue in stage D2 metastatic prostate carcinoma.

Adults: Take at the same time each day. 50mg daily. Start treatment at same time as starting LHRH analogue.

Children: Not applicable.

Contraindications: Women of childbearing potential. Pregnancy (Cat.X).

Warnings/Precautions: Moderate to severe hepatic impairment. Monitor prostate specific antigen and hepatic function (discontinue if ALT >2xULN or if jaundice occurs). Nursing mothers.

Interactions: Monitor oral anticoagulants.

Adverse reactions: Hot flashes, gynecomastia, breast pain, diarrhea, pain, asthenia, infection, dyspnea, impotence, loss of libido, others (see literature); rare: hepatitis.

How supplied: Tabs—30, 100

DELESTROGEN JHP

℞

Estrogen. Estradiol valerate 10mg/mL (in a vehicle containing chlorobutanol 5mg and sesame oil), 20mg/mL (in a vehicle containing benzyl benzoate 224mg, benzyl alcohol 20mg, and castor oil), 40mg/mL (in a vehicle containing benzyl benzoate 447mg, benzyl alcohol 20mg, and castor oil); soln for IM inj.

Indications: Advanced androgen-dependent carcinoma of the prostate (for palliation only).

Adults: Give by deep IM inj into upper, outer quadrant of gluteal muscle. 30mg or more every 1 or 2 weeks.

Children: Not applicable.

Contraindications: Thrombophlebitis.

Thromboembolic disorders. Cerebrovascular disorders. Abnormal undiagnosed genital bleeding. Estrogen-depended neoplasias. Liver dysfunction or disease. Pregnancy (Cat. X).

Warnings/Precautions: Hepatic dysfunction. Conditions aggravated by fluid retention. Cardiovascular disorders, arterial vascular disease, and risks factors (eg, hypertension, diabetes, obesity, SLE). Familial hyperlipoprotenemia. Monitor BP. Discontinue

ELIGARD 7.5mg 1-MONTH

℞

Tolmar

GnRH analogue. Leuprolide acetate 7.5mg per inj; ext-rel susp; for SC inj. ℞ Also: ELIGARD 22.5mg 3-MONTH Sanofi Aventis Leuprolide acetate 22.5mg per inj; ext-rel susp; for SC inj. ℞ Also: ELIGARD 30mg 4-MONTH Sanofi Aventis Leuprolide acetate 30mg per inj; ext-rel susp; for SC inj. ℞ Also: ELIGARD 45mg 6-MONTH Sanofi Aventis Leuprolide acetate 45mg per inj; ext-rel susp; for SC inj.

Indications: Palliative treatment of advanced prostate cancer.

Adults: Allow product to reach room temperature before using; inject within 30 minutes of mixing.

Use correct formulation. 7.5mg SC once per month; or 22.5mg SC once every 3 months; or 30mg SC once every 4 months; or 45mg SC once every 6 months. Rotate inj site.

Children: Not established.

Contraindications: Women. Pregnancy (Cat.X).

Warnings/Precautions: May worsen metastatic vertebral lesions and/or urinary tract obstruction; monitor closely during first few weeks. Increased risk of diabetes, MI, sudden cardiac death, stroke; monitor blood glucose, HbA1c, and for signs/symptoms of CVD during therapy. Risk of QT prolongation in patients with congenital long QT syndrome, CHF, or frequent electrolyte abnormalities. Correct and monitor electrolyte abnormalities; consider monitoring ECGs. Monitor serum testosterone, PSA periodically. Nursing mothers: not recommended.

Interactions: Caution with concomitant drugs known to prolong the QT interval. May interfere with pituitary-gonadal diagnostic tests.

Adverse reactions: Malaise, fatigue, hot flashes/sweats, testicular atrophy, gynecomastia, local reactions, pain, spinal cord compression, decreased bone density; transient worsening of signs/symptoms (eg, bone pain, neuropathy,

hematuria, bladder outlet obstruction); rare: pituitary apoplexy.

How supplied: Single-use kit—1 (with sterile or sterile safety needle)

EMCYT Pfizer

℞

Estramustine phosphate sodium (prodrug of estradiol) 140mg; caps.

Indications: Palliative of metastatic, progressive prostate cancer.

Adults: Take 1 hour before or 2 hours after meals.

14mg/kg in 3 or 4 divided doses; reevaluate after 30 to 90 days. Continue as long as favorable response maintained.

Children: Not applicable.

Contraindications: Active thrombophlebitis or thromboembolic disorders (except when tumor mass caused by thromboembolic phenomenon).

Allergy to estradiol, nitrogen mustard.

Warnings/Precautions: History of thrombophlebitis, thrombosis, thromboembolic disorders. Cerebro- or cardiovascular disease.

Diabetes. Hypertension. Conditions aggravated by fluid retention. Renal or hepatic dysfunction. Monitor bilirubin and hepatic enzymes during and for 2 months after treatment is discontinued.

Metabolic bone diseases associated with hypercalcemia. Use effective contraception.

Interactions: Absorption impaired by calcium.

Adverse reactions: Edema, dyspnea, leg cramps; nausea, diarrhea, GI upset; pruritus, dry skin, easy bruising; breast tenderness and enlargement; lethargy, emotional lability, insomnia; leucopenia; abnormal bilirubin, LDH, SGOT. Thrombosis, MI. How supplied: Caps—100

ESTRACE Allergan

℞

Estrogen. Estradiol 0.5mg, 1mg, 2mg+; scored tabs; +contains tartrazine.

Indications: Palliative treatment of androgendependent advanced prostate cancer.

Adults: 1–2mg 3 times daily.

Children: Not applicable.

Contraindications: Thrombophlebitis.

Thromboembolic disorders. Cerebrovascular disorders. Abnormal undiagnosed genital bleeding. Estrogen-depended neoplasias. Liver dysfunction or disease. Pregnancy (Cat. X).

Warnings/Precautions: Asthma (2mg tabs).

Hepatic dysfunction. Conditions aggravated by fluid retention. Cardiovascular disorders, arterial vascular disease, and risks factors (eg, hypertension, diabetes, obesity, SLE). Familial hyperlipoprotenemia. Monitor BP. Discontinue

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DRUG MONOGRAPHS

GENITOURINARY CANCER if jaundice occurs and before prolonged immobilization (eg, surgery). Nursing mothers.

Adverse reactions: See literature. GI upset, headache, hypertension, edema, hypercalcemia, gallbladder or thromboembolic disease, gynecomastia, impotence, impaired glucose tolerance.

How supplied: Tabs—100

FIRMAGON Ferring

℞

GnRH receptor antagonist. Degarelix 80mg/vial, 120mg/vial; pwd for SC inj after reconstitution.

Indications: Advanced prostate cancer.

Adults: Give by SC inj in abdomen once every 28 days; avoid waist and rib areas. Two 120mg injections once, then one 80mg inj once every 28 days.

Children: Not established.

Contraindications: Pregnancy (Cat.X).

Warnings/Precautions: Congenital long QT syndrome. CHF. Correct electrolyte abnormalities. Monitor electrolytes and ECG periodically. Monitor serum PSA. Discontinue if serious hypersensitivity reaction occurs; do not rechallenge. Moderate or severe renal impairment (CrCl <50mL/min). Severe hepatic impairment.

Nursing mothers: not recommended.

Interactions: Caution with concomitant drugs known to prolong the QT interval.

Adverse reactions: Inj site reactions (eg, pain, erythema, swelling, induration), hot flashes, increased weight, fatigue, increased transaminases, increased gamma-glutamyltransferase; QT prolongation.

How supplied: Treatment Initiation pack (120mg/vial)—2 (w. supplies); Treatment Maintenance pack (80mg/vial)—1 (w. supplies)

Flutamide (various)

℞

Antiandrogen. Flutamide 125mg; caps.

Indications: In combination with LHRH agonists (GnRH analogues) in locally confined stage B2–C and stage D2 metastatic prostate carcinoma.

Adults: 250mg every 8 hrs.

Children: Not applicable.

Contraindications: Severe hepatic impairment.

ALT ≥2xULN: not recommended.

Warnings/Precautions: Monitor liver function at baseline, monthly for first 4 months, then periodically, and if liver dysfunction occurs; if ALT >2xULN or jaundice occurs, discontinue and monitor closely until resolution. Monitor prostate specific antigen (PSA). Consider monitoring methemoglobin levels in patients susceptible to aniline toxicity (e.g., G6PD deficiency, smokers, hemoglobin M disease). Pregnancy (Cat.D); not for use in women.

Interactions: Monitor warfarin.

Adverse reactions: Diarrhea, hot flashes, loss of libido, impotence, GI disturbances, gynecomastia, rash, edema, hypertension, CNS effects, blood dyscrasias, urine discoloration, liver failure.

How supplied: Contact supplier.

IFEX Baxter

℞

Alkylating agent. Ifosfamide 1g, 3g; per vial; pwd for IV infusion after reconstitution.

Indications: Third-line adjunctive treatment of germ cell testicular cancer.

Adults: Give by slow IV infusion over at least 30 mins. 1.2g/m2 per day for 5 consecutive days; repeat every 3 weeks or after hematological recovery (platelets ≥100000/μL, WBC ≥4000/μL).

Children: Not recommended.

Contraindications: Severe bone marrow depression.

Warnings/Precautions: Discontinue if neurologic effects (eg, somnolence, confusion, hallucinations) occur. Do urinalysis before each dose, postpone dose if hematuria occurs. Give mesna and at least 2L fluids daily. Do hematologic profile before each dose; discontinue if WBCs <2000/μL or platelets <50000/μL. May interfere with wound healing. Impaired hepatic, renal, or hematopoetic function. Prior radiation therapy or other cytotoxic agents. Ensure adequate hydration. Pregnancy (Cat.D). Nursing mothers: not recommended.

Interactions: Increased risk of myelosuppression with other chemotherapy agents.

Adverse reactions: Alopecia, GI upset, hematuria, CNS toxicity, infection, renal or liver dysfunction, phlebitis, fever, urotoxicity (eg, hemorrhagic cystitis), leukopenia, thrombocytopenia.

How supplied: Single-dose vials—1

INLYTA Pfizer

℞

Kinase inhibitor. Axitinib 1mg, 5mg; tabs.

Indications: Treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy.

Adults: Take 12hrs apart. Swallow whole with a glass of water. Initially 5mg twice daily. If tolerated for at least two consecutive weeks with no adverse reactions >Grade 2, normotensive, and not receiving antihypertensives, may increase dose to 7mg twice daily, then 10mg twice daily.

May reduce dose from 5mg twice daily to 3mg twice daily, then 2mg twice daily if additional dose reduction required. Concomitant strong CYP3A4/5 inhibitors: avoid; if warranted, decrease Inlyta dose by approximately ½. If strong CYP3A4/5 inhibitor discontinued, return Inlyta dose (after 3–5 half-lives of the inhibitor) to that used prior to CYP3A4/5 inhibitor initiation.

Moderate hepatic impairment: decrease dose by approximately ½.

Children: Not studied.

Warnings/Precautions: Control and monitor BP prior to and during therapy; discontinue if severe and persistent hypertension (despite antihypertensive therapy and dose reduction).

Risk of thromboembolic events. Untreated

brain metastasis, recent active GI bleed: not recommended. Interrupt therapy if bleeding requires medical intervention. Monitor for signs/symptoms of cardiac failure during therapy; permanently discontinue if occurs.

GI perforation and fistula formation; monitor.

Monitor thyroid, liver function (ALT, AST, bilirubin), and for proteinuria before starting therapy, then periodically. Reduce dose or temporarily interrupt for moderate-to-severe proteinuria.

Risk of reversible posterior leukoencephalopathy syndrome (discontinue if occurs). Stop treatment at least 24hrs prior to scheduled surgery.

Severe hepatic impairment. End-stage renal disease. Pregnancy (Cat.D); avoid. Use adequate contraception during therapy. Nursing mothers: not recommended.

Interactions: See Adult dose. Avoid strong CYP3A4/5 inhibitors (eg, grapefruit juice, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), CYP3A4/5 inducers (eg, rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, St. John’s wort), moderate CYP3A4/5 inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin).

Adverse reactions: Diarrhea, nausea, vomiting, hypertension, fatigue, decreased appetite, dysphonia, palmar-plantar erythrodysesthesia (hand-foot) syndrome, weight decreased, asthenia, constipation.

How supplied: Tabs 1mg—180; 5mg—60

JEVTANA Sanofi Aventis

℞

Antimicrotubule agent. Cabazitaxel 60mg/1.5mL; soln for IV infusion after dilution; contains polysorbate 80, diluent contains ethanol.

Indications: In combination with prednisone, hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen.

Adults: Pretreat with IV antihistamine, corticosteroid, and H2 blocker 30 mins before each dose (see full labeling) and with antiemetic (IV or oral as needed). 25mg/m2

by IV infusion over 1hr every 3 weeks, with oral prednisone 10mg/day during treatment. Do not treat if neutrophil count ≤1,500 cells/mm3.

Prolonged grade ≥3 neutropenia (>1 week), febrile neutropenia, grade ≥3 diarrhea, grade 2 peripheral neuropathy: delay treatment and/or reduce dose to 20mg/m2 (see full labeling).

Discontinue if grade ≥3 peripheral neuropathy or if any reactions persist after dosing at 20mg/m2.

Hepatic impairment: (mild): reduce starting dose to 20mg/m2; (moderate): reduce to 15mg/m2. If concomitant a strong CYP3A inhibitor necessary, consider a 25% cabazitaxel dose reduction.

Children: Not established.

Contraindications: Baseline neutrophil count ≤1,500cells/mm3. Allergy to polysorbate 80.

Severe hepatic impairment (total bilirubin >3XULN).

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DRUG MONOGRAPHS

GENITOURINARY CANCER Warnings/Precautions: Increased risk of neutropenia complications; consider G-CSF prophylaxis. Do CBC weekly in 1st cycle and before each subsequent cycle. Patients with hemoglobin <10g/dL. Discontinue if hypersensitivity reactions occur. Increased risk of GI disorders in patients with neutropenia, age, or history of pelvic radiotherapy, adhesions, ulceration, and GI bleeding. Evaluate and treat if serious GI toxicity occurs; treatment delay or discontinuation may be needed. Monitor closely for respiratory disorders; interrupt if new or worsening pulmonary symptoms develop. Hepatic impairment (monitor). ESRD (CrCl <15mL/min).

Elderly (increased susceptibility to adverse reactions); monitor closely. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended.

Interactions: Potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole); avoid. Antagonized by strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital).

Increased GI toxicity with concomitant steroids, NSAIDs, antiplatelets, anticoagulants.

Adverse reactions: Bone marrow suppression (esp. neutropenia, anemia, leukopenia, thrombocytopenia), diarrhea (may be fatal), fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysgeusia, cough, arthralgia, alopecia; febrile neutropenia, renal failure, hypersensitivity reactions (eg, rash, hypotension, bronchospasm).

How supplied: Kit (single-use vial + diluent)—1

event, hepatic failure, nephrotic syndrome, GI perforation or life-threatening fistula, or severe and persistent neurologic symptoms occur. Withhold if Grade 3 hypertension persists despite therapy, Grade 3 cardiac dysfunction or hemorrhage, ≥Grade 3 liver impairment or QT prolongation >500ms, Grade 3 or 4 renal failure/impairment, ≥2g of proteinuria/24hrs, or reversible posterior leukoencephalopathy syndrome (RPLS) occurs. Monitor for signs/symptoms of cardiac decompensation. Monitor liver function prior to treatment, every 2 weeks for the first 2 months, then at least monthly during treatment. Monitor for proteinuria prior to, and periodically during treatment. Monitor for dehydration and treat if diarrhea develops; interrupt if Grade 3 or 4 and permanently discontinue if Grade 4 diarrhea persists despite therapy. Hypovolemia. Congenital long QT syndrome, CHF, bradyarrhythmias, or those taking Class Ia or III antiarrhythmic drugs; monitor ECGs. Monitor and correct electrolyte abnormalities. Monitor blood calcium levels at least monthly; replace as needed during treatment.

Monitor thyroid function prior to initiation and at least monthly thereafter; treat hypothyroidism as needed. ESRD. Embryo-fetal toxicity. Pregnancy: avoid. Use effective contraception during and for at least 2 weeks after treatment completion. Nursing mothers: not recommended.

Adverse reactions: Hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, weight decreased, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, dysphonia.

How supplied: Blister cards—6

℞

LUPRON DEPOT 7.5mg AbbVie ℞

Kinase inhibitor. Lenvatinib 4mg, 10mg; capsules.

Indications: In combination with everolimus, for treatment of advanced renal cell carcinoma, following one prior anti-angiogenic therapy.

Adults: Swallow whole or may dissolve capsule contents into liquid. 18mg (in combination with everolimus 5mg) once daily until disease progression or unacceptable toxicity occurs.

Severe renal impairment (CrCl <30mL/min) or severe hepatic impairment (Child-Pugh C): 10mg once daily. Dose modifications for adverse reactions or lab abnormalities: see full labeling.

Children: Not established.

Warnings/Precautions: Control blood pressure prior to treatment; monitor after 1 week, every 2 weeks for the first 2 months, and then at least monthly thereafter during therapy. Discontinue if life-threatening hypertension, Grade 4 cardiac dysfunction or hemorrhage, arterial thrombotic

GnRH analogue. Leuprolide acetate 7.5mg; depot susp for IM inj.

Indications: Palliative treatment of advanced prostatic carcinoma.

Adults: 7.5mg IM once a month. Rotate inj site.

Children: Not applicable. ℞ Also: LUPRON DEPOT-3 MONTH 22.5mg Leuprolide acetate 22.5mg; depot susp for IM inj.

Adults: 22.5mg IM inj every 3 months (84 days).

Do not split doses.

Children: Not applicable. ℞ Also: LUPRON DEPOT-4 MONTH 30mg Leuprolide acetate 30mg; depot susp for IM inj; preservative-free.

Adults: 30mg as single IM inj every 4 months (16 weeks). Do not split doses.

Children: Not applicable. ℞ Also: LUPRON DEPOT-6 MONTH 45mg Leuprolide acetate 45mg; depot susp for IM inj.

LENVIMA Eisai

Adults: 45mg as single IM inj every 6 months (24 weeks). Do not split doses.

Children: Not applicable.

Contraindications: Pregnancy (Cat.X).

Warnings/Precautions: Metastatic vertebral lesions. Urinary obstruction. Monitor serum testosterone, PSA, acid phosphatase. Increased risk of diabetes, MI, sudden cardiac death, stroke; monitor blood glucose, HbA1c, and for signs/symptoms of CVD during therapy. History of seizures. Risk of QT prolongation: long-term androgen deprivation therapy, congenital long QT syndrome, electrolyte abnormalities, or CHF. Correct and monitor electrolyte abnormalities; consider monitoring ECGs. Instruct patient on correct self administration. Nursing mothers: not recommended.

Interactions: Concomitant antiarrhythmics may prolong the QT interval.

Adverse reactions: Hot flashes/sweats, inj site reaction, initial worsening of signs/symptoms (eg, bone pain, urinary tract obstruction, hematuria), edema, GI disorders, pain, cardiovascular events, CNS and antiandrogenic effects, asthenia, testicular atrophy, urinary disorders, spinal cord compression; hyperglycemia, anaphylactoid, photosensitivity.

How supplied: Depot kit—1 (prefilled dualchamber syringe w. supplies)

MENEST Pfizer

℞

Estrogen. Esterified estrogens 0.3mg, 0.625mg, 1.25mg, 2.5mg; tabs.

Indications: Palliative treatment of androgendependent advanced prostate cancer.

Adults: 1.25–2.5mg 3 times daily.

Children: Not applicable.

Contraindications: Thrombophlebitis.

Thromboembolic disorders. Cerebrovascular or coronary artery disease. Pregnancy (Cat.X).

Warnings/Precautions: Hepatic dysfunction.

Gallbladder disease. Conditions aggravated by fluid retention. Familial hyperlipoproteinemia.

Discontinue if jaundice occurs. Nursing mothers.

Adverse reactions: See literature. Migraine, depression, edema, weight changes, hypertension, GI upset, gynecomastia, impotence.

How supplied: Tabs 2.5mg—50; 0.3mg, 0.625mg, 1.25mg—100

NEXAVAR Bayer and Onyx

℞

Multikinase inhibitor. Sorafenib 200mg; tabs.

Indications: Advanced renal cell carcinoma.

Adults: Take on an empty stomach. 400mg twice daily. If toxicity occurs, may reduce dose to 400mg once daily; if further dose reduction

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CancerTherapyAdvisor.com | JANUARY/FEBRUARY 2017 | CANCER THERAPY ADVISOR 29

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DRUG MONOGRAPHS

GENITOURINARY CANCER required, may reduce dose to 400mg every other day (see full labeling). Concomitant strong CYP3A4 inducers: consider increasing dose, monitor for toxicity.

Children: Not established.

Contraindications: Concomitant carboplatin/paclitaxel in patients with squamous cell lung cancer.

Warnings/Precautions: Avoid in congenital long QT syndrome. Monitor patients with CHF, bradyarrhythmias, drugs known to prolong the QT interval, electrolyte abnormalities. Discontinue if severe dermatologic toxicity, hypertension, GI perforation, hemorrhage, cardiac ischemia, MI occurs. Suspend therapy before major surgery.

Monitor BP weekly during the first 6 weeks and thereafter. Monitor hepatic function regularly; discontinue if transaminases significantly elevated. Severe hepatic impairment (Child-Pugh C) or on dialysis. Use effective contraception during and for 2 weeks after stopping treatment.

Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: See Contraindications. Avoid strong CYP3A4 inducers (eg, St. John’s Wort, dexamethasone, phenytoin, carbamazepine, rifabutin, rifampin, phenobarbital) and neomycin; may decrease sorafenib levels. May potentiate warfarin (monitor PT & INR), other drugs metabolized by UGT1A1 or UGT1A9 pathway, or substrates of CYP2B6, CYP2C8, CYP2C9, P-gp.

Concomitant Class Ia and III antiarrhythmics; may prolong QT interval.

Adverse reactions: Dermatologic toxicity (eg, rash, hand-foot skin reaction, alopecia, pruritus, dry skin, Stevens-Johnson syndrome, toxic epidermal necrolysis), fatigue, weight loss, diarrhea, anorexia, abdominal pain, hypertension, hemorrhage, electrolyte abnormalities; druginduced hepatitis, QT prolongation.

How supplied: Tabs—120

OPDIVO Bristol-Myers Squibb

℞

Human programmed death receptor-1 (PD-1)blocking antibody. Nivolumab 10mg/mL; per vial; soln for IV infusion after dilution; preservativefree; contains mannitol.

Indications: Advanced renal cell carcinoma (RCC) in patients who have received prior antiangiogenic therapy.

Adults: Give as IV infusion over 60mins. 240mg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: See full labeling.

Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for any lifethreatening (Grade 4) adverse reaction, Grade 3 or 4 pneumonitis, Grade 3/4 or recurrent colitis (with ipilimumab), Grade 4 or recurrent colitis (as

single agent), AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash (or confirmed SJS or TEN), immune-mediated encephalitis, recurring Grade 3 adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2 or 3 adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2 or 3 (as single agent) colitis, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN, Grade 2 or 3 hypophysitis, Grade 2 adrenal insufficiency, Grade 3 hyperglycemia, Grade 3 rash (or suspected SJS or TEN), new onset moderate-to-severe neurologic symptoms, other Grade 3 adverse reactions (1st occurrence); withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if mild or moderate infusion reactions occur; discontinue if severe or life-threatening.

Monitor for abnormal liver tests, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism. Monitor for transplantrelated complications (eg, hyperacute or Grade 3/4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease) and treat promptly. Moderate or severe hepatic impairment: not studied. Embryo-fetal toxicity.

Females of reproductive potential should use effective contraception during and for ≥5 months after final dose. Pregnancy (esp. during 2nd & 3rd trimesters), nursing mothers: not recommended.

Adverse reactions: Asthenic conditions, cough, nausea, rash, dyspnea, diarrhea, constipation, decreased appetite, back pain, arthralgia; immune-mediated reactions (may be fatal).

How supplied: Single-use vial (4mL, 10mL)—1

PREMARIN Pfizer

℞

Estrogen. Conjugated estrogens 0.3mg, 0.45mg, 0.625mg, 0.9mg, 1.25mg; tabs.

Indications: Treatment of advanced androgendependent carcinoma of the prostate (for palliation only).

Adults: 1.25mg—2.5mg 3 times daily.

Children: Not applicable.

Contraindications: Known, suspected, or history of breast cancer, except in appropriately selected patients being treated for metastatic disease. Known or suspected estrogen-dependent neoplasia. Undiagnosed abnormal genital bleeding. Pulmonary embolism/DVT (active or history of). Arterial thromboembolism (eg, stroke, MI; active or history of). Liver dysfunction or disease. Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders. Known or suspected pregnancy (Cat.X).

Warnings/Precautions: Not for prevention of cardiovascular disease. Use for shortest duration consistent with treatment goals and risks. Reevaluate periodically. Patients with an intact uterus should almost always receive a progestin with systemic estrogens to

avoid endometrial hyperplasia. Discontinue if cardiovascular events occur or are suspected; if jaundice occurs; and during immobilization or at least 4–6 weeks before surgery associated with thromboembolism. Hepatic dysfunction.

Conditions aggravated by fluid retention.

Gallbladder disease. Bone disease associated with hypercalcemia. Hereditary angioedema. Do initial complete physical and repeat annually (include BP, mammogram, PAP smear). Adolescents.

Nursing mothers: not recommended.

Adverse reactions: See literature. Increased risk of cardiovascular events, estrogen-dependent carcinoma, gallbladder disease, thromboembolic disorders, hepatic tumors. GI upset, breakthrough bleeding, edema, weight changes, mastodynia, hypertension, depression, anaphylactic reactions, angioedema, intolerance to contact lenses.

How supplied: Tabs 0.3mg, 0.625mg, 1.25mg— 100, 1000; 0.45mg, 0.9mg—100

PROLEUKIN Prometheus

℞

Interleukin-2, recombinant. Aldesleukin 22 million IU/vial; pwd for IV infusion after reconstitution and dilution; contains mannitol; preservative-free.

Indications: Metastatic renal cell carcinoma.

Adults: ≥18yrs: 600,000 IU/kg (0.037mg/kg) every 8 hours by IV infusion over 15 minutes for a max of 14 doses, followed by 9 days rest, then repeat for another 14 doses (max 28 doses/course), as tolerated. Retreatment and dose adjustments: see literature.

Children: <18yrs: not established.

Contraindications: Abnormal thallium stress test or pulmonary function tests. Organ allografts.

Previous drug related toxicity (eg, sustained ventricular tachycardia [≥5 beats], uncontrolled or unresponsive arrhythmias, chest pain with ECG changes consistent with angina, or MI, cardiac tamponade, intubation >72hrs, renal failure requiring dialysis >72hrs, coma or toxic psychosis >48hrs, repetitive or difficult seizures, bowel ischemia or perforation, GI bleeding requiring surgery).

Warnings/Precautions: See literature.

History of cardiac or pulmonary disease. Renal, hepatic, or CNS impairment. Seizure disorder.

Bacterial infections (treat prior to starting therapy; esp. patients with indwelling central lines). Withhold dose if organ perfusion is not maintained, urine output is reduced, systolic BP <90mmHg, CHF, cardiac ischemia or arrhythmias occur; or if moderate-to-severe lethargy or somnolence (continuing may result in coma) develops. Evaluate and treat CNS metastases; obtain negative scan before starting treatment.

Do thallium stress test; monitor vital signs, weight, fluid intake and output daily. Correct hypovolemia or fluid accumulations if occur.

Obtain CBCs, differential and platelets, blood chemistries (electrolytes, renal and hepatic function tests), chest X-rays, serum creatinine (should be ≤1.5mg/dL before starting therapy), pulmonary function tests, arterial blood gases.

Monitor for capillary leak syndrome, mental

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DRUG MONOGRAPHS

GENITOURINARY CANCER status changes, thyroid changes, diabetes onset.

Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Psychotropics may increase CNS toxicity. Increased toxicity with other nephrotoxic, hepatotoxic, myelotoxic, or cardiotoxic drugs. Hypersensitivity reactions with other antineoplastics. Myocardial injury and rhabdomyolysis risk increased with interferonalfa. Antagonized by glucocorticoids (avoid). β-blockers and other antihypertensives may potentiate hypotension. Delayed reactions to iodinated contrast media. May increase risk of allograft rejection.

Adverse reactions: Hypotension, GI upset, oliguria, flu-like syndrome, respiratory disorders (eg, dyspnea), CNS effects (eg, confusion, somnolence), rash, metabolic and nutritional disorders (eg, bilirubinemia, increased creatinine), hyperglycemia, thyroid disorder, thrombocytopenia, anemia, impaired neutrophil function, capillary leak syndrome, cardiotoxicity, exacerbation of autoimmune and inflammatory disease, eosinophilia, possible antibody formation; others.

How supplied: Single-use vials—1

PROVENGE Dendreon

℞

Autologous cellular immunotherapy. Sipuleucel-T (autologous CD54+ cells activated with PAP-GMCSF); minimum 50 million cells/dose; suspension for IV infusion.

Indications: Asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer.

Adults: Autologous use only. Obtain product release from manufacturer, match patient identity on product and Cell Product Disposition form, check expiration date and time on product before infusing. Premedicate 30 minutes before infusion with acetaminophen and antihistamine. Give three doses at 2-week intervals. For each dose: give entire contents of bag by IV infusion over 60 minutes; do not use filter; do not use if clumps do not disperse with gentle mixing. Observe patient for at least 30 minutes after infusion. May interrupt or slow infusion if acute transfusion reaction occurs; do not restart if product at room temp for >3 hours.

Children: Not applicable.

Warnings/Precautions: Cardiac or pulmonary conditions. Each dose requires a standard leukapheresis procedure about 3 days before infusion. If scheduled infusion is missed, do an additional leukapheresis procedure if treatment course is to be continued. Risk of

disease transmission. Pregnancy, lactation: not applicable.

Interactions: May be antagonized by concomitant chemotherapy or immunosuppressive therapy.

Adverse reactions: Infusion reactions (eg, chills, fever, respiratory events, GI upset, hypertension, tachycardia), fatigue, back pain, joint ache, headache.

Note: If product sterility tests indicate microbial contamination, manufacturer will contact physician (tests are incomplete at time of infusion).

How supplied: Patient-specific bag (250mL)—1

SUTENT Pfizer

℞

Multikinase inhibitor. Sunitinib (as malate) 12.5mg, 25mg, 37.5mg, 50mg; gelatin caps.

Indications: Advanced renal cell carcinoma (RCC).

Adults: 50mg once daily for 4 weeks, then 2 weeks off (see full labeling). May adjust dose in increments or decrements of 12.5mg.

Concomitant strong CYP3A4 inhibitors (see Interactions): may reduce dose to 37.5mg daily.

Concomitant strong CYP3A4 inducers (see Interactions): may increase to max 87.5mg daily.

Children: Not established.

Warnings/Precautions: Hepatotoxicity; may be severe or fatal. Monitor liver function tests before starting, during each cycle of treatment and as clinically needed; interrupt if Grade 3 or 4 hepatic adverse events occur and discontinue if no resolution; if severe liver function changes or signs/symptoms of failure, do not restart.

Cardiovascular events: monitor for CHF during therapy, and LVEF at baseline and periodically; interrupt or reduce dose if LVEF <50% and >20% below baseline; discontinue if CHF occurs.

History of QT prolongation or proarrythmic conditions (eg, bradycardia, electrolyte disturbances); perform periodic ECG, monitor electrolytes. Monitor BP. Suspend therapy if severe hypertension, seizures, or pancreatitis develops. Obtain CBCs, platelets, serum chemistries at start of each cycle. Concomitant exposure to risk factors (eg, IV bisphosphonates therapy or dental disease) may increase the risk of osteonecrosis of the jaw; avoid or consider preventive dentistry prior to treatment. Risk of tumor lysis syndrome: monitor closely in RCC and GIST patients with high tumor burden. Monitor for thyroid dysfunction; obtain baseline levels prior to treatment. Monitor blood glucose levels during and after treatment discontinuation.

Monitor for proteinuria; perform baseline and

periodic urinalyses; interrupt and reduce dose if 24-hr urine protein ≥3g; discontinue if nephrotic syndrome or repeat urine protein ≥3g persists.

Undergoing major surgery. Stress (monitor for adrenal insufficiency). Discontinue if severe cutaneous reactions (eg, erythema multiforme, SJS, TEN) develop; do not restart if diagnosis suspected. ESRD on dialysis. Severe hepatic impairment. Pregnancy (Cat.D; avoid). Nursing mothers: not recommended.

Interactions: May be potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), grapefruit; consider reducing dose or use alternate drug. May be antagonized by CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital); consider increasing dose or use alternate drug. Concomitant St. John’s wort: not recommended. Caution with concomitant antiarrhythmics.

Adverse reactions: Fatigue, asthenia, fever, diarrhea, nausea, vomiting, mucositis/stomatitis, dyspepsia, abdominal pain, constipation, hypertension, peripheral edema, rash, handfoot syndrome, skin discoloration, dry skin, hair color changes, altered taste, headache, back pain, arthralgia, extremity pain, cough, dyspnea, anorexia, bleeding; hepatotoxicity, left ventricular dysfunction, QT prolongation, osteonecrosis of the jaw, tumor lysis syndrome, thyroid dysfunction, impaired wound healing, hypoglycemia, thrombotic microangiopathy (discontinue if develops), proteinuria, necrotizing fasciitis (discontinue if occurs), others (see full labeling).

How supplied: Caps—28

TECENTRIQ Genentech

℞

PD-L1 inhibitor. Atezolizumab 60mg/mL; soln for IV infusion after dilution; preservative-free.

Indications: Treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Adults: Give as IV infusion over 60mins. 1200mg every 3 weeks until disease progression or unacceptable toxicity. May give subsequent infusions over 30mins if first infusion tolerated.

Children: Not established.

Warnings/Precautions: Permanently discontinue if Grade 3/4 pneumonitis, AST or ALT >5×ULN or total bilirubin >3×ULN, Grade

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DRUG MONOGRAPHS

GENITOURINARY CANCER 4 diarrhea or colitis, Grade 4 hypophysitis, myasthenic syndrome/myasthenia gravis, Guillain-Barre or meningoencephalitis, Grade 3/4 ocular inflammatory toxicity, Grade 4 or recurrent pancreatitis, Grade 3/4 infusionrelated reactions, or Grade 4 rash. Withhold for Grade 2 pneumonitis, AST or ALT >3–5×ULN or total bilirubin >1.5–3×ULN, Grade 2/3 diarrhea or colitis, symptomatic hypophysitis, adrenal insufficiency, hypothyroidism, hyperthyroidism, Grade 3/4 hyperglycemia, Grade 2 ocular inflammatory toxicity, Grade 2/3 pancreatitis or Grade 3/4 increases in amylase or lipase levels (>2×ULN), Grade 3/4 infection, Grade 2 infusionrelated reactions, or Grade 3 rash; may be resumed when recover to Grade 0–1. Monitor for immune-related pneumonitis, hepatitis (obtain AST, ALT, bilirubin prior to and during treatment), diarrhea/colitis, endocrinopathies (hypophysitis, thyroid function, adrenal insufficiency, diabetes), meningitis or encephalitis, motor and sensory neuropathy, and acute pancreatitis; see full labeling for adverse reaction management details.

Monitor for signs/symptoms of infection and treat with antibiotics for suspected or confirmed bacterial infections. Interrupt or slow the infusion rate in patients with mild or moderate infusion reactions. Moderate or severe hepatic impairment: not studied. Embryo-fetal toxicity.

Pregnancy. Use effective contraception during and for ≥5 months after final dose. Nursing mothers: not recommended (during and for ≥5 months after final dose).

Adverse reactions: Fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, constipation; lab abnormalities.

How supplied: Single-dose vial (20mL)—1

THERACYS Sanofi Pasteur

℞

BCG Live. Live Bacillus Calmette and Guerin (BCG) strain of attenuated Mycobacterium bovis; 81mg per vial; pwd for intravesical administration after reconstitution and dilution; preservative-free.

Indications: Treatment and prophylaxis of carcinoma in situ (CIS) of the urinary bladder.

Prophylaxis of stage Ta and/or T1 papillary tumors following transurethral resection (TUR).

Adults: Drain bladder via urethral catheter prior to instillation. Induction: Instill 1 dose intravesically once per week for 6 weeks.

Maintenance: one dose at 3, 6, 12, 18, and 24 months after initial dose. Retain in bladder for up to 2 hours, then void seated. Increase fluid intake to flush bladder.

Children: Not recommended.

Contraindications: Immunosuppressed. Active TB. Febrile illness. UTI (withhold until complete resolution). Gross hematuria. Do not give within 7–14 days after biopsy, TUR, or traumatic catheterization.

Warnings/Precautions: Not for the prevention of cancer or TB. Determine PPD status prior to therapy; rule out active TB if (+). Not for stage TaG1 papillary tumors unless high

tumor recurrence risk. Not for IV, IM, or SC injection. Monitor for systemic BCG reaction; may occur as a hypersensitivity reaction (eg, malaise, fever, chills) or active infection (eg, fever ≥101.3°F, or acute localized inflammation such as epididymitis, prostatitis, or orchitis persisting ≥2 days); if persistent fever or acute febrile illness consistent with BCG infection occurs, discontinue BCG permanently and treat with ≥2 antimycobacterial drugs (except pyrazinamide). Local irritative effects: do not use antimycobacterial drugs prophylactically. Preexisting arterial aneurysm or prosthetic devices: risk of ectopic BCG infection. High-risk for HIV. Latex allergy. Small bladder. PPD seroconversion may occur with treatment. Pregnancy (Cat.C).

Nursing mothers: not recommended.

Interactions: See contraindications.

Immunosuppressants, myelosuppressants, radiation, antimicrobial therapy may reduce efficacy.

Adverse reactions: Bladder irritation, inflammation (begins after 4 hrs and last up to 72 hrs), dysuria, urinary frequency, malaise, hematuria, fever, chills, cystitis, anemia, UTI, GI upset, renal toxicity, genital pain, arthralgia, incontinence, cramps, flu-like syndrome, systemic BCG infection.

How supplied: Vial—1 (w. diluent) ℞

patients should use appropriate contraception), nursing mothers: not recommended.

Interactions: Avoid strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice); if used, consider reducing temsirolimus dose to 12.5mg/week (allow 1 week after discontinuing CYP3A4 inhibitor before readjusting temsirolimus dose). Avoid strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampicin, phenobarbital, St. John’s Wort); if used, consider increasing temsirolimus dose to 50mg/week.

Avoid live vaccines, close contact with vaccinees.

Additive toxicity with sunitinib (rash, gout/cellulitis), anticoagulants (intracerebral bleeding).

Adverse reactions: Rash, asthenia, mucositis, nausea, edema, anorexia, infection, pain, anemia, hyperglycemia, hyperlipemia, hypertriglyceridemia, elevated alkaline phosphatase, elevated serum creatinine, lymphopenia, hypophosphatemia, thrombocytopenia, elevated AST, leukopenia; hypersensitivity/infusion reactions (anaphylaxis, dyspnea, flushing, chest pain), immunosuppression, PJP, ILD, bowel perforation, acute renal failure, abnormal wound healing; others (see full labeling).

How supplied: Kit (vial + diluent)—1

mTOR kinase inhibitor. Temsirolimus 25mg/mL; ethanolic soln for IV infusion after two dilutions (first w. supplied diluent); contains alcohol, polysorbate 80.

Indications: Advanced renal cell carcinoma.

Adults: 25mg once weekly. Infuse IV over 30–60min, using an infusion pump. Continue until disease progression or unacceptable toxicity occurs. Premedicate with IV antihistamine (eg, diphenydramine). Hold dose if ANC <1000/mm3, platelets <75000/mm3, or NCI CTCAE ≥Grade 3 adverse reaction occurs; may restart at a dose reduced by 5mg/week (no lower than 15mg/week) if adverse reactions resolve to ≤Grade 2. Hepatic impairment: bilirubin >1–1.5xULN or AST > ULN but bilirubin ≤ ULN: reduce to 15mg/week; >1.5xULN: contraindicated.

See Interactions.

Children: Not recommended.

Contraindications: Bilirubin >1.5xULN. Warnings/Precautions: Sirolimus or related allergy. Hemodialysis. Perioperative period (may interfere with wound healing). CNS tumors.

Monitor for opportunistic infections; consider prophylaxis for pneumocystis jiroveci pneumonia (PJP) when concomitant corticosteroids, other immunosuppresives required. Monitor for interstitial lung disease (ILD); discontinue if suspected. Monitor CBCs weekly and chemistry panels every 2 weeks, blood glucose, lipids, renal function, and for worsening respiratory or GI symptoms (eg, acute abdomen, blood in stool).

Elderly. Pregnancy (Cat.D) (avoid pregnancy during and for 3 months after therapy, male

GnRH analogue. Triptorelin pamoate 3.75mg, 11.25mg, 22.5mg; lyophilized microgranules for IM inj after reconstitution; contains mannitol.

Indications: Palliative treatment of advanced prostate cancer.

Adults: Give by IM inj in buttock. 3.75mg every 4 weeks, or 11.25mg every 12 weeks, or 22.5mg every 24 weeks.

Children: Not established.

Contraindications: Pregnancy (Cat.X).

Warnings/Precautions: Not for use in women.

Must administer under physician supervision.

Discontinue if hypersensitivity occurs. Initial transient increase in serum testosterone may result in worsening of signs/symptoms including bone pain, neuropathy, hematuria, or urethral/bladder obstruction. Spinal cord compression. Renal or hepatic impairment.

Metastatic vertebral lesions. Upper or lower urinary tract obstruction. May prolong QT/QTc interval in patients with congenital long QT syndrome, CHF, frequent electrolyte abnormalities. Correct any electrolyte abnormalities; monitor ECGs and electrolytes periodically. Increased risk of diabetes, MI, sudden cardiac death, stroke; monitor blood glucose and/or HbA1c, and for signs/symptoms of cardiovascular disease. Measure serum testosterone periodically. Nursing mothers: not recommended.

Interactions: Concomitant hyperprolactinemic drugs: not recommended. Avoid concomitant drugs that are known to prolong the QT interval.

TORISEL Pfizer

TRELSTAR Allergan

℞

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DRUG MONOGRAPHS

GENITOURINARY CANCER May interfere with pituitary gonadotropic function tests.

Adverse reactions: Inj site reactions, hot flushes, skeletal pain, impotence, headache, leg edema/pain, erectile dysfunction, testicular atrophy; hyperglycemia.

How supplied: Single-dose vial—1; MixJect system—1 (vial + vial adapter + prefilled syringe)

VALSTAR Endo

℞

Anthracycline. Valrubicin 40mg/mL; soln for intravesical instillation after dilution; contains 50% polyoxyl castor oil/50% dehydrated alcohol; preservative-free.

Indications: Intravesical therapy of BCGrefractory carcinoma in situ (CIS) of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality.

Adults: Drain bladder before instilliation. 800mg given intravesically via urethral catheter once weekly for 6 weeks. Retain drug for 2 hours before voiding, then void.

Children: Not recommended.

Contraindications: Concurrent UTI. Small bladder capacity (eg, unable to tolerate a 75mL instillation).

Warnings/Precautions: Monitor for disease recurrence or progression with cystoscopy, biopsy, and urine cytology every 3 months; if there is not a complete response of CIS to treatment after 3 months or if CIS recurs, cystectomy must be reconsidered. Severe irritable bladder symptoms. Perforated bladder. Bladder mucosa compromised. Delay administration for at least 2 weeks after transurethral resection and/or fulguration. Maintain adequate hydration.

Pregnancy (Cat. C); avoid, both males and females should use effective birth control. Nursing mothers: not recommended.

Adverse reactions: Bladder symptoms (eg, urinary frequency, dysuria, urinary urgency, spasm, hematuria, pain, incontinence, cystitis, nocturia, local burning, urethral pain, pelvic pain, UTI).

How supplied: Single-use vials—4, 24

VANTAS Endo

℞

GnRH analogue. Histrelin acetate 50mg; SC implant.

Indications: Palliative treatment of advanced prostate cancer.

Adults: Insert 1 implant SC in the inner aspect of the upper arm. Remove after 12 months; may replace.

Children: Not applicable.

Contraindications: Pregnancy (Cat.X). Nursing mothers. Not for use in women or children.

Warnings/Precautions: Initial transient increase in serum testosterone may result in worsening signs/symptoms (eg, bone pain, neuropathy, hematuria). Metastatic vertebral lesions, urinary tract obstruction (monitor closely in 1st few weeks). Avoid wetting inserted arm for 24hrs and heavy lifting or strenuous exertion for 1st week. Increased risk of developing diabetes; monitor blood glucose and HbA1c periodically; treat if occurs. Increased risk of developing MI, sudden cardiac death, stroke; monitor for signs/symptoms of cardiovascular disease. May prolong QT/QTc interval in patients with congenital long QT syndrome, CHF, electrolyte abnormalities; monitor ECGs. If electrolyte abnormalities occur, correct and monitor. Measure serum testosterone, PSA levels periodically. Implant not visible on X-ray.

Interactions: May interfere with pituitary gonadotropic and gonadal function tests. Caution with concomitant drugs known to prolong the QT interval.

Adverse reactions: Hot flashes, fatigue, implant site reactions, testicular atrophy, renal impairment; hyperglycemia, diabetes, cardiovascular disease.

How supplied: Kit—1 (w. implant and supplies)

VOTRIENT GlaxoSmithKline

℞

Tyrosine kinase inhibitor. Pazopanib 200mg; tabs.

Indications: Advanced renal cell carcinoma.

Limitation of use: not for treating adipocytic soft tissue sarcoma or gastrointestinal stromal tumors.

Adults: Take on an empty stomach. Swallow whole.

800mg once daily. Dose adjustments: see full labeling. Hepatic impairment: moderate: 200mg once daily; severe: not recommended. Concomitant strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir, clarithromycin): avoid and consider alternate drug; if warranted, reduce dose of pazopanib to 400mg; may reduce further if toxicity occurs. Concomitant strong CYP3A4 inducers (eg, rifampin): avoid and consider alternate drug.

Children: Not established.

Warnings/Precautions: Not indicated for use in combination with other cancer agents. Risk of severe and fatal hepatotoxicity (esp. ≥65yrs old). Monitor liver tests before starting and at Weeks 3, 5, 7, and 9, thereafter at Months 3 and 4, then periodically. If ALT between 3xULN and 8xULN continue therapy with weekly monitoring until ALT returns to Grade 1 or baseline. If ALT >8xULN interrupt therapy until ALT returns to Grade 1 or baseline; may consider reintroducing at a reduced dose, measure liver tests weekly

for 8 weeks; if ALT>3xULN recurs, permanently discontinue. Permanently discontinue if ALT>3xULN and bilirubin >2xULN. Gilbert’s syndrome (see full labeling). History of QT prolongation. Cardiac dysfunction risk (including previous anthracycline exposure): evaluate LVEF at baseline and periodically; monitor for CHF. Monitor ECG, electrolytes (eg, calcium, magnesium, potassium), thyroid function. History of hemoptysis, cerebral, or clinically significant GI hemorrhage in the past 6 months: not recommended. Risk of arterial thrombotic events (within previous 6 months: not recommended).

Monitor for VTE, PE, infection, proteinuria (reduce dose if 24-hour urine protein ≥3g), thrombotic microangiopathy, interstitial lung disease (ILD)/pneumonitis, GI perforation or fistula.

Monitor BP and manage hypertension promptly.

Discontinue if severe and persistent hypertension (despite antihypertensives and dose reduction), if repeat episodes of proteinuria (despite dose reductions), thrombotic microangiopathy, serious infection, ILD or pneumonitis occurs.

Stop therapy at least 7 days before surgery; discontinue in patients with wound dehiscence.

Females of reproductive potential must use effective contraception during therapy and for ≥2 weeks after last dose. Pregnancy (Cat.D).

Nursing mothers: not recommended.

Interactions: See Adult dosing: Potentiated by strong CYP3A4 inhibitors, grapefruit juice. Avoid concomitant strong Pgp or BCRP inhibitors.

Antagonized by strong CYP3A4 inducers.

Concomitant drugs with narrow therapeutic windows metabolized by CYP3A4, CYP2D6, or CYP2C8: not recommended. Increased risk of ALT elevations with concomitant simvastatin; caution and monitor closely; follow dosing guidelines or consider alternatives to pazopanib, or discontinuing simvastatin if develops. Avoid concomitant drugs that raise gastric pH (eg, PPIs, H2-blockers). Separate antacids by several hours. Caution with concomitant drugs that prolong QT interval (eg, antiarrhythmics).

Adverse reactions: Diarrhea, hypertension, hair color changes, nausea, anorexia, vomiting, fatigue, decreased weight, decreased appetite, tumor pain, musculoskeletal pain, headache, dysgeusia, dyspnea, skin hypopigmentation; hepatotoxicity, QT prolongation, hemorrhagic events, arterial thrombotic events (eg, MI, angina, ischemic stroke, TIA), venous thrombotic events (eg, VTE, PE), GI perforation or fistula, ILD/pneumonitis, impaired wound healing, hypothyroidism, proteinuria, infection, reversible posterior leukoencephalopathy syndrome (discontinue if occurs).

How supplied: Tabs—120

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DRUG MONOGRAPHS

GENITOURINARY CANCER XOFIGO Bayer

℞

Alpha particle-emitting radioactive therapeutic agent. Radium Ra 223 dichloride 1000 kBq/mL (27 microcurie/mL) with a total radioactivity of 6000 kBq/vial (162 microcurie/vial) at the reference date; IV injection.

Indications: Treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.

Adults: See full labeling. Administer by slow IV over 1 min. 50kBq (1.35 microcurie) per kg given at 4 week intervals for 6 injections.

Children: <18yrs: not established.

Contraindications: Women who are or may become pregnant. Pregnancy (Cat. X).

Warnings/Precautions: Not for use in women. Bone marrow suppression. Perform hematologic evaluation at baseline and prior to every dose. Before 1st dose, the ANC should be ≥1.5 X 109/L, platelets ≥100 X 109/L and hemoglobin ≥10g/dL. Before subsequent doses, the ANC should be ≥1 X 109/L and platelets ≥50 X 109/L; discontinue if no recovery within 6–8 weeks after last dose despite receiving supportive care. Monitor closely if evidence of compromised bone marrow reserve. Discontinue if life-threatening complications occur despite supportive care for bone marrow failure.

Monitor oral intake and fluid status carefully.

Males (use condoms) and female partners of reproductive potential should use highly effective contraceptive method during and 6 months after completion. Nursing mothers: not recommended.

Interactions: Concomitant chemotherapy: not established. Discontinue if concomitant with chemotherapy, other systemic radioisotopes or hemibody external radiotherapy.

Adverse reactions: Nausea, diarrhea, vomiting, peripheral edema, anemia, lymphocytopenia, leukopenia, thrombocytopenia, neutropenia.

How supplied: Single-use vials (6mL)—1

XTANDI Astellas

℞

Androgen receptor inhibitor. Enzalutamide 40mg; soft gelatin caps.

Indications: Treatment of metastatic castrationresistant prostate cancer.

Adults: Swallow whole. 160mg once daily. Dose modifications: ≥Grade 3 toxicity or intolerable side effect: withhold dosing for 1 week or until symptoms improve to ≤Grade 2, then resume at same or reduced dose (120mg or 80mg), if warranted. Concomitant strong CYP2C8 inhibitors: avoid if possible. If co-administration necessary, reduce enzalutamide dose to 80mg once daily; if inhibitor is discontinued, return enzalutamide dose to the dose used prior to initiation of inhibitor.

Children: Not established.

Contraindications: Pregnancy (Cat.X).

Warnings/Precautions: Risk of seizure; permanently discontinue if develops during treatment. Severe renal or hepatic impairment.

Nursing mothers: not recommended.

Interactions: Avoid concomitant strong CYP2C8 inhibitors (eg, gemfibrozil) if possible; reduce enzalutamide dose if cannot be avoided.

Avoid concomitant CYP2C8 inducers (eg, rifampin), CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, bosentan, efavirenz, etravirine, modafinil, nafcillin), and St. John’s Wort if possible.

Potentiated by CYP3A4 inhibitors (itraconazole).

Antagonizes midazolam (CYP3A4 substrate), warfarin (CYP2C9 substrate), and omeprazole (CYP2C19 substrate). Avoid concomitant drugs with narrow therapeutic indexes metabolized

by CYP3A4 (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus), CYP2C9 (eg, phenytoin, warfarin), CYP2C19 (eg, S-mephenytoin); enzalutamide may decrease their exposure. Caution with concomitant drugs that may lower the seizure threshold. Conduct more INR monitoring if concomitant warfarin cannot be avoided.

Adverse reactions: Asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, dizziness/vertigo.

How supplied: Caps—120

ZYTIGA Janssen Biotech

℞

CYP17 inhibitor. Abiraterone acetate 250mg; tabs.

Indications: In combination with prednisone for the treatment of metastatic castration-resistant prostate cancer.

Adults: Take on empty stomach (no food 2 hrs before or 1 hr after administration). Swallow whole with water. 1g once daily (in combination with prednisone 5mg twice daily). Moderate hepatic impairment (Child-Pugh Class B): 250mg once daily; monitor frequently. If hepatotoxicity occurs: interrupt, then restart at reduced dose; discontinue if severe (see full labeling). If concomitant strong CYP3A4 inducer necessary, increase abiraterone dose frequency to twice daily during co-administration period (eg, from 1g once daily to 1g twice daily); reduce back to previous dose/frequency when CYP3A4 inducer is discontinued.

Children: Not recommended.

Contraindications: Pregnancy (Cat.X).

Warnings/Precautions: Risk of mineralocorticoid excess: patients with history of cardiovascular disease, LVEF <50%, Class II-IV heart failure, recent MI, ventricular arrhythmias.

Monitor BP, serum potassium, and for fluid retention monthly. Control hypertension and correct hypokalemia before and during treatment.

Monitor for adrenocortical insufficiency. Stress (may need higher corticosteroid dose). Baseline

severe hepatic impairment (Child-Pugh Class C); avoid. Monitor liver function (ALT/AST, bilirubin) prior to starting treatment, every 2 weeks for the first 3 months, and monthly thereafter; interrupt, reduce dose, or discontinue if hepatotoxicity occurs. Permanently discontinue if concurrent ALT elevation >3xULN and total bilirubin >2xULN develops without biliary obstruction or other causes of elevation. Nursing mothers: not recommended.

Interactions: CYP2D6 substrates with narrow therapeutic index (eg, thioridazine); avoid.

Potentiates dextromethorphan. May affect, or be affected by, strong inhibitors or inducers of CYP3A4; avoid or use caution. Concomitant CYP2C8 substrates: monitor closely for signs of toxicity.

Adverse reactions: Joint swelling or discomfort, hypokalemia, edema, myalgia, hot flush, GI upset, UTI, cough, hypertension, arrhythmias, urinary frequency, nocturia, URI, adrenocortical insufficiency, hepatotoxicity.

Note: Pregnant women and those of childbearing potential should not handle Zytiga tablets without protection (eg, gloves). Partners must use appropriate barrier contraception.

How supplied: Tabs—120

GENERIC NAME The active ingredients and strengths are listed under the name of each dosage form. If the product contains tartrazine, alcohol, flavors, or is alcohol-, sugar-, or dye-free, it is noted. Abbreviations are used to describe the dosage form and its formulation, e.g.: tabs = tablets caps = capsules e-c = enteric coated sust rel = sustained-release ext rel = extended-release

ADVERSE REACTIONS Those adverse reactions listed within product monographs represent the potential for adverse effects based upon the active ingredient(s) and/or the drug class. It is not meant to be an inclusive list of responses.

34 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

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DRUG MONOGRAPHS

GYNECOLOGIC CANCER AVASTIN Genentech

℞

Angiogenesis inhibitor. Bevacizumab 100mg, 400mg; per vial; soln for IV infusion after dilution; preservative-free.

Indications: Persistent, recurrent, or metastatic cervical cancer in combination with paclitaxel and cisplatin, or paclitaxel and topotecan. Platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer in patients who received no more than 2 prior chemotherapy regimens, in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan.

Adults: Give by IV infusion. Infuse 1st dose over 90 mins; if tolerated, infuse 2nd dose over 60 mins, and subsequent doses over 30 mins. Cervical cancer: 15mg/kg every 3 weeks with either paclitaxel/cisplatin, or paclitaxel/topotecan. Epithelial ovarian, fallopian tube or primary peritoneal cancer: 10mg/kg every 2 weeks with either paclitaxel, pegylated liposomal doxorubicin, or topotecan (weekly); 15mg/kg every 3 weeks with topotecan (every 3 weeks).

Children: Not established.

Warnings/Precautions: Risk of GI perforations, surgery and wound healing complications, and hemorrhage. Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). Do not administer if recent history of hemoptysis of ≥ ½-teaspoon of red blood.

Permanently discontinue if GI perforation, tracheoesophageal fistula, any grade 4 fistula, or grade 4 venous thromboembolic event.

Discontinue if fistula involving internal organ, wound healing complications, hemorrhage, severe arterial thromboembolic event (ATE), hypertensive crisis or encephalopathy, posterior reversible encephalopathy syndrome, or nephrotic syndrome occurs; suspend therapy if severe hypertension, moderate-to-severe proteinuria (resume when <2g/24hrs), or severe infusion reaction occurs. Avoid in ovarian cancer if evidence of recto-sigmoid involvement by pelvic exam, bowel involvement on CT scan, or symptoms of bowel obstruction. History of arterial thromboembolism. Diabetes. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis; if ≥2+, do further assessment with a 24-hour urine collection. Elderly. Increased risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy: may cause fetal harm; use effective contraception during and for 6 months after last dose. Nursing mothers: not recommended.

Adverse reactions: Epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation and fistulae, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial or venous thromboembolic events, posterior reversible encephalopathy syndrome, infusion reactions, ovarian failure, neutropenia, and infection.

How supplied: Single-use vial—1

DOXIL Janssen Biotech

cardiomyopathy, CHF, acute LV failure), recall of skin reaction from prior radiation therapy, toxoplasmosis, urine discoloration (red/orange).

How supplied: Single-use vials (10mL, 25mL)—1

HEXALEN Eisai

℞

Anthracycline. Doxorubicin HCl (liposomal) 2mg/mL; dispersion for IV infusion after dilution; preservative-free.

Indications: Ovarian cancer refractory to platinum-based chemotherapy.

Adults: Give by IV infusion at initial rate of 1mg/min; may increase rate to complete infusion over 1hr if no infusion reactions occur; may premedicate with antiemetics. 50mg/m2 once every 4 weeks; continue for at least 4 cycles as tolerated. Hepatic dysfunction (serum bilirubin ≥1.2mg/dL), hand-foot syndrome, hematologic toxicity (esp. ANC, platelets), or stomatitis: reduce dose. Consider total anthracycline and anthracenedione doses and irradiation when calculating total cumulative dose. See full labeling.

Children: Not established.

Warnings/Precautions: Not substitutable on a mg/mg basis with other doxorubicin products. Cardiotoxicity, acute infusion-related reactions, myelosuppression may occur.

Have resuscitative/antiallergic equipment and expertise available. Hepatic impairment.

Monitor blood (esp. CBC + platelets), hepatic (esp. SGOT/SGPT, alkaline phosphatase), and cardiac function (esp. myocardial biopsy).

Monitor periodically for secondary oral cancers with long-term use. Avoid extravasation.

Pregnancy (Cat.D); avoid. Nursing mothers: not recommended.

Interactions: Caution with cyclosporine, phenobarbital, phenytoin, streptozocin, digoxin, myelosuppressants, others. Previous mediastinal irradiation, cyclophosphamide, other cardiotoxic drugs: monitor for cardiotoxicity and hepatotoxicity.

Adverse reactions: Asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand and foot syndrome, rash, neutropenia, thrombocytopenia, anemia; infusion reactions, cardiovascular events (eg,

℞

S-triazine derivative. Altretamine 50mg; caps.

Indications: Palliative treatment of persistent or recurrent ovarian cancer following first-line therapy with a cisplatin and/or alkylating agentbased combination.

Adults: 260mg/m2 daily in four divided doses (after meals and at bedtime), for either 14 or 21 consecutive days in a 28-day cycle.

Discontinue for >14 days if GI intolerance is unresponsive to treatment, WBC count <2000/mm3 or granulocyte count <1000/mm3, platelet count <75000/mm3, or progressive neurotoxicity occurs. Restart at 200mg/m2 daily.

Discontinue indefinitely if neurologic symptoms fail to stabilize.

Children: Not recommended.

Contraindications: Severe myelosuppression or neurologic toxicity, except cisplatin-related neuropathy.

Warnings/Precautions: Monitor for myelosuppression (do monthly CBCs) and neurotoxicity. Pregnancy (Cat.D). Nursing mothers: not recommended.

Interactions: Avoid pyridoxine. Severe orthostatic hypotension with MAOIs. Adverse reactions: Nausea, vomiting, peripheral neuropathy, CNS symptoms (eg, mood disorders, ataxia, dizziness), myelosuppression, renal dysfunction, increased alkaline phosphatase.

How supplied: Caps—100

HYCAMTIN GlaxoSmithKline

℞

Topoisomerase inhibitor. Topotecan (as HCl) 4mg/vial; pwd for IV infusion after reconstitution and dilution; contains mannitol; preservativefree.

Indications: Metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.

Stage IV-B, recurrent or persistent carcinoma of the cervix in combination with cisplatin.

Adults: Verify dose using BSA. Usual max dose 4mg IV. Confirm baseline neutrophils ≥1,500cells/mm3 and platelets ≥100,000cells/mm3 prior to 1st course of therapy.

Give by IV infusion over 30 mins. Ovarian cancer: 1.5mg/m2 daily for 5 consecutive days starting on Day 1 of a 21-day cycle. Cervical cancer: 0.75mg/m2 on Days 1 (with cisplatin), 2, and 3, repeated every 21 days. Dose adjustments, renal impairment: see full labeling.

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DRUG MONOGRAPHS

GYNECOLOGIC CANCER Children: Not established.

Warnings/Precautions: Monitor peripheral blood cell counts during therapy; hold subsequent doses until neutrophils >1,000cells/mm3, platelets >100,000cells/mm3, and hemoglobin ≥9g/dL. History of interstitial lung disease, pulmonary fibrosis, lung cancer, thoracic exposure to radiation, use of pneumotoxic drugs and/or colony stimulating factors: increased risk of interstitial lung disease; monitor, discontinue if occurs. Moderate to severe renal impairment. Avoid extravasation.

Elderly. Use effective contraception during and for ≥1 month after last dose (in females), or during and for ≥3 months (in males with female partners). Pregnancy (Cat.D). Nursing mothers: not recommended.

Interactions: Myelosuppression potentiated with platinum agents. Neutropenia potentiated

by G-CSF; administer ≥24hrs after last topotecan dose.

Adverse reactions: See full labeling.

Neutropenia, leukopenia, thrombocytopenia, anemia, nausea, vomiting, diarrhea, anorexia, abdominal pain, stomatitis, headache, dyspnea, cough, pyrexia, alopecia, fatigue; infection, sepsis, interstitial lung disease, neutropenic colitis (may be fatal).

How supplied: Single-use vials—1

LYNPARZA AstraZeneca

℞

Poly (ADP-ribose) polymerase (PARP) inhibitor.

Olaparib 50mg; caps.

Indications: Monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved test) advanced ovarian cancer who have been treated with ≥3 prior lines of chemotherapy.

Adults: Swallow whole. 400mg twice daily; max 800mg daily. Continue until disease progression or unacceptable toxicity. Dose adjustments for adverse reactions: reduce to 200mg twice daily; may further reduce to 100mg twice daily. If concomitant strong CYP3A inhibitor unavoidable: reduce to 150mg twice daily; or if concomitant moderate CYP3A inhibitor unavoidable: reduce to 200mg twice daily.

Children: Not established.

Warnings/Precautions: Monitor CBC at baseline and monthly thereafter; do not start therapy until recovery from hematological toxicity due to previous chemotherapy (CTCAE Grade ≤1). Discontinue if myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) is confirmed. Interrupt therapy and evaluate if new or worsening respiratory symptoms occur; discontinue if pneumonitis is confirmed. Hepatic and moderate-to-severe renal impairment: not studied. Pregnancy (Cat.D); avoid. Use effective contraception during therapy and for at least 1 month after last dose. Nursing mothers: not recommended.

Interactions: Increased myelosuppressive toxicity with concomitant other myelosuppressive

anticancer agents, including DNA damaging agents. Avoid concomitant strong CYP3A inhibitors (eg, itraconazole, telithromycin, clarithromycin, ketoconazole, voriconazole, nefazodone, posaconazole, ritonavir, lopinavir/ritonavir, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) and moderate CYP3A inhibitors (eg, amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil); if unavoidable, reduce dose (see Adults). Avoid grapefruit and Seville oranges. Avoid concomitant strong CYP3A inducers (eg, phenytoin, rifampicin, carbamazepine, St. John’s Wort) and moderate CYP3A inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin); if unavoidable, be aware of potential for decreased efficacy.

Adverse reactions: Anemia, nausea, fatigue, asthenia, vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/URI, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash, abdominal pain/discomfort; lab abnormalities (see full labeling), MDS/AML, pneumonitis.

How supplied: Caps—112

TREXALL Teva

℞

Folic acid antagonist. Methotrexate sodium 5mg, 7.5mg, 10mg, 15mg; scored tabs. ℞ Also: Methotrexate injection Bedford Methotrexate 25mg/mL; soln for IV, IM, intraarterial, or intrathecal administration after dilution; preservative-free. ℞ Also: Methotrexate for injection Bedford Methotrexate 1g/vial; pwd for IV, IM, intra-arterial, or intrathecal administration after dilution; preservative-free.

Indications: Gestational choriocarcinoma.

Chorioadenoma destruens. Hydatidiform mole.

Adults: See literature. Tablet form is often preferred when low doses are being administered.

Choriocarcinoma and similar trophoblastic diseases: 15–30mg orally or by IM inj daily for 5 days; usually repeated 3–5 times as required with a rest period of ≥1 week between courses.

Children: Not applicable.

Contraindications: Pregnancy (Cat. X). Nursing mothers.

Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Discontinue if malignant lymphomas occur. Obtain baseline and monitor CBCs with differential, platelet counts, chest X-ray, and hepatic, renal and pulmonary function. During therapy monitor hematology monthly, renal and hepatic function every 1–2 months, more often if increasing dose or predisposed to toxicity (eg, dehydration).

Discontinue immediately if blood counts drop significantly. Rule out pregnancy in women of childbearing potential; use effective contraception during therapy and for at least 1 ovulatory cycle afterwards for women and for

at least 3 months afterwards for men. Interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur. Hepatic or renal impairment. Obesity. Diabetes. Peptic ulcer.

Ulcerative colitis. Infection. Dehydration. Folate deficiency. Ascites, pleural effusions: evacuate fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated.

Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin, sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, non-absorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy.

Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin).

Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, Stevens-Johnson syndrome).

How supplied: Tabs—30; soln (2mL, 4mL, 8mL, 10mL)—10 (single-use vials); pwd (1 gram)—1 (single-use vial)

HYPERSENSITIVITY to

a drug or its class is assumed to be a contraindication in all product monographs, although not explicitly stated.

SEE LITERATURE Consult the manufacturer’s labeling for full prescribing information.

ADVERSE REACTIONS Those adverse reactions listed within product monographs represent the potential for adverse effects based upon the active ingredient(s) and/or the drug class. It is not meant to be an inclusive list of responses.

36 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

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DRUG MONOGRAPHS

HEAD AND NECK CANCER ERBITUX Bristol-Myers Squibb

℞

Epidermal growth factor receptor blocker.

Cetuximab 100mg/vial, 200mg/vial; soln for IV infusion; preservative-free.

Indications: In combination with radiation therapy for treating locally or regionally advanced squamous cell carcinoma of the head and neck (SCCHN). In combination with platinum-based therapy with 5-fluorouracil (5-FU) for first-line treatment of recurrent locoregional disease or metastatic SCCHN. As a single agent for recurrent or metastatic SCCHN after failure of prior platinum-based therapy.

Adults: Pretreat with H1 blocker. Give by IV infusion (use filter); max rate: 10mg/min.

Initial dose: 400mg/m2 once over 2hrs; then 250mg/m2 once weekly over 1 hour.

Combination therapy: Give initial dose 1 week prior to initiation of radiation therapy. Complete administration 1 hour prior to platinum-based therapy with 5-FU. Give subsequent weekly dose for duration of radiation therapy (6–7 weeks) or until disease progression or unacceptable toxicity. Permanently reduce infusion rate by 50% if Grade 1 or 2 and non-serious Grade 3 infusion reaction occurs; permanently discontinue if Grade 3 or 4 serious reaction occurs. Monitor patient during and for 1hr postinfusion. Skin toxicity: see full labeling.

Children: Not established.

Warnings/Precautions: Discontinue if severe infusion reactions or interstitial lung disease occur. Monitor for infusion reactions, cardiopulmonary arrest, pulmonary toxicity, dermatologic toxicities/infection; avoid sun, UV light. Additive cutaneous reactions with irradiation. Cardiovascular diseases (w. irradiation or platinum-based therapy with 5-FU). Monitor electrolytes (eg, magnesium, potassium, calcium) during and after cetuximab therapy. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Increased mucositis (Grade 3–4), radiation recall syndrome, acneiform rash, cardiac events, and electrolyte disturbances with radiation and cisplatin.

Adverse reactions: Cutaneous reactions (pruritus, nail changes), acneform rash, headache, diarrhea, infection, asthenia, mucositis, weight loss, xerostomia, dehydration, electrolyte abnormalities; infusion reactions (may be severe: eg, bronchospasm, dyspnea), interstitial lung disease, cardiopulmonary arrest, hypomagnesemia, fever, sepsis, kidney failure, pulmonary embolus; others (see full labeling).

How supplied: Single-use vials—1

HYDREA Bristol-Myers Squibb

℞

Antimetabolite. Hydroxyurea 500mg; caps.

Indications: Adjunct with irradiation therapy in locally advanced squamous cell carcinomas of the head and neck, excluding the lip.

Adults: Base dose on ideal or actual weight, whichever is less. Individualize. Initially 15mg/kg/day. Renal impairment (CrCl <60mL/min or ESRD): initially 7.5mg/kg/day; give dose following dialysis (monitor). Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Risk of severe myelosuppression; reduce dose or discontinue if necessary. Monitor blood counts at baseline and at least once a week during therapy. Correct severe anemia before starting. Markedly depressed bone marrow function: do not initiate. Monitor for malignancies. Avoid sun exposure. Previous irradiation therapy (monitor for skin erythema) or chemotherapy. Macrocytosis may mask folic acid deficiency; prophylactic folic acid is recommended.

Myeloproliferative disorders; discontinue if cutaneous vasculitic ulcerations occur. Renal or hepatic impairment. Elderly. Embryo-fetal toxicity.

Pregnancy; avoid. Exclude pregnancy prior to initiating; use effective contraception during and for ≥6 months (females) or ≥1 year (males) after therapy. Nursing mothers: not recommended.

Interactions: Avoid concomitant didanosine, with or without stavudine, or other antiretrovirals (may cause pancreatitis [monitor], fatal hepatotoxicity, peripheral neuropathy). Avoid live vaccines. Increased risk of vasculitic toxicities with interferon therapy. May cause falsely elevated results in urea, uric acid, and lactic acid assays.

Adverse reactions: Leukopenia, thrombocytopenia, anemia, GI upset, anorexia; secondary malignancies, macrocytosis.

Note: Wear disposable gloves when handling caps or bottle.

How supplied: Caps—100

KEYTRUDA Merck

℞

Human programmed death receptor-1 (PD-1)-blocking antibody. Pembrolizumab 50mg/vial; lyophilized pwd for IV infusion after reconstitution; 25mg/mL; per vial; soln for IV infusion after dilution; both: preservative-free.

Indications: Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinumcontaining chemotherapy.

Adults: Give as IV infusion over 30mins.

200mg every 3 weeks until disease progression,

unacceptable toxicity, or up to 24 months in patients without disease progression. Dose modifications: see full labeling. Administer corticosteroids for most Grade ≥2 related immune-mediated reactions.

Children: Not established.

Warnings/Precautions: Monitor for pneumonitis; withhold dose if Grade 2 pneumonitis; permanently discontinue if Grade 3 or 4, or recurrent Grade 2 develops. Monitor for colitis; withhold dose if Grade 2 or 3 colitis; permanently discontinue if Grade 4 develops.

Monitor for changes in liver function; withhold dose or discontinue based on severity of elevated liver enzymes. Monitor for changes in renal function; withhold dose if Grade 2 nephritis; permanently discontinue if Grade 3 or 4 develops.

Monitor for hypophysitis; withhold dose if Grade 2 hypophysitis; withhold or discontinue if Grade 3 or 4 develops. Monitor for changes in thyroid function (at treatment initiation, during, and as clinically indicated) and signs/symptoms of thyroid disorders; withhold or discontinue if Grade 3 or 4 hyperthyroidism develops. Monitor for hyperglycemia and other diabetes symptoms; withhold if severe hyperglycemia until controlled.

Permanently discontinue if any severe or Grade 3 immune-mediated adverse reaction recurs, for any life-threatening immune-mediated adverse reaction, persistent Grade 2 or 3 reactions that do not recover to Grade 0–1 within 12wks after last dose, or inability to reduce corticosteroid dose to ≤10mg/day of prednisone or equivalent within 12wks. Monitor for infusion-related reactions; permanently discontinue if Grade 3 or 4 develops.

Embryo-fetal toxicity. Use highly effective contraception during treatment and for 4 months after the final dose. Pregnancy: avoid. Nursing mothers: not recommended (during treatment and for 4 months after the final dose).

Adverse reactions: Fatigue, decreased appetite, dyspnea, pruritus, rash, constipation, diarrhea, nausea, cough; immune-mediated disorders, infusion-related reactions.

How supplied: Single-use vial 50mg—1; Singleuse vial 25mg/mL—1

OPDIVO Bristol-Myers Squibb

℞

Human programmed death receptor-1 (PD-1)blocking antibody. Nivolumab 10mg/mL; per vial; soln for IV infusion after dilution; preservativefree; contains mannitol.

Indications: Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinumbased therapy.

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DRUG MONOGRAPHS

HEAD AND NECK CANCER Adults: Give as IV infusion over 60mins.

3mg/kg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: See full labeling.

Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for any lifethreatening (Grade 4) adverse reaction, Grade 3 or 4 pneumonitis, Grade 3/4 or recurrent colitis (with ipilimumab), Grade 4 or recurrent colitis (as single agent), AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash (or confirmed SJS or TEN), immune-mediated encephalitis, recurring Grade 3 adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2 or 3 adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2 or 3 (as single agent) colitis, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN, Grade 2 or 3 hypophysitis, Grade 2 adrenal insufficiency, Grade 3 hyperglycemia, Grade 3 rash (or suspected SJS or TEN), new onset moderate-to-severe neurologic symptoms, other Grade 3 adverse reactions (1st occurrence); withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if mild or moderate infusion reactions occur; discontinue if severe or life-threatening.

Monitor for abnormal liver tests, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism. Monitor for

transplant-related complications (eg, hyperacute or Grade 3/4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease) and treat promptly. Moderate or severe hepatic impairment: not studied. Embryo-fetal toxicity.

Females of reproductive potential should use effective contraception during and for ≥5 months after final dose. Pregnancy (esp. during 2nd & 3rd trimesters), nursing mothers: not recommended.

Adverse reactions: Fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea; immune-mediated reactions (may be fatal).

How supplied: Single-use vial (4mL, 10mL)—1

TREXALL Teva

℞

Folic acid antagonist. Methotrexate sodium 5mg, 7.5mg, 10mg, 15mg; scored tabs. ℞ Also: Methotrexate injection Bedford Methotrexate 25mg/mL; soln for IV, IM, intraarterial, or intrathecal administration after dilution; preservative-free. ℞ Also: Methotrexate for injection Bedford Methotrexate 1g/vial; pwd for IV, IM, intra-arterial, or intrathecal administration after dilution; preservative-free.

Indications: Epidermoid cancers of the head and neck.

Adults: See literature.

Children: Not established.

Contraindications: Pregnancy (Cat. X). Nursing mothers.

Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Discontinue if malignant lymphomas occur. Obtain baseline and monitor CBCs with differential, platelet counts, chest X-ray, and hepatic, renal and pulmonary function. During therapy monitor hematology monthly, renal and

hepatic function every 1–2 months, more often if increasing dose or predisposed to toxicity (eg, dehydration). Discontinue immediately if blood counts drop significantly. Rule out pregnancy in women of childbearing potential; use effective contraception during therapy and for at least 1 ovulatory cycle afterwards for women and for at least 3 months afterwards for men. Interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur. Hepatic or renal impairment.

Obesity. Diabetes. Peptic ulcer. Ulcerative colitis.

Infection. Dehydration. Folate deficiency. Ascites, pleural effusions: evacuate fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated.

Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin, sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, nonabsorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy. Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin).

Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, Stevens-Johnson syndrome).

How supplied: Tabs—30; soln (2mL, 4mL, 8mL, 10mL)—10 (single-use vials); pwd (1 gram)—1 (single-use vial)

DOSAGES FOR THE ELDERLY Special caution is advised when prescribing drugs for elderly patients. Keep the following points in mind when prescribing drugs for patients of approximately 60 years or older:

1. Renal Function: Glomerular filtration rate, renal tubular secretion and blood flow tend to decrease with advancing age, while the incidence of renal pathology increases.

2. Drug Sensitivity: Elderly patients may show unusual sensitivity or paradoxical reactions to a number of drugs. Refer to the complete prescribing information.

3. Drug Distribution: The ratio of fat to lean body weight may increase in the elderly, which affects the volume of distribution of fat-soluble drugs. Plasma albumin concentrations may be decreased in the elderly. This potentiates plasma-protein bound drugs and increases the potential for drug interactions caused by plasma-protein displacement.

4. Polypharmacy: It is important to determine the patient’s current medication use, including nonprescription products, before adding any medication to determine any possible interactions.

5. Hepatic Function: Reduced function of metabolic enzymes in the liver may occur in the elderly.

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CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Non-Hodgkin Lymphoma (NHL) Treatment Regimens: Diffuse Large B-cell Lymphoma Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team.

Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly.

The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Systemic Therapy for Diffuse Large B-cell Lymphoma1 Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

First-line Therapy R-CHOP (category 1)2–4

Days 1, 22, and 43: Rituximab 375mg/m2 IV 7 days prior to beginning CHOP regimen Day 1: Cyclophosphamide 750mg/m2 IV + doxorubicin 50mg/m2 IV bolus + vincristine 1.4mg/m2 IV bolus (max dose 2mg) Days 3, 24, and 45: Prednisone 100mg orally 5 days.

Repeat each cycle every 3 weeks for 3 cycles. Radiotherapy begins 3 weeks after last cycle of R-CHOP.

Dose-dense R-CHOP 14 (category 3)5,6

Day 1: Cyclophosphamide 750mg/m2 IV + doxorubicin 50mg/m2 IV + vincristine 2mg IV Days 1-5: Prednisone 100mg orally.

Repeat every 2 weeks for 6 cycles. Granulocyte colony-stimulating factor (G-CSF) was given on day 4 or 6.

Dose-adjusted EPOCH + rituximab (category 2B)7–9

Day 1: Rituximab 375mg/m2 IV Days 1–4: Etoposide 50mg/m2 IV + doxorubicin 10mg/m2 IV + vincristine 0.4mg/m2 IV Day 5: Cyclophosphamide 750mg/m2 IV Days 1–5: Prednisone 60mg/m2 orally twice daily.

Administer G-CSF 5 mcg/kg SQ daily until an ANC >5 × 109/L above nadir level starting day 6.

Repeat cycle every 3 weeks for 6 cycles.

First-line Therapy for Patients With Poor Left Ventricular Function or Very Frailab RCEPP10

Days 1 and 8: Cyclophosphamide 600mg/m2 IV Day 1: Etoposide IV 70mg/m2 IV (or days 1–3 if not giving oral etoposide) Days 2 and 3: Etoposide 140 mg/m2 orally (rounded to the nearest 50mg capsule) Days 1–10: Procarbazine 60mg/m2 orally + prednisone 60mg/m2 orally.

Repeat every 28 days until disease progression, or unacceptable toxicity.

RCNOP11,12

Day 1: Cyclophosphamide 750mg/m2 IV + liposomal doxorubicin 30mg/m2 IV + vincristine 2mg IV Days 1–5: Prednisone 60mg/m2 IV Day 8: Rituximab 375mg/m2 IV for cycle 1; administer on day 0 in subsequent cycles.

Repeat cycle every 3 weeks for 6–8 cycles.

RGCVP13

Day 1: Rituximab 375mg/m2 IV + cyclophosphamide 750mg/m2 IV + vincristine 1.4mg/m2 (maximum dose 2mg) IV Days 1 and 8: Gemcitabine 750-1000mg/m2 IV Days 1–5: Prednisolone 100mg orally per day.

Day 9: Pegfilgrastim 6mg SC. Repeat every 3 weeks for 6 cycles (Patients considered high risk for CNS relapse can receive methotrexate 12.5mg IT for 3 cycles).

DA-EPOCH + rituximab14

Day 1: Rituximab 275mg/m2 Days 1–4: Doxorubicin 10mg/m2 IV + etoposide 50mg/m2 IV + vincristine 0.4mg/m2 IV Day 5: Cyclophosphamide 750mg/m2 IV Days 1–5: Prednisone 60mg/m2 orally.

Administer G-SCF on day 6 until ANC exceeds nadir.

Repeat cycle every 3 weeks.

RCEOP15

Day 1: Rituximab 375mg/m2 IV Day 1: Cyclophosphamide 750mg/m2 IV + etoposide 50mg/m2 IV + vincristine 1.4mg/m2 IV (max dose 2mg) Days 1–5: Prednisone 100mg orally Days 2–3: Etoposide 100mg/m2 orally.

For limited-stage disease, repeat cycle every 3 weeks for 3–4 cycles; for advanced-stage disease, repeat cycle every 3 weeks for 6 cycles. continued CancerTherapyAdvisor.com | JANUARY/FEBRUARY 2017 | CANCER THERAPY ADVISOR 39

CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Non-Hodgkin Lymphoma (NHL) Treatment Regimens: Diffuse Large B-cell Lymphoma (continued) Systemic Therapy for Diffuse Large B-cell Lymphoma1 (continued) REGIMEN

DOSING

Patients >#80 Years of Age With Comorbidities R-mini-CHOP16

Day 1: Rituximab 375mg/m2 IV Day 1: Cyclophosphamide 400mg/m2 IV + doxorubicin 25mg/m2 IV + vincristine 1mg IV Days 1–5: Prednisone 40mg/m2 orally.

Repeat every 3 weeks for 6 cycles.

RGCVP13

Day 1: Rituximab 375mg/m2 IV + cyclophosphamide 750mg/m2 IV + vincristine 1.4mg/m2 (maximum dose 2mg) IV Days 1 and 8: Gemcitabine 750-1000mg/m2 IV Days 1-5: Prednisolone 100mg orally per day.

Day 9: Pegfilgrastim 6mg SC. Repeat every 3 weeks for 6 cycles (Patients considered high risk for CNS relapse can receive methotrexate 12.5mg IT for 3 cycles).

First-line Consolidation (optional) High-dose therapy with autologous stem cell rescue in patients with age-adjusted IPI high-risk disease (Category 2B)17

Induced with 5 cycles of CHOP or R-CHOP followed by autotransplantation at the first response to induction therapy with CHOP with or without rituximab for 3 cycles.

High-dose therapy with autologous stem cell rescue in patients with double-hit DLBCL17

Induced with 5 cycles of CHOP or R-CHOP followed by autotransplantation at the first response to induction therapy with CHOP with or without rituximab for 3 cycles.

Concurrent Presentation With CNS Disease Parenchymal1

Systemic methotrexate 3g/m2 or more on day 15 of a 21-day R-CHOP cycle that has been supported by growth factors.

Leptomeningeal1

Methotrexate/cytarabine IT. Consider Ommaya reservoir placement and/or systemic methotrexate 3–3.5g/m2.

Second-line Therapy (for patients with intention to proceed to high-dose therapy with autologous stem cell rescue) DHAP ± rituximab18–20

Days 1–4: Cisplatin 100mg/m2 IV via 24-hour infusion + cytosine 2g/m2 in 2 pulses each given 12 hours apart IV + dexamethasone 40mg orally or IV  rituximab 375mg/m2 IV prior to DHAP. Repeat in 3–4 weeks for 6–10 cycles.

ESHAP ± rituximab21,22

Days 1–4: Etoposide 40–60mg/m2 Days 1–5: Methylprednisolone 250–500mg IV Day 5: Cytarabine 2g/m2 IV over 2–3 hours Days 1–4: Cisplatin 25mg/m2 IV via 24-hour infusion,  Day 1 or 5: Rituximab 375mg/m2 IV. Repeat every 3–4 weeks for 3 cycles.

GDP ± rituximab23,24

Days 1 and 8: Gemcitabine 1000mg/m2 IV over 30 minutes Days 1–4: Dexamethasone 40mg orally Day 1: Cisplatin 75mg/m2 IV OR carboplatin at AUC 5mg·min/mL IV over 30 minutes,  Day 8: Rituximab 375mg/m2 slow IV infusion for CD20-positive disease.

Repeat every 3 weeks for up to 6 cycles.

GemOX ± rituximab25

Day 1: Gemcitabine 1000mg/m2 and oxaliplatin 100mg/m2  rituximab 375mg/m2 IV. Repeat every 15 days if ANC >1 × 109/L and platelet count >100 × 109/L; if not, then every 3 weeks.

ICE ± rituximab26–28

Days 1–3: Etoposide 100mg/m2 IV bolus Day 2: Carboplatin AUC 5mg·min/mL (max dose 800mg) IV bolus and ifosfamide admixed with mesna both at a dose of 5g/m2 via 24-hour continuous IV beginning day 2 Days 5–12 (or days 7–14): Filgrastim 5mcg/kg/day for cycles 1–2, increased to 10mcg/kg/day following cycle 3 until completion of peripheral blood stem cell collection,  Days 1 and 3: Rituximab 375mg/m2 IV and on cycle 1, give additional dose rituximab 375mg/m2 on Day 2.

Repeat every 14 days or when ANC >1000 cells/mcL and platelet count >50000/mcL.

MINE ± rituximab29,30c

Day 1: Mitoxantrone 8mg/m2 IV Days 1-3: Ifosfamide 2g/m2 IV + mesna IV + etoposide 100mg/m2 IV, ± Day 1: Rituximab 375mg/m2 IV. Repeat cycle every 4 weeks for 2 cycles, followed by high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT). Patients in remission after HDC-ASCT may receive rituximab 375mg/m2 IV weekly for 4 weeks.

40 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER

Systemic Therapy for Diffuse Large B-cell Lymphoma1 (continued) REGIMEN

DOSING

Second-line Therapy (non-candidates for high-dose therapy) Bendamustine ± rituximab31–33d

Days 1–2: Bendamustine 120mg/m2 IV,  Day 1: Rituximab 375mg/m2 IV. Repeat every 28 days for up to 6 cycles.

Brentuximab vedotin for CD30+ disease (Category 2B)34

Brentuximab vedotin 1.8mg/kg IV over 30 minutes every 3 weeks.

Repeat cycle until a maximum of 16 cycles, disease progression, or unacceptable toxicity.

CEPP ± rituximab (PO and IV)10

Days 1 and 8: Cyclophosphamide 600mg/m2 IV Day 1: Etoposide IV 70mg/m2 IV (or on days 1–3 if not giving oral etoposide) Days 2 and 3: Etoposide 140mg/m2 orally (rounded to the nearest 50 mg capsule) Days 1–10: Procarbazine 60mg/m2 orally + prednisone 60mg/m2 orally,  Day 1: Rituximab 375mg/m2 IV. Repeat every 28 days until disease progression or unacceptable toxicity.

CEOP ± rituximab35

Day 1: Cyclophosphamide 750mg/m2 IV, vincristine 1.4mg/m2 IV, and epirubicin 60mg/m2 IV Days 1–5: Prednisone 100mg/day orally,  Day 0: Rituximab 375mg/m2 IV. Repeat every 3 weeks for at least 6 cycles.

DA-EPOCH ± rituximab36,37

Days 2–4: Doxorubicin 15mg/m2 via continuous IV infusion + etoposide 65mg/m2 via continuous IV infusion + vincristine 0.5mg via continuous IV infusion Day 5: Cyclophosphamide 750mg/m2 IV Days 1–14: Prednisone 60mg/m2 orally,  Day 1: Rituximab 375mg/m2 IV. Repeat every 21 days for 4-6 cycles.

GDP ± rituximab38,39

Days 1 and 8: Gemcitabine 1000mg/m2 IV Days 1–4: Dexamethasone 40mg IV Days 1–3: Cisplatin 25mg/m2 IV Or carboplatin AUC 5mg·min/mL on day 1,  Day 1: Rituximab 375mg/m2 IV. Repeat every 21 days for 2–6 cycles (max of 4 cycles if using carboplatin).

GemOx ± rituximab40,41

Days 1 and 8: Gemcitabine 1200mg/m2 30-minute IV infusion Day 2: Oxaliplatin 120mg/m2 2-hour IV infusion,  Day 1: Rituximab 375mg/m2 IV. Repeat every 21 days for 6 cycles.

Lenalidomide ± rituximab (non-GCB DLBCL)42-44

Days 1–21: Lenalidomide 20mg orally  rituximab 375mg/m2 IV weekly during cycle 1.

Repeat every 28 days until complete response.

Rituximab45

Day 1: Rituximab 375mg/m2 IV during each cycle of chemotherapy for up to 8 infusions.

Inclusion of any anthracycline or anthracenedione in patients with impaired cardiac functioning should have more frequent cardiac monitoring.

There are limited published data regarding the use of these regimens; however, they are used at NCCN Member Institutions for the first-line treatment of DLBCL for patients with poor left ventricular function. c Used in patients receiving consolidation treatment following CHOP in those achieving complete response or near-complete response. d Preferred for elderly patients. a

b

References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Hodgkin’s Lymphomas. v 3.2016. Available at: http://www.nccn.org. Accessed August 31, 2016.

2. Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemo- therapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010;116: 2040–2045.

3. Feugier P, Van Hoof A, Sebban C, et al, Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. J Clin Oncol. 2005;23:4117–4126.

4. Pfreundschuh M, Trumper L, Osterborg A, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7:379–391.

5. Pfreundschuh M, Schubert J, Ziepert M, et al. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomized controlled trial (RICOVER-60). Lancet Oncol.

2008;9:105–116.

6. Cunningham D, Hawkes EA, Jack A, et al. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013;381:1817–1826.

7. Purroy N, Lopez A, Vallespi T, et al. Dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor risk large B-cell lymphoma. A phase 2 study conducted by the Spanish PETHEMA Group [Abstract]. Blood. 2009; 114: Abstract 2701.

8. Wilson WH, Dunleavy K, Pittaluga S, et al. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008;26: 2717–2724.

continued CancerTherapyAdvisor.com | JANUARY/FEBRUARY 2017 | CANCER THERAPY ADVISOR 41

CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Non-Hodgkin Lymphoma (NHL) Treatment Regimens: Diffuse Large B-cell Lymphoma (continued) References (continued) 9. Wilson WH, Jung SH, Porcu P, et al. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. Haematologica. 2012;97: 758–765.

10. Chao NJ, Rosenberg SA, Horning SJ. CEPP(B): An effective and well-tolerated regimen in poor-risk, aggressive non-Hodgkin’s lymphoma. Blood. 1990;76: 1293–1298.

11. Martino R, Perea G, Caballero MD, et al. Cyclophosphamide, pegylated liposomal doxorubicin (Caelyx), vincristine and prednisone (CCOP) in elderly patients with diffuse large B- cell lymphoma: results from a prospective phase II study. Haematologica. 2002;87:822–827.

12. Zaja F, Tomadini V, Zaccaria A, et al. CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2006;47:2174–2180.

13. Fields PA, Townsend W, Webb A, et al. De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United Kingdom National Cancer Research Institute trial. J Clin Oncol. 2014;32:282–287.

14. Garcia-Suarez J, Banas H, Arribas I, et al. Dose-adjusted EPOCH plus rituximab is an effective regimen in patients with poor-prognostic untreated diffuse large B-cell lymphoma: results from a prospective observational study. Br J ­Haematol. 2006; 126:276–285.

15. Moccia AA, Schaff K, Hoskins P, et al. R-CHOP with etoposide substituted for doxorubicin (R-CEOP): excellent outcome in diffuse large B cell lymphoma for patients with a contraindi- cation to anthracyclines. Presented at: 51st American Society of Hematology Annual Meeting and Exposition; December 7, 2009; New Orleans, LA. Blood. 2009;114: Abstract 408.

16. Peyrade F, Jardin F, Thieblemont C, et al. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol.

2011;12:460–468.

17. Stiff PJ, Unger JM, Cook J, et al. Randomized phase III U.S./ Canadian intergroup trial (SWOG S9704) comparing CHOP {+/-} R for eight cycles to CHOP {+/-} R for six cycles followed by autotransplant for patients with high-intermediate (H-Int) or high IPI grade diffuse aggressive non-Hodgkin lymphoma (NHL). J Clin Oncol.

2011;29:8001.

18. Velasquez WS, Cabanillas F, Salvador P, et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988;71:117–122.

19. Mey UJ, Orlopp KS, Flieger D, et al. Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab as salvage treatment for patients with relapsed or refractory aggressive non-Hodgkin’s lymphoma. Cancer Invest.

2006;24:593–600.

20. Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol.

2010;28:4184–4190.

21. Velasquez WS, McLaughlin P, Tucker S, et al. ESHAP—an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994;12:1169–1176.

22. Martin A, Conde E, Arnan M, et al. R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica.

2008;93:1829–1836.

23. Crump M, Baetz T, Couban S, et al. Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). Cancer. 2004;101:1835–1842.

24. Gopal AK, Press OW, Shustov AR, et al. Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium. Leuk Lymphoma. 2010;51:1523–1529.

25. Lopez A, Gutierrez A, Palacios A, et al. GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study. Eur J Haematol. 2008;80:127–132.

26. Zelenetz AD, Hamlin P, Kewalramani T, et al. Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin’s lymphoma. Ann Oncol. 2003;14:5–10.

27. Kewalramani T, Zelenetz AD, Nimer SD, et al. Rituximab and ICE (RICE) as secondline therapy prior to autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004;103:3684–3688.

28. Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28:4184–4190.

29. Joyce RM, Regan M, Ottaway J, et al. A phase I–II study of rituximab, ifosfamide, mitoxantrone and etoposide (R-IME) for B cell non-Hodgkin’s lymphoma prior to and after high-dose chemotherapy and autologous stem cell transplantation (HDCASCT). Ann Oncol. 2003; 14 (suppl 1): i21-i27.

30. Emmanouilides C, Lill M, Telatar M, et al. Mitoxantrone/ifosfamide/etoposide salvage regimen with rituximab for in vivo purging in patients with relapsed lymphoma. Clin Lymphoma. 2002;3:111–116.

31. Weidmann E, Kim SZ, Rost A, et al. Bendamustine is effective in relapsed or refractory aggressive non-Hodgkin’s lymphoma. Ann Oncol. 2002;13:1285–1289.

32. Vacirca J, Tabbara I, Acs P, Shumaker G. Bendamustine + rituximab as treatment for elderly patients with relapsed or refractory diffuse large B-cell lymphoma [abstract]. Blood. 2010;116: Abstract 2806.

33. Ohmachi K, Niitsu N, Uchida T, et al. Multicenter phase II study of bendamustine plus rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2013;31:2103–2109.

34. Bartlett N, Sharman J, Oki Y, et al. A phase 2 study of brentuximab vedotin in patients with relapsed or refractory CD30-positive non-Hodgkin lymphomas: interim results in patients with DLBCL and other B-cell lymphomas [abstract].

Blood. 2013;122;Abstract:848.

35. Yan L, Yimamu M, Wang X, et al. Addition of rituximab to a CEOP regimen improved the outcome in the treatment of non-germinal center immunophenotype diffuse large B cell lymphoma cells with high Bcl-2 expression. Int J Hematol.

2014:99:79–86.

36. Gutierrez M, Chabner BA, Pearson D, et al. Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: An 8-year follow-up study of EPOCH. J Clin Oncol. 2000;18:3633–3642.

37. Jermann M, Jost LM, Taverna C, et al. Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: Results of a phase II study. Ann Oncol. 2004;15:511–516.

38. Hou Y, Wang H, Ba Y. Rituximab, gemcitabine, cisplatin, and dexamethasone in patients with refractory or relapsed or aggressive B-cell lymphoma. Med Oncol.

2012;29:2409–2416.

39. Gopal A, Press O, Pagel J. Efficacy and Safety of Gemcitabine (G), Carboplatin©, Dexamethasone (D), and Rituximab in Patients with Relapsed/Refractory ­Lymphoma: A Prospective Multi-center Phase II Study of by the Puget Sound ­Oncology Consortium (PSOC). Leuk Lymphoma. 2010;51:1523–1529.

40. Corazzelli G, Capobianco G, Arcamone M, et al. Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-­ ineligible patients with refractory/relapsing B-cell lymphoma. Cancer Chemother Pharmacol. 2009;64:907–916.

41. El Gnaoui T, Dupuis J, Belhadj K, et al. Rituximab, gemcitabine and oxaliplatin: An effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy. Ann Oncol. 2007;18:1363–1368.

42. Witzig TE, Vose JM, Zinzani PL, et al. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin’s lymphoma. Ann Oncol. 2011;22:1622–1627.

43. Wiernik PH, Lossos IS, Tuscano JM, et al. Lenalidomide monotherapy in relapsed or refractory aggressive Non- Hodgkin’s lymphoma. J Clin Oncol.

2008;26:4952–4957.

44. Wang M, Fowler N, Wagner-Bartak N, et al. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular, and transformed lymphoma: a phase II clinical trial. Leukemia. 2013.

45. Rituxan® (rituximab) [package insert]. Genentech, Inc. South San Francisco, CA. (Revised 9/2016) © 2017 by Haymarket Media, Inc.

42 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

DRUG MONOGRAPHS

HEMATOLOGIC CANCER ADCETRIS Seattle Genetics

℞

CD30-directed antibody-drug conjugate.

Brentuximab vedotin 50mg/vial; lyophilized pwd for IV infusion after reconstitution; preservativefree.

Indications: Treatment of patients with classical Hodgkin lymphoma (HL) after failure of autologous hematopoietic stem cell transplant (auto-HSCT) or after failure of ≥2 prior multiagent chemotherapy regimens in patients who are not auto-HSCT candidates or are at high risk of relapse or progression as post-autoHSCT consolidation. Treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of ≥1 prior multi-agent chemotherapy regimen.

Adults: Give by IV infusion over 30mins. 1.8mg/kg up to max 180mg/dose every 3 weeks; continue until disease progression or unacceptable toxicity.

Post-auto-HSCT consolidation: initiate within 4–6 weeks post-auto-HSCT or upon recovery from auto-HSCT; max 16 cycles. Mild hepatic impairment: initially 1.2mg/kg up to 120mg. Peripheral neuropathy: if Grade 2/3: withhold until resolve to ≤Grade 1, then restart with 1.2mg/kg; if Grade 4: discontinue therapy. Neutropenia: Grade 3/4: withhold until resolve to ≤Grade 2; may consider G-CSF prophylaxis for subsequent cycles; recurrent Grade 4: consider discontinue or dose reduction to 1.2mg/kg. Patients with prior infusion-related reaction: premedicate with APAP, antihistamine, and corticosteroid for subsequent doses.

Children: Not established.

Contraindications: Concomitant bleomycin.

Warnings/Precautions: Risk of JC virus infection. Monitor for progressive multifocal leukoencephalopathy (PML); withhold dose if suspected and discontinue if confirmed.

Monitor for neuropathy; delay, change dose, or discontinue if new or worsening symptoms occur. Monitor for infusion-related reactions; permanently discontinue and treat if anaphylaxis occurs. Monitor CBCs prior to each dose and frequently for fever or Grade 3 or 4 neutropenia; delay, reduce, discontinue dose or consider G-CSF prophylaxis if develops. Increased risk of tumor lysis syndrome in rapidly proliferating tumor/high tumor burden patients; monitor closely. Monitor for emergence of bacterial, fungal, or viral infections. Monitor for pulmonary toxicity; if symptoms occur, withhold dose during evaluation and until improvement. Monitor liver enzymes and bilirubin; delay, change dose, or discontinue if hepatotoxicity occurs. Severe renal impairment or moderate or severe hepatic impairment: avoid.

Discontinue if serious skin reactions (eg, SJS,

TEN) occur. GI complications: evaluate and treat if new or worsening GI symptoms develop. Embryofetal toxicity. Females and males of reproductive potential should use effective contraception during and for ≥6 months after final dose.

Pregnancy: verify status before initiation. Nursing mothers: not recommended.

Interactions: See Contraindications.

Potentiated by strong CYP3A4 inhibitors (eg, ketoconazole) or P-gp inhibitors; monitor closely.

Antagonized by potent CYP3A4 inducers (eg, rifampin).

Adverse reactions: Neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough, vomiting.

How supplied: Single-use vial—1

ARRANON GlaxoSmithKline

℞

Nucleoside analogue. Nelarabine 250mg/vial; soln for IV infusion.

Indications: T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) that is unresponsive or has relapsed after ≥2 chemotherapy regimens.

Adults and Children: Contact manufacturer.

From the pediatric trial: Patients ≤21 yrs: 650mg/m2 by IV infusion over 1 hour daily for 5 consecutive days; repeat every 21 days. From the adult trial: Patients 16–65yrs: 1500mg/m2

by IV infusion over 2 hours on days 1, 3, and 5; repeat every 21 days. The recommended duration of treatment has not been clearly established.

Treatment was generally continued until there was evidence of disease progression, the patient experienced unacceptable toxicity, the patient became a candidate for bone marrow transplant, or the patient no longer continued to benefit from treatment. See literature.

Warnings/Precautions: Discontinue if ≥ Grade 2 neurotoxicity occurs; may delay dosing if other toxicities occur (eg, hematologic toxicity).

Prior or concurrent intrathecal chemotherapy or craniospinal irradiation (increased risk of neurotoxicity). Renal or hepatic impairment. Obtain CBCs, platelet counts. Monitor for signs/symptoms of infection, tumor lysis syndrome. Ensure adequate hydration. Elderly. Pregnancy (Cat.D); use effective contraception. Nursing mothers: not recommended.

Interactions: Avoid live vaccines. Concomitant adenosine deaminase inhibitors (eg, pentostatin): not recommended.

Adverse reactions: Hematologic disorders (eg, anemia, neutropenia, thrombocytopenia), headache, GI upset, constipation, fatigue,

somnolence, dizziness, peripheral neuropathy, seizures, respiratory disorders, pyrexia; increased transaminase levels, bilirubin; decreased potassium, albumin.

How supplied: Vials—6

ARZERRA Novartis

℞

CD20-directed cytolytic monoclonal antibody.

Ofatumumab 20mg/mL; soln for IV infusion after dilution; preservative-free.

Indications: In combination with chlorambucil in previously untreated patients with chronic lymphocytic leukemia (CLL), for whom fludarabinebased therapy is considered inappropriate.

Extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL. Treatment of CLL refractory to fludarabine and alemtuzumab.

Adults: Premedicate with acetaminophen (oral), antihistamine (oral or IV), corticosteroid (IV) 30mins to 2hrs prior to each infusion. Give by IV infusion (rate varies with dose and during infusion); see full labeling. Previously untreated: initially 300mg on Day 1, then 1 week later by 1000mg on Day 8 (Cycle 1), followed by 1000mg on Day 1 of subsequent 28-day cycles for at least 3 cycles until best response or max 12 cycles. Extended treatment: initially 300mg on Day 1, then by 1000mg 1 week later on Day 8, followed by 1000mg 7 weeks later and every 8 weeks thereafter for up to max 2 years. Refractory: initially 300mg on Day 1, then 1 week later by 2000mg weekly for 7 doses, followed 4 weeks later by 2000mg every 4 weeks for 4 doses. Dose modification for infusion reactions: see full labeling.

Children: Not established.

Warnings/Precautions: Increased risk of HBV reactivation. Test/treat HBV infection prior to initiating therapy. Monitor for signs of hepatitis or HBV reactivation during and for several months after therapy; discontinue if HBV reactivation occurs. Monitor CBCs at regular intervals during and after therapy, increase frequency if Grade 3/4 cytopenias develop. Monitor for new onset of or changes in neurological signs/symptoms.

Increased risk of tumor lysis syndrome (TLS) in high tumor burden and/or high circulating lymphocytes; consider prophylaxis with anti-hyperuricemics and hydration beginning 12–24hrs prior to infusion. Pregnancy (Cat.C).

Nursing mothers.

Interactions: Avoid vaccination with live viral vaccines.

Adverse reactions: Neutropenia, thrombocytopenia, anemia, pneumonia, pyrexia,

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CancerTherapyAdvisor.com | JANUARY/FEBRUARY 2017 | CANCER THERAPY ADVISOR 43

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER cough, fatigue, dyspnea, rash, nausea, diarrhea, bronchitis, upper respiratory tract infections; infusion reactions (eg, bronchospasm; laryngeal, pulmonary, or angioedema; flushing, hyper- or hypotension, syncope, cardiac ischemia, back or abdominal pain, fever, urticaria) (interrupt, adjust infusion rate and monitor; permanently discontinue if anaphylaxis occurs), progressive multifocal leukoencephalopathy (discontinue if suspected and evaluate), infections (eg, sepsis), hepatotoxicity, TLS. How supplied: Single-use vial (5mL)—3; (50mL)—1

BELEODAQ Spectrum

℞

Histone deacetylase inhibitor. Belinostat 500mg; per vial; lyophilized pwd for IV inj after reconstitution and dilution.

Indications: Relapsed or refractory peripheral T-cell lymphoma.

Adults: Give 1000mg/m2 once daily by IV infusion over 30 mins on Days 1–5 of a 21-day cycle; can repeat cycles every 21 days until disease progression or unacceptable toxicity.

Dose modifications: Hematologic toxicities: if ANC nadir <0.5x109/L or platelet count <25x109/L: decrease dose by 25% (750mg/m2); discontinue if recurrent ANC <0.5x109/L or platelet count <25x109/L nadirs after 2 dose reductions; Non-hematologic toxicities: if any CTCAE Grade 3/4 reaction: decrease dose by 25% (750mg/m2); discontinue if recurrent CTCAE Grade 3/4 reaction after 2 dose reductions.

Patients with homozygous UGT1A1*28 allele: initially 750mg/m2.

Children: Not established.

Warnings/Precautions: Risk of hematologic toxicity; monitor blood counts with differential at baseline and weekly during therapy; adjust dose as necessary. Active infection: do not administer.

History of extensive or intensive chemotherapy: may be at higher risk of life-threatening infections.

Renal or hepatic impairment. Monitor serum chemistry, renal and hepatic function before treatment and the start of each cycle; interrupt, adjust, or discontinue dose based on severity of hepatotoxicity. Tumor lysis syndrome; monitor patients with advanced stage disease and/or high tumor syndrome. GI toxicity; may require use of antiemetics and antidiarrheals. Embryo-fetal toxicity. Pregnancy (Cat. D), nursing mothers: not recommended.

Interactions: Avoid concomitant use of strong UGT1A1 inhibitors.

Adverse reactions: Nausea, fatigue, pyrexia, anemia, vomiting; hematologic toxicity, infection, hepatotoxicity, tumor lysis syndrome, GI toxicity.

How supplied: Single-use vial (30mL)—1

BENDEKA Teva

℞

Alkylating agent. Bendamustine HCl 25mg/mL; soln for IV infusion after dilution; preservative-free.

Indications: Chronic lymphocytic leukemia (CLL). Indolent B-cell non-Hodgkin’s lymphoma

(NHL) that has progressed during or within 6 months of treatment with rituximab or a rituximab–containing regimen.

Adults: CLL: Give by IV infusion over 10mins.

100mg/m2 on Days 1 and 2 of a 28-day cycle, up to 6 cycles. Hematologic toxicity (≥Grade 3): reduce dose to 50mg/m2 on Days 1 and 2 of each cycle; if toxicity recurs, reduce dose to 25mg/m2 on Days 1 and 2. Non-hematologic toxicity (clinically significant ≥Grade 3): reduce dose to 50mg/m2 on Days 1 and 2 of each cycle. Subsequent cycles: may consider dose re-escalation. NHL: Give by IV infusion over 10mins. 120mg/m2 on Days 1 and 2 of a 21-day cycle, up to 8 cycles. Hematologic toxicity (Grade 4) or non-hematologic toxicity (≥Grade 3): reduce dose to 90mg/m2 on Days 1 and 2 of each cycle; if toxicity recurs, reduce dose to 60mg/m2 on Days 1 and 2. Delay treatment for Grade 4 hematologic toxicity or clinically significant ≥Grade 2 non-hematologic toxicity. Severe renal impairment (CrCl <40mL/min) or moderate to severe hepatic impairment: not recommended.

Children: Not established.

Warnings/Precautions: Myelosuppression; monitor CBCs including leukocytes, platelets, hemoglobin, neutrophils frequently; restart treatment based on ANC and platelet count recovery. Monitor for signs of infection or reactivation of infections (eg, hepatitis B, CMV, tuberculosis, herpes zoster); prophylaxis and treat prior to therapy if occur. Monitor for infusion or skin reactions, tumor lysis syndrome. Renal or hepatic impairment. Avoid extravasation. Pregnancy (Cat.D); avoid during and for 3 months after therapy cessation. Nursing mothers: not recommended.

Interactions: May be potentiated by CYP1A2 inhibitors (eg, fluvoxamine, ciprofloxacin) or antagonized by CYP1A2 inducers (eg, omeprazole, smoking); if needed, consider alternatives.

Adverse reactions: Lymphopenia, anemia, leukopenia, thrombocytopenia, neutropenia, pyrexia, nausea, vomiting, fatigue, diarrhea, constipation, anorexia, cough, headache, weight loss, dyspnea, stomatitis; infection, infusion reactions (discontinue if severe), tumor lysis syndrome, skin reactions (if severe or progressive, withhold dose or discontinue), other malignancies (eg, myelodysplastic syndrome, acute myeloid leukemia, bronchial carcinoma).

How supplied: Multi-dose vial (4mL)—1

BEXXAR GlaxoSmithKline

℞

Radionuclide (B-lymphocyte-restricted differentiation antigen [CD20] inhibitor).

Tositumomab 35mg/vial, 225mg/vial; soln; Iodine I131 tositumomab 0.61mCi/mL, 5.6mCi/mL soln; both for IV infusion after dilution; preservative-free.

Indications: Non-Hodgkin’s lymphoma (CD20 antigen-expressing relapsed or refractory, low grade, follicular, transformed, or rituximabrefractory).

Adults: See literature. Pretreat with acetaminophen 650mg and oral

diphenhydramine 50mg and thyroid blockers; continue thyroid blockers 2 weeks after therapeutic dose. Give by IV infusion. Dosimetric step: Tositumomab 450mg over 1hr, then Iodine I131 tositumomab (containing 5mCi I131 and 35mg tositumomab) over 20 minutes. Therapeutic step (7–14 days after dosimetric step if biodistribution acceptable): tositumomab 450mg over 1hr, then calculated therapeutic dose of Iodine I131 tositumomab over 20 minutes. Reduce infusion rate by 50% if infusional toxicity occurs; stop if severe; may continue at 50% rate if severe symptoms resolve.

Children: Not recommended.

Contraindications: Hypersensitivity to murine proteins. Pregnancy (Cat.X).

Warnings/Precautions: Use only by physicians trained in radionuclide therapy. Handle and dispose of properly. See literature on patient contact restrictions. Not for initial treatment. >25% lymphoma marrow involvement and/or impaired bone marrow reserve, platelet count <100000cells/mm3, neutrophil count <1500cells/mm3, or intolerant to thyroid blockers: not recommended. High tumor burden.

Splenomegaly. Renal impairment. Screen for human anti-mouse antibodies (increases anaphylaxis risk). Obtain CBCs and platelet counts before and for up to 12 weeks after therapy. Monitor TSH (before and annually), serum creatinine (before). Use adequate contraception during and for 12 months after therapy. Elderly. Nursing mothers: not recommended.

Interactions: Concomitant other forms of irradiation or chemotherapy: not recommended.

Caution with live viral vaccines, anticoagulants, platelet aggregation inhibitors.

Adverse reactions: Thrombocytopenia, neutropenia, anemia, headache, asthenia, fever, chills, pain, GI upset, cough, pneumonia, pleural effusion, dehydration, rash, infection, hemorrhage, hypersensitivity reactions (may be fatal), myelodysplastic syndrome, secondary malignancies, antibody formation.

Note: For technical questions call (877) 423-9927.

How supplied: Dosimetric pack (tositumomab 2 × 225mg/vial + 1 × 35mg/vial and Iodine I131 tositumomab 1 × 20mL single-use vial)—1; Therapeutic pack (tositumomab 2 × 225mg/vial + 1 × 35mg/vial and Iodine I131 tositumomab 1 or 2 × 20mL single-use vial)—1

BLINCYTO Amgen

℞

Bispecific CD19-directed CD3 T-cell engager.

Blinatumomab 35mcg; per vial; lyophilized pwd for IV infusion after reconstitution; preservativefree.

Indications: Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia.

Adults and Children: Strictly follow preparation and administration instructions. Pre-medicate with dexamethasone 20mg (adults) or 5mg/m2

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER to max 20mg (pediatrics) 1 hour prior to 1st dose of each cycle, prior to a step dose, or when restarting infusion after interruption (≥4 hours).

Hospitalization recommended for first 9 days of Cycle 1 and first 2 days of Cycle 2. One single cycle = 28 days of continuous IV infusion followed by a 14-day treatment-free interval. Treat up to a total of 5 cycles. ≥45kg: Give by continuous IV infusion at a rate of 10mL/hr for 24 hours or 5mL/hr for 48 hours. Cycle 1: 9mcg/day on Days 1–7 and 28mcg/day on Days 8–28. Subsequent cycles: 28mcg/day on Days 1–28. <45kg: Cycle 1: 5mcg/m2/day (max 9mcg/day) on Days 1–7 and 15mcg/m2/day (max 28mcg/day) on Days 8–28.

Subsequent cycles: 15mcg/m2/day (max 28mcg/day) on Days 1–28. Dose adjustments: see full labeling.

Warnings/Precautions: Monitor for signs/symptoms of cytokine release syndrome or neurological toxicities; interrupt or discontinue as recommended (see full labeling). Monitor for infections; give antibiotic prophylaxis as appropriate. Monitor for tumor lysis syndrome; interrupt or discontinue as needed. Obtain lab tests (including WBC, ANC) during infusion; interrupt if prolonged neutropenia occurs.

Monitor ALT, AST, GGT, and total bilirubin prior to and during treatment; interrupt if transaminases rise >5XULN or if bilirubin rises >3XULN. Evaluate if signs/symptoms of pancreatitis develop; interrupt or discontinue as appropriate. Risk of leukoencephalopathy, esp. in those with prior treatment with cranial irradiation and antileukemic chemotherapy (including highdose methotrexate or intrathecal cytarabine).

Elderly. Pregnancy; verify status prior to initiation.

Females of reproductive potential should use effective contraception during and for at least 48hrs after last dose. Nursing mothers: not recommended (during and for at least 48hrs after last dose).

Interactions: Concomitant live vaccines: not recommended (for at least 2 weeks prior to initiation, during treatment, and until immune recovery after last cycle). Caution with concomitant CYP450 substrates esp. drugs with narrow therapeutic index (eg, warfarin, cyclosporine); monitor and adjust dose as needed.

Adverse reactions: Pyrexia, headache, nausea, vomiting, edema, hypokalemia, anemia, febrile neutropenia, neutropenia, thrombocytopenia, abdominal pain, infections; pneumonia, sepsis, device-related infection, tremor, overdose, encephalopathy, confusion.

How supplied: Pack—1 (single-use vial + IV solution stabilizer)

BOSULIF Pfizer

℞

Tyrosine kinase inhibitor. Bosutinib 100mg, 500mg; tabs.

Indications: Treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy.

Adults: Initially 500mg once daily with food.

Continue until disease progression or patient intolerance. Consider dose escalation to 600mg once daily in patients who do not reach complete hematological response (CHR) by Week 8 or a complete cytogenetic response (CCyR) by Week 12, who did not have Grade 3 or higher adverse reactions. Adjust dose for hematologic and non-hematologic toxicity: see full labeling.

Hepatic impairment: initially 200mg daily. Renal impairment (CrCl 30–50mL/min): initially 400mg daily; (CrCl <30mL/min): initially 300mg daily.

Children: <18yrs: not established.

Warnings/Precautions: Monitor and manage GI toxicity, fluid retention; withhold, reduce dose, or discontinue as necessary. Perform CBC weekly for first month, then monthly; hepatic enzyme tests monthly for first three months (more frequently if transaminase elevations occur); withhold, reduce dose, or discontinue as necessary. Monitor renal function at baseline and during therapy; consider adjusting dose if renal impairment occurs. Pregnancy (Cat.D); avoid.

Nursing mothers: not recommended.

Interactions: Potentiated by concomitant strong or moderate CYP3A and/or P-gp inhibitors (eg, ritonavir, indinavir, nelfinavir, saquinavir, ketoconazole, boceprevir, telaprevir, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone, conivaptan, fluconazole, darunavir, erythromycin, diltiazem, atazanavir, aprepitant, amprenavir, fosamprenavir, crizotinib, imatinib, verapamil, grapefruit products, ciprofloxacin); avoid. Antagonized by concomitant strong or moderate CYP3A inducers (eg, rifampin, phenytoin, carbamazepine, St. John’s Wort, rifabutin, phenobarbital, bosentan, nafcillin, efavirenz, modafinil, etravirine); avoid. Antagonized by proton pump inhibitors (eg, lansoprazole); consider shortacting antacids or H2 blockers instead; separate dosing by more than 2hrs. May potentiate drugs that are P-gp substrates (eg, digoxin).

Adverse reactions: Diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, fatigue; fluid retention (monitor), hepatic toxicity.

How supplied: Tabs 100mg—120; 500mg—30

BUSULFEX Otsuka

℞

Alkylating agent. Busulfan 6mg/mL; soln for IV administration after dilution.

Indications: In combination with cyclophosphamide, as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia.

Adults: See full labeling. Premedicate with anticonvulsants and antiemetics. Give by IV infusion over 2 hours. 0.8mg/kg of ideal body weight or actual body weight, whichever is lower, every 6 hours for 4 days for total of 16 doses (on Days -7, -6, -5, and -4). Give cyclophosphamide after the 16th dose of busulfan (Days -3 and -2).

Give hematopoietic progenitor cells on Day 0.

Obese: base dose on adjusted ideal body weight.

Children: See full labeling.

Warnings/Precautions: Risk of severe and prolonged myelosuppression; requires hematopoietic progenitor cell transplantation.

Seizure disorder. Head trauma. Renal or hepatic impairment. Monitor CBCs with differential, platelet counts, liver enzymes, bilirubin during treatment and until recovery. Monitor for infection and bleeding. Embryo-fetal toxicity. Pregnancy.

Use effective contraception during and after treatment. Nursing mothers: not recommended.

Interactions: Potentiated by itraconazole and acetaminophen. May be antagonized by phenytoin. Caution with potentially epileptogenic drugs.

Adverse reactions: Myelosuppression, nausea, stomatitis, vomiting, anorexia, diarrhea, insomnia, fever, hypomagnesemia, abdominal pain, anxiety, headache, hyperglycemia, hypokalemia; seizures (with higher doses), hepatic veno-occlusive disease (with high AUC), cardiac tamponade (in pediatric patients with thalassemia), cellular dysplasia; rare: bronchopulmonary dysplasia with pulmonary fibrosis.

How supplied: Single-use vials (10mL)—8

CAMPATH Genzyme

℞

Monoclonal antibody, CD52 (recombinant, humanized). Alemtuzumab 30mg/mL; soln; for IV infusion after dilution; preservative-free.

Indications: B-cell chronic lymphocytic leukemia (B-CLL).

Adults: Premedicate with antihistamine and acetaminophen before 1st dose, and at dose escalations. Give by IV infusion over 2 hrs. Initially 3mg per day until infusion reactions are ≤ grade 2, then increase to 10mg per day until infusion reactions are ≤ grade 2, then to maintenance

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 30mg/day three times per week (on alternate days); duration of therapy (including escalation): 12 weeks. Do not exceed max single dose 30mg/dose or 90mg/week. Give prophylactic antibiotics and antivirals during treatment and for at least 2 months after completion or until CD4+ counts resolve (whichever occurs later). Dose adjustments for neutropenia and thrombocytopenia: see literature. Retitrate if therapy interrupted for ≥7 days.

Children: Not recommended.

Warnings/Precautions: Discontinue dose for autoimmune or recurrent/persistent severe cytopenias (except lymphopenia). Withhold dose for severe cytopenias (except lymphopenia), grade 3 or 4 infusion reactions, serious infections, or during antiviral treatment for cytomegalovirus (CMV) infection or confirmed CMV viremia. Obtain CBCs, platelet counts weekly, assess CD4+ counts after treatment until recovery to ≥200cells/μL. Monitor for infusion reactions; CMV infection (continue for 2 months after therapy ends). Pregnancy (Cat.C).

Nursing mothers: not recommended.

Interactions: Avoid live virus vaccines (after recent therapy). May interfere with tests using antibodies. Irradiate any blood products given (GVHD may occur).

Adverse reactions: See literature; may be fatal.

Infusion reactions, cytopenias (eg, neutropenia, lymphopenia, thrombocytopenia, anemia), infections (eg, CMV), GI upset, insomnia, anxiety; others.

How supplied: Single-use vials—1, 3

CERUBIDINE Bedford

℞

Anthracycline. Daunorubicin HCl 20mg/vial; lyophilized pwd for IV infusion after reconstitution; contains mannitol.

Indications: In combination with other chemotherapy for remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults.

Adults: Give by IV infusion. Acute nonlymphocytic leukemia (in combination with cytosine arabinoside): <60yrs: 45mg/m2 daily on days 1, 2 and 3 of the first course and on days 1, 2 of subsequent courses; ≥60yrs: 30mg/m2 daily on days 1, 2 and 3 of the first course and on days 1, 2 of subsequent courses.

Acute lymphocytic leukemia (in combination with vincristine, prednisone, L-asparaginase): 45mg/m2 daily on days 1, 2 and 3. Hepatic or renal impairment: reduce dose (see literature).

Children: Give by IV infusion. <2yrs or BSA<0.5m2: use weight (mg/kg) to calculate dose. 25mg/m2 on day 1 every week (in combination with vincristine and prednisone).

Warnings/Precautions: Treat if any systemic infections 1st. Pre-existing drug-induced bone marrow suppression. Cardiovascular disease, thoracic irradiation, previous doxorubicin therapy (cumulative doses >550mg/m2): increased risk of cardiotoxicity. Monitor blood counts, cardiac, hepatic and renal function prior to each treatment.

Renal or hepatic impairment. Hyperuricemia; monitor blood uric acid levels and give allopurinol prophylatically. Avoid extravasation. Children.

Elderly. Pregnancy (Cat. D); avoid use. Nursing mothers: not recommended.

Interactions: Do not use if previously received max cumulative doxorubicin dose; or if concomitant with cyclophosphamide: increased cardiotoxicity.

Concomitant myelosuppressives: consider dose reduction. Increased risk of liver toxicity with hepatotoxic agents (eg, high-dose methotrexate).

Adverse reactions: Myelosuppression, cardiotoxicity, alopecia, rash, inj site reactions, GI upset, mucositis, abdominal pain, hyperuricemia; rare: anaphylaxis.

How supplied: Single-dose vials—10

CLOLAR Genzyme

℞

Purine nucleoside antimetabolite. Clofarabine 1mg/mL; soln for IV infusion after dilution; preservative-free.

Indications: Acute lymphoblastic leukemia (ALL) in patients 1–21 years of age after relapses from, and/or refractoriness to, at least two prior regimens.

Adults: Not established.

Children: Monitor blood pressure, cardiac, renal, and hepatic function before and during therapy. Give by IV infusion over 2 hours.

1–21yrs: 52mg/m2 daily for 5 consecutive days; repeat approximately every 2–6 weeks following recovery or return to baseline organ function. Provide supportive care (eg, IV fluids, antihyperuricemics, alkalinize urine, steroids, antiemetics, diuretics, albumin) throughout treatment. Renal impairment (CrCl 30–60mL/min): reduce dose by 50%. Dose modifications: see full labeling.

Warnings/Precautions: Obtain CBCs, platelets, and coagulation parameters during the 5 days of therapy. Discontinue if hypotension develops during administration. Monitor for signs/symptoms of infection, tumor lysis syndrome, cytokine release (eg, tachypnea, hypotension); if cytokine release progresses to systemic inflammatory response syndrome (SIRS)/capillary leak syndrome and/or if organ dysfunction (Grade 3 or 4 hepatic or renal toxicity) occurs, discontinue and treat; may restart at lower dose if organ function recovers and patient is stable. Discontinue immediately if Grade ≥3 liver enzyme and/or bilirubin elevation occurs. Monitor for venous occlusive disease of the liver in patients who previously received hematopoietic stem cell transplant; discontinue if suspected. Pregnancy (Cat.D); use effective contraception. Nursing mothers: not recommended.

Interactions: Minimize exposure to drugs with known renal toxicity during treatment. Consider avoiding concomitant drugs known to induce hepatic toxicity. Caution with drugs that affect BP or cardiac function; monitor.

Adverse reactions: Nausea, vomiting, diarrhea, headache, rash, pruritus, pyrexia, fatigue, palmar-

plantar erythrodysesthesia syndrome, anxiety, flushing, mucosal inflammation; bone marrow suppression (eg, febrile neutropenia, anemia, leukopenia, thrombocytopenia), infections, hyperuricemia, hypotension, cardiac events, SIRS/capillary leak syndrome, hemorrhage (may be fatal), enterocolitis (monitor), serious skin reactions (discontinue for exfoliative or bullous rash or if Stevens-Johnson syndrome or toxic epidermal necrolysis suspected), hepatotoxicity (may be fatal), embryo-fetal toxicity.

How supplied: Single-use vial (20mL)—1

DACOGEN Otsuka

℞

Nucleoside analogue. Decitabine 50mg/vial; lyophilized pwd for IV infusion after reconstitution and dilution.

Indications: Myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all FrenchAmerican-British subtypes and Intermediate-1, Intermediate-2, and High-risk International Prognostic Scoring System groups.

Adults: May premedicate with antiemetics. Treat for a minimum of 4 cycles; may take longer for a complete or partial response. Regimen 1: Give by continuous IV infusion over 3 hours. 15mg/m2 every 8 hours for 3 days; repeat every 6 weeks.

Regimen 2: Give by continuous IV infusion over 1 hour. 20mg/m2 once daily for 5 days; repeat every 4 weeks. Both: dose adjustment based on hematology values: see literature. Non-hematologic toxicities (eg, serum creatinine ≥2mg/dL; SGPT, total bilirubin ≥ 2 X ULN; active or uncontrolled infection): do not restart until toxicity resolved.

Children: Not recommended.

Warnings/Precautions: Renal or hepatic impairment. Obtain CBC and platelet counts before each dosing cycle and as needed. Monitor hepatic function (do baseline liver chemistries and serum creatinine). Pregnancy (Cat.D); use appropriate contraception (both men and women). Nursing mothers: not recommended.

Adverse reactions: Neutropenia, thrombocytopenia, anemia, leukopenia, fatigue, pyrexia, nausea, cough, petechiae, constipation, diarrhea, hyperglycemia.

How supplied: Single-use vial—1

DARZALEX Janssen Biotech

℞

CD38-directed monoclonal antibody.

Daratumumab 100mg/5mL, 400mg/20mL; per vial; soln for IV infusion after dilution; contains mannitol; preservative-free.

Indications: Treatment of multiple myeloma in patients who have received ≥3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are doublerefractory to a PI and an immunomodulatory agent.

Adults: Premedicate with IV corticosteroid, oral antipyretic, oral or IV antihistamine 1 hour prior to every infusion; and give oral corticosteroid on

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER the 1st and 2nd day after all infusions. Give only as IV infusion. 16mg/kg weekly on Weeks 1–8, every 2 weeks on Weeks 9–24, then every 4 weeks on Week 25 onwards until disease progression.

Infusion rates and modifications for infusion reactions: see full labeling. Prophylaxis for herpes zoster reactivation: initiate antiviral prophylaxis within 1 week of starting therapy and continue for 3 months after treatment.

Children: Not established.

Warnings/Precautions: Should be administered by a healthcare professional with immediate access to emergency equipment and appropriate medical support. Monitor for infusion reactions; interrupt treatment for infusion reactions of any severity. Permanently discontinue if lifethreatening (Grade 4) infusion reactions occur; for Grade 1, 2, or 3 reactions, reduce the infusion rate when restarting the infusion. History of obstructive pulmonary disorders: may require additional post-infusion drugs; consider prescribing shortor long-acting bronchodilators and inhaled corticosteroids. Interference with cross-matching and RBC antibody screening; type/screen patients prior to initiating treatment. Moderate-to-severe hepatic impairment. Pregnancy. Females of reproductive potential should use effective contraception during treatment and for 3 months after. Nursing mothers.

Interactions: Interferes with Indirect Antiglobulin (Coombs) Test, serum protein electrophoresis and immunofixation assays leading to false (+) results.

Adverse reactions: Infusion reactions, fatigue, nausea, back pain, pyrexia, cough, upper respiratory tract infection.

How supplied: Single-dose vial—1

DEPOCYT Sigma-Tau

℞

Antimetabolite. Cytarabine 50mg/vial; liposomal suspension for intrathecal administration; preservative-free.

Indications: Intrathecal treatment of lymphomatous meningitis.

Adults: See literature. Give intrathecally over 1–5 minutes. Administer dexamethasone 4mg twice daily for 5 days with each cycle of treatment.

Induction: 50mg every 14 days for 2 doses (weeks 1 and 3). Consolidation: 50mg every 14 days for 3 doses (weeks 5, 7 and 9) followed by 1 additional dose at week 13. Maintenance: 50mg every 28 days for 4 doses (weeks 17, 21, 25 and 29). Reduce dose to 25mg if neurotoxicity develops and discontinue if it persists.

Children: Not recommended.

Contraindications: Active meningeal infection.

Warnings/Precautions: Chemical arachnoiditis; reduce symptoms with dexamethasone. Previous irradiation, cytotoxic chemotherapy. Monitor blood counts and for development of neurotoxicity. Renal and hepatic impairment. Pregnancy (Cat.D); avoid use.

Nursing mothers: not recommended.

Interactions: Increased risk of neurotoxicity with concomitant cranial/spinal irradiation or other intrathecal antineoplastics.

Adverse reactions: See literature. Arachnoiditis, GI upset, headache, fever, neurological toxicity (myelopathy), hydrocephalus, elevated CSF protein and WBC, weakness, back pain, insomnia, blurred vision, anaphylactic reactions; others.

How supplied: Single-use vials (5mL)—1

DOXIL Janssen Biotech

℞

Anthracycline. Doxorubicin HCl (liposomal) 2mg/mL; dispersion for IV infusion after dilution; preservative-free.

Indications: Multiple myeloma, in combination with bortezomib, in patients not previously treated with bortezomib and who have received at least one prior therapy.

Adults: Give by IV infusion at initial rate of 1mg/min; may increase rate to complete infusion over 1hr if no infusion reactions occur; may premedicate with antiemetics. 30mg/m2 on day 4 of each cycle following bortezomib (see full labeling for bortezomib dose); may treat for up to 8 cycles. Hepatic dysfunction (serum bilirubin ≥1.2mg/dL), hand-foot syndrome, hematologic toxicity (esp. ANC, platelets), or stomatitis: reduce dose. Consider total anthracycline and anthracenedione doses and irradiation when calculating total cumulative dose. See full labeling.

Children: Not established.

Warnings/Precautions: Not substitutable on a mg/mg basis with other doxorubicin products. Cardiotoxicity, acute infusion-related reactions, myelosuppression may occur. Have resuscitative/antiallergic equipment and expertise available. Hepatic impairment. Monitor blood (esp. CBC + platelets), hepatic (esp.

SGOT/SGPT, alkaline phosphatase), and cardiac function (esp. myocardial biopsy). Monitor periodically for secondary oral cancers with longterm use. Avoid extravasation. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended.

Interactions: Caution with cyclosporine, phenobarbital, phenytoin, streptozocin, digoxin, myelosuppressants, others. Previous mediastinal irradiation, cyclophosphamide, other cardiotoxic drugs: monitor for cardiotoxicity and hepatotoxicity.

Adverse reactions: Asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand and foot syndrome, rash, neutropenia, thrombocytopenia, anemia; infusion reactions, cardiovascular events (eg, cardiomyopathy, CHF, acute LV failure), recall of skin reaction from prior radiation therapy, toxoplasmosis, urine discoloration (red/orange).

How supplied: Single-use vials (10mL, 25mL)—1

EMPLICITI Bristol-Myers Squibb

℞

SLAMF7-directed immunostimulatory antibody.

Elotuzumab 300mg, 400mg; per vial; lyophilized pwd for IV infusion after reconstitution; preservative-free.

Indications: In combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received 1–3 prior therapies.

Adults: Give by IV infusion at initial rate of 0.5mL/min; may increase stepwise if no reactions develop; max rate 2mL/min. After 4 cycles, infusion rate may be increased up to max 5mL/min. Administer with lenalidomide and dexamethasone (see full labeling for dosing schedule). 10mg/kg every week for the first 2 cycles then every 2 weeks thereafter; continue until disease progression or unacceptable toxicity. Premedicate with dexamethasone, H1 blocker, H2 blocker, and acetaminophen before each infusion. Dose modifications: see full labeling.

Children: Not established.

Contraindications: Consult lenalidomide and dexamethasone prescribing information for contraindications before starting therapy.

Warnings/Precautions: Interrupt infusion if Grade ≥2 infusion reactions occur and manage appropriately. Monitor for development of infections and treat promptly. Monitor for second primary malignancies. Monitor liver function periodically; discontinue if Grade ≥3 elevation of liver enzymes occur; consider resuming after return to baseline values. Pregnancy: not studied.

Nursing mothers: not recommended.

Interactions: May interfere with correct response classification in SPEP and serum immunofixation assays.

Adverse reactions: Fatigue, diarrhea, pyrexia, constipation, cough, peripheral neuropathy, nasopharyngitis, upper respiratory tract infection, decreased appetite, pneumonia.

Note: For lenalidomide and dexamethasone specific dosing and safety information, refer to the respective full prescribing labels.

How supplied: Single-dose vial—1

Access Cancer Therapy Advisor treatment regimens in a user-friendly format.

CancerTherapyAdvisor.com/TreatmentRegimens.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER ERWINAZE Jazz

℞

Asparagine-specific enzyme. Asparaginase Erwinia chrysanthemi 10,000 IU; per vial; lyophilized pwd for IM or IV inj after reconstitution.

Indications: As a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coliderived asparaginase.

Adults and Children: Give by IM inj (max 2mL/inj site) or IV (infuse over 1hr). To substitute for a pegaspargase dose: 25,000 IU/m2 three times weekly (M/W/F) for 6 doses for each planned pegaspargase dose. To substitute for a native E. coli asparaginase dose: 25,000 IU/m2 for each scheduled native E. coli asparaginase dose within a treatment. When IV use: consider monitoring nadir serum asparaginase activity (NSAA) levels; switch to IM inj if levels are inadequate.

Contraindications: History of serious pancreatitis, thrombosis, hemorrhagic events with prior L-asparaginase therapy.

Warnings/Precautions: Have resuscitation equipment available and other agents necessary to treat anaphylaxis. Discontinue if serious hypersensitivity reactions occur. Monitor for pancreatitis; discontinue if severe or hemorrhagic pancreatitis manifested by abdominal pain >72hrs and amylase elevation ≥2XULN occurs.

Withhold therapy if mild pancreatitis; may resume after resolution. Monitor glucose levels at baseline and during therapy. Discontinue if thrombotic or hemorrhagic event occurs; may resume after resolution. Pregnancy (Cat.C). Nursing mothers: not recommended.

Adverse reactions: Systemic hypersensitivity, hyperglycemia, abnormal transaminases, fever, pancreatitis, local reactions, vomiting, nausea, thrombosis, hyperbilirubinemia, abdominal pain/discomfort, diarrhea.

How supplied: Vials (3mL)—5

EVOMELA Spectrum

℞

Alkylating agent. Melphalan HCl 50mg/vial; pwd for IV infusion after reconstitution.

Indications: High-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation in patients with multiple myeloma. Palliative treatment of multiple myeloma when oral therapy is not appropriate.

Adults: Give prophylactic antiemetics.

Conditioning treatment: Give by IV infusion over 30 minutes. 100mg/m2 daily for 2 consecutive days (Days -3 and -2) prior to transplantation (Day 0). If patient weighs >130% of their ideal body weight, use adjusted ideal body weight.

Palliative treatment: Give by IV infusion over 15–20 minutes. 16mg/m2 as a single infusion at 2-week intervals for 4 doses, then at 4-week intervals after recovery from toxicity. Renal impairment (BUN ≥30mg/dL): consider up to 50% dose reduction for palliative treatment.

Children: Not established.

Warnings/Precautions: Prior irradiation or chemotherapy. Severe bone marrow suppression. Monitor CBCs during treatment; provide supportive care for infections, anemia, thrombocytopenia until adequate recovery. GI toxicity; provide supportive care. Monitor LFTs. Renal impairment. Embryo-fetal toxicity; use effective contraception during and after treatment.

Pregnancy, nursing mothers: not recommended.

Interactions: Caution with cyclosporine, BCNU, nalidixic acid.

Adverse reactions: Decreased neutrophil, WBC, lymphocyte, and platelet counts, diarrhea, nausea, fatigue, hypokalemia, anemia, vomiting; hypersensitivity reactions, hepatic disorders, secondary malignancies, infertility.

How supplied: Single-dose vial (20mL)—1

FARYDAK Novartis

℞

Histone deacetylase inhibitor. Panobinostat 10mg, 15mg, 20mg; caps.

Indications: Multiple myeloma, in patients who have received at least two prior therapies (including bortezomib and an immunomodulatory agent), in combination with bortezomib and dexamethasone.

Adults: Swallow whole with water. Take at same time on scheduled days. Initially 20mg once every other day for 3 doses/wk in Weeks 1 and 2 of each 21-day cycle for up to 8 cycles. Consider 8 more cycles for patients with clinical benefit if no severe or significant toxicity; max 16 cycles (48 wks).

Give with bortezomib inj and oral dexamethasone per scheduled day. Hepatic impairment: mild: initially 15mg; moderate: initially 10mg; severe: avoid. Concomitant strong CYP3A inhibitors: initially 10mg. Dose adjustments and modifications for toxicity: see full labeling.

Children: Not established.

Warnings/Precautions: Risk of severe diarrhea and cardiac toxicities. Monitor hydration and electrolytes at baseline, weekly during therapy, or more as indicated. Initiate antidiarrheals at onset of diarrhea; interrupt dose if 4–6 stools/day. Do not initiate if history of recent MI or unstable angina, QTcF >450msec, significant baseline ST-segment or T-wave abnormalities, active infections. Perform ECG prior to initiation and repeat during treatment as indicated. Correct electrolyte abnormalities prior to initiation and monitor; interrupt if QTcF ≥480msec; discontinue if QT prolongation does not resolve. Serious hemorrhage. Obtain CBC prior to initiation; monitor weekly during therapy or more as indicated. Monitor for infections; treat and consider interruption or discontinuation if diagnosed. Monitor liver function prior to and during treatment; consider dose adjustments if abnormal tests observed. ESRD or dialysis: not studied. Elderly: monitor for toxicity more frequently (esp. GI, myelosuppression, cardiac).

Embryo-fetal toxicity. Pregnancy: avoid. Obtain pregnancy test prior to and during treatment. Use effective contraception during and for ≥3 months

after last dose; males: use condoms during and for ≥6 months after last dose. Nursing mothers: not recommended.

Interactions: Potentiated by strong CYP3A inhibitors (eg, boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, others); see Adults. Avoid star fruit, pomegranate or grapefruit juice. Avoid concomitant strong CYP3A inducers. Avoid concomitant sensitive CYP2D6 substrates (eg, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine) or substrates with narrow therapeutic index (eg, thioridazine, pimozide); if unavoidable, monitor frequently. Concomitant antiarrhythmics or QT prolonging drugs: not recommended.

Antiemetics that prolong QT interval (eg, dolasetron, ondansetron, tropisetron): monitor ECG frequently.

Adverse reactions: Diarrhea, fatigue, nausea, peripheral edema, decreased appetite, pyrexia, vomiting, electrolyte imbalance, increased creatinine, thrombocytopenia, lymphopenia, leukopenia, neutropenia, anemia.

How supplied: Blister packs—6

FLUDARA Genzyme

℞

Antimetabolite. Fludarabine phosphate 50mg/vial; lyophilized pwd for IV infusion after reconstitution and dilution; preservative-free; contains mannitol.

Indications: B-cell chronic lymphocytic leukemia (CLL) in patients who have not responded to or whose disease progressed during treatment with at least 1 alkylating-agent containing regimen.

Adults: Give by IV infusion over 30 minutes.

25mg/m2 daily for 5 days every 28 days. Renal dysfunction (CrCl 30–70mL/min): reduce dose by 20%; CrCl <30mL/min: not recommended. Give for 3 cycles after the max response. Reduce or delay dose if toxicity occurs.

Children: Not recommended.

Warnings/Precautions: Myelosuppression.

Evaluate and monitor for hemolysis. Monitor blood (esp CBC, platelets). Use irradiated blood products if transfusions are required. May need to prophylax for tumor lysis syndrome with large tumors. Renal insufficiency. Delay or stop therapy if neurotoxicity occurs. Elderly. Pregnancy (Cat.D); avoid use.

Nursing mothers: not recommended.

Interactions: Severe pulmonary toxicity with pentostatin (not recommended).

Adverse reactions: Myelosuppression (severe/cumulative), bone marrow hypoplasia, autoimmune hemolytic anemia (fatal/severe), infection, fever, chills, GI upset, malaise, fatigue, CNS effects (eg, weakness, agitation, confusion, visual disturbances, coma, peripheral neuropathy), pneumonia, pulmonary hypersensitivity (eg, dyspnea, interstitial pulmonary infiltrate), stomatitis, GI bleeding, edema, tumor lysis syndrome, rash, hemorrhagic cystitis (rare); others.

How supplied: Single-dose vials—5

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER GAZYVA Genentech

℞

Cytolytic monoclonal antibody (CD20-directed).

Obinutuzumab 25mg/mL; soln for IV infusion after dilution; preservative-free.

Indications: In combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL).

In combination with bendamustine followed

by Gazyva monotherapy, for the treatment of patients with follicular lymphoma (FL) who relapsed after, or are refractory to, a rituximabcontaining regimen.

Adults: See full labeling. Premedicate (eg, glucocorticoid, APAP, antihistamine) before each infusion. Provide prophylactic hydration and antihyperuricemics to those at high risk of TLS. Give by IV infusion for 6 treatment cycles (28 days duration). CLL: Cycle 1: 100mg on Day 1 at 25mg/hr over 4 hours; 900mg on Day 2 at 50mg/hr, can increase at 50mg/hr every 30mins to max 400mg/hr; 1000mg on Days 8 and 15 at 100mg/hr if no infusion reaction occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr; Cycles 2–6: 1000mg on Day 1 at 100mg/hr if no infusion reaction occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr. FL: Cycle 1: 1000mg on Day 1 at 50mg/hr, can increase at 50mg/hr every 30mins to max 400mg/hr; 1000mg on Days 8 and 15 at 100mg/hr if no infusion reaction occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr; Cycles 2–6: 1000mg on Day 1 at 100mg/hr if no infusion reaction occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr; followed by Gazyva monotherapy: 1000mg every 2 months for 2 years at 100mg/hr if no infusion reaction occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr. Management of infusion reactions, premedication: see full labeling.

Children: Not established.

Warnings/Precautions: Risk of hepatitis B virus (HBV) reactivation; immediately discontinue and any concomitant chemotherapy if occurs.

Screen for HBV infection prior to initiation; if positive evidence, monitor and consider antiviral therapy. Discontinue treatment and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressives if progressive multifocal leukoencephalopathy (PML) develops. Monitor closely for infusion reactions; if Grade 4: discontinue permanently; if Grade 3: interrupt until resolved; if Grade 1 or 2: interrupt or reduce the infusion rate and manage symptoms.

Preexisting cardiac or pulmonary conditions:

monitor more frequently during and post-infusion period for severe reactions. Risk of TLS in high tumor burden, high circulating lymphocyte count (>25 × 109/L), or renal impairment.

Active infection: do not administer. Risk of neutropenia; monitor for signs of infection. Severe or prolonged neutropenia, give antimicrobial prophylaxis until resolved to Grade 1 or 2; consider antiviral and antifungal prophylaxis. Monitor for thrombocytopenia and hemorrhagic events esp. during the 1st cycle; obtain blood and platelet counts frequently; transfusion of blood products may be necessary. Hepatic or renal impairment (CrCl <30mL/min). Pregnancy; risk of fetal B-cell depletion. Nursing mothers.

Interactions: Concomitant live viral vaccines: not recommended during treatment and until B-cell recovery (esp. neonates/infants if exposed to Gazyva in utero). Consider withholding antihypertensives for 12hrs prior to, during, and for 1hr after infusion until BP is stable. Consider withholding drugs that may increase bleeding risk (eg, platelet inhibitors, anticoagulants) esp. during 1st cycle.

Adverse reactions: Infusion reactions, neutropenia, thrombocytopenia, anemia, pyrexia, cough, nausea, diarrhea; HBV reactivation, PML, TLS, infections.

How supplied: Single-use vial (40mL)—1

GLEEVEC Novartis

℞

Kinase inhibitor. Imatinib (as mesylate) 100mg, 400mg; scored tabs.

Indications: Philadelphia-chromosome (+) chronic myeloid leukemia (CML): in newly-diagnosed adults and children in chronic phase; in patients in blast crisis, accelerated phase, or chronic phase after failure of interferon-alpha therapy. Adults with relapsed or refractory Ph (+) acute lymphoblastic leukemia (ALL). Children with newly diagnosed Ph+ ALL in combination with chemotherapy.

Adults with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor) gene rearrangements. Adults with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown.

Adults: Take with food and water. May disperse tab in water or apple juice and take promptly. ≥18yrs: Chronic phase CML: 400mg once daily; may increase to 600mg if clinically indicated.

Accelerated phase or blast crisis: 600mg once daily; may increase to 800mg (given as 400mg twice daily) if clinically indicated.

Relapsed/refractory Ph+ ALL: 600mg once daily.

MDS/MPD: 400mg once daily. HES/CEL: 400mg once daily. HES/CEL w. FIP1L1-PDGFRα fusion kinase: initially 100mg once daily; may increase to 400mg once daily if insufficient response.

If severe non-hematologic reactions develop: interrupt dose; resume at a lower dose in hepatic dysfunction. Severe hepatic impairment: reduce dose by 25%. Renal or hematologic reactions: see full labeling. Avoid concomitant strong CYP3A4 inducers (eg, rifampin): if needed, increase imatinib dose by at least 50%.

Children: Take with food and water in 1 or 2 divided doses; may disperse tab in water or apple juice and take promptly. <1yrs: not recommended. ≥1yrs: Newly diagnosed Ph+CML: 340mg/m2 per day (max 600mg). Newly diagnosed Ph+ALL: 340mg/m2 per day (max 600mg); give with chemotherapy. If severe nonhematologic reactions develop: interrupt dose; resume at a lower dose in hepatic dysfunction.

Renal or hematologic reactions: see full labeling.

Avoid concomitant strong CYP3A4 inducers (eg, phenytoin): if needed, increase imatinib dose by at least 50%; monitor closely.

Warnings/Precautions: Hepatic or renal impairment. Monitor weight and for fluid retention regularly; CBCs weekly for 1st month, bi-weekly for 2nd month, then periodically (eg, every 2–3 months); liver function at baseline then monthly or as needed; GI symptoms at baseline.

Cardiovascular disease or risk factors; monitor.

Immunosuppression and potential toxicities (liver, kidney, cardiac) from long-term use. Monitor for tumor lysis syndrome; correct clinically significant dehydration and treat high uric acid levels before initiating therapy. Monitor growth in children. Possible cardiogenic shock/LV dysfunction in conditions with high eosinophil levels (eg, HES/CEL, MDS/MPD, ASM); consider concomitant systemic steroid prophylaxis (1–2mg/kg) for 1 or 2 wks if abnormal ECG or serum troponin. Monitor TSH levels in thyroidectomy patients undergoing levothyroxine replacement. Pregnancy (Cat.D); avoid. Use highly effective contraception during treatment. Nursing mothers: not recommended.

Interactions: Avoid grapefruit juice. Potentiated

by CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, nefazodone, clarithromycin, telithromycin). Antagonized by strong CYP3A4 inducers (eg, dexamethasone, fosphenytoin, phenytoin, phenobarbital, carbamazepine, oxcarbamazepine, primidone, St. John’s wort, rifampin, rifabutin, rifampicin); consider alternatives. May potentiate drugs metabolized

by CYP3A4 (eg, benzodiazepines, dihydropyridine calcium channel blockers, cyclosporine, ergots, alfentanil, fentanyl, pimozide, quinidine, certain

Take advantage of our free online medical calculators at CancerTherapyAdvisor.com/MedicalCalculators.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER statins, sirolimus, tacrolimus), CYP2D6, or CYP2C9 (use heparin instead of warfarin).

Adverse reactions: Edema (may be severe), nausea, vomiting, musculoskeletal pain, diarrhea, muscle cramps, rash (may be severe; eg, erythema multiforme, Stevens-Johnson syndrome), fatigue, abdominal pain, dizziness, blurred vision, somnolence, fever, headache, cough, arthralgia/myalgia, dyspnea, hypokalemia, night sweats, anorexia, pruritus, hemorrhage, anemia, neutropenia, thrombocytopenia, weight gain, renal or hepatotoxicity, immunosuppression, hypothyroidism; rare: severe CHF, LV dysfunction.

Testing considerations: BCR-Abl t(9;22) in Ph+CML patients How supplied: 100mg—90; 400mg—30

HYDREA Bristol-Myers Squibb

℞

Antimetabolite. Hydroxyurea 500mg; caps.

Indications: Resistant chronic myeloid leukemia.

Adults: Base dose on ideal or actual weight, whichever is less. Individualize. Initially 15mg/kg/day. Renal impairment (CrCl <60mL/min or ESRD): initially 7.5mg/kg/day; give dose following dialysis (monitor). Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Risk of severe myelosuppression; reduce dose or discontinue if necessary. Monitor blood counts at baseline and at least once a week during therapy. Correct severe anemia before starting. Markedly depressed bone marrow function: do not initiate. Monitor for malignancies. Avoid sun exposure. Previous irradiation therapy (monitor for skin erythema) or chemotherapy. Macrocytosis may mask folic acid deficiency; prophylactic folic acid is recommended.

Myeloproliferative disorders; discontinue if cutaneous vasculitic ulcerations occur. Renal or hepatic impairment. Elderly. Embryo-fetal toxicity.

Pregnancy; avoid. Exclude pregnancy prior to initiating; use effective contraception during and for ≥6 months (females) or ≥1 year (males) after therapy. Nursing mothers: not recommended.

Interactions: Avoid concomitant didanosine, with or without stavudine, or other antiretrovirals (may cause pancreatitis [monitor], fatal hepatotoxicity, peripheral neuropathy). Avoid live vaccines. Increased risk of vasculitic toxicities with interferon therapy. May cause falsely elevated results in urea, uric acid, and lactic acid assays.

Adverse reactions: Leukopenia, thrombocytopenia, anemia, GI upset, anorexia; secondary malignancies, macrocytosis.

Note: Wear disposable gloves when handling caps or bottle.

How supplied: Caps—100

ICLUSIG ARIAD Kinase inhibitor. Ponatinib 15mg, 30mg, 45mg; tabs; contains lactose.

Indications: Treatment of adults with T315Ipositive chronic, accelerated, or blast phase

℞

chronic myeloid leukemia (CML) or T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Treatment of adults with chronic, accelerated, or blast phase CML or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated.

Limitations of use: not for treating patients with newly diagnosed chronic phase CML. Adults: Swallow whole. ≥18yrs: initially 45mg once daily; consider reducing dose in chronic and accelerated phase CML if major cytogenic response achieved. Consider discontinuing if no response occurred by 3 months. Concomitant strong CYP3A inhibitors or hepatic impairment: reduce to 30mg once daily. Dose modification for hematologic and non-hematologic toxicity: see full labeling.

Children: <18yrs: not established.

Warnings/Precautions: Risk of vascular occlusion (eg, arterial and venous thrombosis, fatal MI, stroke, stenosis of arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures) in patients with or without CV risk factors (including ≤50yrs old, or increasing age, history of ischemia, HTN, diabetes, hyperlipidemia); monitor and interrupt or discontinue if occurs. Monitor for signs/symptoms of heart failure; interrupt or consider discontinuing if develops or worsens.

Monitor hepatic function at baseline, then at least monthly or as needed; interrupt, reduce or discontinue as clinically indicated. Monitor and manage BP elevations; interrupt, reduce dose or discontinue if not controlled; evaluate for renal artery stenosis if significant worsening, labile or treatment-resistant hypertension occurs. Risk of pancreatitis; check serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated; do not restart until complete resolution and lipase levels <1.5XULN. Increased toxicity in newly diagnosed chronic phase CML: not recommended. Monitor for neuropathy; consider interrupting and evaluate if suspected.

Conduct eye exams at baseline and periodically during treatment. Interrupt therapy and evaluate for serious/severe hemorrhage or cardiac arrhythmias. Monitor for fluid retention; interrupt, reduce, or discontinue as indicated. Obtain CBCs every 2 weeks for the first 3 months, then monthly or as indicated. Tumor lysis syndrome; ensure adequate hydration and treat uric levels prior to therapy. Compromised wound healing (withhold for 1 week prior to major surgery) and GI perforation.

Elderly. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended.

Interactions: Potentiated by strong CYP3A inhibitors (eg, boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole); see Adult dose. Avoid concomitant strong CYP3A inducers (eg, carbamazepine, rifampin, phenytoin, St. John’s Wort). Caution with concomitant drugs

that elevate gastric pH (eg, PPIs), P-gp and ABCG2 substrates.

Adverse reactions: Hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, pyrexia, anemia, thrombocytopenia, leukopenia, neutropenia, lymphopenia; vascular occlusion, heart failure, hepatotoxicity, ocular toxicities, hemorrhage, myelosuppression.

How supplied: Tabs 15mg—30, 60, 180; 30mg— 30; 45mg—30, 90

IDAMYCIN Pfizer

℞

Anthracycline. Idarubicin HCl 20mg/vial; lyophilized pwd for IV infusion after reconstitution. ℞ Also: IDAMYCIN PFS Idarubicin 1mg/mL; soln for IV infusion; preservative-free.

Indications: Acute myeloid leukemia.

Adults: Give by slow IV infusion (over 10–15 mins). 12mg/m2 daily for 3 days (in combination with cytarabine). May give 2nd course if needed; if toxicity develops after 1st course, delay until resolved; reduce dose by 25%. Hepatic and renal impairment: consider reduce dose.

Children: Not established.

Warnings/Precautions: Pre-existing bone marrow suppression. Cardiovascular disease.

Thoracic irradiation. Previous anthracycline therapy at high cumulative doses. Renal or hepatic impairment. Monitor CBCs, cardiac, renal and hepatic function prior to and during treatment.

Avoid extravasation. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended.

Interactions: Concomitant drugs that suppress cardiac contractility or cardiotoxic drugs (eg, trastuzumab, cyclophosphamide, paclitaxel): not recommended; avoid use for 5 half-lives after discontinuing cardiotoxic drug.

Adverse reactions: Myelosuppression, GI upset, mucositis, abdominal pain, alopecia, rash, inj site reactions, hepatotoxicity, renal toxicity, cardiotoxicity (eg, CHF, arrhythmias, chest pain, MI, asymptomatic declines in LVEF), hyperuricemia.

How supplied: Single-dose vials—1; PFS: Singledose vials (5mL, 10mL, 20mL)—1

IMBRUVICA

℞

Pharmacyclics and Janssen Biotech

Bruton’s tyrosine kinase (BTK) inhibitor. Ibrutinib 140mg; caps.

Indications: Mantle cell lymphoma (MCL) in patients who have received at least one prior therapy. Chronic lymphocytic leukemia (CLL).

CLL in patients with 17p deletion. Waldenstrom’s macroglobulinemia (WM).

Adults: Swallow whole with water. MCL: 560mg once daily. CLL and WM: 420mg once daily.

Concomitant moderate CYP3A inhibitors: 140mg once daily. Mild hepatic impairment (Child-Pugh Class A): 140mg once daily. Dose modifications for toxicities: see full labeling.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER Children: Not established.

Warnings/Precautions: Risk of hemorrhage; consider the benefit/risk of withholding treatment for 3–7 days pre-and post-surgery. Monitor for fever and infections; evaluate promptly if occurs. Monitor for myelosuppression; obtain CBCs monthly. Periodically monitor for atrial fibrillation (esp. in those with cardiac risk factors, acute infections, history of atrial fibrillation); do ECG if arrhythmic symptoms or new onset dyspnea develop. Monitor for new onset or uncontrolled hypertension; adjust and/or initiate anti-hypertensives as appropriate. Risk of second primary malignancies (eg, skin cancer or other carcinomas). Monitor for tumor lysis syndrome in patients at risk (eg, high tumor burden). Moderate or severe hepatic impairment: not recommended.

Maintain adequate hydration. Pregnancy; avoid during and for 1 month after treatment cessation.

Nursing mothers: not recommended.

Interactions: Concomitant strong CYP3A inhibitors taken chronically (eg, ritonavir, indinavir, nelfinavir, saquinavir, boceprevir, telaprevir, nefazodone): not recommended; for shortterm (≤7days) use of strong CYP3A inhibitors (eg, ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin); consider interrupting ibrutinib therapy. If concomitant moderate CYP3A inhibitors must be used (eg, fluconazole, darunavir, erythromycin, diltiazem, atazanavir, aprepitant, amprenavir, fosamprevir, crizotinib, imatinib, verapamil, ciprofloxacin): reduce ibrutinib dose (see Adults). Avoid grapefruit and Seville oranges during treatment. Avoid concomitant strong CYP3A inducers (eg, carbamazepine, rifampin, phenytoin, St. John’s Wort); consider alternatives.

Increased risk of hemorrhage with concomitant antiplatelets or anticoagulants; monitor.

Adverse reactions: Thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, peripheral edema, upper respiratory tract infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, vomiting, decreased appetite, pyrexia, cough.

How supplied: Caps—90, 120

INTRON A Merck

℞

Alpha interferon. Interferon alfa-2b, recombinant; 10 million, 18 million, or 50 million IU per vial; pwd; for inj after reconstitution/dilution; preservativefree; contains albumin. ℞ Also: INTRON A SOLN Interferon alfa-2b, recombinant; 10 million IU, 18 million IU, 25 million IU; per vial; for inj; contains m-cresol.

Indications: Hairy cell leukemia. Initial treatment of clinically aggressive follicular Non-Hodgkin’s lymphoma in conjunction with anthracyclinecontaining combination chemotherapy.

Adults: Use SC route if platelets <50,000/mm3.

Hairy cell leukemia: 2 million IU/m2 IM or SC 3 times a week for up to 6 months. Follicular lymphoma: 5 million IU SC 3 times a week for up to 18 months in conjunction with anthracyclinecontaining chemotherapy regimen and following completion of the chemotherapy regimen. See literature for appropriate preparation and route and for dose adjustments.

Children: Not recommended.

Contraindications: Decompensated liver disease. Autoimmune hepatitis.

Warnings/Precautions: May cause or exacerbate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, or infectious disorders: monitor closely, discontinue if they worsen.

Severe psychiatric disorders (esp. depression).

Cardiovascular or pulmonary disease. Severe myelosuppression; discontinue if neutrophil count <0.5 X109/L or platelets 25X109/L. Permanently discontinue if severe (Grade 3) hepatic injury or decompensation (Child-Pugh score >6 [Class B and C]) develop. Thyroid abnormalities; discontinue if uncontrolled by medication. Diabetes. Coagulation disorders. Maintain adequate hydration. Monitor blood, thyroid, visual and liver function before and during therapy; EKG in cardiovascular disease and cancer patients. Psoriasis. Renal dysfunction.

Transplant recipients. Elderly. Debilitated. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Caution with myelosuppressives, and drugs that can exacerbate depression. May potentiate theophylline (may double its levels).

Adverse reactions: Flu-like symptoms (fever, headache, myalgia, fatigue); hepatic, hematologic, respiratory, skin, genitourinary system, CNS, cardiovascular, endocrine (esp. thyroid), GI, or visual disorders; colitis, hypertriglyceridemia, pancreatitis, infections, injection site reactions, dental and periodontal disorders; others (see full labeling).

How supplied: Pwd (w. diluent): 10million, 18million, 50million IU/vial—1; Soln (multidose vials): 18million, 25million IU/vial—1

ISTODAX Celgene

℞

Histone deacetylase inhibitor. Romidepsin 10mg/vial; pwd for IV infusion after reconstitution and dilution; contains povidone.

Indications: Cutaneous T-cell lymphoma in patients who have received at least one prior systemic therapy. Peripheral T-cell lymphoma in patients who have received at least one prior therapy.

Adults: ≥18yrs: Give by IV infusion over 4hrs.

14mg/m2 on days 1, 8, and 15 of a 28-day cycle; repeat cycle every 28 days; continue as tolerated and as beneficial. May interrupt, reduce dose to 10mg/m2, or discontinue based on toxicities (see full labeling).

Children: <18yrs: not established.

Warnings/Precautions: Increased risk of serious infections (eg, pneumonia, sepsis, Epstein Barr, HBV). Prior history of hep B infection; consider monitoring for reactivation and give antiviral prophylaxis. Correct electrolyte imbalances (esp. K+, Mg++) before starting. Monitor ECG and electrolytes in congenital long QT syndrome, significant cardiovascular disease. Advanced stage disease and/or high tumor syndrome: monitor closely for tumor lysis syndrome. Moderateto-severe hepatic impairment. End-stage renal disease. Monitor CBC with differential. Pregnancy (Cat.D; may cause fetal harm). Nursing mothers: not recommended.

Interactions: Caution with other drugs that can cause QT prolongation (monitor). Monitor PT/INR with warfarin. Potentiated by drugs that inhibit P-gp and CYP3A4; avoid concomitant strong CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, clarithromycin, telithromycin, nefazodone). Caution with moderate CYP3A4 inhibitors. Avoid concomitant rifampin. May be antagonized by other strong CYP3A4 inducers (eg, dexamethasone, carbamazepine, phenytoin, phenobarbital, rifabutin, rifapentine, St. John’s Wort); avoid when possible.

Adverse reactions: Neutropenia, lymphopenia, thrombocytopenia, anemia, nausea, vomiting, fatigue, infections, anorexia, ECG T-wave changes; tumor lysis syndrome.

How supplied: Kit—1 (single-use vial + diluent and supplies)

JAKAFI Incyte

℞

Kinase inhibitor. Ruxolitinib 5mg, 10mg, 15mg, 20mg, 25mg; tabs.

Indications: Treatment of intermediate or highrisk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis.

Treatment of polycythemia vera (PV) in patients with inadequate response to, or intolerant of, hydroxyurea.

Adults: Doses may be given by NG tube if unable to swallow tabs. Myelofibrosis: Platelets >200X109/L: initially 20mg twice daily. Platelets 100–200X109/L: initially 15mg twice daily.

Platelets 50–<100X109/L: initially 5mg twice daily.

May increase doses by 5mg twice daily to a max

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER of 25mg twice daily; do not increase during the first 4 weeks of therapy and not more frequently than every 2 weeks. Discontinue treatment after 6 months if no reduction in spleen size or symptom improvement. Interrupt treatment if platelets <50X109/L or ANC <0.5X109/L. May restart after recovery of platelets or ANC (see full labeling for max allowable restarting doses).

Consider dose reductions if platelets decrease but remain ≥50X109/L (see full labeling). Dose modifications for patients starting treatment with platelets 50–<100X109/L: see full labeling.

PV: initially 10mg twice daily. May increase doses by 5mg twice daily to a max of 25mg twice daily; do not increase during the first 4 weeks of therapy and not more frequently than every 2 weeks. Consider dose reductions for Hgb and/or platelet decreases (see full labeling). Interrupt treatment if Hgb <8g/dL, platelets <50X109/L, or ANC <1.0X109/L. May restart after recovery of hematologic parameters (see full labeling for max allowable restarting doses). Concomitant strong CYP3A4 inhibitors (see Interactions) or fluconazole ≤200mg (Myelofibrosis): initially 10mg twice daily if platelets ≥100X109/L; if platelets 50–<100X109/L: initially 5mg once daily; (PV): initially 5mg twice daily. Other reductions, hepatic or renal impairment, ESRD: see full labeling.

Children: Not established.

Warnings/Precautions: Monitor for thrombocytopenia, anemia, neutropenia; manage by reducing dose, interrupt, or transfusion if occur. Obtain CBC and platelets before initiating therapy, every 2–4 weeks until doses are stabilized, and then as clinically indicated.

Risk of serious bacterial, mycobacterial, fungal, and viral infections; evaluate and treat if signs/symptoms occur. Confirm resolution of active infections before starting. May exacerbate myelofibrosis following treatment interruption or discontinuation. Risk of non-melanoma skin cancer; perform periodic skin exams. Increases in lipid parameters including total-C, LDL, triglycerides; assess 8–12 weeks after starting and treat if hyperlipidemia develops. Avoid abrupt cessation. Renal or hepatic impairment. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Avoid concomitant fluconazole doses >200mg daily. Potentiated by strong CYP3A4 inhibitors (eg, boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) and mild or moderate CYP3A4 inhibitors (eg, erythromycin).

Antagonized by strong CYP3A4 inducers (eg, rifampin).

Adverse reactions: Thrombocytopenia, anemia, bruising, dizziness, headache; herpes zoster, tuberculosis (monitor promptly and test for latent infection), progressive multifocal leukoencephalopathy (discontinue if occurs), Hepatitis B. How supplied: Tabs—60

KYPROLIS Amgen

℞

Proteasome inhibitor. Carfilzomib 30mg/vial, 60mg/vial; lyophilized pwd for IV inj after reconstitution; preservative-free.

Indications: In combination with dexamethasone or lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received 1–3 lines of therapy. As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received ≥1 lines of therapy.

Adults: See full labeling. Hydrate prior to and following administration as needed. Premedicate with dexamethasone prior to all Cycle 1 doses, during subsequent cycles, and if infusion reactions occur. Give by IV on two consecutive days each week for 3 weeks (Days 1, 2, 8, 9, 15, and 16), followed by a 12-day rest period (Days 17–28).

Lenalidomide/dexamethasone combination: Infuse over 10 mins. In Cycle 1: initially 20mg/m2 per dose on Days 1 and 2; if tolerated increase to 27mg/m2 on Day 8 and subsequent cycles. From Cycle 13, omit the Day 8 and 9 doses. Discontinue carfilzomib after Cycle 18. See full labeling for lenalidomide and dexamethasone dosing. Dexamethasone combination: Infuse over 30 mins. In Cycle 1: initially 20mg/m2 per dose on Days 1 and 2; if tolerated increase to 56mg/m2 on Day 8 and subsequent cycles. Monotherapy: initially 20mg/m2 per dose in Cycle 1 on Days 1 and 2; if tolerated increase to 27mg/m2 on Day 8 (by 10-min infusion regimen) or 56mg/m2 on Day 8 (by 30-min infusion regimen) and continue same dose for subsequent cycles.

From Cycle 13, omit the Day 8 and 9 doses. All: continue until disease progression or unacceptable toxicity occurs. On dialysis: give dose after session.

Toxicity dose modification: see full labeling.

Children: Not established.

Warnings/Precautions: Monitor for signs/symptoms of cardiac failure or ischemia; evaluate promptly if toxicity is suspected.

Increased risk of cardiac complications in patients with NYHA Class III and IV heart failure, recent MI, conduction abnormalities, angina, uncontrolled arrhythmias; do full medical assessment prior to starting. Pulmonary hypertension; if suspected, withhold therapy until resolved; may consider restarting after reevaluation. Discontinue if pulmonary toxicity occurs. Monitor for dyspnea or tumor lysis syndrome (TLS), and manage promptly if occurs; interrupt therapy until resolved.

Maintain adequate hydration. Monitor for volume overload. Monitor platelets frequently during therapy. Evaluate signs/symptoms of blood loss; reduce or withhold dose as appropriate. Monitor for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS); discontinue and evaluate if suspected. Discontinue and evaluate if posterior reversible encephalopathy syndrome (PRES) is suspected. Monitor BP, renal function, liver enzymes, electrolytes (eg, potassium) regularly; reduce or withhold dose as needed. Renal or hepatic impairment. Give thromboprophylaxis

for combination therapy. Consider antiviral prophylaxis to prevent herpes zoster reactivation.

Elderly (≥75yrs). Embry-fetal toxicity. Use effective contraception during and for ≥30 days (females) or ≥90 days (males) after therapy completion.

Pregnancy; avoid. Nursing mothers.

Interactions: Increased risk of thrombosis with oral or hormonal contraceptives; consider alternatives during combination therapy.

Adverse reactions: Anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper RTI, hypokalemia, nausea, headache, peripheral edema; cardiac events, pulmonary HTN, acute kidney injury, infusion reactions, hemorrhage, TLS, hepatic toxicity/failure, TTP/HUS, PRES. How supplied: Single-use vial—1

LEUKERAN GlaxoSmithKline

℞

Alkylating agent. Chlorambucil 2mg; tabs.

Indications: Palliative treatment of chronic lymphatic (lymphocytic) leukemia and malignant lymphomas (including lymphosarcoma, giant follicular lymphoma, and Hodgkin’s disease).

Adults: See literature. 0.1–0.2mg/kg per day for 3–6 weeks. Reduce dose if leukocyte or platelet counts fall below normal values and discontinue if more severe depression occurs. Do not give full dose within 4 weeks of radio- or chemotherapy.

Children: Not recommended.

Warnings/Precautions: Compromised bone marrow function. History of seizure disorder or head trauma. Monitor blood weekly (during first 3–6 weeks, do WBC count 3–4 days after each weekly CBC). Discontinue if skin reactions occur.

Elderly. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Avoid live vaccines.

Myelosuppressives, radiotherapy potentiate antineoplastic effect. Caution with drugs that lower seizure threshold.

Adverse reactions: Bone marrow suppression, seizures, fever, rash, hypersensitivity, urticaria, azoospermia, amenorrhea, sterility, hepato- and pulmonary toxicity, secondary malignancies, GI upset.

How supplied: Tabs—50

MARQIBO Spectrum

℞

Vinca alkaloid. Vincristine sulfate liposome injection; after preparation, each vial contains 0.16mg/mL; for IV infusion.

Indications: Philadelphia chromosome-negative (Ph–) acute lymphoblastic leukemia (ALL) in second or greater relapse or has progressed following ≥2 anti-leukemia therapies.

Adults: 2.25mg/m2 IV over 1hr once every 7 days.

Dose modifications for peripheral neuropathy: see full labeling.

Children: Not established.

Contraindications: Demyelinating conditions, including Charcot-Marie-Tooth syndrome.

Intrathecal administration (death has occurred).

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER Warnings/Precautions: For IV use only; fatal if given by other routes. Discontinue and treat if extravasation is suspected. Preexisting neuromuscular disorders. Monitor for symptoms of neuropathy before and during therapy; if occurs or worsens, delay, reduce or discontinue dose.

Monitor CBCs prior to each dose; if Grade 3 or 4 myelosuppression develops, consider dose modification or reduction. Monitor for tumor lysis syndrome; manage if occurs. Institute a prophylactic bowel regimen to mitigate potential constipation, bowel obstruction, and/or paralytic ileus; consider dietary fiber intake, hydration, stool softeners.

Monitor liver function tests; if hepatotoxicity occurs, reduce or interrupt dosing. Elderly. Pregnancy (Cat. D); avoid. Nursing mothers: not recommended.

Interactions: Drugs known to interact with non-liposomal vincristine sulfate (eg, phenytoin: increased seizure risk). Avoid concomitant strong CYP3A inhibitors (eg, ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin) or strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s Wort). Avoid concomitant potent P-gp inhibitors or inducers.

Adverse reactions: Constipation, nausea, pyrexia, fatigue (may be severe; adjust dose or discontinue), peripheral neuropathy, febrile neutropenia, diarrhea, anemia, decreased appetite, insomnia.

How supplied: Kit—1, 3 (vials + supplies)

MUSTARGEN Recordati

℞

Alkylating agent. Mechlorethamine HCl 10mg/vial; pwd for IV or intracavitary inj after reconstitution.

Indications: Palliative treatment of Hodgkin’s disease (stages III and IV), lymphosarcoma, chronic myelocytic or chronic lymphocytic leukemia, polycythemia vera, mycosis fungoides.

Palliative treatment of metastatic carcinoma resulting in effusion.

Adults: By IV infusion, per therapeutic course: 0.4mg/kg (lean body weight) as single dose or in divided doses of 0.1–0.2mg/kg per day.

See literature for intracavitary (eg, intrapleural) administration. Do not exceed recommended dose. Repeat course only after hematological recovery (eg, every 3 weeks).

Children: See literature.

Contraindications: Infectious diseases.

Warnings/Precautions: Drug is highly toxic; verify potential benefits outweigh risks; avoid inadvertent contact with powder or vapor. Do

not use if foci of acute and chronic suppurative inflammation are present. Ensure adequate hydration. Avoid extravasation. Chronic lymphatic leukemia. Bone marrow suppression. Previous X-ray, cytotoxic chemotherapy. Infection.

Hemorrhagic tendency. Monitor renal, hepatic and bone marrow function. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended.

Adverse reactions: Bone marrow suppression, hyperheparinemia, GI upset (may be severe), anorexia, weakness, thrombosis, thrombophlebitis, hypersensitivity, jaundice, alopecia, vertigo, auditory disturbances, hemolytic anemia, skin reactions, infection, amyloidosis, hyperuricemia, gonad damage.

How supplied: Vials—4

MYLERAN GlaxoSmithKline

℞

Alkylating agent. Busulfan 2mg; tabs.

Indications: Palliative treatment of chronic myelogenous leukemia.

Adults: Remission induction: 4–8mg/day or 60micrograms/kg or 1.8mg/m2, daily. Reserve doses >4mg/day for severe cases. Reduce dose or discontinue at first sign of reduced bone marrow reserve. Discontinue before leukocyte count normalizes; see literature. Normal leukocyte counts usually achieved in 12–20 weeks. If remission <3 months, maintenance therapy of 1–3mg/day may be advisable.

Children: Remission induction: 60micrograms/kg or 1.8mg/m2, daily. Reduce dose or discontinue at first sign of reduced bone marrow reserve. Discontinue before leukocyte count normalizes. Normal leukocyte counts usually achieved in 12–20 weeks. See literature.

Warnings/Precautions: Confirm diagnosis.

Monitor hepatic and bone marrow function.

Obtain CBCs and differential weekly; monitor for anemia. Previously compromised bone marrow (irradiation, chemotherapy). Seizure disorder or risk. Head trauma. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Myelosuppression increased with other myelosuppressives. Increased pulmonary toxicity with other cytotoxic drugs. Potentiated by itraconazole, cyclophosphamide (see literature). May be antagonized by phenytoin. Hepatotoxicity possible with long-term continuous thioguanine therapy.

Caution with drugs that lower seizure threshold.

Adverse reactions: See literature. Bone marrow suppression (eg, pancytopenia, anemia, leukopenia, thrombocytopenia, aplastic anemia), pulmonary toxicity, cellular dysplasia, malignant tumors, acute leukemias, cardiac tamponade (esp. in thalassemia), hyperpigmentation, adrenal

insufficiency, seizures, hepatic veno-occlusive disease, infection (eg, pneumonia, sepsis), mucositis, myasthenia gravis, gonadal suppression, rash; rare: cataracts, bronchopulmonary dysplasia (discontinue if occurs).

How supplied: Tabs—25

NINLARO Takeda

℞

Proteasome inhibitor. Ixazomib 2.3mg, 3mg, 4mg; gel caps.

Indications: In combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least 1 prior therapy.

Adults: Swallow whole. Take ≥1hr before or ≥2hrs after food. Initially 4mg once weekly on Days 1, 8, and 15 of a 28-day cycle; continue until disease progression or unacceptable toxicity. Give with lenalidomide 25mg daily on Days 1–21 and dexamethasone 40mg on Days 1, 8, 15, and 22. Moderate or severe hepatic impairment, severe renal impairment, or ESRD on dialysis: initially 3mg. Prior to new cycle, ensure ANC ≥1,000/mm3, platelets ≥75,000/mm3, recovery of non-hematologic toxicities to baseline or Grade ≤1. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Thrombocytopenia: monitor platelets at least monthly during treatment; consider more frequently for first 3 cycles. Adjust dose for Grade 3/4 GI symptoms or Grade ≥2 rash. Monitor for peripheral neuropathy; adjust dose if worsens. Adjust dosing of dexamethasone or ixazomib if Grade 3/4 peripheral edema symptoms occur. Hepatic impairment; monitor enzymes regularly and adjust for Grade 3/4 symptoms. Severe renal impairment or ESRD. Pregnancy; avoid. Males and females of reproductive potential must use effective contraception during therapy and for 90 days after final dose. Nursing mothers: not recommended.

Interactions: Avoid concomitant strong CYP3A inducers (eg, rifampin, phenytoin, carbamazepine, St. John’s Wort).

Adverse reactions: Diarrhea, constipation, thrombocytopenia, peripheral neuropathy, nausea, peripheral edema, vomiting, back pain; rash, hepatotoxicity.

How supplied: Caps—1, 3

ONCASPAR Sigma-Tau

℞

Enzyme. Pegaspargase 750 IU/mL; soln for IV or IM inj; preservative-free.

Indications: First-line acute lymphoblastic leukemia (including patients with asparaginase hypersensitivity).

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER Adults and Children: Give by IV inj over 1–2hrs or by IM inj (max 2mL/inj site). 2500 IU/m2 no more frequently than every 14 days.

Contraindications: History of pancreatitis, serious hemorrhage, or thrombosis with prior L-asparaginase therapy.

Warnings/Precautions: Have resuscitation equipment available and observe patient for 1hr postdose. Monitor coagulation parameters. Discontinue if serious allergic reactions, thrombotic events, or pancreatitis occurs. Monitor for hepatotoxicity and abnormal liver function. Pregnancy (Cat.C). Nursing mothers: not recommended.

Adverse reactions: Allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, CNS thrombosis, coagulopathy, hyperbilirubinemia, hepatotoxicity, elevated transaminases, hyperlipidemia.

How supplied: Single-use vial (5mL)—1

ONTAK Eisai

℞

Interleukin 2-diphtheria toxin fusion protein.

Denileukin diftitox 150mcg/mL; soln for IV infusion after thawing and dilution.

Indications: Persistent or recurrent cutaneous T-cell lymphoma in which malignant cells express the CD25 component of the IL-2 receptor.

Adults: Premedicate with an antihistamine or acetaminophen prior to each infusion. Give by IV infusion over 30–60 minutes. 9 or 18mcg/kg per day for 5 consecutive days every 21 days for 8 cycles.

Children: Not recommended.

Warnings/Precautions: Ensure CD25 expression before starting therapy. Have resuscitative equipment available during administration. Permanently discontinue if serious infusion reactions occur. Monitor for signs/symptoms of capillary leak syndrome (hypotension, edema, hypoalbuminemia) and weight gain. Monitor serum albumin levels prior to each treatment course; withhold treatment if serum albumin <3g/dL. Pregnancy (Cat.C).

Nursing mothers: not recommended.

Adverse reactions: Fever, fatigue, rigors, GI upset, headache, edema, cough, dyspnea, pruritus, rash, hypotension, back pain, myalgia, chest pain, tachycardia, hypoalbuminemia, asthenia, elevated transaminases; capillary leak syndrome (may be fatal), serious infusion reactions, visual impairment (monitor).

Testing considerations: CD25 expression How supplied: Single-use vials (2mL)—6

OPDIVO Bristol-Myers Squibb

℞

Human programmed death receptor-1 (PD-1)blocking antibody. Nivolumab 10mg/mL; per vial; soln for IV infusion after dilution; preservativefree; contains mannitol.

Indications: Classical Hodgkin lymphoma (cHL) that relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin.

Adults: Give as IV infusion over 60mins.

3mg/kg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: See full labeling. Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for any life-threatening (Grade 4) adverse reaction, Grade 3 or 4 pneumonitis, Grade 3/4 or recurrent colitis (with ipilimumab), Grade 4 or recurrent colitis (as single agent), AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash (or confirmed SJS or TEN), immune-mediated encephalitis, recurring Grade 3 adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2 or 3 adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2 or 3 (as single agent) colitis, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN, Grade 2 or 3 hypophysitis, Grade 2 adrenal insufficiency, Grade 3 hyperglycemia, Grade 3 rash (or suspected SJS or TEN), new onset moderate-to-severe neurologic symptoms, other Grade 3 adverse reactions (1st occurrence); withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if mild or moderate infusion reactions occur; discontinue if severe or life-threatening.

Monitor for abnormal liver tests, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism. Monitor for transplantrelated complications (eg, hyperacute or Grade 3/4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease) and treat promptly. Moderate or severe hepatic impairment: not studied. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for ≥5 months after final dose. Pregnancy (esp. during 2nd & 3rd trimesters), nursing mothers: not recommended.

Adverse reactions: Fatigue, upper RTI, pyrexia, diarrhea, cough; immune-mediated reactions (may be fatal).

How supplied: Single-use vial (4mL, 10mL)—1

POMALYST Celgene

℞

Immunomodulator. Pomalidomide 1mg, 2mg, 3mg, 4mg; caps.

Indications: In combination with dexamethasone for multiple myeloma, in patients who have received at least two prior therapies (including lenalidomide and a proteasome inhibitor), and have shown disease progression on or within 60 days of completion of the last therapy.

Adults: Swallow whole; may be taken with water (with or without food). 4mg once daily on Days 1–21 of repeated 28-day cycles until disease progression; give with dexamethasone.

Concomitant strong CYP1A2 inhibitors: consider alternatives, if necessary, reduce Pomalyst dose by 50%. Severe renal impairment requiring dialysis: initially 3mg daily; give dose after dialysis session on hemodialysis days. Hepatic impairment (mild or moderate): initially 3mg daily; (severe): 2mg daily. Dose modification for hematologic and other Grade 3/4 toxicities: see full labeling.

Children: <18yrs: not established.

Contraindications: Pregnancy (Cat.X): avoid during and for at least 4 weeks after completing therapy.

Warnings/Precautions: Females of reproductive potential must commit either to abstain from heterosexual sex or to use two methods of reliable contraception, beginning 4 weeks prior to initiating, during therapy, dose interruptions and for 4 weeks after discontinuation. Obtain two negative pregnancy tests prior to initiating therapy: perform first test within 10–14 days, and second test within 24hrs prior to prescribing, and then weekly during first month, then monthly thereafter in women with regular menstrual cycles or every 2 weeks if irregular cycles. Males: must use latex or synthetic condom during therapy and up to 28 days after discontinuing, even after successful vasectomy; do not donate sperm. Patients must not donate blood during therapy and for 1 month after discontinuation.

Venous and arterial thromboembolism; consider anticoagulation prophylaxis. Monitor for hematologic toxicities (esp. neutropenia); obtain CBCs weekly for first 8 weeks and monthly thereafter; may need dose interruption and/or modification. Hepatic or severe renal impairment on hemodialysis: adjust doses (see Adults).

Monitor LFTs monthly; discontinue and evaluate if elevated liver enzymes occur; consider using lower dose when restarting. Risk of second primary malignancies. High tumor burden (monitor).

Discontinue if angioedema, skin exfoliation, bullae, or other severe dermatologic reactions occur; do not restart. Nursing mothers: not recommended.

Interactions: Potentiated by strong CYP1A2 (eg, ciprofloxacin, fluvoxamine), CYP3A or P-gp inhibitors (eg, ketoconazole); avoid. May be antagonized by strong CYP1A2 or CYP3A (eg, carbamazepine) inducers. Smoking may reduce efficacy.

Adverse reactions: Fatigue, asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, pyrexia; thromboembolism, dizziness, confusion, neuropathy, pneumonia, thrombocytopenia, tumor lysis syndrome.

Note: Available only through Pomalyst REMS program.

How supplied: Caps—21, 100

PURINETHOL Teva

℞

Antimetabolite. Mercaptopurine (6-MP) 50mg; scored tabs.

Indications: Maintenance therapy of acute lymphatic leukemia as part of a combination regimen.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER Adults and Children: 1.5–2.5mg/kg per day as a single dose. Concomitant allopurinol: reduce dose of mercaptopurine to 1/3–1/4 of the usual dose. TPMT-deficient, renal or hepatic impairment: reduce dose, see literature.

Contraindications: Prior resistance to mercaptopurine.

Warnings/Precautions: Not effective in CNS leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, the lymphomas (including Hodgkin’s disease), or solid tumors. Renal impairment. Monitor liver function tests weekly at start of therapy, then monthly thereafter; discontinue if hepatotoxicity occurs. Preexisting liver disease (monitor more frequently).

Obtain CBCs with differential, hemoglobin, hematocrit, platelets; discontinue if severe bone marrow suppression occurs. ThiopurineS-methyltransferase (TPMT) deficient: increased risk of myelosuppression, consider genotypic/phenotypic testing. Pregnancy (Cat. D); esp. 1st trimester, nursing mothers: not recommended.

Interactions: Increased risk of bone marrow suppression with allopurinol, aminosalicylate derivatives (eg, olsalazine, mesalazine, sulphasalazine), trimethoprim-sulfamethoxazole.

Antagonizes warfarin. Caution with concomitant hepatotoxic agents.

Adverse reactions: Myelosuppression, hyperuricemia/hyperuricosuria, GI upset, intestinal ulceration, rash, hyperpigmentation, alopecia, oligospermia; hepatotoxicity, infection, immunosuppression.

How supplied: Tabs—60

PURIXAN Rare Disease

℞

Antimetabolite. Mercaptopurine (6-MP) 20mg/mL; oral susp; contains fruit extract, aspartame.

Indications: Maintenance therapy of acute lymphoblastic leukemia as part of a combination regimen.

Adults and Children: Shake bottle vigorously for at least 30 secs. Initially 1.5–2.5mg/kg (50–75mg/m2) per day as a single dose. Monitor subsequent doses to maintain desirable ANC level and adjust for excessive hematological toxicity. Thiopurine-S-methyltransferase (TPMT)deficient: if homozygous, may require up to a 90% dose reduction; if heterozygous, some may require dose reduction based on toxicities. Renal or hepatic impairment: use lower starting doses; monitor for toxicity. See full labeling.

Warnings/Precautions: Myelosuppression; monitor CBCs and adjust dose for severe

neutropenia and thrombocytopenia. Consider testing for TPMT gene polymorphism in patients who experience repeated severe bone marrow toxicities. Monitor serum transaminase, alkaline phosphatase, and bilirubin levels at weekly intervals when starting therapy, then monthly thereafter; interrupt treatment if evidence of hepatotoxicity occurs. Concomitant other hepatotoxic drugs or with pre-existing liver disease; monitor LFTs more frequently.

Immunosuppression. Increased risk of secondary malignancies. Renal or hepatic impairment.

Elderly. Pregnancy (Cat.D); esp. 1st trimester, nursing mothers: not recommended.

Interactions: Avoid concomitant allopurinol.

Increased risk of bone marrow suppression with allopurinol, aminosalicylate derivatives (eg, olsalazine, mesalamine, sulfasalazine), trimethoprim-sulfamethoxazole. Possibly decreased effectiveness with concomitant warfarin; monitor PT or INR; may need warfarin dose adjustments. Concomitant live virus vaccines: may get suboptimal response and risk of infection.

Adverse reactions: Myelosuppression, nausea, vomiting, anorexia, diarrhea, malaise, rashes, oral lesions, elevated transaminases and bilirubin, intestinal ulceration; hepatotoxicity.

How supplied: Susp—100mL

REVLIMID Celgene

℞

Immunomodulator. Lenalidomide 2.5mg, 5mg, 10mg, 15mg, 20mg, 25mg; caps; contains lactose.

Indications: In combination with dexamethasone for treatment of patients with multiple myeloma (MM). Treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib.

Limitations of use: not for treating patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials.

Adults: Swallow whole with water. ≥18yrs: initially 25mg once daily on Days 1–21 of each 28-day cycle until disease progression or unacceptable toxicity. >75yrs: may reduce dexamethasone initial dose. Renal impairment: MCL: Moderate (CrCl 30–60mL/min): 10mg per day; MM: Moderate (CrCl 30–50mL/min): 10mg per day; consider increasing to 15mg after 2 cycles, if tolerant. Severe (CrCl <30mL/min without dialysis): 15mg every 48hrs. ESRD (CrCl <30mL/min with dialysis): 5mg once daily; administer after dialysis (on dialysis days).

Autologous stem cell transplantation (ASCT) eligible: refer for hematopoietic cell mobilization

within 4 cycles; if non-eligible, continue therapy until disease progression or unacceptable toxicity.

Dose adjustments if thrombocytopenia or neutropenia develops: see full labeling.

Children: <18yrs: not established.

Contraindications: Pregnancy (Cat. X).

Warnings/Precautions: Must register patient in Revlimid REMS program; patient must understand toxicity with fetal exposure. Counsel patient on need for contraception; females: use 2 forms of contraception 1 month before, during therapy, during dose interruptions, and 1 month after therapy; males: use condom during and 1 month after therapy; obtain 2 negative pregnancy tests (one within 10–14 days, and then another within 24hrs prior to starting therapy), repeat at least weekly for 1st month then every 4 weeks (regular menstrual cycles) or every 2 weeks (irregular cycles); get informed consent. Do not donate blood during and for 1 month after therapy. Monitor for signs/symptoms of thromboembolic events; base thromboprophylaxis on patient’s risks. For MM: obtain CBCs weekly for the first 2 cycles, on Days 1 and 15 of Cycle 3, and every 28 days thereafter; for MCL: obtain CBCs weekly for the first cycle, every 2 weeks during Cycles 2–4, and then monthly thereafter; both: dose interruption and/or reduction may be needed. May require blood product support and/or growth factors.

Renal impairment (monitor). Monitor for tumor lysis syndrome in those with high tumor burden.

Monitor liver enzymes; discontinue if elevation occurs. Monitor for second primary malignancies.

Lactose intolerance. Maximum 1 month per ℞.

Nursing mothers: not recommended.

Interactions: Monitor digoxin. Concomitant warfarin; monitor PT, INR. May increase risk of thrombosis with dexamethasone, erythropoietic agents, or estrogen containing therapies.

Adverse reactions: Birth defects, thrombocytopenia, neutropenia, anemia, leukopenia, constipation, diarrhea, nausea, vomiting, pruritus, rash, fatigue, arthralgia, pyrexia, back pain, cough, dizziness, headache, dyspnea, nasopharyngitis, epistaxis, upper respiratory tract infection, tremor, blurred vision, muscle cramp, decreased appetite, peripheral edema; thrombosis/embolism, allergic reactions (discontinue if occurs; do not resume), tumor flare reaction (monitor; esp. in treating MCL), hepatotoxicity.

Note: Available only through Revlimid REMS program. Report any suspected fetal exposure to the FDA at (800) FDA-1088 and Celgene at (888) 423-5436.

How supplied: Caps 2.5mg, 5mg, 10mg—28, 100; 15mg, 20mg, 25mg—21, 100

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER RITUXAN Genentech

℞

CD20-directed cytolytic monoclonal antibody.

Rituximab 10mg/mL; soln for IV infusion; preservative-free.

Indications: Relapsed or refractory, low-grade or follicular, CD20(+), B-cell non-Hodgkin’s lymphoma (NHL). Previously untreated follcular, CD20(+), B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to Rituxan in combination with chemotherapy, as singleagent maintenance therapy. Non-progressing (including stable disease), low-grade, CD20(+), B-cell NHL as a single agent after first-line CVP chemotherapy. Previously untreated diffuse large B-cell, CD20(+) NHL (DLBCL) in combination with CHOP or other anthracycline-based chemotherapy regimens. CD20(+) chronic lymphocytic leukemia (CLL) in combination with fludarabine and cyclophosphamide. Limitation of use: not recommended for use in patients with severe, active infections.

Adults: Give by IV infusion. Premedicate with an antihistamine and acetaminophen prior to each infusion. First infusion: initially at a rate of 50mg/hr; may increase infusion rate in 50mg/hr increments every 30 mins. Subsequent infusions: initially at a rate of 100mg/hr; may increase infusion rate in 100mg/hr increments every 30 mins. Both: max 400mg/hr if infusion reactions do not occur. Previously untreated follicular NHL and DLBCL patients: if no Grade 3 or 4 infusion related adverse events during Cycle 1, a 90-minute infusion may be given in Cycle 2 with a glucocorticoid-containing chemotherapy regimen (see full labeling).

NHL: 375mg/m2 once weekly for 4 or 8 doses.

Retreatment therapy: 375mg/m2 once weekly for 4 doses. Previously untreated, follicular, CD20(+), B-cell NHL: 375mg/m2 on day 1 of each cycle of CVP chemotherapy for up to 8 doses. In patients with complete or partial response, initiate Rituxan maintenance 8 weeks following completion of Rituxan in combination with chemotherapy.

Administer Rituxan as a single-agent every 8 weeks for 12 doses. Low-grade, CD20(+), B-cell NHL after CVP chemotherapy: 375mg/m2 once weekly for 4 doses every 6 months for up to 16 doses. Diffuse large B-cell NHL: 375mg/m2 on day 1 of each cycle for up to 8 infusions. CLL: 375mg/m2 the day prior to FC chemotherapy, then 500mg/m2 on day 1 of cycles 2–6 (every 28 days). Give PCP and antiherpetic viral prophylaxis during and up to 12 months after CLL therapy. As a component of Zevalin regimen: see full labeling.

Children: Not established.

Warnings/Precautions: Discontinue if severe infusion or mucocutaneous reactions occur (eg, urticaria, hypotension, angioedema, hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, MI, ventricular fibrillation, cardiogenic shock, paraneoplastic pemphigus, Stevens-

Johnson syndrome, lichenoid or vesiculobullous dermatitis, toxic epidermal necrolysis). Increased risk of HBV reactivation. Test/treat HBV infection prior to initiating therapy. Monitor for signs of hepatitis or HBV reactivation during and for several months after therapy; discontinue if HBV reactivation occurs. Tumor lysis syndrome (esp. with high tumor burden); monitor for renal toxicity, fluid balance, electrolyte abnormalities (correct if occurs); discontinue if SCr rises or oliguria occurs. Monitor for new-onset neurologic manifestations; discontinue if progressive multifocal leukoencephalopathy (PML) develops.

Discontinue and treat if serious infections (eg, bacterial, fungal, viral) occur. Pre-existing cardiovascular disease; monitor during and after treatment. Monitor CBCs, platelet counts during treatment, then periodically. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Live virus vaccines: not recommended. Renal toxicity with cisplatin.

Adverse reactions: Fever, chills, rigors, nausea, vomiting, diarrhea, asthenia, fatigue, headache, throat irritation, flushing, rash, pruritus, urticaria, angioedema, cough, rhinitis, bronchospasm, dizziness, myalgia, arthralgia, hypotension, hypertension, chest tightness; myelosuppression (eg, lymphopenia, neutropenia, leukopenia, anemia, thrombocytopenia), infusion reactions (may be fatal), mucocutaneous reactions (may be fatal), PML, serious infections, tumor lysis syndrome, renal toxicity, bowel obstruction/perforation, HBV reactivation with fulminant hepatitis, cardiac arrhythmias (discontinue if serious).

Testing considerations: FCGR3A genotype testing How supplied: Single-use vial (10mL, 50mL)—1

SPRYCEL Bristol-Myers Squibb

℞

Tyrosine kinase inhibitor. Dasatinib 20mg, 50mg, 70mg, 80mg, 100mg, 140mg; tabs.

Indications: Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. Chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib. Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.

Adults: Swallow whole. ≥18yrs: Chronic phase CML: 100mg once daily. Doses of up to 140mg once daily have been used. Accelerated phase CML, myeloid or lymphoid blast CML, Ph+ ALL: 140mg once daily. Doses of up to 180mg once daily have been used. Treat until disease progression or unable to tolerate. Concomitant CYP3A4 inhibitors (see Interactions): consider reducing dose. Concomitant CYP3A4 inducers (see Interactions): consider increasing dose. See full labeling for dose adjustments with toxicity.

Children: <18yrs: not established.

Warnings/Precautions: Monitor for signs/symptoms of cardiac dysfunction; treat appropriately if occur. Congenital long QT syndrome. Proarrhythmic conditions. Cumulative high-dose anthracycline therapy. Hypokalemia, hypomagnesemia; correct electrolyte imbalances before starting and during therapy. Monitor for pleural effusions. Increased risk of pulmonary arterial hypertension (PAH); evaluate for signs/symptoms of underlying cardiopulmonary disease before and during treatment; permanently discontinue if occurs. Obtain CBCs every 2 weeks for 12 weeks, then every 3 months thereafter (chronic phase CML) or weekly for the first 2 months, then monthly thereafter (advanced phase CML or Ph+ ALL). Permanently discontinue if severe skin reactions (eg, StevensJohnson syndrome) occur. Increased risk of tumor lysis syndrome in advanced stage disease and/or high tumor burden. Maintain adequate hydration. Correct uric acid levels before therapy and monitor electrolytes. Hepatic impairment.

Elderly. Pregnancy. Use effective contraception during and for 30 days after last dose. Nursing mothers: not recommended.

Interactions: Avoid potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, ritonavir, atazanavir, indinavir, nefazodone, nelfinavir, saquinavir, telithromycin, voriconazole), grapefruit juice. May be antagonized by strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital), St. John’s wort: not recommended. Separate dosing of antacids by at least 2hrs; H2 blockers, proton pump inhibitors: not recommended.

May potentiate drugs metabolized by CYP3A4 (eg, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, ergot alkaloids). Caution with concomitant anticoagulants or drugs that inhibit platelet function. Caution with antiarrhythmics or other drugs that may lead to QT prolongation.

Adverse reactions: Myelosuppression (eg, severe thrombocytopenia, neutropenia, anemia), fluid retention, diarrhea, headache, dyspnea, musculoskeletal pain, rash, fatigue, nausea, severe hemorrhage (eg, CNS, GI); QT prolongation, cardiac events, PAH, severe skin reactions.

How supplied: Tabs 20mg, 50mg, 70mg—60; 80mg, 100mg, 140mg—30

SYNRIBO Teva

℞

Protein synthesis inhibitor. Omacetaxine mepesuccinate 3.5mg/vial; lyophilized powder for SC injection after reconstitution; contains mannitol; preservative-free.

Indications: Treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKI).

Adults: Induction: 1.25mg/m2 by SC injection twice daily for 14 consecutive days every

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 28 days, over a 28-day cycle. Repeat cycles every 28 days until hematologic response achieved.

Maintenance: 1.25mg/m2 by SC injection twice daily for 7 consecutive days every 28 days, over a 28-day cycle, as long as clinically beneficial. Dose adjustments and modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Risk of myelosuppression (thrombocytopenia, neutropenia, anemia), hemorrhage (cerebral, GI). Monitor CBCs with platelets weekly during induction, initial maintenance cycles, and every 2 weeks during later cycles. Monitor glucose levels (esp. in diabetics). Avoid in poorly controlled diabetes until glycemic control is established. Elderly.

Pregnancy (Cat. D); avoid. Nursing mothers: not recommended.

Interactions: Avoid concomitant anticoagulants, aspirin, NSAIDs if platelets <50,000/microliters; may increase risk of bleeding.

Adverse reactions: Thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, lymphopenia; bleeding, hyperglycemia.

How supplied: Single-use vial—1

TABLOID GlaxoSmithKline

℞

Antimetabolite. Thioguanine 40mg; tabs; scored.

Indications: Remission induction and remission consolidation treatment of acute nonlymphocytic leukemias. Treatment of the chronic phase of chronic myelogenous leukemia (see literature).

Adults and Children: See literature. Initially, 2mg/kg per day. If, after 4 weeks, with no improvement, no leukocyte or platelet depression, may increase to 3mg/kg per day. Total daily dose may be given at one time.

Contraindications: Allergy to mercaptopurine.

Warnings/Precautions: Not recommended for maintenance therapy or long-term continuous treatments; increased risk of liver toxicity (discontinue if occurs). Pre-existing liver disease.

Monitor liver function tests weekly at start of therapy, then monthly thereafter. Thiopurine methyltransferase (TPMT) enzyme deficiency (may need to reduce dose to avoid severe bone marrow suppression); consider testing for TPMT deficiency. Obtain hemoglobin, hematocrit, WBCs with differential, platelets frequently during therapy. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended.

Interactions: Avoid live vaccines (if immunocompromised). Caution with drugs that inhibit TPMT (eg, olsalazine, mesalazine, or sulphasalazine).

Adverse reactions: Myelosuppression, hyperuricemia, GI upset, anorexia, stomatitis, hepatotoxicity, elevated liver enzymes, jaundice (discontinue if occurs).

How supplied: Tabs—25

TARGRETIN Valeant

℞

Retinoid. Bexarotene 75mg; caps.

Indications: Cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy.

Adults: Take with food. Initially 300mg/m2 once daily; may increase after 8 weeks to 400mg/m2 once daily if no tumor response and if well tolerated; monitor carefully. If toxicity occurs, reduce to 200mg/m2 then 100mg/m2 once daily, or suspend therapy.

Children: Not recommended.

Contraindications: Pregnancy (Cat.X).

Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Pancreatitis or risk of pancreatitis (eg, history of pancreatitis, uncontrolled hyperlipidemia, excess alcohol consumption, uncontrolled diabetes, biliary tract disease, drugs that can cause pancreatitis).

Counsel patients monthly about need for contraception. Women of childbearing potential: obtain reliable negative pregnancy test within 1 week of start; repeat monthly. Start therapy on 2nd or 3rd day of normal menstrual period. Use two effective forms of contraception 1 month prior to, during, and for 1 month after therapy. Max 1 month/℞. Men with partners who are or may become pregnant: use condoms during and for at least 1 month after therapy. Monitor lipids before treatment, weekly until stable, then every 8 weeks; try to keep triglycerides <400mg/dL; treat hyperlipidemia, or reduce or suspend bexarotene if needed. Hepatic or renal insufficiency. Monitor liver function at baseline, 1, 2, and 4 weeks after start, then (if stable) at least every 8 weeks during therapy; consider suspending or discontinuing treatment if SGOT/AST, SGPT/ALT, or bilirubin >3xULN occurs. Monitor WBC with differential and thyroid function at baseline and during treatment; treat hypothyroidism if needed. Avoid sun and UV light. Nursing mothers: not recommended.

Interactions: Concomitant gemfibrozil: not recommended. Levels may be increased by CYP3A4 inhibitors (eg, ketoconazole, itraconazole, erythromycin, grapefruit juice). Levels may be reduced by CYP3A4 inducers (eg, rifampin, phenobarbital, phenytoin). May potentiate antihyperglycemics (eg, insulin, sulfonylureas, thiazolidinediones); monitor. May potentiate or be potentiated by protein-bound drugs. May

antagonize tamoxifen, hormonal contraceptives, other CYP3A4 substrates. Limit Vit. A supplements to avoid toxicity. May increase CA125 assay values.

Adverse reactions: Lipid abnormalities, headache, hypothyroidism, asthenia, leukopenia, anemia, rash, GI disturbances, peripheral edema, dry skin, exfoliative dermatitis, alopecia, insomnia, fatigue, abnormal liver function tests, pancreatitis, pruritus, photosensitivity.

How supplied: Caps—100

TARGRETIN GEL Valeant

℞

Retinoid. Bexarotene 1%; gel.

Indications: Cutaneous lesions in patients with CTCL (Stage IA and IB) who have refractory or persistent disease after other therapies or who have not tolerated other therapies.

Adults: Apply once every other day for the 1st week; then increase frequency at weekly intervals to once daily, then twice daily, then 3 times daily, then 4 times daily based on lesion tolerance.

Usual dosing frequency: 2–4 times daily; may reduce if application site toxicity occurs. Allow gel to dry. Do not occlude.

Children: Not recommended.

Contraindications: Pregnancy (Cat.X).

Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Counsel patients monthly about need for contraception. Women of childbearing potential: obtain reliable negative pregnancy test within 1 week of start; repeat monthly. Start therapy on 2nd or 3rd day of normal menstrual period. Use two effective forms of contraception 1 month prior to, during, and for 1 month after therapy. Max 1 month/℞. Men with partners who are or may become pregnant: use condoms during and for at least 1 month after therapy. Hepatic or renal insufficiency.

Discontinue temporarily if severe irritation occurs.

Avoid sun, UV light, and mucosal membranes.

Nursing mothers: not recommended.

Interactions: Avoid concomitant products that contain DEET. May be potentiated by CYP3A4 inhibitors (eg, ketoconazole, itraconazole, erythromycin, grapefruit juice). Caution with gemfibrozil. Limit Vit. A supplements to avoid toxicity.

Adverse reactions: Application site reactions (eg, rash, pruritus, skin disorders, pain, contact dermatitis).

How supplied: Gel—60g

TASIGNA Novartis

℞

Kinase inhibitor. Nilotinib (as HCl monohydrate) 150mg, 200mg; caps; contains lactose.

Indications: Newly diagnosed adults with Philadelphia chromosome positive chronic

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER myeloid leukemia (Ph+ CML) in chronic phase.

Chronic and accelerated phase Ph+ CML in adults resistant or intolerant to imatinib.

Adults: Take on an empty stomach. Swallow whole with water; if unable, may disperse capsule contents in 1 tsp of applesauce, then take immediately (within 15 mins). Newly diagnosed Ph+ CML: 300mg every 12hrs. Hepatic impairment (mild, moderate, severe): initially 200mg twice daily, followed by dose increase to 300mg twice daily if tolerated. Resistant or intolerant Ph+ CML: 400mg every 12hrs. Hepatic impairment (mild or moderate): initially 300mg twice daily, followed by dose increase to 400mg twice daily if tolerated; severe: initially 200mg twice daily, followed by sequential dose increase to 300mg twice daily, and then 400mg twice daily if tolerated. May give concomitant hematopoietic growth factors, hydroxyurea, or anagrelide if clinically indicated. See full labeling for dose adjustments in QT prolongation, hematological and non-hematological toxicities, concomitant strong CYP3A4 inhibitors and inducers.

Children: Not established.

Contraindications: Hypokalemia.

Hypomagnesemia. Long QT syndrome.

Warnings/Precautions: Prolongs QT interval, sudden deaths have been reported; correct electrolyte abnormalities before starting; monitor. Monitor ECG at baseline, after 7 days, then periodically and after dose changes.

Cardiovascular status should be evaluated; monitor cardiovascular risk factors and actively manage during therapy. Hereditary galactose intolerance, severe lactase deficiency, glucosegalactose malabsorption: not recommended.

Hepatic impairment. History of pancreatitis.

Monitor for myelosuppression; withhold or reduce dose if occurs; perform CBCs every 2 weeks for 1st 2 months then once monthly. Monitor serum lipase, liver function monthly. Monitor lipids and glucose periodically during first year, then yearly.

Total gastrectomy (monitor frequently); consider dose increase or alternative therapy. Tumor lysis syndrome possible; maintain adequate hydration, correct uric acid levels prior to initiating therapy.

Pregnancy (Cat.D) (use adequate contraception), nursing mothers: not recommended.

Interactions: Avoid concomitant food (for at least 2hrs before and 1hr after dose), antiarrhythmics (eg, amiodarone, disopyramide, procainamide, quinidine, sotalol), or other drugs that may prolong QT interval (eg, chloroquine, haloperidol, methadone, moxifloxacin, pimozide). Avoid strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), grapefruit; if necessary, interrupt therapy or consider dose reduction of nilotinib; if unavoidable, monitor closely for QT prolongation. Avoid strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital), St. John’s wort. May affect, or be affected by, other

drugs metabolized by CYP3A4, 2B6, 2C8, 2C9, 2D6, UGT1A1, P-glycoprotein. Concomitant proton pump inhibitors: not recommended. Administer H2-blockers at least 10hrs before or 2hrs after nilotinib dose. Separate dosing of antacids by at least 2hrs of nilotinib dose.

Adverse reactions: Rash, pruritus, nausea, fatigue, headache, myalgia, nasopharyngitis, constipation, diarrhea, abdominal pain, vomiting, arthralgia, pyrexia, upper respiratory tract infection, back pain, cough, asthenia, pneumonia, febrile neutropenia, leukopenia, intracranial hemorrhage, reversible myelosuppression (thrombocytopenia, neutropenia, anemia); QT prolongation, elevated serum lipase, electrolyte disturbances (hypophosphatemia, hypo- and hyperkalemia, hypocalcemia, hyponatremia), sudden death, hepatotoxicity, cardiac and arterial vascular occlusive events, severe fluid retention (monitor).

Testing considerations: BCR-Abl t(9;22) How supplied: Blister pack (28 caps)—1, 4

THALOMID Celgene

℞

Immunomodulator. Thalidomide 50mg, 100mg, 150mg, 200mg; caps.

Indications: Newly diagnosed multiple myeloma in combination with dexamethasone. Treatment, suppression and prevention of cutaneous manifestations of erythema nodosum leprosum (ENL).

Adults: Take at bedtime, at least 1 hour after evening meal. Multiple myeloma: 200mg once daily in combination with dexamethasone in 28-day treatment cycles. ENL: initially 100–300mg/day; <50kg: start with lower dose; continue until signs/symptoms of active reaction have subsided (usually at least 2 weeks), then taper off in 50mg decrements every 2–4 weeks. Severe ENL: may start at higher doses; max 400mg/day. Moderate-tosevere neuritis with severe ENL: give concomitant corticosteroids (see full labeling). Consider dose reduction, delay, or discontinuation in those who develop NCI CTC Grade 3/4 adverse reactions.

Children: Not established.

Contraindications: Pregnancy (Cat.X). Nursing mothers. Women who may become pregnant.

Warnings/Precautions: Must register patient in STEPS program; patient must understand toxicity with fetal exposure. Counsel patient on need for contraception; female: use 2 forms of contraception 1 month before, during, and 1 month after therapy; male: use condom during and 1 month after therapy; obtain negative pregnancy test within 24 hours prior to starting treatment; repeat at least weekly for 1st month then every 4 weeks; get informed consent. Monitor for neuropathy monthly for first 3 months; discontinue if symptoms develop.

Monitor for signs/symptoms of thromboembolic events, neutropenia, bradycardia, syncope, orthostatic hypotension, tumor lysis syndrome.

Reevaluate if ANC <750/mm2; consider withholding if neutropenia persists. Monitor blood and platelet counts. Monitor for signs/symptoms of bleeding including petechiae, epistaxis, and GI bleed.

Measure HIV viral load after 1st and 3rd months, and every 3 months thereafter. Discontinue if pregnancy or severe skin rash occurs. History of seizure. Avoid contact with non-intact capsule or powder content.

Maximum 1 month per ℞.

Interactions: Increased sedative effect with barbiturates, alcohol, chlorpromazine, reserpine. Caution with drugs associated with peripheral neuropathy. Avoid drugs (eg, rifampin, carbamazepine, St. John’s wort) that decrease effectiveness of hormonal contraceptives.

Increased risk of thromboembolism with concomitant erythropoietic agents, or estrogencontaining therapies in those receiving thalidomide with dexamethasone.

Adverse reactions: Fatigue, birth defects, somnolence, skin rash (eg, Stevens-Johnson Syndrome, toxic epidermal necrolysis), headache, bradycardia, peripheral neuropathy, seizures, drowsiness, dizziness, orthostatic hypotension, leukopenia, anorexia, nausea, anxiety, asthenia, tremor, fever, weight loss, dry skin, neutropenia, increased HIV viral load, constipation, confusion, hypocalcemia, edema, dyspnea, thrombosis/embolism, thrombocytopenia.

Note: Available only through STEPS program.

Suspected fetal exposure must be reported to the FDA at (800) FDA-1088 and Celgene at (888) 423-5436.

How supplied: Blister packs (50mg)—1, 28; (100mg, 150mg, 200mg)—28

TREANDA Teva

℞

Alkylating agent. Bendamustine HCl 25mg, 100mg; per vial; lyophilized pwd for IV infusion after reconstitution; preservative-free.

Indications: Chronic lymphocytic leukemia (CLL). Indolent B-cell non-Hodgkin’s lymphoma (NHL) that has progressed during or within 6 months of treatment with rituximab or a rituximab–containing regimen.

Adults: CLL: Give by IV infusion over 30mins.

100mg/m2 on Days 1 and 2 of a 28-day cycle, up to 6 cycles. Hematologic toxicity (≥Grade 3): reduce dose to 50mg/m2 on Days 1 and 2 of each cycle; if toxicity recurs, reduce dose to 25mg/m2 on Days 1 and 2. Non-hematologic toxicity (clinically significant ≥Grade 3): reduce dose to 50mg/m2 on Days 1 and 2 of each cycle. Subsequent cycles: may consider dose re-escalation. NHL: Give by IV infusion over 60mins. 120mg/m2 on Days 1 and 2 of a 21-day cycle, up to 8 cycles. Hematologic toxicity (Grade 4) or non-hematologic toxicity (≥Grade 3): reduce dose to 90mg/m2 on Days 1 and 2 of each cycle; if toxicity recurs, reduce dose to 60mg/m2 on Days 1 and 2. Delay treatment for Grade 4 hematologic toxicity or clinically significant ≥Grade 2 non-hematologic toxicity. Severe renal impairment (CrCl <40mL/min) or moderate to severe hepatic impairment: not recommended.

Children: Not established.

Warnings/Precautions: Myelosuppression; monitor CBCs including leukocytes, platelets, hemoglobin, neutrophils frequently; restart

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER treatment based on ANC and platelet count recovery. Monitor for signs of infection or reactivation of infections (eg, hepatitis B, CMV, tuberculosis, herpes zoster); prophylaxis and treat prior to therapy if occur. Monitor for infusion or skin reactions, tumor lysis syndrome. Renal or hepatic impairment. Avoid extravasation. Pregnancy (Cat.D); avoid during and for 3 months after therapy cessation. Nursing mothers: not recommended.

Interactions: May be potentiated CYP1A2 inhibitors (eg, fluvoxamine, ciprofloxacin) or antagonized by CYP1A2 inducers (eg, omeprazole, smoking); if needed, consider alternatives.

Adverse reactions: Lymphopenia, anemia, leukopenia, thrombocytopenia, neutropenia, pyrexia, nausea, vomiting, fatigue, diarrhea, constipation, anorexia, cough, headache, weight loss, dyspnea, stomatitis, increased bilirubin, increased AST/ALT; infection, infusion reactions (discontinue if severe), tumor lysis syndrome, skin reactions (if severe or progressive, withhold dose or discontinue), other malignancies (eg, myelodysplastic syndrome, acute myeloid leukemia, bronchial carcinoma).

How supplied: Single-use vial—1

TREXALL Teva

℞

Folic acid antagonist. Methotrexate sodium 5mg, 7.5mg, 10mg, 15mg; scored tabs. ℞ Also: Methotrexate injection Bedford Methotrexate 25mg/mL; soln for IV, IM, intraarterial, or intrathecal administration after dilution; preservative-free. ℞ Also: Methotrexate for injection Bedford Methotrexate 1g/vial; pwd for IV, IM, intra-arterial, or intrathecal administration after dilution; preservative-free.

Indications: Prophylaxis and treatment of meningeal leukemia. Advanced mycosis fungoids (cutaneous T cell lymphoma). Advanced nonHodgkin’s lymphomas.

Adults: See literature. Tablet form is often preferred when low doses are being administered. Leukemia: Induction: 3.3mg/m2 + prednisone, given daily; maintenance: give twice weekly either orally or by IM inj for a total weekly dose of 30mg/m2; or 2.5mg/kg IV every 14 days. Meningeal leukemia (treatment): 12mg/m2 intrathecally (max 15mg) at intervals of 2–5 days; see literature for prophylaxis treatment.

Burkitt’s tumor (stage I–II): 10–25mg per day orally for 4–8 days. Lymphosarcomas (stage III): 0.625– 2.5mg/kg daily. Mycosis fungoides (cutaneous T cell lymphoma): 5–50mg once weekly.

Children: See literature.

Contraindications: Pregnancy (Cat. X). Nursing mothers.

Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Discontinue if malignant lymphomas occur. Obtain baseline and monitor CBCs with differential, platelet counts, chest X-ray, and hepatic, renal and pulmonary function. During therapy monitor hematology monthly, renal and hepatic function every 1–2 months, more often if increasing dose or predisposed to toxicity (eg, dehydration).

Discontinue immediately if blood counts drop significantly. Rule out pregnancy in women of childbearing potential; use effective contraception during therapy and for at least 1 ovulatory cycle afterwards for women and for at least 3 months afterwards for men. Interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur. Hepatic or renal impairment. Obesity. Diabetes. Peptic ulcer.

Ulcerative colitis. Infection. Dehydration. Folate deficiency. Ascites, pleural effusions: evacuate fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated.

Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin, sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, nonabsorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy. Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin).

Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, StevensJohnson syndrome).

How supplied: Tabs—30; soln (2mL, 4mL, 8mL, 10mL)—10 (single-use vials); pwd (1 gram)—1 (single-use vial)

TRISENOX Teva

℞

Antineoplastic. Arsenic trioxide 1mg/mL; soln for IV inj after dilution; preservative-free.

Indications: Induction of remission and consolidation in acute promyelocytic leukemia (APL) refractory to or relapsed from retinoid and anthracycline chemotherapy, and whose APL has the t(15;17) translocation or PML/RAR-alpha gene expression.

Adults: Give by IV infusion over 1–2 hours; may extend infusion up to 4 hours if acute vasomotor symptoms occur. Induction: 0.15mg/kg per day until bone marrow remission; max 60 doses.

Consolidation treatment (begin 3–6 weeks after completion of induction therapy): 0.15mg/kg per day for 25 doses for up to 5 weeks.

Children: See literature. <5yrs: not recommended. 5–16yrs: doses of 0.15mg/kg per day have been used.

Warnings/Precautions: Renal or hepatic dysfunction. History of torsades de pointes.

Preexisting QT interval prolongation. CHF. Monitor hematology, renal function, and electrolytes at least twice weekly, perform ECG at baseline then weekly (hospitalize if cardiac irregularities develop); unstable patients: monitor more frequently. Correct electrolyte imbalances before starting therapy (maintain K+ above 4mEq/dL and Mg++ above 1.8mg/dL).

Pregnancy: (Cat.D), nursing mothers: not recommended.

Interactions: Caution with drugs that can cause QT prolongation (discontinue these before starting therapy, if possible) or electrolyte imbalances.

Adverse reactions: Leukocytosis, GI upset, fatigue, edema, hyperglycemia, cough, rash, headache, dizziness, paresthesia, arthralgia, renal failure, electrolyte disorders (eg,hypokalemia, hypomagnesemia), abnormal LFTs; APL differentiation syndrome (eg, fever, dyspnea, weight gain, pulmonary infiltrates, pericardial effusion; give high-dose IV steroids at 1st sign), hyperleukocytosis, QT interval prolongation/heart block, atrial dysrhythmias, tachycardia, others (see literature).

How supplied: Single-use amps (10mL)—10

UVADEX Therakos

℞

Photoactive agent. Methoxsalen 20mcg/mL; sterile soln.

Indications: Extracorporeal administration with the UVAR Photopheresis System in the palliative treatment of skin manifestations of cutaneous T-cell lymphoma that is unresponsive to other forms of treatment.

Adults: Consult UVAR Photopheresis System Operator’s Manual before administering. Give on two consecutive days every 4 weeks for minimum of 7 treatment cycles (6 months). 200mcg per photopheresis treatment. Accelerated treatment schedule: see literature.

Children: Not recommended.

Contraindications: Idiosyncratic reactions to psoralen compounds. History of light sensitive disease. Lupus erythematosus. Porphyria cutanea tarda. Erythropoietic protoporphyria. Variegate

Visit the CTA Resource Centers at CancerTherapyAdvisor.com/Topics to view news, treatment regimens,patient fact sheets, and slideshows about a variety of cancer types.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER porphyria. Xeroderma pigmentosum. Albinism.

Aphakia.

Warnings/Precautions: Exposure to sun or UV light may cause actinic degeneration, skin burning, cataracts; wear UVA-absorbing, wraparound sunglasses and cover exposed skin (or use sunblock: SPF ≥15) for 24hrs after treatment.

Basal cell carcinomas (monitor and treat if occur). Pregnancy (Cat.D); nursing mothers: not recommended.

Interactions: Increased photosensitivity with anthralin, coal tar, griseofulvin, phenothiazines, nalidixic acid, halogenated salicylanilides, sulfonamides, tetracyclines, thiazides, organic staining dyes.

Adverse reactions: Hypotension secondary to changes in extracorporeal volume.

How supplied: Vials (10mL)—12

VALCHLOR Actelion

℞

Alkylating agent. Mechlorethamine 0.016%; topical gel; contains propylene glycol, isopropyl alcohol.

Indications: Treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy.

Adults: Apply a thin film once daily to affected areas of the skin. Apply to completely dry skin ≥4 hours before or 30 minutes after showering or washing. Allow treated areas to completely dry for 5–10 minutes after applying. Wash hands thoroughly after application. Discontinue if any grade of skin ulceration, blistering, or moderatelyto-severe, or severe dermatitis occur; restart at reduced frequency of once every 3 days upon improvement; if reintroduction is tolerated for at least 1 week, can increase to every other day for 1 week and then once daily if tolerated.

Children: Not established.

Warnings/Precautions: Mucosal (oral, nasal) or eye exposure; blindness and severe irreversible anterior eye injury may occur; immediately irrigate for ≥15 minutes with copious amounts of water. Secondary exposure; avoid direct skin contact with patient. Risk of dermatitis (eg, face, genitalia, anus, and intertriginous skin); monitor for redness, swelling, inflammation, itchiness, blisters, ulceration, and secondary skin infections.

Monitor for nonmelanoma skin cancer during and after treatment. Flammable (avoid fire and flame until gel has dried). Pregnancy (Cat.D); may cause fetal harm. Nursing mothers: not recommended.

Adverse reactions: Dermatitis, pruritus, bacterial skin infection, skin ulceration or blistering, hyperpigmentation.

How supplied: Gel—60g

VELCADE Millennium Proteasome inhibitor. Bortezomib 3.5mg/vial; lyophilized pwd for IV or SC inj after reconstitution; contains mannitol.

Indications: Multiple myeloma. Mantle cell lymphoma.

℞

Adults: Give as a 3–5 second IV bolus inj or as SC inj into thigh or abdomen (rotate sites). Previously untreated multiple myeloma: Treat for nine 6-week cycles in combination with oral melphalan and oral prednisone. Cycles 1–4: 1.3mg/m2 twice weekly (Days 1, 4, 8, 11, 22, 25, 29, 32); Cycles 5–9: 1.3mg/m2 once weekly (Days 1, 8, 22, 29).

Previously untreated mantle cell lymphoma: Treat for six 3-week cycles in combination with IV rituximab, cyclophosphamide, doxorubicin, and oral prednisone. 1.3mg/m2 twice weekly for 2 weeks (Days 1, 4, 8, 11) then 10 day rest period (Days 12–21); if response first documented at Cycle 6, two more cycles are recommended.

Relapsed multiple myeloma or mantle cell lymphoma: Standard schedule: 1.3mg/m2 twice weekly for 2 weeks (Days 1, 4, 8, 11) then 10 day rest period (Days 12–21); Extended therapy (if using >8 cycles): may use standard schedule, or maintenance schedule: 1.3mg/m2 once weekly for 4 weeks (Days 1, 8, 15, 22) then 13-day rest period (Days 23–35). Multiple myeloma patients who have previously responded to bortezomib (alone or in combination) and have relapsed at least 6 months after completing prior bortezomib therapy: may retreat starting at last tolerated dose, given twice weekly every 3 weeks (Days 1, 4, 8, 11); max 8 cycles. Allow at least 72hrs between consecutive doses. May be given as a single agent or in combination with dexamethasone.

Dose modifications: see full labeling. SC inj may be considered for patients with pre-existing or at high-risk of peripheral neuropathy. Moderate-tosevere hepatic impairment: reduce to 0.7mg/m2 in 1st cycle; may consider dose increase to 1mg/m2 or further decrease to 0.5mg/m2 in subsequent cycles based on tolerance.

Children: Not established.

Contraindications: Boron or mannitol sensitivity. Intrathecal administration.

Warnings/Precautions: Hepatic impairment.

Pre-existing severe neuropathy; treat only after careful risk-benefit assessment. Monitor for development or worsening of peripheral neuropathy; consider dose and/or schedule adjustment. Diabetes (closely monitor blood glucose). History of syncope. Avoid dehydration; give fluids and electrolytes. Heart disease (monitor for CHF). Interrupt therapy and evaluate if new or worsening cardiopulmonary symptoms develop. Monitor CBC frequently during therapy and platelets prior to each dose; adjust dose/schedule for thrombocytopenia (see full labeling). Monitor for toxicities. High tumor burden (monitor for tumor lysis syndrome).

Pregnancy (Cat.D); avoid. Nursing mothers: not recommended.

Interactions: Concomitant strong CYP3A4 inducers (eg, rifampin): not recommended; efficacy may be reduced. Avoid St. John’s Wort.

Potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir); consider reducing bortezomib dose. Caution with hypotensives and hypoglycemics.

Adverse reactions: GI toxicity (eg, nausea, diarrhea, constipation, vomiting; interrupt therapy if severe), thrombocytopenia, neutropenia, anemia, leukopenia, lymphopenia, peripheral neuropathy, fatigue, neuralgia, rash, pyrexia, anorexia, asthenia, herpes reactivation, insomnia, dyspnea, paresthesia, headache, decreased appetite, dizziness, blurred vision, edema, arthralgia, pain, dysesthesia, psychiatric disorders, cough, pruritus, orthostatic hypotension, CHF, decreased LVEF, hepatotoxicity; rare: posterior reversible encephalopathy syndrome (discontinue if occurs).

How supplied: Single-dose vial—1

VENCLEXTA AbbVie and Genentech ℞ BCL-2 inhibitor. Venetoclax 10mg, 50mg, 100mg; tabs.

Indications: Treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy.

Adults: Assess for level of tumor lysis syndrome risk; provide prophylactic hydration and antihyperuricemics prior to 1st dose. Swallow whole.

Take with food and water. Initially 20mg once daily for Week 1, then 50mg once daily for Week 2, then 100mg once daily for Week 3, then 200mg once daily for Week 4, then 400mg once daily for Week 5 and beyond until disease progression or unacceptable toxicity. Dose modifications for toxicities: see full labeling.

Children: Not established.

Contraindications: Concomitant strong CYP3A inhibitors at initiation or during dose ramp-up phase.

Warnings/Precautions: Risk of tumor lysis syndrome (esp. with high tumor burden, comorbidities, CrCl <80mL/min); perform tumor burden assessment, radiographic evaluation, blood chemistry; correct preexisting abnormalities prior to initiation. Risk of neutropenia; monitor CBCs during therapy; interrupt or reduce dose if severe. Severe renal impairment or on dialysis. Moderate or severe hepatic impairment: monitor closely.

Embryo-fetal toxicity. Females of reproductive potential: should undergo pregnancy testing prior to initiation. Pregnancy; avoid. Use effective contraception during and for ≥1 month after final dose. Nursing mothers: not recommended.

Interactions: See Contraindications.

Concomitant strong CYP3A inhibitors after ramp-up phase (eg, ketoconazole, conivaptan, clarithromycin, indinavir, itraconazole, lopinavir, ritonavir, telaprevir, posaconazole, voriconazole); avoid use or reduce venetoclax steady daily dose by ≥75%. Avoid concomitant moderate CYP3A inhibitors (eg, erythromycin, ciprofloxacin, diltiazem, dronedarone, fluconazole, verapamil) or P-gp inhibitors (eg, amiodarone, azithromycin, captopril, carvedilol, cyclosporine, felodipine, quercetin, quinidine, ranolazine, rifampin,

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER ticagrelor); consider alternatives; if inhibitor necessary, reduce venetoclax dose by ≥50% and monitor closely. Resume at prior venetoclax dose 2–3 days after discontinuing the inhibitor.

Avoid concomitant strong CYP3A inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s Wort) or moderate CYP3A inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin); consider alternatives. Avoid live attenuated vaccines until B-cell recovery. Avoid grapefruit, Seville oranges, and starfruit during treatment. Monitor INR closely with concomitant warfarin. Avoid P-gp substrates with narrow therapeutic index (eg, digoxin, everolimus, sirolimus); if necessary, take ≥6hrs before venetoclax.

Adverse reactions: Neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, fatigue.

How supplied: Starting Packs—1; Wallets 10mg—14; 50mg—7; Tabs 100mg—120

VESANOID Roche

℞

Retinoid. Tretinoin 10mg; soft gelatin caps; contain parabens.

Indications: Induction of remission in patients with acute promyelocytic leukemia (APL), French-American-British (FAB) classification M3 (including the M3 variant), characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene who are refractory to, or who have relapsed from, anthracycline chemotherapy, or for whom anthracycline-based chemotherapy is contraindicated.

Adults: Use only for induction of remission.

45mg/m2 per day in two divided doses until complete remission is documented. Discontinue 30 days after complete remission or after 90 days of treatment, whichever occurs first.

Children: See literature.

Warnings/Precautions: Confirm APL diagnosis. Monitor for Retinoic Acid-APL (RA-APL) syndrome, leukocytosis, pseudotumor cerebri, or respiratory compromise. Consider temporarily interrupting therapy if moderate to severe RA-APL syndrome develops. Monitor blood counts, coagulation profile, lipids, liver function; consider temporary withdrawal if tests >5XULN. Pregnancy (Cat.D); obtain negative pregnancy test 1 week before starting treatment, counsel patient about need to use 2 effective methods of contraception during, and 1 month after therapy. Nursing mothers: not recommended.

Interactions: Do not administer with Vitamin A. May be potentiated or antagonized by CYP450 enzyme inducers or inhibitors. Caution with

anti-fibrinolytic agents; and other agents known to cause pseudotumor cerebri/intracranial hypertension.

Adverse reactions: Headache, fever, skin/mucous membrane dryness, bone pain, GI upset, rash, mucositis, pruritus, increased sweating, visual disturbances, alopecia; RA-APL syndrome, leukocytosis, pseudotumor cerebri, hypercholesterolemia/hypertriglyceridemia, others.

How supplied: Caps—100

VIDAZA Celgene

℞

Cytidine analogue. Azacitidine 100mg/vial; lyophilized pwd for SC inj after reconstitution or IV inj after reconstitution and dilution; contains mannitol; preservative-free.

Indications: Myelodysplastic syndromes (refractory anemias, chronic myelomonocytic leukemia).

Adults: Premedicate for nausea & vomiting.

Rotate SC inj sites. Initially 75mg/m2 SC (doses >4mL divide equally into 2 syringes and inject into 2 separate sites, must administer within 1hr of reconstitution) or IV (infuse over 10–40mins, must complete within 1hr of reconstitution) daily for 7 days; repeat cycle every 4 weeks.

May increase to 100mg/m2 after 2 cycles if no response and no toxicity. Treat for at least 4–6 cycles. Adjust subsequent doses based on nadir counts, hematologic response, and toxicities (eg, neutropenia, thrombocytopenia, decreased serum bicarbonate, BUN or SCr elevation); see full labeling.

Children: Not established.

Contraindications: Advanced malignant hepatic tumors.

Warnings/Precautions: Myelosuppression.

Monitor CBCs frequently for response and/or toxicity, at a minimum, prior to each dosing cycle.

Renal or hepatic impairment. High tumor burden.

Monitor serum bicarbonate, liver chemistries, and serum creatinine prior to initiation and with each cycle. Monitor for tumor lysis syndrome and treat as appropriate. Elderly. Embryo-fetal toxicity.

Females and males of reproductive potential should use effective contraception. Pregnancy: avoid; verify status prior to initiation. Nursing mothers: not recommended.

Adverse reactions: Nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, inj site erythema, constipation, neutropenia, ecchymosis, petechiae, rigors, weakness, hypokalemia; renal failure/tubular acidosis, hepatic coma.

How supplied: Single-use vial—1

VUMON Bristol-Myers Squibb

℞

Topoisomerase inhibitor. Teniposide 10mg/mL; soln for IV infusion after dilution; contains benzyl alcohol, Cremophor EL (polyoxyethylated castor oil), dehydrated alcohol.

Indications: Refractory childhood acute lymphoblastic leukemia.

Adults and Children: See literature. Give as slow IV infusion (at least 30–60 minutes).

Patients failing induction therapy with a cytarabine-containing regimen: 165mg/m2 + cytarabine twice weekly for 8 to 9 doses.

Refractory to vincristine/prednisone-containing regimen: 250mg/m2 + vincristine weekly for 4 to 8 weeks + oral prednisone for 28 days.

Warnings/Precautions: Severe myelosuppression. Monitor for hypersensitivity reactions following infusion; have epinephrine available. Risk of hypotension with rapid IV administration. Hepatic dysfunction. Monitor and obtain CBCs with differential, hemoglobin, platelets, renal and hepatic functions before, during, and after therapy. Down syndrome (use reduced dose). Monitor children with hypoalbuminemia. Avoid extravasation.

Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended.

Interactions: Potentiated by tolbutamide, sodium salicylate, and sulfamethizole.

Concomitant vincristine sulfate may cause neuropathy. Concomitant antiemetics in patients given high doses of teniposide may increase risk of CNS depression, hypotension.

Adverse reactions: Myelosuppression (leukopenia, neutropenia, thrombocytopenia, anemia), mucositis, GI upset, infection, alopecia, bleeding, rash, fever, hypotension, CNS depression, hypersensitivity reactions (may be fatal).

How supplied: Ampules (5mL)—1

ZEVALIN Spectrum

℞

Radionuclide (B-lymphocyte-restricted differentiation antigen [CD20] inhibitor).

Ibritumomab tiuxetan 3.2mg/2mL; soln for IV inj; contains albumin; preservative-free.

Indications: B-cell non-Hodgkin’s lymphoma (relapsed or refractory, low grade or follicular).

Previously untreated follicular non-Hodgkin’s lymphoma in patients who achieve a partial or complete response to first-line chemotherapy.

Adults: See literature. Prepare In-111 Zevalin and Y-90 Zevalin as directed. Initiate Zevalin therapy after recovery of platelets to ≥150,000/mm3 at least 6 weeks, but no more than 12 weeks,

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER after the last dose of first-line chemotherapy.

Administered in two steps. Step 1: Single infusion of rituximab followed by a fixed dose of 5mCi (1.6mg total antibody dose) of In-111 Zevalin given as a 10-minute IV push. Step 2 (7–9 days after Step 1): Second rituximab infusion followed by 0.4mCi/kg of Y-90 Zevalin given as a 10-minute IV push; if platelet count 100,000– 149,000cells/mm3, reduce dose to 0.3 mCi/kg.

Do not treat if platelets <100,000cells/mm3. Max Y-90 Zevalin dose: 32mCi. Children: Not recommended.

Contraindications: Hypersensitivity to murine proteins.

Warnings/Precautions: See literature. Use only if trained in radionuclide therapy. Do not treat patients with altered biodistribution. ≥25% lymphoma marrow involvement and/or impaired bone marrow reserve (eg, prior myeloablative therapies, platelet count <100,000cells/mm3, neutrophil count <1,500cells/mm3), or history of failed stem cell collection: not recommended.

Monitor for cytopenias and complications (eg, febrile neutropenia, hemorrhage) for up to 3 months after treatment. Obtain CBCs, platelets weekly until levels recover. Avoid extravasation.

Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended.

Interactions: Caution with anticoagulants, platelet aggregation inhibitors, or live viral vaccines. Separate growth factor treatment by 2 weeks before and after Zevalin therapy.

Adverse reactions: Neutropenia, leukopenia, thrombocytopenia, anemia, infections, asthenia, musculoskeletal symptoms, GI upset, abdominal pain, fatigue, nasopharyngitis, cough, dizziness, hemorrhage, altered biodistribution; infusion reactions, severe cutaneous/mucocutaneous reactions: both may be fatal, discontinue if occurs; leukemia and myelodysplastic syndrome.

Note: Indium-11 chloride sterile solution must be ordered separately at the time the In-11 Zevalin kit is ordered. Yttrium-90 chloride sterile solution will be shipped directly upon placement of order for Y-90 Zevalin kit.

How supplied: In-111 Zevalin kit (ibritumomab tiuxetan 3.2mg/2mL vial + sodium acetate vial + formulation buffer vial + empty reaction vial)—1 Y-90 Zevalin kit (ibritumomab tiuxetan 3.2mg/2mL vial + sodium acetate vial + formulation buffer vial + empty reaction vial)—1

ZOLINZA Merck

℞

Histone deacetylase inhibitor. Vorinostat 100mg; caps.

Indications: Refractory cutaneous T-cell lymphoma.

Adults: Take with food. Swallow whole. 400mg once daily. If not tolerated, may reduce to 300mg once daily, then to 300mg once daily 5 days/week if needed. Continue until disease progression or not tolerated.

Children: <18yrs: not recommended.

Warnings/Precautions: Renal or hepatic impairment. Monitor for DVT, pulmonary embolism. Correct electrolyte disturbances before starting therapy. Maintain adequate hydration. Diabetes. Monitor CBC, platelets, blood glucose, serum creatinine, electrolytes (esp. potassium, calcium, magnesium) every 2 weeks for 1st 2 months, then monthly.

Pregnancy (Cat.D). Nursing mothers: not recommended.

Interactions: Increased risk of thrombocytopenia and GI bleed with other HDAC inhibitors (eg, valproic acid). Concomitant warfarin: monitor PT, INR. Adverse reactions: GI upset, fatigue, chills; thrombocytopenia, anemia (may need to modify dose or discontinue); anorexia, dysgeusia, pulmonary embolism, DVT, hyperglycemia.

How supplied: Caps—120

ZOMETA Novartis

℞

Bisphosphonate. Zoledronic acid 4mg/5mL concentrated soln for IV infusion after dilution; 4mg/100mL ready-to-use soln for IV infusion.

Indications: Hypercalcemia of malignancy.

Limitations of use: not established for use in hyperparathyroidism or nontumor-related hypercalcemia.

Adults: Give by IV infusion over at least 15 minutes. CrCl >60mL/min: 4mg; CrCl 50–60mL/min: 3.5mg; CrCl 40–49mL/min: 3.3mg; CrCl 30–39mL/min: 3mg; CrCl <30mL/min: see full labeling; all: every 3–4 weeks (give oral multivitamin supplement with calcium 500mg + Vit. D 400 IU daily).

Children: Not indicated.

Warnings/Precautions: Not recommended for use in patients with bone metastases with severe renal impairment. Renal or hepatic insufficiency. Check serum creatinine before each dose: withhold until serum creatinine is within 10% of baseline if serum creatinine increases by 0.5mg/dL from a normal pre-treatment level, or by 1mg/dL from an abnormal pre-treatment level, within 2 weeks of next dose. Assure adequate hydration when treating hypercalcemia of malignancy. Correct hypocalcemia before initiating treatment; supplement with calcium and vitamin D. Closely monitor electrolytes (esp. calcium, magnesium, phosphate), CBC/differential, hematocrit, hemoglobin. Evaluate if thigh or groin pain develops and consider discontinuing if atypical femur fracture is suspected. Aspirin-sensitive asthma. Avoid invasive dental surgery (do preventative dental work before therapy).

Pregnancy (Cat.D). Nursing mothers: not recommended.

Interactions: Avoid concomitant other bisphosphonates. Additive hypocalcemic effect with aminoglycosides, calcitonin, loop diuretics.

Caution with other nephrotoxic drugs.

Adverse reactions: Nausea, fatigue, anemia, musculoskeletal pain (discontinue if severe),

constipation, fever, vomiting, dyspnea, flu-like syndrome, electrolyte disturbances, hypotension, CNS effects, rigors, headache, paresthesia, renal toxicity; osteonecrosis of the jaw, atypical subtrochanteric, diaphyseal femoral fractures, severe hypocalcemia.

How supplied: Single-use vial, ready-to-use bottle—1

ZYDELIG Gilead

℞

Phosphatidylinositol 3-kinase inhibitor. Idelalisib 100mg, 150mg; tabs.

Indications: Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate due to other co-morbidities. Relapsed follicular B-cell nonHodgkin lymphoma (FL) in patients who have received at least 2 prior systemic therapies.

Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least 2 prior systemic therapies.

Adults: Swallow whole. ≥18yrs: initially 150mg twice daily; continue until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: <18yrs: not established.

Contraindications: History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis.

Warnings/Precautions: Risk of fatal/serious hepatotoxicity: monitor ALT/AST every 2 weeks for the first 3 months, every 4 weeks for the next 3 months, then every 1–3 months thereafter; if ALT/AST >3XULN, monitor weekly until resolved; if ALT/AST >5XULN, withhold and continue monitoring weekly until resolved.

Monitor for diarrhea or colitis; withhold if severe and discontinue if life-threatening. Risk of fatal/serious pneumonitis; monitor for pulmonary symptoms, interstitial infiltrates, or a decline by >5% in oxygen saturation; if suspected, interrupt or discontinue as indicated. Risk of fatal/serious intestinal perforation; discontinue permanently if occurs. Monitor for severe cutaneous or serious allergic reactions; discontinue if occur.

Monitor CBCs at least every 2 weeks for the first 3 months, and at least weekly if neutrophils <1.0Gi/L. Pregnancy (Cat.D); avoid. Use effective contraception during treatment and for at least 1 month after last dose. Nursing mothers: not recommended.

Interactions: Avoid concomitant drugs that may cause hepatotoxicity or diarrhea. Avoid concomitant strong CYP3A inducers (eg, rifampin, phenytoin, St. John’s wort, carbamazepine) or CYP3A substrates (eg, oral midazolam).

Concomitant strong CYP3A inhibitors (eg, ketoconazole); monitor for idelalisib toxicity.

Adverse reactions: Diarrhea, pyrexia, fatigue, nausea, cough, pneumonia, abdominal pain, chills, rash, neutropenia, hypertriglyceridemia, hyperglycemia, ALT/AST elevations.

How supplied: Tabs—60

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CANCER TREATMENT REGIMEN

LUNG CANCER Non-small Cell Lung Cancer Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team.

Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly.

The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy1 Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

Cisplatin + vinorelbine

Days 1 and 8: Cisplatin 50mg/m2 IV Days 1, 8, 15 and 22: Vinorelbine 25mg/m2 IV. Repeat cycle every 4 weeks for 4 cycles.

OR Day 1: Cisplatin 100mg/m2 IV Days 1, 8, 15 and 22: Vinorelbine 30mg/m2 IV. Repeat cycle every 4 weeks for 4 cycles.

OR Day 1: Cisplatin 75–80mg/m2 Days 1 and 8: Vinorelbine 25–30mg/m2.

Repeat every 3 weeks for 4 cycles.

Cisplatin + etoposide3

Day 1: Cisplatin 100mg/m2 IV Days 1–3: Etoposide 100mg/m2 IV. Repeat cycle every 4 weeks for 4 cycles.

Cisplatin + gemcitabine5

Day 1: Cisplatin 75mg/m2 IV Days 1 and 8: Gemcitabine 1,250mg/m2 IV. Repeat cycle every 3 weeks.

Cisplatin + docetaxel6

Day 1: Docetaxel 75mg/m2 IV + cisplatin 75mg/m2 IV. Repeat every 3 weeks for 4 cycles.

Cisplatin + pemetrexed7

Day 1: Cisplatin 75mg/m2 IV + pemetrexed 500mg/m2 IV.* Repeat every 3 weeks for 4 cycles.

2–4

For patients with comorbidities or patients not able to tolerate cisplatin1 Paclitaxel + carboplatin9

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks for 4 cycles.

Chemotherapy Regimens Used With Radiation Therapy (RT)1 Concurrent Chemotherapy/RT1ab Cisplatin + etoposide9,10

Days 1, 8, 29 and 36: Cisplatin 50mg/m2 IV Days 1–5 and 29–33: Etoposide 50mg/m2 IV Concurrent thoracic radiotherapy 1.8Gy/day for 5 days/week (total dose, 61Gy).

Cisplatin + vinblastine10

Days 1 and 29: Cisplatin 100mg/m2 IV Days 1, 8, 15, 22 and 29: Vinblastine 5mg/m2 IV with concurrent thoracic radiotherapy (total dose, 60Gy).

Carboplatin + pemetrexed (nonsquamous)11

Day 1: Carboplatin AUC 5mg • min/mL IV Day 1: Pemetrexed 500 mg/m2 IV with concurrent thoracic radiotherapy.

Repeat every 3 weeks for 4 cycles.

Cisplatin + pemetrexed (nonsquamous)12

Day 1: Cisplatin 75 mg/m2 IV. Day 1: Pemetrexed 500 mg/m2 IV with concurrent thoracic radiotherapy.

Repeat every 3 weeks for 3 cycles.

Paclitaxel + carboplatin13

Paclitaxel 45mg/m2 IV + carboplatin AUC 2mg • min/mL IV weekly with concurrent thoracic radiotherapy (total dose, 60Gy) given 5 days per weeks in 2Gy fractions. continued

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CANCER TREATMENT REGIMEN

LUNG CANCER Non-small Cell Lung Cancer Treatment Regimens (continued) Chemotherapy Regimens Used With Radiation Therapy (RT)1 (continued) REGIMEN

DOSING

Sequential Chemotherapy/RT (Adjuvant)1 Cisplatin + vinblastine10

Days 1 and 29: Cisplatin 100mg/m2 IV. Days 1, 8, 15, 22 and 29: Vinblastine 5mg/m2 IV; followed by thoracic radiotherapy with 60Gy in 30 fractions beginning on Day 50.

Paclitaxel + carboplatin14

Day 1: Paclitaxel 200mg/m2 IV over 3 hours + carboplatin AUC 6mg • min/mL IV over 1 hour.

Repeat every 3 weeks for 2 cycles; followed by thoracic radiotherapy 63Gy beginning on Day 42.

Concurrent Chemotherapy/RT Followed by Chemotherapy1 Paclitaxel + carboplatin14

Day 1 (weekly): Paclitaxel 45–50mg/m2 IV and carboplatin AUC 2mg • min/mL IV. Concurrent thoracic radiotherapy; followed by 2 additional cycles of paclitaxel 200mg/m2 IV and carboplatin AUC 6mg • min/mL IV.

Cisplatin + etoposide10

Days 1, 8, 29, and 36: Cisplatin 50mg/m2 IV. Days 1–5, 29–33: Etoposide 50mg/m2 IV with concurrent thoracic radiotherapy; followed by 2 additional cycles of cisplatin 50mg/m2 IV and etoposide 50mg/m2 IV.

Systemic Therapy for Advanced & Metastatic Disease1 Principles of Therapy1 • The drug regimen with the highest likelihood of benefit, with toxicity deemed acceptable to both the physician and the patient, should be given as initial therapy for advanced lung cancer.

• Stage, weight loss, performance status (PS), and gender predict survival.

• Platinum-based chemotherapy prolongs survival, improves symptom control, and yields superior quality of life compared to best supportive care.

• Histology of NSCLC is important in the selection of systemic therapy.

• New agent/platinum combinations have generated a plateau in overall response rate (25%–35%), time to progression (4–6 months), median survival (8–10 months), 1-year survival rate (30%–40%), and 2-year survival rate (10%–15%) in fit patients.

• Unfit patients of any age (PS 3–4) do not benefit from cytotoxic treatment, except erlotinib for those who are epidermal growth factor receptor (EGFR) mutation-positive.

First-line Systemic Therapy Options1 Principles of Therapy1 • There is superior efficacy and reduced toxicity for cisplatin/pemetrexed in patients with nonsquamous histology compared with cisplatin/gemcitabine.

• There is superior efficacy for cisplatin/gemcitabine in patients with squamous histology, in comparison to cisplatin/pemetrexed.

• Two drug regimens are preferred; a third cytotoxic drug increases response rate but not survival.

• Single-agent therapy may be appropriate in select patients.

• Response assessment after 1–2 cycles, then every 2–4 cycles.

Adenocarcinoma, Large Cell, NSCLC NOS (PS 0-1)1 Bevacizumab + carboplatin + paclitaxel (Category 1)15

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks for 6 cycles.

Day 1: Bevacizumab 15mg/kg IV every 3 weeks until disease progression.

Bevacizumab + carboplatin + pemetrexed16

Day 1: Pemetrexed 500mg/m2 IV + carboplatin AUC 6mg • min/mL IV + bevacizumab 15mg/kg IV. Repeat cycle every 3 weeks for up to 4 cycles, followed by: Day 1: Pemetrexed 500mg/m2 IV + bevacizumab 15mg/kg IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Bevacizumab + cisplatin + pemetrexed17

Day 1: Bevacizumab 7.5mg/kg IV + cisplatin 75mg/m2 IV + pemetrexed 500mg/m2 IV. Repeat cycle every 3 weeks for 4 cycles, followed by: Day 1: Bevacizumab 7.5mg/kg IV + pemetrexed 500mg/m2 IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + albumin-bound paclitaxel (Category 1)18

Day 1: Carboplatin AUC 6mg • min/mL IV Days 1, 8, and 15: Nab-paclitaxel 100mg/m2 IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + docetaxel (Category 1)19c

Day 1: Docetaxel 75mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

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First-line Systemic Therapy Options1 (continued) Adenocarcinoma, Large Cell, NSCLC NOS (PS 0-1)1 (continued) Carboplatin + etoposide (Category 1)20,21

Day 1: Carboplatin 325mg/m2 IV Days 1, 2, and 3: Etoposide 100mg/m2 IV. Repeat cycle every 3 to 4 weeks until disease progression or unacceptable toxicity.

OR First Course Day 1: Carboplatin AUC 4mg • min/mL IV Days 1–14: Etoposide 50mg orally twice daily Second Course Day 1: Carboplatin AUC 5mg • min/mLIV Days 1–14: Etoposide 50mg orally twice daily Third Course Day 1: Carboplatin AUC 5mg • min/mLIV Days 1–21: Etoposide 50mg orally twice daily.

Patients achieving a complete or partial response should receive an additional 3 courses at the same doses given in the third course.

Carboplatin + gemcitabine (Category 1)22

Day 1: Carboplatin AUC 5mg • min/mL IV Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV Repeat cycle every 4 weeks for 4 cycles.

Carboplatin + paclitaxel (Category 1)23c

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + pemetrexed (Category 1)24

Day 1: Pemetrexed 500mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks for up to 6 cycles.

Carboplatin + vinorelbine (Category 1)25

Day 1: Carboplatin AUC 6mg • min/mL IV Days 1 and 8: Vinorelbine 30mg/m2 IV Day 9: Pegfilgrastim 6mg SC. Repeat cycle every 3 weeks for 4 cycles.

Cisplatin + docetaxel (Category 1)19c

Day 1: Cisplatin 75mg/m2 IV + docetaxel 75mg/m2 IV. Repeat cycle every 3 weeks.

Cisplatin + etoposide (Category 1)26

Day 1: Cisplatin 100mg/m2 IV Days 1–3: Etoposide 100mg/m2 IV. Repeat cycle every 3 weeks for up to 6 cycles.

Cisplatin + gemcitabine (Category 1)23,27

Day 1: Cisplatin 80mg/m2 IV Days 1 and 8: Gemcitabine 1,000mg/m2 IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

OR Day 1: Cisplatin 75mg/m2 IV Days 1 and 8: Gemcitabine 1,250mg/m2 IV. Repeat cycle every 3 weeks for up to 6 cycles.

Cisplatin + paclitaxel (Category 1)28c

Day 1: Paclitaxel 135mg/m2 IV over 24 hours Day 2: Cisplatin 75mg/m2 IV. Repeat cycle every 3 weeks.

Cisplatin + pemetrexed (Category 1)27

Day 1: Pemetrexed 500mg/m2 IV + cisplatin 75mg/m2 IV. Repeat cycle every 3 weeks.

Cisplatin + vinorelbine (Category 1)19,23,29

Day 1: Cisplatin 100mg/m2 IV Days 1, 8, 15 and 22: Vinorelbine 25mg/m2 IV over 10 minutes.

Repeat cycle every 4 weeks.

Gemcitabine + docetaxel (Category 1)30c

Days 1 and 8: Gemcitabine 1,000mg/m2 IV Day 8: Docetaxel 85mg/m2 IV. Repeat cycle every 3 weeks for 8 cycles.

Gemcitabine + vinorelbine (Category 1)31

Days 1 and 8: Vinorelbine 25mg/m2 IV + gemcitabine 1,000mg/m2 IV. Repeat cycle every 3 weeks. continued

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First-line Systemic Therapy Options1 (continued) Adenocarcinoma, Large Cell, NSCLC NOS (PS 2)1 Albumin-bound paclitaxel32

Day 1: Albumin-bound paclitaxel 260mg/m2 IV. Repeat cycle every 3 weeks.

Carboplatin + albumin-bound paclitaxel33,34

Day 1: Carboplatin AUC 6mg • min/mL IV Days 1, 8, and 15: Albumin-bound paclitaxel 100mg/m2 IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + docetaxel19c

Day 1: Docetaxel 75mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + etoposide20,21

Day 1: Carboplatin 325mg/m2 IV Days 1, 2, and 3: Etoposide 100mg/m2 IV. Repeat cycle every 3 to 4 weeks until disease progression or unacceptable toxicity.

OR First Course Day 1: Carboplatin AUC 4mg • min/mL IV Days 1–14: Etoposide 50mg orally twice daily Second Course Day 1: Carboplatin AUC 5mg • min/mL IV Days 1–14: Etoposide 50mg orally twice daily Third Course Day 1: Carboplatin AUC 5mg • min/mL IV Days 1–21: Etoposide 50mg orally twice daily.

Patients achieving a complete or partial response should receive an additional 3 courses at the same doses given in the third course.

Carboplatin + gemcitabine22

Day 1: Carboplatin AUC 5mg • min/mL IV Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV Repeat cycle every 4 weeks for 4 cycles.

Carboplatin + paclitaxel23c

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + pemetrexed24

Day 1: Pemetrexed 500mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks for up to 6 cycles.

Carboplatin + vinorelbine25

Day 1: Carboplatin AUC 6mg • min/mL IV Days 1 and 8: Vinorelbine 30mg/m2 IV Day 9: Pegfilgrastim 6mg SC. Repeat cycle every 3 weeks for 4 cycles.

Docetaxel35,36c

Day 1: Docetaxel 75mg/m2 IV over 1 hour.

Repeat cycle every 3 weeks.

Etoposide37

Days 1–21: Etoposide 50mg/m2 orally daily.

Repeat cycle every 4 to 5 weeks.

Gemcitabine38-40

Days 1 and 8: Gemcitabine 1,250mg/m2 IV. Repeat cycle every 3 weeks.

Gemcitabine + docetaxel30c

Days 1 and 8: Gemcitabine 1,000mg/m2 IV Day 8: Docetaxel 85mg/m2 IV. Repeat cycle every 3 weeks for 8 cycles.

Gemcitabine + vinorelbine31

Days 1 and 8: Vinorelbine 25mg/m2 IV + gemcitabine 1,000mg/m2 IV. Repeat cycle every 3 weeks.

Irinotecan41,42

Day 1: Irinotecan 300mg/m2 IV. Repeat cycle every 3 weeks.

Paclitaxel43-45

Days 1, 8, and 15: Paclitaxel 80mg/m2 IV. Repeat cycle every 4 weeks for up to 4 cycles.

Pemetrexed46

Day 1: Pemetrexed 500mg/m2 IV. Repeat cycle every 3 weeks.

Vinorelbine35

Days 1, 8, and 15: Vinorelbine 30mg/m2 IV. Repeat cycle every 3 weeks.

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First-line Systemic Therapy Options1 (continued) Squamous Cell Carcinoma (PS 0-1)1 Carboplatin + albumin-bound paclitaxel (Category 1)18

Day 1: Carboplatin AUC 6mg • min/mL IV Days 1, 8, and 15: Albumin-bound paclitaxel 100mg/m2 IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + docetaxel (Category 1)19

Day 1: Docetaxel 75mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + etoposide (Category 1)20,21

Day 1: Carboplatin 325mg/m2 IV Days 1, 2, and 3: Etoposide 100mg/m2 IV. Repeat cycle every 3 to 4 weeks until disease progression or unacceptable toxicity.

OR First Course Day 1: Carboplatin AUC 4mg • min/mL IV Days 1–14: Etoposide 50mg orally twice daily Second Course Day 1: Carboplatin AUC 5mg • min/mL IV Days 1–14: Etoposide 50mg orally twice daily Third Course Day 1: Carboplatin AUC 5mg • min/mL IV Days 1–21: Etoposide 50mg orally twice daily.

Patients achieving a complete or partial response should receive an additional 3 courses at the same doses given in the third course.

Carboplatin + gemcitabine (Category 1)22

Day 1: Carboplatin AUC 5mg • min/mL IV Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV Repeat cycle every 4 weeks for 4 cycles.

Carboplatin + paclitaxel (Category 1)23c

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + vinorelbine (Category 1)25

Day 1: Carboplatin AUC 6mg • min/mL IV Days 1 and 8: Vinorelbine 30mg/m2 IV Day 9: Pegfilgrastim 6mg SC. Repeat cycle every 3 weeks for 4 cycles.

Cisplatin + docetaxel (Category 1)19

Day 1: Cisplatin 75mg/m2 IV + docetaxel 75mg/m2 IV. Repeat cycle every 3 weeks.

Cisplatin + etoposide (Category 1)26 Day 1: Cisplatin 100mg/m2 IV Days 1–3: Etoposide 100mg/m2 IV. Repeat cycle every 3 weeks for up to 6 cycles.

Cisplatin + gemcitabine (Category 1)23,27

Day 1: Cisplatin 80mg/m2 IV Days 1 and 8: Gemcitabine 1,000mg/m2 IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

OR Day 1: Cisplatin 75mg/m2 IV Days 1 and 8: Gemcitabine 1,250mg/m2 IV. Repeat cycle every 3 weeks for up to 6 cycles.

Cisplatin + paclitaxel (Category 1)28c Day 1: Paclitaxel 135mg/m2 IV over 24 hours Day 2: Cisplatin 75mg/m2 IV. Repeat cycle every 3 weeks.

Cisplatin + vinorelbine (Category 1)19,23,29

Day 1: Cisplatin 100mg/m2 IV Days 1, 8, 15 and 22: Vinorelbine 25mg/m2 IV over 10 minutes.

Repeat cycle every 4 weeks.

Cisplatin + gemcitabine + necitumumab (Category 3)47

Day 1: Cisplatin 75mg/m2 IV over 120 minutes Days 1 and 8: Gemcitabine 1,250mg/m2 IV over 30 minutes + necitumumab 800mg IV over a minimum of 50 minutes.

Repeat cycle every 3 weeks for up to 6 cycles. Patients free of disease progression should continue single-agent necitumumab on the same treatment schedule until disease progression or unacceptable toxicity. continued

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First-line Systemic Therapy Options1 (continued) Squamous Cell Carcinoma (PS 0-1)1 (continued) Gemcitabine + docetaxel (Category 1)30c

Days 1 and 8: Gemcitabine 1,000mg/m2 IV Day 8: Docetaxel 85mg/m2 IV. Repeat cycle every 3 weeks for 8 cycles.

Gemcitabine + vinorelbine (Category 1)31

Days 1 and 8: Vinorelbine 25mg/m2 IV + gemcitabine 1,000mg/m2 IV. Repeat cycle every 3 weeks.

Squamous Cell Carcinoma (PS 2)1 Albumin-bound paclitaxel32

Day 1: Albumin-bound paclitaxel 260mg/m2 IV. Repeat cycle every 3 weeks.

Carboplatin + albumin-bound paclitaxel33,34

Day 1: Carboplatin AUC 6mg • min/mL IV Days 1, 8, and 15: Albumin-bound paclitaxel 100mg/m2 IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + docetaxel19c

Day 1: Docetaxel 75mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + etoposide20,21

Day 1: Carboplatin 325mg/m2 IV Days 1, 2, and 3: Etoposide 100mg/m2 IV. Repeat cycle every 3 to 4 weeks until disease progression or unacceptable toxicity.

OR First Course Day 1: Carboplatin AUC 4mg • min/mL IV Days 1–14: Etoposide 50mg orally twice daily Second Course Day 1: Carboplatin AUC 5mg • min/mL IV Days 1–14: Etoposide 50mg orally twice daily Third Course Day 1: Carboplatin AUC 5mg • min/mL IV Days 1–21: Etoposide 50mg orally twice daily.

Patients achieving a complete or partial response should receive an additional 3 courses at the same doses given in the third course.

Carboplatin + gemcitabine22

Day 1: Carboplatin AUC 5mg • min/mL IV Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV Repeat cycle every 4 weeks for 4 cycles.

Carboplatin + paclitaxel23c

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + vinorelbine24

Day 1: Carboplatin AUC 6mg • min/mL IV Days 1 and 8: Vinorelbine 30mg/m2 IV Day 9: Pegfilgrastim 6mg SC. Repeat cycle every 3 weeks for 4 cycles.

Cisplatin + gemcitabine + necitumumab (Category 3)47

Day 1: Cisplatin 75mg/m2 IV over 120 minutes Days 1 and 8: Gemcitabine 1,250mg/m2 IV over 30 minutes + necitumumab 800mg IV over a minimum of 50 minutes.

Repeat cycle every 3 weeks for up to 6 cycles. Patients free of disease progression should continue single-agent necitumumab on the same treatment schedule until disease progression or unacceptable toxicity.

Docetaxel35,36c

Day 1: Docetaxel 75mg/m2 IV over 1 hour.

Repeat cycle every 3 weeks.

Etoposide37

Days 1–21: Etoposide 50mg/m2 orally daily.

Repeat cycle every 4 to 5 weeks.

Gemcitabine38-40

Days 1 and 8: Gemcitabine 1,250mg/m2 IV. Repeat cycle every 3 weeks.

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First-line Systemic Therapy Options1 (continued) Squamous Cell Carcinoma (PS 2)1 (continued) Gemcitabine + docetaxel30c

Days 1 and 8: Gemcitabine 1,000mg/m2 IV Day 8: Docetaxel 85mg/m2 IV. Repeat cycle every 3 weeks for 8 cycles.

Gemcitabine + vinorelbine31

Days 1 and 8: Vinorelbine 25mg/m2 IV + gemcitabine 1,000mg/m2 IV. Repeat cycle every 3 weeks.

Irinotecan41,42

Day 1: Irinotecan 300mg/m2 IV. Repeat cycle every 3 weeks.

Paclitaxel43-45

Days 1, 8, and 15: Paclitaxel 80mg/m2 IV. Repeat cycle every 4 weeks for up to 4 cycles.

Vinorelbine35

Days 1, 8, and 15: Vinorelbine 30mg/m2 IV. Repeat cycle every 3 weeks.

Principles of Maintenance Therapy1 Continuation maintenance refers to the use of at least one of the agents given in first line, beyond 4 to 6 cycles, in the absence of disease progression. Switch maintenance refers to the initiation of a different agent, not included as part of the first-line regimen, in the absence of disease progression, after 4 to 6 cycles of initial therapy.

• Continuation Maintenance: Bevacizumab and cetuximab given in combination with chemotherapy should be continued until evidence of disease progression or unacceptable toxicity, as per the design of the clinical trials supporting their use.

—— Continuation of bevacizumab after 4–6 cycles of platinum-doublet chemotherapy and bevacizumab (category 1).

—— Continuation of cetuximab after 4–6 cycles of cisplatin, vinorelbine, and cetuximab (category 1).

—— Continuation of pemetrexed after 4–6 cycles of cisplatin and pemetrexed chemotherapy, for patients with histologies other than squamous cell carcinoma (category 1).

—— Continuation of bevacizumab + pemetrexed after 4–6 cycles of bevacizumab, pemetrexed, cisplatin/carboplatin, for patients with histologies other than squamous cell carcinoma.

—— Continuation of gemcitabine after 4–6 cycles of platinum-doublet chemotherapy (category 2B).

• Switch Maintenance: Two studies have shown a benefit in progression-free and overall survival with the initiation of pemetrexed or erlotinib after first-line chemotherapy, in patients without disease progression after 4–6 cycles of therapy.

—— Initiation of pemetrexed after 4–6 cycles of first-line platinum-doublet chemotherapy for patients with histologies other than squamous cell carcinoma (category 2B).

—— Initiation of erlotinib after 4–6 cycles of first-line platinum-doublet chemotherapy (category 2B).

—— Initiation of docetaxel after 4–6 cycles of first-line platinum-doublet chemotherapy in patients with squamous cell carcinoma (category 2B).

• Close surveillance of patients without therapy is a reasonable alternative to maintenance.

Subsequent Therapy for Advanced & Metastatic Disease1 Principles of Subsequent Therapy1 • In patients who have experienced disease progression either during or after first-line therapy, single-agent docetaxel, pemetrexed, or erlotinib are established second-line agents.

—— Nivolumab improves survival when compared with docetaxel —— Pembrolizumab improves overall survival in PD-L1 positive tumors when compared with docetaxel.

—— Docetaxel is superior to vinorelbine or ifosfamide.

—— Pemetrexed is considered equivalent to docetaxel with less toxicity in patients with adenocarcinoma and large cell carcinoma.

—— Ramucirumab + docetaxel improves survival when compared to docetaxel alone.

—— Erlotinib is superior to best supportive care.

• If not already given, options for patients with PS 0–2 include docetaxel, pemetrexed (nonsquamous), erlotinib, or gemcitabine (category 2B for all options).

Day 1: Nivolumab 240mg IV over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.

Nivolumab (Category 1)48,49 Pembrolizumab (Category 1)

50d

Day 1: Pembrolizumab 2mg/kg IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Docetaxel35,36

Day 1: Docetaxel 75mg/m2 IV over 1 hour.

Repeat cycle every 3 weeks.

Pemetrexed46

Day 1: Pemetrexed 500mg/m2 IV. Repeat cycle every 3 weeks. continued

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LUNG CANCER Non-small Cell Lung Cancer Treatment Regimens (continued) Systemic Therapy for Advanced & Metastatic Disease1 (continued) REGIMEN

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First-line Systemic Therapy Options1 (continued) Subsequent Therapy for Advanced & Metastatic Disease1 (continued) Gemcitabine38-40

Days 1 and 8: Gemcitabine 1,250mg/m2 IV. Repeat cycle every 3 weeks.

Ramucirumab + docetaxel51

Day 1: Ramucirumab 10mg/kg IV + docetaxel 75mg/m2 IV. Repeat cycle every 3 weeks.

First-line Targeted Therapy for Advanced & Metastatic Disease1 Sensitizing EGFR Mutation Positive1 Erlotinib (Category 1)52

Erlotinib 150mg orally once daily until disease progression or unacceptable toxicity.

Afatinib (Category 1)

Afatinib 40mg orally once daily until disease progression or unacceptable toxicity.

53

Gefitinib (Category 1)54 ALK Positive

Gefitinib 250mg orally once daily until disease progression or unacceptable toxicity.

1

Crizotinib (Category 1)55

Crizotinib 250mg orally twice daily until disease progression or unacceptable toxicity.

Subsequent Targeted Therapy for Advanced & Metastatic Disease1 Sensitizing EGFR Mutation Positive1 Osimertinib56

Osimertinib 80mg orally once daily until disease progression or unacceptable toxicity.

Erlotinib52

Erlotinib 150mg orally once daily until disease progression or unacceptable toxicity.

Afatinib

Afatinib 40mg orally once daily until disease progression or unacceptable toxicity.

53

Gefitinib54 ALK Positive

Gefitinib 250mg orally once daily until disease progression or unacceptable toxicity.

1

Crizotinib55

Crizotinib 250mg orally twice daily until disease progression or unacceptable toxicity.

Ceritinib

Ceritinib 750mg orally once daily until disease progression or unacceptable toxicity.

57

Alectinib58

Alectinib 600mg orally twice daily until disease progression or unacceptable toxicity.

Regimens can be used as neoadjuvant/preoperative/induction chemradiotherapy. b Regimens can be used as adjuvant or definitive concurrent chemotherapy/RT. c Albumin-bound paclitaxel may be substituted for either paclitaxel or docetaxel in patients who have experienced hypersensitivity reactions after receiving paclitaxel or docetaxel despite premedication, or for patients where the standard premedications (ie, dexamethasone, H2 blockers, H1 blockers) are contraindicated. d Pembrolizumab is approved for patients with NSCLC tumors with PD-L1 expression, as determined by an FDA-approved test for PD-L1 with use of pembrolizumab. a

References 1. Referenced with permission from NCCN Clinical Practice Guidelines in Oncology™ Non-Small Cell Lung Cancer. v 4.2016. Available at: http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed September 15, 2016.

2. Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-lung cancer. N Engl J Med. 2005;352:2589–2597.

3. Arriagada R, Bergman B, Dunant A, et al. The International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med. 2004;350:351–360.

4. Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a ­randomised controlled trial. Lancet Oncol. 2006;7:719–727.

5. Pérol M, Chouaid C, Pérol D, et al. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced nonsmall-cell lung cancer. J Clin Oncol. 2012;30:3516–3524.

6. Fossella F, Pereira JR, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced nonsmall-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003;21: 3016–3024.

7. Kreuter M, Vansteenkiste J, Fishcer JR, et al. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013;24: 986–992.

8. Strauss GM, Herndon III JE, Maddaus MA, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008;26:5043–5051.

9. Albain KS, Crowley JJ, Turrisi AT III, et al. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: A Southwest Oncology Group Phase II Study, SWOG 9019. J Clin Oncol. 2002;20: 3454–3460.

10. Curran WJ Jr, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410.

J Natl Cancer Inst. 2011;103:1452–1460.

11. Govindan R, Bogart J, Stinchcombe T, et al. Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small-cell lung cancer: Cancer and Leukemia Group B trial 30407. J Clin Oncol. 2011;29: 3120–3125.

12. Choy H, Gerber DE, Bradley JD, et al. Concurrent pemetrexed and radiation therapy in the treatment of patients with inoperable stage III non-small cell lung cancer: a e systematic review of completed and ongoing studies. Lung Cancer. 2015;87:232–240.

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LUNG CANCER References (continued) 13. Bradley JD, Paulus R, Komaki R, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol.

2015;16:187–199.

14. Belani CP, Choy H, Bonomi P, et al. Combined chemoradiotherapy regimens of ­paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a ­randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005;23:5883–5891.

15. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small cell lung cancer. N Engl J Med. 2006;355:2542–2550.

16. Patel JD, Socinski MA, Garon EB, et al. Pointbreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small cell lung cancer. J Clin Oncol. 2013;31:4349–4357.

17. Barlesi F, Scherpereel A, Rittmeywr A, et al. Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small cell lung cancer: AVAPERL. J Clin Oncol. 2013;31: 3004–3011.

18. Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012:30:2055–2062.

19. Fossella F, Periera JR, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003; 21(16):3016–3024.

20. Klastersky J, Sculier JP, Lacroix H, et al. A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861.

J Clin Oncol. 1990;8:1556–1562.

21. Frasci G, Comella P, Panza N, eta l. Carboplatin-oral etoposide personalized dosing in elderly non-small cell lung cancer patients. Gruppo Oncologico Cooperativo Sud-Italia. Eur J Cancer. 1998;34:1710–1714.

22. Danson S, Middleton MR, O’Byrne KJ, et al. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and ciplatin in patients with advanced non-small cell lung carcinoma. Cancer. 2003;98:542–553.

23. Ohe Y, Ohashi Y, Kubota K, et al. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non- small-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol. 2007;18:317–323.

24. Scagliotti GV, Kortsik C, Dark GG, et al. Pemetrexed combined with oxaliplatin or carboplatin as first-line treatment in advanced non-small cell lung cancer: a multicenter, randomized, phase II trial. Clin Cancer Res. 2005;11:690–696.

25. Riedel RF, Andrews C, Garst J, et al. A phase II trial of carboplatin/vinorelbine with pegfilgrastim support for the treatment of patients with advanced non-small cell lung cancer. J Thorac Oncol. 2007;2:520–526.

26. Cardenal F, Lopez-Cabrerizo MP, Anton A, et al. Randomized phase III study of ­gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally ­advanced or metastatic non-small cell lung cancer. J Clin Oncol. 1999;17:12–18.

27. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage NSCLC. J Clin Oncol. 2008;26:3543–3551.

28. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Engl J Med. 2002;346:92–98.

29. Kelly K, Crowley J, Bunn PA, et al. Randomized phase III trial of paclitaxel plus ­carboplatin versus vinorelbine plus cisplatin in the treatment of patients with ­advanced non-small cell lung cancer: A Southwest Oncology Group trial. J Clin Oncol. 2001;19:3210–3218.

30. Pujol JL, Breton JL, Gervais R, et al. Gemcitabine-docetaxel versus cisplatin-­ vinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin. Ann Oncol. 2005;16:602–610.

31. Tan EH, Szczesna A, Krzakowski M, et al. Randomized study of vinorelbine—­ gemcitabine versus vinorelbine—carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 2005;49:233–240.

32. Green M, Manikhas G, Orlov S, et al. Abraxane®, a novel Cremophor® -free, albuminbound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Ann Oncol. 2006;17:1263–1268.

33. Rizvi N, Riely G, Azzoli, C, et al. Phase I/II Trial of weekly intravenous 130-nm albuminbound paclitaxel as initial chemotherapy in patients with stage IV non–small-cell lung cancer. J Clin Oncol. 2008;26:639–643.

34. Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012:30:2055–2062.

35. Fossella FV, DeVore R, Kerr RN, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small cell lung cancer ­previously treated with platinum- containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol. 2000;18:2354–2362.

36. Fidias PM, Dakhil SR, Lyss AP, et al. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in ­advanced non-small cell lung cancer. J Clin Oncol. 2009;27:591–598.

37. Waits TM, Johnson DH, Hainsworth JD, et al. Prolonged administration of oral etoposide in non-small cell lung cancer: a phase II trial. J Clin Oncol. 1992;292–296.

38. Zatloukal P, Kanitz E, Magyar P, et al Gemcitabine in locally advanced and metastatic non-small cell lung cancer: the Central European phase II study. Lung ­Cancer. 1998;22: 243–250.

39. Sederholm C, Hillerdal G, Lamberg K, et al. Phase III trial of gemcitabine plus carboplatin versus single agent gemcitabine in the treatment of locally advanced or metastatic non-small cell lung cancer: the Swedish Lung Cancer Study group.

J Clin Oncol. 2005;23:8380–8288.

40. Perol M, Chouaid C, Perol D, et al. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin- gemcitabine induction chemotherapy in advanced nonsmall cell lung cancer. J Clin Oncol. 2012;30:3516–3524.

41. Georgoulias V, Kouroussis C, Agelidou A, et al. Irinotecan plus gemcitabine vs irinotecan for the second-line treatment of patients with advanced non-small cell lung cancer pretreated with docetaxel and cisplatin: a multicentre, randomised, phase II study. Br J Cancer. 2004;91:482–488.

42. Fukuoka M, Niitani H, Suzuki A, et al. A phase II study of CPT-11, a new derivative of camptothecin, for previously untreated non-small cell lung cancer. J Clin Oncol. 1992;10:16–20.

43. Lilenbaum RC, Herndon JE, List MA, et al. Single-agent versus combination chemotherapy in advanced non-small cell lung cancer: the cancer and leukemia group B (study 9730). J Clin Oncol. 2005;23:190–196.

44. Ceresoli GL, Gregorc V, Cordio S, et al. Phase II study of weekly paclitaxel as secondline therapy in patients with advanced non-small cell lung cancer. Lung Cancer.

2004;44:231–239.

45. Yasuda K, Igishi T, Kawasaki Y, et al. Phase II study of weekly paclitaxel in patients with non-small cell lung cancer who have failed previous treatments. Oncology.

2004;66:347–352.

46. Hanna NH, Sheperd FA, Fossella FV, et al. Randomized phase III study of pemetrexed versus docetaxel in patients with non-small cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22:1589–1597.

47. Thatcher N, Hirsch FR, Luft AV, et al. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015;16:763–774.

48. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–1639.

49. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123–135.

50. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small- cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2015.

51. Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, ­double-blind, randomised phase 3 trial. Lancet. 2014;384:665–673.

52. Tarceva [prescribing information]. South San Francisco, CA: Genentech, Inc.; 2016.

53. Gilotrif [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2016.

54. Iressa [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals; 2015.

55. Xalkori [prescribing information]. New York, NY: Pfizer Inc.; 2016.

56. Tagrisso [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals; 2016.

57. Zykadia [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; 2016.

58. Alecensa [prescribing information]. South San Francisco, CA: Genentech, Inc.; 2016.

(Revised 5/2016) © 2017 by Haymarket Media, Inc.

CancerTherapyAdvisor.com | JANUARY/FEBRUARY 2017 | CANCER THERAPY ADVISOR 71

CANCER TREATMENT REGIMEN

LUNG CANCER Small Cell Lung Cancer Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team.

Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly.

The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Systemic Therapy as Primary or Adjuvant Therapy1a Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

Limited Stage (maximum of 4–6 cycles)1bc Cisplatin + etoposide2,3

Day 1: Cisplatin 60mg/m2 IV Days 1–3: Etoposide 120mg/m2 IV. Repeat cycle every 3 weeks for at least 4 cycles.

OR Day 1: Cisplatin 80mg/m2 IV Days 1–3: Etoposide 100mg/m2 IV. Repeat cycle every 4 weeks for 4–6 cycles.

Carboplatin + etoposide4

Day 1: Carboplatin AUC 5–6mg • min/mL IV Days 1–3: Etoposide 100mg/m2 IV. Repeat cycle every 3 weeks for 4–6 cycles.

Extensive Stage (maximum of 4–6 cycles)1 Carboplatin + etoposide5

Day 1: Carboplatin AUC 5–6mg • min/mL IV Days 1–3: Etoposide 100mg/m2 IV. Repeat cycle every 4 weeks for 4–6 cycles.

Cisplatin + etoposide6-8

Day 1: Cisplatin 75–80mg/m2 IV Days 1–3: Etoposide 80–100mg/m2 IV. Repeat cycle every 3 weeks for 4–6 cycles.

OR Days 1–3: Cisplatin 25mg/m2 IV + etoposide 100mg/m2 IV. Repeat cycle every 3 weeks for 4-6 cycles.

Carboplatin + irinotecan9

Day 1: Carboplatin AUC 5mg • min/mL IV Days 1, 8, and 15: Irinotecan 50mg/m2 IV. Repeat cycle every 4 weeks for 4–6 cycles.

Cisplatin + irinotecan10,11

Day 1: Cisplatin 60mg/m2 IV Days 1, 8, and 15: Irinotecan 60mg/m2 IV. Repeat cycle every 4 weeks for 4 cycles.

OR Day 1 and 8: Cisplatin 30mg/m2 IV + irinotecan 65mg/m2 IV. Repeat cycle every 3 weeks for 4–6 cycles.

Subsequent Systemic Therapy1 Relapse ≤6 months, PS 0-21 Topotecan12-14

Days 1–5: Topotecan 1.5mg/m2 IV daily over 30 minutes.

Repeat cycle every 3 weeks.

OR Days 1–5: Topotecan 2.3mg/m2 orally once daily.

Repeat cycle every 3 weeks.

Irinotecan15

Day 1: Irinotecan 100mg/m2 IV over 90 minutes.

Repeat cycle every week.

72 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

CANCER TREATMENT REGIMEN

LUNG CANCER Subsequent Systemic Therapy1 (continued) REGIMEN

DOSING

Relapse ≤6 months, PS 0-21 (continued) Paclitaxel16,17

Day 1: Paclitaxel 80mg/m2 IV over 1 hour.

Repeat every week for 6 weeks, followed by a 2-week break.

Docetaxel18

Day 1: Docetaxel 100 mg/m2 IV over 1 hour.

Repeat cycle every 3 weeks.

Temozolomide19,20

Day 1–21: Temozolomide 75mg/m2 orally.

Repeat cycle every 4 weeks.

Nivolumab  ipilimumab21

Day 1: Nivolumab 3mg/kg IV. Repeat cycle every 2 weeks until disease progression or unacceptable toxicity.

OR Day 1: Nivolumab 1mg/kg IV + ipilimumab 3mg/kg IV. Repeat cycle every 3 weeks for 4 cycles, followed by nivolumab 3mg/kg IV every 2 weeks.

OR Nivolumab 3mg/kg IV + ipilimumab 1mg/kg IV. Repeat cycle every 3 weeks for 4 cycles, followed by nivolumab 3mg/kg IV every 2 weeks.

Vinorelbine22,23

Day 1: Vinorelbine 25–30mg/m2 IV. Repeat cycle every week.

Etoposide24,25

Day 1–21: Etoposide 50mg/m2 orally.

Repeat cycle every 4 to 5 weeks.

Gemcitabine26,27

Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV. Repeat cycle every 4 weeks.

Cyclophosphamide + doxorubicin + vincristine (CAV)12

Day 1: Cyclophosphamide 1,000mg/m2 IV + doxorubicin 45mg/m2 IV + vincristine 2mg IV. Repeat cycle every 3 weeks.

Bendamustine (Category 2B)28

Days 1 and 2: Bendamustine 120mg/m2 IV. Repeat cycle every 3 weeks for up to 6 cycles.

Relapse >6 months1 • Original regimen29,30 Leucovorin 400mg/m2 is the equivalent of levoleucovorin 200mg/m2.

NCCN recommends limiting chemotherapy orders to 24-hour units (i.e., 1,200mg/m2/day NOT 2,400mg/m2 over 48 hours) to minimize medication errors. c The majority of safety and efficacy data for this regimen have been developed in Europe, where a capecitabine starting dose of 1,000mg/m2 twice daily for 14 days, repeated every 21 days, is standard. Evidence suggests that North American patients may experience greater toxicity with capecitabine (as well as with other fluoropyrimidines) than European patients, and may require a lower dose of capecitabine. The relative efficacy of CapeOx with lower starting doses of capecitabine has not been addressed in large-scale randomized trials. a

b

References 1. Referenced with permission from NCCN Clinical Practice Guidelines in Oncology™ Small Cell Lung Cancer. v 2.2017. Available at: http://www.nccn.org/professionals/ physician_gls/pdf/sclc.pdf. Accessed September 15, 2016.

2. Turrisi AT 3rd, Kim K, Blum R, et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999;340(4):265–271.

3. Saito H, Takada Y, Ichinose Y, et al. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006;24(33): 5247–5252.

4. Skarlos DV, Samantas E, Briassoulis E, et al. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol. 2001;12(9): 1231–1238.

5. Okamoto H, Watanabe K, Nishiwaki Y, et al. Phase II study of area under the plasma-­ concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small cell lung cancer. J Clin Oncol. 1999;17(11): 3540–3545.

6. Spigel DR, Townley PM, Waterhouse DM, et al. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011;29: 2215–2222.

7. Niell HB, Herndon JE, Miller AA, et al. Randomized phase III Intergroup trial of etoposide with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B trial 9732. J Clin Oncol. 2005;23:3752–3759.

8. Evans WK, Shepherd FA, Feld R, et al. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985;3(11): 1471–1477.

9. Schmittel A, Fischer von Weikersthal L, Sebastian M, et al. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006;17:663–667.

continued

CancerTherapyAdvisor.com | JANUARY/FEBRUARY 2017 | CANCER THERAPY ADVISOR 73

CANCER TREATMENT REGIMEN

LUNG CANCER Small Cell Lung Cancer Treatment Regimens (continued) References (continued) 10. Noda K, Nishiwaki Y, Kawahara M, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002;346(2):85–91.

11. Hanna N, Bunn Jr. PA, Langer C, et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensivestage disease small-cell lung cancer. J Clin Oncol. 2006;24(13):2038–2043.

12. von Pawel J, Schiller JH, Shepherd FA, et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer.

J Clin Oncol. 1999;17(2):658–667.

13. O’Brien ME, Ciuleanu TE, Tsekov H, et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006;24(34):5441–5447.

14. Eckardt JR, von Pawel J, Pujol JL, et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007;25(15):2086–2092.

15. Masuda N, Fukuoka M, Kusunoki Y, et al. CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol.

1992;10:1225–1229.

16. Smit EF, Fokkema E, Biesma B, et al. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. Br J Cancer. 1998;77:347–351.

17. Yamamoto N, Tsurutani J, Yoshimura N, et al. Phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer. Anticancer Res. 2006;26:777–781.

18. Smyth JF, Smith IE, Sessa C, et al. Activity of docetaxel (Taxotere) in small cell lung cancer. Eur J Cancer. 1994; 30A:1058–1060.

19. Pietanza MC, Kadota K, Huberman K, et al. Phase II trial of temozolomide with relapsed sensitive or refractory small cell lung cancer, with assessment of methylguanine-DNA methyltransferase as a potential biomarker. Clin Cancer Res. 2012;18:1138–1145.

20. Zauderer MG, Drilon A, Kadota K, et al. Trial of a 5-day dosing regimen of temozolomide in patients with relapsed small cell lung cancers with assessment of methylguanine-DNA methyltransferase. Lung Cancer. 2014;86:237–240.

21. Antonia SJ, López-Martin JA, Bendell J, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (Checkmate 032): a multicentre, open-label phase 1/2 trial. Lancet Oncol. 2016;17:883–895.

22. Jassem J, Karnicka-Mlodkowska H, van Pottelsberghe C, et al. Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients. Eur J Cancer. 1993;29A: 1720–1722.

23. Furuse K, Kuboa K, Kawahara M, et al. Phase II study of vinorelbine in heavily previously treated small cell lung cancer. Oncology. 1996;53:169–172.

24. Einhorn LH, Pennington K, McClean J. Phase II trial of daily oral VP-16 in refractory small cell lung cancer. Semin Oncol. 1990; 17:32–35.

25. Johnson DH, Greco FA, Strupp J, et al. Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin Oncol. 1990; 8:1613–1617.

26. Van der Lee I, Smit EF, van Putten JW, et al. Single-agent gemcitabine in patients with resistant small-cell lung cancer. Ann Oncol. 2001;12:557–561.

27. Masters GA, Declerck L, Blanke C, et al. Phase II trial of gemcitabine in refractory or relapsed small-cell lung cancer. J Clin Oncol. 2003;21:1550–1555.

28. Lammers PE, Shyr Y, Li CI, et al. Phase II study of bendamustine in relapsed chemotherapy sensitive or resistant small-cell lung cancer. J Thorac Oncol. 2014; 9:559–562.

29. Postmus PE, Berendsen HH, van Zandwijk N, et al. Retreatment with the induction regimen in small cell lung cancer relapsing after an initial response to short term chemotherapy. Eur J Cancer Clin Oncol. 1987;23:1409–1411.

30. Giaccone G, Ferrati P, Donadio M, et al. Reinduction chemotherapy in small cell lung cancer. Eur J Cancer Clin Oncol. 1987;23: 1697–1699.

31. Bunn PA, Crowley J, Kelly K, et al. Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol. 1995;13:1632–1641.

(Revised 10/2016) © 2017 by Haymarket Media, Inc.

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DRUG MONOGRAPHS

LUNG CANCER ABRAXANE Celgene

℞

Taxane antimicrotubule. Paclitaxel [bound to albumin (human)] 100mg/vial; pwd for IV infusion after reconstitution; solvent-free.

Indications: First-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.

Adults: Do not treat if neutrophil count <1,500 cells/mm3 or platelets <100,000 cells/mm3. In combination with carboplatin: 100mg/m2 IV over 30 mins on Days 1, 8, and 15 of each 21-day cycle.

Dose reductions for hematologic and neurologic adverse reactions, hepatic impairment: see full labeling. Avoid extravasation.

Children: Not evaluated.

Contraindications: Baseline neutrophil count <1,500 cells/mm3. Prior severe hypersensitivity reaction (do not rechallenge).

Warnings/Precautions: Do not substitute for, or with, other paclitaxel products (due to formulation differences). Do frequent complete blood cell counts. Hepatic impairment (total bilirubin >5XULN or AST >10XULN): not recommended. Monitor for sensory neuropathy, sepsis, or pneumonitis. Renal dysfunction.

Contains human albumin; remote risk of viral transmission. Use appropriate contraception (men and women). Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: May potentiate or be potentiated

by CYP2C8 and/or CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin, efavirenz, nevirapine) and/or inhibitors (eg, ketoconazole, other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, nelfinavir).

Adverse reactions: Bone marrow suppression (eg, neutropenia, anemia), infections, alopecia, sensory neuropathy (may require dose reduction or interruption), peripheral neuropathy, GI upset, mucositis, fatigue/asthenia, myalgia/arthralgia, abnormal ECG; alkaline phosphatase or AST elevation; dyspnea, edema, hypotension, rash (may be serious); rare: thrombotic events.

How supplied: Single-use vial—1

ALECENSA Genentech Kinase inhibitor. Alectinib 150mg; caps.

Indications: Treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.

℞

Adults: Swallow whole. Take with food.

600mg twice daily until disease progression or unacceptable toxicity. Dose modifications or dose reduction schedule: see full labeling.

Children: Not established.

Warnings/Precautions: Monitor liver function tests (eg, ALT, AST, total bilirubin) every 2 weeks for the first 2 months, then periodically during treatment; test more frequently if transaminase and bilirubin elevated; withhold, resume at reduced dose, or permanently discontinue based on severity. Evaluate if presence of worsening respiratory symptoms; withhold if ILD/pneumonitis diagnosed; permanently discontinue if no other cause identified. Monitor HR, BP regularly. If nonlife-threatening symptomatic bradycardia occurs, withhold until asymptomatic or HR ≥60bpm; permanently discontinue in case(s) of recurrence or life-threatening bradycardia if no contributing concomitant medication identified. Assess CPK every 2 weeks for the first month and as clinically indicated; withhold, resume, or reduce dose based on severity. Pregnancy. Females of reproductive potential should use effective contraception during treatment and for 1 week after final dose; males should use effective contraception during treatment and for 3 months after final dose.

Nursing mothers: not recommended (during and for 1 week after final dose).

Interactions: Increased bradycardia with concomitant antihypertensives or other drugs known to cause bradycardia.

Adverse reactions: Fatigue, constipation, edema, myalgia; hepatotoxicity, ILD/pneumonitis, bradycardia, CPK elevation, embryo-fetal toxicity.

How supplied: Caps—240

ALIMTA Lilly

Combination therapy: Give cisplatin beginning 30 mins after pemetrexed infusion. Supplement with oral folic acid and intramuscular vitamin B12 prior to initiating pemetrexed and continue during treatment. Pretreat with corticosteroid the day before, the day of, and day after pemetrexed.

Children: Not recommended.

Warnings/Precautions: See full labeling.

Renal impairment (CrCl <45mL/min): not recommended. Discontinue if Grade 3 or 4 neurotoxicity occurs, or if any Grade 3 or 4 toxicity occurs after two dose reductions.

Do not start a treatment cycle unless ANC is ≥1500cells/mm3, platelets ≥100,000cells/mm3 and CrCl ≥45mL/min. Hepatic impairment.

Monitor CBCs, platelets, renal and hepatic function. Clinically significant third space fluid: consider draining effusion first. Pregnancy (Cat.D); avoid, use effective contraception.

Nursing mothers: not recommended.

Interactions: May be potentiated by nephrotoxic agents, drugs eliminated by renal tubular secretion (eg, probenecid). Concomitant NSAIDs: use caution in patients with mild to moderate renal insufficiency (esp. ibuprofen).

Adverse reactions: Fatigue, nausea, anorexia, vomiting, stomatitis, pharyngitis, constipation, fever, infection with neutropenia, rash, desquamation, neutropenia, leukopenia, anemia, thrombocytopenia, elevated creatinine, chest pain, neuropathy; rare: renal failure.

Testing considerations: TS (thymidylate synthase) expression for response and toxicity How supplied: Single-use vial—1

AVASTIN Genentech ℞

Antifolate. Pemetrexed 100mg/vial, 500mg/vial; pwd for IV inj after reconstitution and dilution; preservative-free.

Indications: Locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC): in combination with cisplatin as initial treatment, or as maintenance in patients whose disease has not progressed after 4 cycles of platinum-based 1st-line chemotherapy; or as a single agent after prior chemotherapy. Malignant pleural mesothelioma (MPM): in combination with cisplatin in patients whose disease is either unresectable or who are otherwise not candidates for curative surgery. Limitations of use: not for the treatment of squamous cell NSCLC. Adults: See full labeling. 500mg/m2 by IV infusion over 10 mins on Day 1 of each 21-day cycle. Adjust dose if toxicity (esp. myelosuppression) develops.

℞

Angiogenesis inhibitor. Bevacizumab 100mg, 400mg; per vial; soln for IV infusion after dilution; preservative-free.

Indications: First-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (NSCLC), in combination with carboplatin and paclitaxel.

Adults: Give by IV infusion. Infuse 1st dose over 90 mins; if tolerated, infuse 2nd dose over 60 mins, and subsequent doses over 30 mins. 15mg/kg every 3 weeks with carboplatin/paclitaxel.

Children: Not established.

Warnings/Precautions: Risk of GI perforations, surgery and wound healing complications, and hemorrhage. Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). Do not administer if recent history

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DRUG MONOGRAPHS

LUNG CANCER of hemoptysis of ≥ ½-teaspoon of red blood.

Permanently discontinue if GI perforation, tracheoesophageal fistula, any grade 4 fistula, or grade 4 venous thromboembolic event.

Discontinue if fistula involving internal organ, wound healing complications, hemorrhage, severe arterial thromboembolic event (ATE), hypertensive crisis or encephalopathy, posterior reversible encephalopathy syndrome, or nephrotic syndrome occurs; suspend therapy if severe hypertension, moderate-to-severe proteinuria (resume when <2g/24hrs), or severe infusion reaction occurs. Avoid in ovarian cancer if evidence of recto-sigmoid involvement by pelvic exam, bowel involvement on CT scan, or symptoms of bowel obstruction. History of arterial thromboembolism. Diabetes. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis; if ≥2+, do further assessment with a 24-hour urine collection. Elderly. Increased risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy: may cause fetal harm; use effective contraception during and for 6 months after last dose. Nursing mothers: not recommended.

Adverse reactions: Epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation and fistulae, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial or venous thromboembolic events, posterior reversible encephalopathy syndrome, infusion reactions, ovarian failure, neutropenia, and infection.

How supplied: Single-use vial—1

CYRAMZA Lilly

℞

Human IgG1 monoclonal antibody. Ramucirumab 10mg/mL; per vial; soln for IV infusion after dilution; preservative-free.

Indications: In combination with docetaxel, for treatment of metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy; patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDAapproved therapy for these aberrations prior to initiation.

Adults: Give by IV infusion over 60 mins.

Premedicate with IV histamine H1-antagonist (eg, diphenhydramine) prior to each infusion; or with dexamethasone and acetaminophen in those who have experienced Grade 1 or 2 infusion reaction. 10mg/kg on Day 1 of a 21-day cycle prior to docetaxel; continue until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Increased risk of hemorrhage; permanently discontinue if severe bleeding occurs. Control hypertension prior to initiating. Monitor blood pressure every 2 weeks

or more frequently as indicated; if severe hypertension develops, temporarily suspend until medically controlled. Monitor for infusionrelated reactions during therapy. Have emergency resuscitative equipment available. Permanently discontinue if severe arterial thromboembolic events, severe uncontrolled hypertension (despite antihypertensives), hypertensive crisis or encephalopathy, Grade 3 or 4 infusion-related reactions, urine protein >3g/24hrs, nephrotic syndrome, or GI perforation occurs. Impaired wound healing: withhold Cyramza prior to surgery. Clinical deterioration in patients with Child-Pugh B or C cirrhosis (eg, new or worsening encephalopathy, ascites, hepatorenal syndrome). Discontinue if reversible posterior leukoencephalopathy syndrome develops. Monitor proteinuria by urine dipstick and/or urinary protein creatinine ratio.

Monitor thyroid function. Pregnancy: avoid. Use effective contraception during therapy and for ≥3 months after last ramucirumab dose. Nursing mothers: not recommended.

Adverse reactions: Hypertension, diarrhea, headache, fatigue, asthenia, hyponatremia, anemia, intestinal obstruction, neutropenia, epistaxis, stomatitis/mucosal inflammation, rash, decreased appetite; arterial thromboembolic events, proteinuria, GI perforation, infusionrelated reactions.

How supplied: Single-dose vial (10mL, 50mL)—1

GILOTRIF Boehringer Ingelheim

℞

Tyrosine kinase inhibitor. Afatinib 20mg, 30mg, 40mg; tabs.

Indications: First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitutions as detected by an FDAapproved test. Limitations of use: safety and efficacy have not been established in patients whose tumors have other EGFR mutations.

Treatment of patients with metastatic squamous NSCLC progressing after platinum-based chemotherapy.

Adults: Take on an empty stomach at least 1 hr before or 2 hrs after a meal. 40mg once daily until disease progression or not tolerated. Severe renal impairment (CrCl 15–29mL/min): 30mg once daily. Concomitant P-gp inhibitors: reduce afatinib daily dose by 10mg if not tolerated; resume previous dose after discontinuing the inhibitor.

Concomitant P-gp inducers: increase afatinib daily dose by 10mg as tolerated; resume previous dose 2–3 days after discontinuing the inducer.

Dose modification: see full labeling.

Children: Not established.

Warnings/Precautions: Permanently discontinue for life-threatening bullous, blistering, or exfoliative skin lesions, confirmed interstitial lung disease (ILD), severe drug-induced hepatic impairment, persistent ulcerative keratitis, symptomatic left ventricular dysfunction, or severe/intolerable adverse reactions (at dose

20mg/day). Withhold for severe or prolonged diarrhea Grade ≥2 lasting for ≥2 consecutive days while taking antidiarrheal, prolonged cutaneous reaction Grade ≥2 (lasting >7 days) or intolerable, during evaluation of suspected ILD, renal dysfunction Grade ≥2, or worsening liver function. History of keratitis, ulcerative keratitis, or severe dry eye. Obtain LFTs periodically during treatment. Monitor closely in moderate-to-severe renal impairment or severe hepatic impairment; adjust dose if not tolerated. Embryo-fetal toxicity.

Females of reproductive potential should use effective contraception during therapy and for at least 2 weeks after final dose. Pregnancy (Cat.D).

Nursing mothers: not recommended (during therapy and for 2 weeks after final dose).

Interactions: Potentiated by P-gp inhibitors (eg, ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, amiodarone). Antagonized

by P-gp inducers (eg, rifampicin, carbamazepine, phenytoin, phenobarbital, St. John’s wort).

Adverse reactions: Diarrhea, rash/dermatitis acneiform, stomatitis, paronychia, dry skin, decreased appetite, nausea, vomiting, pruritus; bullous/exfoliative skin disorders, ILD, hepatotoxicity, keratitis.

How supplied: Tabs—30

HYCAMTIN GlaxoSmithKline

℞

Topoisomerase inhibitor. Topotecan (as HCl) 4mg/vial; pwd for IV infusion after reconstitution and dilution; contains mannitol; preservative-free.

Indications: Small cell lung cancer sensitive disease after failure of 1st line chemotherapy.

Adults: Verify dose using BSA. Usual max dose 4mg IV. Confirm baseline neutrophils ≥1,500cells/mm3 and platelets ≥100,000cells/mm3 prior to 1st course of therapy.

Give by IV infusion over 30 mins. 1.5mg/m2 daily for 5 consecutive days starting on Day 1 of a 21-day cycle. Dose adjustments, renal impairment: see full labeling.

Children: Not established. ℞ Also: HYCAMTIN CAPSULES Topotecan (as HCl) 0.25mg, 1mg; caps.

Indications: Relapsed small cell lung cancer with prior complete or partial response and at least 45 days from the end of 1st line chemotherapy.

Adults: Confirm baseline neutrophils ≥1,500cells/mm3 and platelets ≥100,000cells/mm3 prior to 1st course of therapy. Swallow whole.

2.3mg/m2/day once daily for 5 consecutive days; repeat every 21 days. Dose adjustments, renal impairment: see full labeling.

Children: Not established.

Warnings/Precautions: Monitor peripheral blood cell counts during therapy; hold subsequent doses until neutrophils >1,000cells/mm3, platelets >100,000cells/mm3, and hemoglobin ≥9g/dL. History of interstitial lung disease, pulmonary fibrosis, lung cancer, thoracic exposure to radiation, use of pneumotoxic drugs and/or colony stimulating factors: increased risk

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DRUG MONOGRAPHS

LUNG CANCER of interstitial lung disease; monitor, discontinue if occurs. Moderate to severe renal impairment.

Caps: severe diarrhea; may need to reduce dose.

IV: avoid extravasation. Elderly. Use effective contraception during and for ≥1 month after last dose (in females), or during and for ≥3 months (in males with female partners). Pregnancy (Cat.D).

Nursing mothers: not recommended.

Interactions: IV: Myelosuppression potentiated with platinum agents. Neutropenia potentiated

by G-CSF; administer ≥24hrs after last topotecan dose. Caps: Avoid concomitant P-glycoprotein inhibitors (eg, amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole, ketoconazole, lopinavir, ritonavir, quercetin, quinidine, ranolazine, ticagrelor, verapamil) and BCRP inhibitors (eg, cyclosporine, eltrombopag).

Adverse reactions: See full labeling. Neutropenia, leukopenia, thrombocytopenia, anemia, nausea, vomiting, diarrhea, anorexia, abdominal pain, stomatitis, headache, dyspnea, cough, pyrexia, alopecia, fatigue; infection, sepsis, interstitial lung disease, neutropenic colitis (may be fatal).

How supplied: Single-use vials—1; Caps—10

IRESSA AstraZeneca

℞

Tyrosine kinase inhibitor. Gefitinib 250mg; tabs.

Indications: First-line treatment of metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.

Limitations of use: not established in metastatic NSCLC with EGFR mutations other than exon 19 deletions or exon 21 substitution mutations.

Adults: May disperse tabs in water; drink immediately or give via NG tube. Give 250mg once daily until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions: see full labeling.

Concomitant strong CYP3A4 inducers: increase to 500mg daily; resume at 250mg seven days after discontinuation of the CYP3A4 inducer.

Children: Not established.

Warnings/Precautions: Permanently discontinue if confirmed interstitial lung disease (ILD), severe hepatic impairment, GI perforation, or persistent ulcerative keratitis occurs. Withhold for up to 14 days if acute onset or worsening pulmonary symptoms, NCI CTCAE Grade ≥2 ALT and/or AST elevations, Grade ≥3 diarrhea or skin reactions, or severe or worsening ocular disorders (including keratitis) occurs. Interrupt or discontinue therapy if severe bullous and exfoliative skin disorders develop. Obtain

periodic LFTs. Moderate and severe hepatic impairment; monitor. Use effective contraception during treatment and for at least 2 weeks after completion. Pregnancy, nursing mothers: not recommended.

Interactions: Potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole); monitor.

Antagonized by strong CYP3A4 inducers (eg, rifampicin, phenytoin, tricyclics); see Adults. May be antagonized by drugs that increase gastric pH (eg, H2-blockers, antacids); take gefitinib 6 hours after or 6 hours before an H2-blocker or antacid. Avoid concomitant PPIs; if necessary, take gefitinib 12 hours after last dose or 12 hours before next PPI dose. May potentiate warfarin; monitor INR. Adverse reactions: Skin reactions, diarrhea, vomiting, decreased appetite, stomatitis; ILD, hepatotoxicity, GI perforation, ocular disorders.

Testing considerations: EGFR mutation analysis.

How supplied: Tabs—30

KEYTRUDA Merck

℞

Human programmed death receptor-1 (PD-1)-blocking antibody. Pembrolizumab 50mg/vial; lyophilized pwd for IV infusion after reconstitution; 25mg/mL; per vial; soln for IV infusion after dilution; both: preservative-free.

Indications: First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) ≥50%)] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. Treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy.

Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Keytruda.

Adults: Give as IV infusion over 30mins.

200mg every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Dose modifications: see full labeling. Administer corticosteroids for most Grade ≥2 related immune-mediated reactions.

Children: Not established.

Warnings/Precautions: Monitor for pneumonitis; withhold dose if Grade 2 pneumonitis; permanently discontinue if Grade 3 or 4, or recurrent Grade 2 develops. Monitor for colitis; withhold dose if Grade 2 or 3 colitis; permanently discontinue if Grade 4 develops.

Monitor for changes in liver function; withhold

dose or discontinue based on severity of elevated liver enzymes. Monitor for changes in renal function; withhold dose if Grade 2 nephritis; permanently discontinue if Grade 3 or 4 develops.

Monitor for hypophysitis; withhold dose if Grade 2 hypophysitis; withhold or discontinue if Grade 3 or 4 develops. Monitor for changes in thyroid function (at treatment initiation, during, and as clinically indicated) and signs/symptoms of thyroid disorders; withhold or discontinue if Grade 3 or 4 hyperthyroidism develops. Monitor for hyperglycemia and other diabetes symptoms; withhold if severe hyperglycemia until controlled.

Permanently discontinue if any severe or Grade 3 immune-mediated adverse reaction recurs, for any life-threatening immune-mediated adverse reaction, persistent Grade 2 or 3 reactions that do not recover to Grade 0–1 within 12wks after last dose, or inability to reduce corticosteroid dose to ≤10mg/day of prednisone or equivalent within 12wks. Monitor for infusion-related reactions; permanently discontinue if Grade 3 or 4 develops.

Embryo-fetal toxicity. Use highly effective contraception during treatment and for 4 months after the final dose. Pregnancy: avoid. Nursing mothers: not recommended (during treatment and for 4 months after the final dose).

Adverse reactions: Fatigue, decreased appetite, dyspnea, pruritus, rash, constipation, diarrhea, nausea, cough; immune-mediated disorders, infusion-related reactions.

How supplied: Single-use vial 50mg—1; Singleuse vial 25mg/mL—1

MUSTARGEN Recordati

℞

Alkylating agent. Mechlorethamine HCl 10mg/vial; pwd for IV or intracavitary inj after reconstitution.

Indications: Palliative treatment of bronchogenic carcinoma.

Adults: By IV infusion, per therapeutic course: 0.4mg/kg (lean body weight) as single dose or in divided doses of 0.1–0.2mg/kg per day.

See literature for intracavitary (eg, intrapleural) administration. Do not exceed recommended dose. Repeat course only after hematological recovery (eg, every 3 weeks).

Children: See literature.

Contraindications: Infectious diseases.

Warnings/Precautions: Drug is highly toxic; verify potential benefits outweigh risks; avoid inadvertent contact with powder or vapor. Do not use if foci of acute and chronic suppurative inflammation are present. Ensure adequate hydration. Avoid extravasation. Chronic lymphatic leukemia. Bone marrow suppression. Previous

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DRUG MONOGRAPHS

LUNG CANCER X-ray, cytotoxic chemotherapy. Infection.

Hemorrhagic tendency. Monitor renal, hepatic and bone marrow function. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended.

Adverse reactions: Bone marrow suppression, hyperheparinemia, GI upset (may be severe), anorexia, weakness, thrombosis, thrombophlebitis, hypersensitivity, jaundice, alopecia, vertigo, auditory disturbances, hemolytic anemia, skin reactions, infection, amyloidosis, hyperuricemia, gonad damage.

How supplied: Vials—4

NAVELBINE Pierre Fabre

℞

Antimicrotubule agent. Vinorelbine (as tartrate) 10mg/mL; soln for IV inj after dilution; preservative-free.

Indications: First-line treatment of ambulatory patients with unresectable, advanced non-small cell lung cancer (NSCLC), as a single agent or in combination with cisplatin. In Stage III NSCLC, use in combination with cisplatin.

Adults: See literature. Give by IV inj over 6–10 minutes. Monotherapy: 30mg/m2 once weekly. Combination therapy: 25mg/m2 once weekly with cisplatin given every 4 weeks; or 30mg/m2 once weekly with cisplatin given on Days 1 and 29, then every 6 weeks. Dose adjustment for toxicities, hepatic impairment: see literature.

Children: Not recommended.

Contraindications: Pretreatment granulocyte counts <1000 cells/mm3.

Warnings/Precautions: IV use only; fatal if given intrathecally. Discontinue if neurotoxicity ≥grade 2.

Pre-existing pulmonary dysfunction or neuropathy.

Prior irradiation or chemotherapy. Cardiovascular disease. Monitor for myelosuppression, infection, and/or fever; obtain CBCs with differentials prior to each dose. Avoid contamination of the eyes or injecting into an extremity with poor circulation (thrombosis possible). Hepatic injury or impairment. Avoid extravasation. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: May be potentiated by CYP3A inhibitors. Acute pulmonary reactions possible with mitomycin. Increased risk of granulocytopenia with cisplatin. May increase risk of neurotoxicity with paclitaxel. Prior or concomitant radiation therapy; may result in radiosensitizing effects.

Adverse reactions: Myelosuppression (esp. granulocytopenia), inj site reactions, elevated liver enzymes, chest pain, fatigue, GI upset, alopecia, jaw pain, myalgia, arthralgia, rash, severe constipation, paralytic ileus, intestinal obstruction, necrosis, and/or perforation; dyspnea, severe bronchospasm.

How supplied: Single-use vial (1mL, 5mL)—1

OPDIVO Bristol-Myers Squibb

℞

Human programmed death receptor-1 (PD-1)blocking antibody. Nivolumab 10mg/mL; per vial; soln for IV infusion after dilution; preservativefree; contains mannitol.

Indications: Metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.

Adults: Give as IV infusion over 60mins. 240mg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: See full labeling.

Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for any lifethreatening (Grade 4) adverse reaction, Grade 3 or 4 pneumonitis, Grade 3/4 or recurrent colitis (with ipilimumab), Grade 4 or recurrent colitis (as single agent), AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash (or confirmed SJS or TEN), immune-mediated encephalitis, recurring Grade 3 adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2 or 3 adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2 or 3 (as single agent) colitis, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN, Grade 2 or 3 hypophysitis, Grade 2 adrenal insufficiency, Grade 3 hyperglycemia, Grade 3 rash (or suspected SJS or TEN), new onset moderate-to-severe neurologic symptoms, other Grade 3 adverse reactions (1st occurrence); withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if mild or moderate infusion reactions occur; discontinue if severe or life-threatening.

Monitor for abnormal liver tests, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism. Monitor for transplantrelated complications (eg, hyperacute or Grade 3/4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease) and treat promptly. Moderate or severe hepatic impairment: not studied. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for ≥5 months after final dose. Pregnancy (esp. during 2nd & 3rd trimesters), nursing mothers: not recommended.

Adverse reactions: Fatigue, musculoskeletal pain, decreased appetite, cough, constipation; immune-mediated reactions (may be fatal).

How supplied: Single-use vial (4mL, 10mL)—1

PORTRAZZA Lilly

℞

Human epidermal growth factor receptor (EGFR) inhibitor. Necitumumab 800mg/50mL; soln for IV infusion after dilution; preservative-free.

Indications: In combination with gemcitabine and cisplatin, for first-line treatment of metastatic squamous non-small cell lung cancer. Limitations of use: not for treatment of non-squamous nonsmall cell lung cancer.

Adults: Give by IV infusion over 60 mins prior to gemcitabine and cisplatin infusion. 800mg on Days 1 and 8 of each 3-week cycle; continue until disease progression or unacceptable toxicity.

May premedicate with diphenhydramine HCl (or equivalent) if previously experienced a Grade 1/2 infusion-related reaction. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Risk of cardiopulmonary arrest and/or sudden death, hypomagnesemia.

History of coronary artery disease, CHF, or arrhythmias. Monitor serum electrolytes (eg, magnesium, potassium, calcium) prior to each infusion during therapy and for 8 weeks after last dose; withhold for Grade 3/4 electrolyte abnormalities and may resume once improved to Grade ≤2. Discontinue if serious or life-threatening venous/arterial thromboembolic events or infusionrelated reactions occur. Discontinue if Grade 4 skin reactions or Grade 3 skin induration/fibrosis occurs. Limit sun exposure. Embryo-fetal toxicity.

Pregnancy; avoid. Use effective contraception during treatment and for 3 months after last dose.

Nursing mothers: not recommended (during therapy and for 3 months after last dose).

Adverse reactions: Rash, dermatitis acneiform, vomiting, diarrhea, thromboembolic events, hypomagnesemia, hypocalcemia, hypokalemia; cardiopulmonary arrest, dermatologic toxicities, infusion reactions.

How supplied: Single-use vial—1

TAGRISSO AstraZeneca

℞

Kinase inhibitor. Osimertinib 40mg, 80mg; tabs.

Indications: Treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDAapproved test, who have progressed on or after EGFR tyrosine kinase inhibitor therapy.

Adults: 80mg once daily until disease progression or unacceptable toxicity. If swallowing difficulty, may disperse tab in 2oz (60mL) of non-carbonated water only; stir and swallow immediately, then rinse container with 4–8oz water and drink immediately; or if administration via NG tube is required, disperse tab in 15mL of non-carbonated water and use an additional 15mL of water to transfer any residues to the syringe; give resulting 30mL via NG tube as instructed with appropriate water flushes (~30mL). Concomitant strong CYP3A4 inducers (if use is unavoidable): increase dose to 160mg daily; resume at 80mg 3 weeks after discontinuing CYP3A4 inducer. Dose modification: see full labeling.

Children: Not established.

Warnings/Precautions: Confirm presence of T790M mutation prior to treatment initiation.

Permanently discontinue if interstitial lung disease (ILD)/pneumonitis is confirmed; QTc interval prolongation with signs/symptoms of lifethreatening arrhythmia; persistent, asymptomatic LV dysfunction that does not resolve within

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DRUG MONOGRAPHS

LUNG CANCER 4 weeks; symptomatic CHF; or if no improvement of Grade ≥3 adverse reaction within 3 weeks occurs. Withhold dose if worsening respiratory symptoms indicative of ILD occur or if QTc interval >500msec on ≥2 separate ECGs. Monitor ECGs and electrolytes periodically in patients with congenital long QTc syndrome, CHF, electrolyte abnormalities, or those who are taking drugs known to prolong the QTc interval. Assess LVEF by echocardiogram or MUGA scan prior to initiation and every 3 months during treatment. Severe renal impairment (CrCl <30mL/min) or ESRD. Moderate or severe hepatic impairment. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for 6 weeks after final dose; males (with female partners of reproductive potential) should use effective contraception during and for 4 months after final dose. Pregnancy.

Nursing mothers: not recommended (during and for 2 weeks after final dose).

Interactions: Antagonized by strong CYP3A inducers (eg, phenytoin, rifampicin, carbamazepine, St. John’s Wort); avoid; if use is unavoidable, increase Tagrisso dose (see Adults).

Potentiates BCRP substrates (eg, rosuvastatin, sulfasalazine, topotecan); monitor closely for related toxicity.

Adverse reactions: Diarrhea, rash, dry skin, nail toxicity; possibly infertility.

How supplied: Tabs—30

TARCEVA Astellas and Genentech

℞

Kinase inhibitor. Erlotinib (as HCl) 25mg, 100mg, 150mg; tabs.

Indications: First-line treatment in patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. Maintenance treatment of patients with locally advanced or metastatic NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. Treatment of locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen.

Limitations of use: Do not use in combination with platinum-based chemotherapy. Not evaluated as first-line treatment in patients with metastatic NSCLC whose tumors have EGFR mutations other than exon 19 deletions or exon 21 (L858R) substitution.

Adults: Take on empty stomach. 150mg once daily.

Use until disease progression or unacceptable toxicity occurs. Diarrhea unresponsive to loperamide, severe skin reactions, strong CYP3A4 inhibitors (see Interactions), hepatic impairment:

reduce in 50mg decrements. Concomitant CYP3A4 inducers (see Interactions): increase in 50mg increments at 2-week intervals; max 450mg (see full labeling). Concurrent cigarette smoking: increase in 50mg increments at 2-week intervals; max 300mg (see full labeling); upon cessation, reduce to 150mg or 100mg daily.

Children: Not established.

Warnings/Precautions: Discontinue if interstitial lung disease, severe hepatic toxicity, GI perforation, severe bullous, blistering or exfoliating skin conditions, or corneal perforation or severe ulceration occurs. Withhold or consider discontinuing therapy if severe renal failure due to dehydration, or acute/worsening ocular disorders occur. Monitor LFTs periodically; withhold in patients without history of hepatic impairment for total bilirubin >3XULN or transaminases >5XULN, or in patients with history of hepatic impairment or biliary obstruction for doubling of bilirubin or tripling of transaminases over baseline. Discontinue if abnormal LFTs do not improve or resolve within 3 weeks. Withhold for persistent severe diarrhea unresponsive to loperamide, severe rash, or grade 3–4 keratitis. Monitor renal function, serum electrolytes, pulmonary function, INR, prothrombin time. History of peptic ulcers or diverticular disease.

Pregnancy (Cat.D); use effective contraception during therapy and at least 2 weeks after the last dose. Nursing mothers: not recommended.

Interactions: Potentiated by CYP3A4 inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, grapefruit) and CYP1A2 inhibitors (eg, ciprofloxacin); avoid if possible. Plasma levels decreased by CYP3A4 inducers (eg, rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, St. John’s wort), proton pump inhibitors or H2 blockers (take erlotinib 10hrs after and at least 2hrs before next dose), and smoking; avoid if possible. Increased risk of GI perforation with concomitant anti-angiogenic agents, steroids, NSAIDs, taxane-based chemotherapy. Monitor for bleeding with oral anticoagulants, NSAIDs. Adverse reactions: Rash, diarrhea, nausea, vomiting, anorexia, fatigue, elevated LFTs, unexplained pulmonary symptoms (eg, dyspnea, cough, fever; discontinue and follow-up if occurs), stomatitis, infection; rare: GI perforation (may be fatal), ocular disorders (eg, conjunctivitis, keratitis, corneal ulceration/perforation), MI/ischemia, hemolytic anemia, cerebrovascular accidents, interstitial lung disease; hepatic or renal failure and hepatorenal syndrome (may be fatal); bullous, blistering and exfoliative skin

conditions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis).

Testing considerations: K-RAS mutation analysis, EGFR amplification analysis How supplied: Tabs—30

TREXALL Teva

℞

Folic acid antagonist. Methotrexate sodium 5mg, 7.5mg, 10mg, 15mg; scored tabs. ℞ Also: Methotrexate injection Bedford Methotrexate 25mg/mL; soln for IV, IM, intraarterial, or intrathecal administration after dilution; preservative-free. ℞ Also: Methotrexate for injection Bedford Methotrexate 1g/vial; pwd for IV, IM, intra-arterial, or intrathecal administration after dilution; preservative-free.

Indications: Lung cancer (squamous cell and small cell types).

Adults: See literature.

Children: Not established.

Contraindications: Pregnancy (Cat. X). Nursing mothers.

Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Discontinue if malignant lymphomas occur. Obtain baseline and monitor CBCs with differential, platelet counts, chest X-ray, and hepatic, renal and pulmonary function. During therapy monitor hematology monthly, renal and hepatic function every 1–2 months, more often if increasing dose or predisposed to toxicity (eg, dehydration).

Discontinue immediately if blood counts drop significantly. Rule out pregnancy in women of childbearing potential; use effective contraception during therapy and for at least 1 ovulatory cycle afterwards for women and for at least 3 months afterwards for men. Interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur. Hepatic or renal impairment. Obesity.

Diabetes. Peptic ulcer. Ulcerative colitis. Infection.

Dehydration. Folate deficiency. Ascites, pleural effusions: evacuate fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated.

Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin, sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, non-absorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy.

Caution with other hepatotoxic drugs (eg,

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DRUG MONOGRAPHS

LUNG CANCER azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin).

Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, Stevens-Johnson syndrome).

How supplied: Tabs—30; soln (2mL, 4mL, 8mL, 10mL)—10 (single-use vials); pwd (1 gram)—1 (single-use vial)

XALKORI Pfizer

℞

Tyrosine kinase inhibitor. Crizotinib 200mg, 250mg; hard gel caps.

Indications: Treatment of metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. Treatment of metastatic NSCLC that is ROS1-positive.

Adults: Swallow whole. 250mg twice daily until disease progression or intolerance. Dose modification and/or dose reduction to 200mg twice daily may be required based on Grade 3 or 4 severity, then to 250mg once daily, or permanently discontinue if intolerable. Severe renal impairment (CrCl <30mL/min) not requiring dialysis: 250mg once daily. Dose reduction for hematologic and nonhematologic toxicities: see full labeling.

Children: Not established.

Warnings/Precautions: Confirm ALK-positive NSCLC with an FDA-approved test before treating. Monitor ALT and total bilirubin every 2 weeks during first 2 months, then monthly, and more frequently for elevated transaminases; temporarily suspend, reduce dose, or permanently discontinue as clinically indicated.

Monitor CBCs with differential monthly and more frequently if Grade 3 or 4 abnormalities, fever or infection occurs. Risk of severe pneumonitis: monitor for pulmonary symptoms; permanently discontinue if occurs. Congenital long QT syndrome; avoid. History of or predisposition for QTc prolongation (eg, CHF, bradyarrhythmias, electrolyte abnormalities, or those who are taking drugs known to prolong the QT interval): consider monitoring ECG, electrolytes periodically.

Torsade de pointes, ventricular tachycardia, serious arrhythmia: permanently discontinue if QTc >500ms or ≥60ms change from baseline.

Monitor HR and BP regularly; discontinue if life-threatening bradycardia occurs. Discontinue if onset of severe visual loss; perform eye evaluation. Hepatic impairment. Severe renal impairment. Embryo-fetal toxicity. Pregnancy; avoid. Use effective contraception during therapy and for at least 45 days (females) or 90 days (males) after final dose. Nursing mothers: not recommended (during therapy and for 45 days after final dose).

Interactions: Avoid concomitant strong CYP3A inhibitors (eg, atazanavir, clarithromycin, indinavir,

itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole), grapefruit juice, or strong CYP3A inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John’s Wort).

Avoid concomitant CYP3A substrates with narrow therapeutic indices (eg, alfentanil, cyclosporine, ergots, fentanyl, pimozide, quinidine, sirolimus, tacrolimus); if needed, reduce doses. Avoid concomitant agents known to cause bradycardia (eg, beta-blockers, non-dihydropyridine calcium channel blockers, clonidine, digoxin); adjust dose or discontinue. Caution with moderate CYP3A inhibitors. Dose reduction may be needed with coadministered drugs metabolized by CYP3A. Adverse reactions: Vision disorders, nausea, diarrhea, vomiting, constipation, edema, upper RTI, decreased appetite, dysgeusia, Grade 3–4 events: ALT increased, neutropenia; elevated total bilirubin, pneumonitis (may be fatal), QT prolongation, bradycardia, hepatotoxicity (may be fatal).

How supplied: Caps—60

ZYKADIA Novartis

potential should use effective contraception during treatment and for at least 2 weeks after completion.

Nursing mothers: not recommended.

Interactions: See Adults. Potentiated by strong CYP3A4 inhibitors (eg, ritonavir, macrolides, ketoconazole, nefazodone), grapefruit juice; avoid. Avoid concomitant strong CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s Wort). Avoid concomitant CYP3A substrates (eg, alfentanil, cyclosporine, ergots, fentanyl, pimozide, quinidine, sirolimus, tacrolimus) or CYP2C9 substrates (eg, phenytoin, warfarin) with narrow therapeutic indices; if unavoidable, reduce doses of these drugs. Avoid concomitant agents known to cause bradycardia (eg, beta-blockers, nondihydropyridine CCBs, clonidine, digoxin).

Adverse reactions: Diarrhea, nausea, vomiting, abdominal pain, constipation, elevated transaminases, fatigue, decreased appetite; bradycardia, hepatotoxicity, ILD/pneumonitis, QTc prolongation, hyperglycemia, pancreatitis.

How supplied: Caps—70

℞

Tyrosine kinase inhibitor. Ceritinib 150mg; hard gel caps.

Indications: Treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. Not established for improvement in survival or disease-related symptoms.

Adults: Take on an empty stomach (at least 2 hours before or after a meal). 750mg once daily until disease progression or unacceptable toxicity.

Discontinue if 300mg once daily not tolerated.

Moderate-to-severe hepatic impairment: not established. Dose modifications: see full labeling.

If concomitant use of strong CYP3A4 inhibitors unavoidable: reduce ceritinib dose by 1/3.

Children: Not established.

Warnings/Precautions: Monitor for severe or persistent GI toxicity; if occurs, withhold until improved; resume at reduced dose. Monitor ALT/AST and total bilirubin once monthly, and more frequently if elevated transaminases develop; withhold then reduce dose, or permanently discontinue as clinically indicated. Congenital long QT syndrome; avoid. Patients with CHF, bradyarrhythmias, electrolyte abnormalities, or those who are taking drugs known to prolong the QTc interval; monitor ECG, electrolytes periodically.

Permanently discontinue if QTc prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or serious arrhythmia develop. Monitor HR and BP regularly; fasting serum glucose, lipase, amylase prior to initiation and periodically thereafter. Monitor for pulmonary symptoms as clinically indicated. Permanently discontinue if treatment-related interstitial lung disease (ILD)/pneumonitis, uncontrolled hyperglycemia, or life-threatening bradycardia occur. Pregnancy (Cat.D). Females of reproductive

SEE LITERATURE Consult the manufacturer’s labeling for full prescribing information.

ADVERSE REACTIONS Those adverse reactions listed within product monographs represent the potential for adverse effects based upon the active ingredient(s) and/or the drug class. It is not meant to be an inclusive list of responses.

DOSAGE Recommended adult dosage and, where appropriate, the dosage for children. Doses are given for children <12 years of age unless stated otherwise.

Assume the adult dosage for children ≥12 years. Dosages for children are presented in ascending age order.

PHARMACOLOGIC CLASS The chemical/therapeutic class of the drug is listed in italics.

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CANCER TREATMENT REGIMEN

SARCOMA Soft Tissue Sarcoma Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team.

Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly.

The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Systemic Therapy With Activity in Soft Tissue Sarcoma Subtypes With Non–specific Histologies1abc Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

Combination Regimens Doxorubicin + dacarbazine (AD)2-5

Days 1–4: Doxorubicin 60mg/m2 + dacarbazine 750mg/m2 as a continuous IV infusion over 96 hours.

Repeat cycle every 3 weeks.

Doxorubicin + ifosfamide + mesna (AIM)4-7

Days 1 and 2: Doxorubicin 30mg/m2/day IV + ifosfamide 3,750mg/m2/day IV + mesna 750mg/m2 IV immediately preceding and then 4 and 8 hours after ifosfamide administration.

Repeat cycle every 3 weeks.

Mesna + doxorubicin + ifosfamide + dacarbazine (MAID)4,5,8,9

Days 1–3: Doxorubicin 20mg/m2/day + ifosfamide 2,500mg/m2/day + dacarbazine 300mg/m2/day as continuous IV infusion over 72 hours, plus Mesna 2,500mg/m2/day IV for 84 to 96 hours.

Repeat cycle every 3 weeks.

Ifosfamide + epirubicin + mesna10

Days 1 and 2: Epirubicin 60mg/m2/day IV Days 1–5: Ifosfamide 1.8g/m2/day IV over 1 hour + mesna at 20% of the ifosfamide dose IV immediately preceding and then 4 and 8 hours after ifosfamide administration.

Repeat cycle every 3 weeks for 5 cycles.

Gemcitabine + docetaxel11,12

Days 1 and 8: Gemcitabine 900mg/m2 IV Day 8: Docetaxel 100mg/m2 IV. Repeat cycle every 3 weeks.

Gemcitabine + vinorelbine13

Days 1 and 8: Vinorelbine 25mg/m2 IV over 10 minutes + gemcitabine 800mg/m2 IV over 90 minutes.

Repeat cycle every 3 weeks.

Gemcitabine + dacarbazine14

Day 1: Gemcitabine 1,800mg/m2 IV + dacarbazine 500mg/m2 IV. Repeat cycle ever y 2 weeks for a total of 12 cycles; continuation of treatment after 24 weeks was allowed at investigator discretion.

Single Agents Doxorubicin4,5,15

Doxorubicin 60–75mg/m2 IV every 3 weeks.

Ifosfamide10,16

Ifosfamide 2,000–3,000mg/m2/day IV for 3 to 4 days + mesna at 20% of the ifosfamide dose IV immediately preceding and then 4 and 8 hours after ifosfamide administration every 3 weeks.

OR Ifosfamide 5,000mg/m2 + mesna 5,000mg/m2 as a continuous IV infusion over 24 hours followed by additional mesna 400–600mg/m2 IV over 2 hours after completion of ifosfamide administration.

Repeat every 3 weeks.

Epirubicin17

Epirubicin 160mg/m2 IV every 3 weeks.

Gemcitabine

Days 1 and 8: Gemcitabine 1,200mg/m2 IV over 90 to 120 minutes.

Repeat cycle every 3 weeks.

Dacarbazine

Dacarbazine 250mg/m2/day IV for 5 days every 3 weeks.

OR Dacarbazine 800–1,000mg/m2 IV every 3 weeks. continued

CancerTherapyAdvisor.com | JANUARY/FEBRUARY 2017 | CANCER THERAPY ADVISOR 81

CANCER TREATMENT REGIMEN

SARCOMA Soft Tissue Sarcoma Treatment Regimens (continued) Systemic Therapy With Activity in Soft Tissue Sarcoma Subtypes With Non–specific Histologies1abc(continued) REGIMEN

DOSING

Single Agents (continued) Liposomal doxorubicin18

Liposomal doxorubicin 30–50mg/m2 IV every 4 weeks.

Temozolomide19d

Temozolomide 200mg/m2 orally twice daily for 5 days, followed by 9 doses of 90mg/m2 orally every 4 weeks.

Vinorelbine20d

Vinorelbine 30mg/m2 IV weekly for 6 weeks during an 8-week interval.

Pazopanib21de

Pazopanib 800mg orally once daily without food until disease progression or unacceptable toxicity.

Eribulin

Days 1 and 8: Eribulin mesylate 1.4mg/m2 IV. Repeat every 3 weeks until disease progression or unacceptable toxicity.

22d

Trabectedin23-25

Trabectedin 1.5mg/m2 as a 24-hour continuous IV infusion every 3 weeks.

Alveolar soft part sarcomas (ASPS), well-differentiated liposarcoma/atypical lipomatous tumor, and clear cell sarcomas are generally non sensitive to cytotoxic chemotherapy.

Anthracycline-based regimens are preferred in the neoadjuvant and adjuvant setting. c Regimens appropriate for pleomorphic rhabdomyosarcoma. d Recommended only for palliative therapy. e Pazopanib should not be used for lipogenic sarcomas. a

b

References 1. Referenced with permission from NCCN Clinical Practice Guidelines in Oncology™ Soft Tissue Sarcoma. V2.2016. Available at: http://www.nccn.org/professionals/ physician_gls/pdf/sarcoma.pdf. Accessed September 30, 2016.

2. Zalupski M, Metch B, Balcerzak S, et al. Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: A Southwest Oncology Group Study. J Natl Cancer Inst. 1991;83:926–932.

3. Antman K, Crowley J, Balcerzak SP, et al. An intergroup phase Ill randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol. 1993;11:1276–1285.

4. Adjuvant chemotherapy for localized resectable soft-tissue sarcoma of adults: Meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet.

1997;350:1647–1654.

5. Pervaiz N, Colterjohn N, Farrokhyar F, et al. A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. 1. 2008;113:573–581.

6. Grobmyer SR, Maki RG, Demetri GD, et al. Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma. Ann Oncol. 2004;15:1667–1672.

7. Edmonson J, Ryan L, Blum R, et al. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol. 1993;11:1269–1275.

8. Elias A, Ryan L, Sulkes A, et al. Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy. J Clin Oncol. 1989;7:1208–1216.

9. Kraybill WG, Harris J, Spiro IJ, et al. Long-term results of a phase 2 study of neoadjuvant chemotherapy and radiotherapy in the management of high-risk, highgrade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514. Cancer. 2010;116:4613–4621.

10. Frustaci S, Gherlinzoni F, De Paoli A, et al. Adjuvant chemotherapy for soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial. J Clin Oncol. 2001;19:1238–1247.

11. Hensley ML, Maki R, Venkatraman E, et al. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol. 2002;20: 2824–2831.

12. Maki RG, Wathen JK, Patel SR, et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002. J Clin Oncol. 2007; 25:2755–2763.

13. Dileo P, Morgan JA, Zahrieh D, et al. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a phase II trial. Cancer. 2007;109:1863–1869.

14. Garcia-Del-Muro X, Lopez-Pousa A, Maurel J, et al. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011;29:2528–2533.

15. Mack LA, Crowe PJ, Yang JL, et al. Preoperative chemoradiotherapy (modified ­Eilber protocol) provides maximum local control and minimal morbidity in patients with soft tissue sarcoma. Ann Surg Oncol. 2005;12:646–653.

16. Antman KH, Elias A. Dana-Farber Cancer Institute studies in advanced sarcoma.

Semin Oncol. 1990;1(Suppl 2):7–15.

17. Petrioli R, Coratti A, Correale P, et al. Adjuvant epirubicin with or without Ifosfamide for adult soft-tissue sarcoma. Am J Clin Oncol. 2002;25:468–473.

18. Judson I, Radford J, Harris M, et al. Randomized phase II trial of pegylated liposomal doxorubicin versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2001; 37:870–877.

19. Talbot SM, Keohan ML, Hesdorffer M, et al. A Phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma. Cancer. 2003;98: 1942–1946.

20. Kuttesch JF Jr, Krailo MD, Madden T, et al. Phase II evaluation of intravenous vinorelbine (Navelbine) in recurrent or refractory pediatric malignancies: a Children’s Oncology Group study. Pediatr Blood Cancer. 2009; 53:590–593.

21. van der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial.

Lancet. 2012;379:1879–1886.

22. Schöffski P, Ray-Coquard IL, Cioffi A, et al. Activity of eribulin mesylate in patients with soft-tissue sarcoma: a phase 2 study in four independent histological subtypes. Lancet Oncol. 2011;12(11):1045–1052.

23. Demetri GD, von Mehren M, Jones RL, et al. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial.

J Clin Oncol. 2015;33:1–8.

24. Kawai A, Araki N, Sugiura H, et al. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol.

2015;16(4):406–416.

25. Samuels BL, Chawla S, Patel S, et al. Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study. Ann Oncol.

2013;24(6):1703–1709.

(Revised 10/2016) © 2017 by Haymarket Media, Inc.

82 CANCER THERAPY ADVISOR | JANUARY/FEBRUARY 2017 | CancerTherapyAdvisor.com

DRUG MONOGRAPHS

SARCOMA DOXIL Janssen Biotech

℞

Anthracycline. Doxorubicin HCl (liposomal) 2mg/mL; dispersion for IV infusion after dilution; preservative-free.

Indications: AIDS-related Kaposi’s sarcoma refractory to combination chemotherapy.

Adults: Give by IV infusion at initial rate of 1mg/min; may increase rate to complete infusion over 1hr if no infusion reactions occur; may premedicate with antiemetics.

20mg/m2 once every 3 weeks. Hepatic dysfunction (serum bilirubin ≥1.2mg/dL), hand-foot syndrome, hematologic toxicity (esp. ANC, platelets), or stomatitis: reduce dose. Consider total anthracycline and anthracenedione doses and irradiation when calculating total cumulative dose. See full labeling.

Children: Not established.

Warnings/Precautions: Not substitutable on a mg/mg basis with other doxorubicin products. Cardiotoxicity, acute infusion-related reactions, myelosuppression may occur. Have resuscitative/antiallergic equipment and expertise available. Hepatic impairment. Monitor blood (esp. CBC + platelets), hepatic (esp.

SGOT/SGPT, alkaline phosphatase), and cardiac function (esp. myocardial biopsy). Monitor periodically for secondary oral cancers with long-term use. Avoid extravasation. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended.

Interactions: Caution with cyclosporine, phenobarbital, phenytoin, streptozocin, digoxin, myelosuppressants, others. Previous mediastinal irradiation, cyclophosphamide, other cardiotoxic drugs: monitor for cardiotoxicity and hepatotoxicity.

Adverse reactions: Asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand and foot syndrome, rash, neutropenia, thrombocytopenia, anemia; infusion reactions, cardiovascular events (eg, cardiomyopathy, CHF, acute LV failure), recall of skin reaction from prior radiation therapy, toxoplasmosis, urine discoloration (red/orange).

How supplied: Single-use vials (10mL, 25mL)—1

INTRON A Merck

℞ Also: INTRON A SOLN Interferon alfa-2b, recombinant; 10 million IU, 18 million IU, 25 million IU; per vial; for inj; contains m-cresol.

Indications: AIDS-related Kaposi’s sarcoma.

Adults: Use appropriate preparation and route: see full labeling. Use SC route if platelets <50,000/mm3. 30 million IU/m2 IM or SC three times weekly; continue until rapid disease progression or maximal response achieved after 16 weeks; reduce dose by ½ or suspend therapy if severe adverse reactions occur; discontinue if persists.

Children: Not recommended.

Contraindications: Decompensated liver disease. Autoimmune hepatitis.

Warnings/Precautions: May cause or exacerbate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, or infectious disorders: monitor closely, discontinue if they worsen.

Severe psychiatric disorders (esp. depression).

Cardiovascular or pulmonary disease. Severe myelosuppression; discontinue if neutrophil count <0.5 X109/L or platelets 25X109/L. Permanently discontinue if severe (Grade 3) hepatic injury or decompensation (Child-Pugh score >6 [Class B and C]) develop. Thyroid abnormalities; discontinue if uncontrolled by medication. Diabetes. Coagulation disorders.

Maintain adequate hydration. Monitor blood, thyroid, visual and liver function before and during therapy; EKG in cardiovascular disease and cancer patients. Psoriasis. Renal dysfunction.

Transplant recipients. Elderly. Debilitated.

Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Caution with myelosuppressives, and drugs that can exacerbate depression. May potentiate theophylline (may double its levels).

Adverse reactions: Flu-like symptoms (fever, headache, myalgia, fatigue); hepatic, hematologic, respiratory, skin, genitourinary system, CNS, cardiovascular, endocrine (esp. thyroid), GI, or visual disorders; colitis, hypertriglyceridemia, pancreatitis, infections, injection site reactions, dental and periodontal disorders; others (see full labeling).

How supplied: Pwd (w. diluent): 10million, 18million, 50million IU/vial—1; Soln (multidose vials): 18million, 25million IU/vial—1

PANRETIN Eisai ℞

Alpha interferon. Interferon alfa-2b, recombinant; 10 million, 18 million, or 50 million IU per vial; pwd; for inj after reconstitution/dilution; preservativefree; contains albumin.

℞

Retinoid. Alitretinoin 0.1%; gel.

Indications: Cutaneous lesions of AIDS-related Kaposi’s sarcoma (KS).

Adults: Apply twice daily to lesions (avoid mucous membranes and normal skin); do

not occlude; may increase to 3–4 times daily as tolerated. Reduce frequency or suspend treatment if local toxicity occurs.

Children: Not recommended.

Warnings/Precautions: Not for use when systemic KS therapy required. Avoid sun, UV light.

Flammable. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Increases DEET toxicity (avoid).

Adverse reactions: Photosensitivity, rash, pruritus, pain, exfoliative dermatitis, paresthesia, edema.

How supplied: Gel—60g

GENERIC NAME The active ingredients and strengths are listed under the name of each dosage form. If the product contains tartrazine, alcohol, flavors, or is alcohol-, sugar-, or dye-free, it is noted. Abbreviations are used to describe the dosage form and its formulation, e.g.: tabs = tablets caps = capsules e-c = enteric coated sust rel = sustained-release ext rel = extended-release

BRAND NAME The main name under which the product and all other dosage forms in the monograph are marketed.

LEGAL CATEGORY Federal schedule. The laws governing the prescribing/dispensing of products vary from state to state.

Oncology Nurse Advisor provides important clinical information, including a CE activity in each issue.

Go to OncologyNurseAdvisor.com/Subscribe to sign up for a free subscription.

CancerTherapyAdvisor.com | JANUARY/FEBRUARY 2017 | CANCER THERAPY ADVISOR 83

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DRUG MONOGRAPHS

SKIN CANCER COTELLIC Genentech

℞

Kinase inhibitor. Cobimetinib 20mg; tabs.

Indications: In combination with vemurafenib for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations.

Adults: Confirm presence of BRAF V600E or V600K mutation prior to initiation. In combination with vemurafenib: 60mg once daily for first 21 days of each 28-day cycle until disease progression or unacceptable toxicity.

Concomitant CYP3A inhibitors: see Interactions.

Other dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Review full labeling for vemurafenib prior to initiation. Monitor for new malignancies (cutaneous and non-cutaneous); perform skin evaluations prior to initiation, every 2 months during therapy, and for 6 months after discontinuation. Monitor for signs/symptoms of bleeding; withhold if Grade 3 hemorrhagic events occur; resume at lower dose if improved to Grade 0/1 within 4 weeks; discontinue if no improvement. Risk of cardiomyopathy; assess LVEF prior to initiation, after 1 month, and then every 3 months thereafter until discontinuation.

Patients with baseline LVEF below institutional lower limit of normal or <50%: not established.

Interrupt, reduce dose, or discontinue if severe skin reactions occur. Perform eye exams at regular intervals and for any visual disturbances.

Manage serous retinopathy with treatment interruption, dose reduction, or discontinuation.

Permanently discontinue if retinal vein occlusion occurs. Monitor liver tests prior to initiation, monthly during treatment, or more frequently as indicated; dose interruption, reduction, or discontinuation if Grade 3/4 abnormalities occur.

Obtain baseline CPK and creatinine levels prior to initiation, periodically during treatment, and as clinically indicated for signs/symptoms of rhabdomyolysis. Avoid sun exposure. Severe renal impairment. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during therapy and for 2 weeks after final dose. Pregnancy. Nursing mothers: not recommended (during therapy and for 2 weeks after final dose).

Interactions: Avoid concomitant strong or moderate CYP3A inhibitors (eg, itraconazole, erythromycin, ciprofloxacin). If short-term (≤14 days) use of moderate CYP3A inhibitors is unavoidable for patients taking cobimetinib 60mg, reduce to 20mg and resume at previous dose upon discontinuing the CYP3A inhibitor; for patients taking cobimetinib 20mg or 40mg, use alternative. Avoid concomitant strong or moderate CYP3A inducers (eg, carbamazepine, efavirenz, phenytoin, rifampin, St. John’s wort).

Adverse reactions: Diarrhea, photosensitivity, nausea, pyrexia, vomiting, increased GGT, CPK, ALT/AST and alkaline phosphatase, hypophosphatemia, lymphopenia, hyponatremia.

How supplied: Tabs—63

EFUDEX Valeant

℞

Antimetabolite. Fluorouracil 2%, 5%; soln. ℞ Also: EFUDEX CREAM Fluorouracil 5%.

Indications: Multiple actinic or solar keratoses.

Superficial basal cell carcinoma when conventional therapy is impractical (5% only); see literature.

Adults: Keratoses: Apply twice daily until erosion occurs (usually 2–4 wks). Basal cell carcinoma (5% only): Apply twice daily, usually for 3–6 weeks (obliteration may take 10–12 weeks).

Children: Not recommended.

Contraindications: Dihydropyrimidine dehydrogenase (DPD) deficiency. Pregnancy (Cat.X).

Warnings/Precautions: Apply cautiously near eyes, nose, mouth. Avoid mucous membranes, occlusion, ulcerated/inflamed skin, exposure to UV light. Wash hands after application if fingers were used. Notify patients of expected skin reaction. Biopsy unresponsive lesions. Nursing mothers: not recommended.

Adverse reactions: Pain or burning at application site, pruritus, irritation, hyperpigmentation.

How supplied: Soln—10mL (w. drop dispenser); Crm—25g

ERIVEDGE Genentech

℞

Hedgehog pathway inhibitor. Vismodegib 150mg; caps.

Indications: Treatment of adults with metastatic basal cell carcinoma, or locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation.

Adults: Swallow whole. 150mg once daily, until disease progression or unacceptable toxicity.

Children: Not established.

Warnings/Precautions: Risk of embryo-fetal death and severe birth defects in pregnant women.

Verify pregnancy status within 7 days prior to initiation of therapy. Counsel patients (males and females) on the need for contraception during and after treatment. Advise patients not to donate blood or blood products while on therapy and for 7 months after last dose. Advise male patients not to donate semen during and for 3 months after final dose. Nursing mothers: not recommended during and for 7 months after final dose.

Interactions: May be potentiated by P-gp inhibitors (eg, clarithromycin, erythromycin, azithromycin). May be antagonized by drugs that affect gastric pH (eg, proton pump inhibitors, H2receptor antagonists, antacids).

Adverse reactions: Muscle spasms, alopecia, dysgeusia, weight loss, fatigue, GI upset, decreased appetite, constipation, arthralgias, ageusia; amenorrhea.

Note: Report immediately exposure to Erivedge during pregnancy by contacting the Genentech Adverse Event Line at (888) 835-2555.

How supplied: Caps—28

GLEEVEC Novartis

℞

Kinase inhibitor. Imatinib (as mesylate) 100mg, 400mg; scored tabs.

Indications: Adults with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown. Adults with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP).

Adults: Take with food and water. May disperse tab in water or apple juice and take promptly. ≥18yrs: ASM without D816V c-Kit mutation or status unknown: 400mg once daily. ASM associated with eosinophilia: initially 100mg once daily; may increase to 400mg once daily if insufficient response. If severe non-hematologic reactions develop: interrupt dose; resume at a lower dose in hepatic dysfunction. Severe hepatic impairment: reduce dose by 25%. Renal or hematologic reactions: see full labeling.

Avoid concomitant strong CYP3A4 inducers (eg, rifampin): if needed, increase imatinib dose by at least 50%.

Children: Not recommended.

Warnings/Precautions: Hepatic or renal impairment. Monitor weight and for fluid retention regularly; CBCs weekly for 1st month, bi-weekly for 2nd month, then periodically (eg, every 2–3 months); liver function at baseline then monthly or as needed; GI symptoms at baseline. Cardiovascular disease or risk factors; monitor. Immunosuppression and potential toxicities (liver, kidney, cardiac) from long-term use. Monitor for tumor lysis syndrome; correct clinically significant dehydration and treat high uric acid levels before initiating therapy.

Monitor growth in children. Possible cardiogenic shock/LV dysfunction in conditions with high eosinophil levels (eg, HES/CEL, MDS/MPD, ASM); consider concomitant systemic steroid prophylaxis (1–2mg/kg) for 1 or 2 wks if abnormal ECG or serum troponin. Monitor TSH levels in thyroidectomy patients undergoing levothyroxine replacement. Pregnancy (Cat.D); avoid. Use highly effective contraception during treatment.

Nursing mothers: not recommended.

Interactions: Avoid grapefruit juice. Potentiated

by CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, nefazodone, clarithromycin, telithromycin). Antagonized by strong CYP3A4 inducers (eg, dexamethasone, fosphenytoin, phenytoin, phenobarbital, carbamazepine, oxcarbamazepine, primidone, St. John’s wort, rifampin, rifabutin, rifampicin); consider alternatives. May potentiate drugs metabolized

by CYP3A4 (eg, benzodiazepines, dihydropyridine calcium channel blockers, cyclosporine, ergots, alfentanil, fentanyl, pimozide, quinidine, certain statins, sirolimus, tacrolimus), CYP2D6, or CYP2C9 (use heparin instead of warfarin).

Adverse reactions: Edema (may be severe), nausea, vomiting, musculoskeletal pain, diarrhea, muscle cramps, rash (may be severe;

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DRUG MONOGRAPHS

SKIN CANCER eg, erythema multiforme, Stevens-Johnson syndrome), fatigue, abdominal pain, dizziness, blurred vision, somnolence, fever, headache, cough, arthralgia/myalgia, dyspnea, hypokalemia, night sweats, anorexia, pruritus, hemorrhage, anemia, neutropenia, thrombocytopenia, weight gain, renal or hepatotoxicity, immunosuppression, hypothyroidism; rare: severe CHF, LV dysfunction.

How supplied: 100mg—90; 400mg—30

IMLYGIC Amgen

℞

Genetically modified oncolytic viral therapy.

Talimogene laherparepvec 106 (1 million) PFU/mL, 108 (100 million) PFU/mL; susp for intralesional inj; preservative-free.

Indications: Treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. Limitations of use: not shown to improve overall survival or have an effect on visceral metastases.

Adults: See full labeling. Inject intralesionally into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable, or detectable by ultrasound guidance. Total inj volume per treatment visit: max 4mL for all injected lesions combined. Initial dose: up to 4mL of 106 (1 million) PFU/mL. 2nd dose: up to 4mL of 108 (100 million) PFU/mL given 3 weeks later. All subsequent doses (including reinitiation): up to 4mL of 108 (100 million) PFU/mL given 2 weeks apart.

Continue for ≥6 months unless other treatment required or until no injectable lesions to treat; reinitiate if new lesions appear after a complete response.

Children: Not established.

Contraindications: Immunocompromised or pregnant patients.

Warnings/Precautions: For intralesional inj only.

Avoid accidental exposure (esp. skin, eyes, mucous membranes) and direct contact with patient’s injected lesions, dressings, or body fluids. Advise patients to avoid inadvertent transfer of drug to other areas of the body (eg, touching/scratching inj sites or occlusive dressings). Evaluate lesions if suspected herpetic infection occurs. Inj site complications (eg, necrosis or ulceration of tumor tissue, cellulitis, systemic bacterial infection).

Persistent infection or delayed healing of inj site. Underlying autoimmune disease. Multiple myeloma or plasmacytoma. Pregnancy. Women of childbearing potential should use effective method of contraception. Nursing mothers: not recommended.

Interactions: Acyclovir or other antiherpetic viral agents may interfere with efficacy.

Adverse reactions: Fatigue, chills, pyrexia, nausea, influenza-like illness, inj site pain; immune-mediated events.

Note: Report suspected herpetic lesions to Amgen at (855) 465-9442.

How supplied: Single-use vial (1mL)—1

INTRON A Merck

dental and periodontal disorders; others (see full labeling).

How supplied: Pwd (w. diluent): 10million, 18million, 50million IU/vial—1; Soln (multidose vials): 18million, 25million IU/vial—1

KEYTRUDA Merck ℞

Alpha interferon. Interferon alfa-2b, recombinant; 10 million, 18 million, or 50 million IU per vial; pwd; for inj after reconstitution/dilution; preservativefree; contains albumin. ℞ Also: INTRON A SOLN Interferon alfa-2b, recombinant; 10 million IU, 18 million IU, 25 million IU; per vial; for inj; contains m-cresol.

Indications: Malignant melanoma.

Adults: Induction: 20million IU/m2 IV over 20 mins, 5 consecutive days per week, for 4 weeks. Maintenance: 10 million IU/m2 SC 3 times per week for 48 weeks. See full labeling for appropriate preparation and route and for dose adjustments.

Children: Not recommended.

Contraindications: Decompensated liver disease. Autoimmune hepatitis.

Warnings/Precautions: May cause or exacerbate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, or infectious disorders: monitor closely, discontinue if they worsen. Severe psychiatric disorders (esp. depression). Cardiovascular or pulmonary disease. Severe myelosuppression; discontinue if neutrophil count <0.5 X109/L or platelets 25X109/L. Permanently discontinue if severe (Grade 3) hepatic injury or decompensation (Child-Pugh score >6 [Class B and C]) develop.

Thyroid abnormalities; discontinue if uncontrolled by medication. Diabetes. Coagulation disorders.

Maintain adequate hydration. Monitor blood, thyroid, visual and liver function before and during therapy; EKG in cardiovascular disease and cancer patients. Psoriasis. Renal dysfunction.

Transplant recipients. Elderly. Debilitated.

Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Caution with myelosuppressives, and drugs that can exacerbate depression.

May potentiate theophylline (may double its levels).

Adverse reactions: Flu-like symptoms (fever, headache, myalgia, fatigue); hepatic, hematologic, respiratory, skin, genitourinary system, CNS, cardiovascular, endocrine (esp. thyroid), GI, or visual disorders; colitis, hypertriglyceridemia, pancreatitis, infections, injection site reactions,

℞

Human programmed death receptor-1 (PD-1)-blocking antibody. Pembrolizumab 50mg/vial; lyophilized pwd for IV infusion after reconstitution; 25mg/mL; per vial; soln for IV infusion after dilution; both: preservative-free.

Indications: Unresectable or metastatic melanoma.

Adults: Give as IV infusion over 30mins.

2mg/kg every 3 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling. Administer corticosteroids for most Grade ≥2 related immune-mediated reactions.

Children: Not established.

Warnings/Precautions: Monitor for pneumonitis; withhold dose if Grade 2 pneumonitis; permanently discontinue if Grade 3 or 4, or recurrent Grade 2 develops. Monitor for colitis; withhold dose if Grade 2 or 3 colitis; permanently discontinue if Grade 4 develops.

Monitor for changes in liver function; withhold dose or discontinue based on severity of elevated liver enzymes. Monitor for changes in renal function; withhold dose if Grade 2 nephritis; permanently discontinue if Grade 3 or 4 develops.

Monitor for hypophysitis; withhold dose if Grade 2 hypophysitis; withhold or discontinue if Grade 3 or 4 develops. Monitor for changes in thyroid function (at treatment initiation, during, and as clinically indicated) and signs/symptoms of thyroid disorders; withhold or discontinue if Grade 3 or 4 hyperthyroidism develops. Monitor for hyperglycemia and other diabetes symptoms; withhold if severe hyperglycemia until controlled.

Permanently discontinue if any severe or Grade 3 immune-mediated adverse reaction recurs, for any life-threatening immune-mediated adverse reaction, persistent Grade 2 or 3 reactions that do not recover to Grade 0–1 within 12wks after last dose, or inability to reduce corticosteroid dose to ≤10mg/day of prednisone or equivalent within 12wks. Monitor for infusion-related reactions; permanently discontinue if Grade 3 or 4 develops.

Embryo-fetal toxicity. Use highly effective contraception during treatment and for 4 months after the final dose. Pregnancy: avoid. Nursing mothers: not recommended (during treatment and for 4 months after the final dose).

Adverse reactions: Fatigue, decreased appetite, dyspnea, pruritus, rash, constipation, diarrhea,

Visit OncologyNurseAdvisor.com for practical clinical information geared toward oncology nurses and other cancer care professionals.

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DRUG MONOGRAPHS

SKIN CANCER nausea, cough; immune-mediated disorders, infusion-related reactions.

How supplied: Single-use vial 50mg—1; Singleuse vial 25mg/mL—1

MEKINIST GlaxoSmithKline

℞

Kinase inhibitor. Trametinib 0.5mg, 1mg, 2mg; tabs.

Indications: As monotherapy or in combination with dabrafenib for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDAapproved test. Limitation of use: as a single agent is not indicated for the treatment of patients who have received prior BRAF-inhibitor therapy.

Adults: Confirm presence of BRAF V600E or V600K mutation prior to initiation. Take at least 1hr before or 2hrs after a meal. Monotherapy or in combination with dabrafenib: 2mg once daily; continue until disease progression or unacceptable toxicity occurs. In combination therapy: take at same time each day either with the AM or PM dose of dabrafenib. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: See full labeling for dabrafenib prior to starting combination therapy. Risk of cardiomyopathy; assess LVEF prior to initiation, after one month, and then at every 2–3 month intervals during treatment; withhold if absolute LVEF decreases by 10% from pre-treatment values and is less than the lower limit of normal; permanently discontinue if symptomatic cardiomyopathy or persistent asymptomatic LVEF dysfunction is unresolved within 4 weeks. Perform eye exam at any time for visual disturbances and compare to baseline.

Retinal pigment epithelial detachment; withhold if diagnosed; if resolved within 3 weeks, may resume at reduced dose. Withhold if new or progressive pulmonary symptoms or findings develop. Permanently discontinue if retinal vein occlusion, interstitial lung disease, or pneumonitis occurs. Monitor for skin toxicities and secondary infections. Embryo-fetal toxicity. Females of reproductive potential should use highly effective contraception during and for 4 months after treatment. Pregnancy (Cat. D). Nursing mothers: not recommended.

Adverse reactions: Rash, diarrhea, lymphedema; combination with dabrafenib: pyrexia, chills, fatigue, rash, nausea, vomiting, constipation, abdominal pain, peripheral edema, cough, headache, arthralgia, night sweats, decreased appetite, myalgia; hemorrhage, thromboembolic events.

How supplied: Tabs—30

ODOMZO Novartis Hedgehog pathway inhibitor. Sonidegib 200mg; caps.

Indications: Treatment of adults with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation, or those

℞

who are not candidates for surgery or radiation therapy.

Adults: Take on empty stomach. 200mg once daily until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Risk of embryofetal death or severe birth defects in pregnant women. Verify pregnancy status of females of reproductive potential prior to initiation. Advise females to use effective contraception during therapy and for at least 20 months after the last dose; male patients must use condoms and not to donate semen during therapy and for at least 8 months after last dose. Advise patients not to donate blood or blood products during therapy and for at least 20 months after last dose. Risk of musculoskeletal adverse reactions accompanied by serum creatine kinase (CK) elevations; temporarily interrupt or discontinue based on severity of reactions. Obtain baseline serum CK and creatinine (SCr) levels prior to initiation; periodically during treatment and as clinically indicated. Obtain serum CK and SCr levels at least weekly in those with musculoskeletal adverse reactions with concurrent serum CK elevation >2.5XULN until symptoms resolve. Pregnancy.

Nursing mothers: not recommended during therapy and for 20 months after last dose.

Interactions: Avoid concomitant strong CYP3A inhibitors (eg, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone) or moderate CYP3A inhibitors (eg, atazanavir, diltiazem, fluconazole); if moderate CYP3A inhibitor use necessary, administer for <14 days and monitor closely.

Avoid concomitant strong or moderate CYP3A inducers (eg, carbamazepine, efavirenz, modafinil, phenobarbital, phenytoin, rifabutin, rifampin, St. John’s Wort).

Adverse reactions: Muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, pruritus; anemia, hyperglycemia, increased SCr, CK, and LFTs. Note: To report exposure to Odomzo during pregnancy, call Novartis at (888) 669-6682.

How supplied: Caps—30

OPDIVO Bristol-Myers Squibb

℞

Human programmed death receptor-1 (PD-1)blocking antibody. Nivolumab 10mg/mL; per vial; soln for IV infusion after dilution; preservativefree; contains mannitol.

Indications: As a single agent for patients with BRAF V600 wild-type or BRAF V600 mutation (+) unresectable or metastatic melanoma. In combination with ipilimumab for unresectable or metastatic melanoma.

Adults: Give as IV infusion over 60mins.

240mg every 2 weeks until disease progression or unacceptable toxicity. In combination with ipilimumab: 1mg/kg (followed by ipilimumab on

the same day) every 3 weeks for 4 doses, then followed by 240mg every 2 weeks (as single agent) until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: See full labeling. Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for any life-threatening (Grade 4) adverse reaction, Grade 3 or 4 pneumonitis, Grade 3/4 or recurrent colitis (with ipilimumab), Grade 4 or recurrent colitis (as single agent), AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash (or confirmed SJS or TEN), immune-mediated encephalitis, recurring Grade 3 adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2 or 3 adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2 or 3 (as single agent) colitis, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5– 6XULN, Grade 2 or 3 hypophysitis, Grade 2 adrenal insufficiency, Grade 3 hyperglycemia, Grade 3 rash (or suspected SJS or TEN), new onset moderate-tosevere neurologic symptoms, other Grade 3 adverse reactions (1st occurrence); withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if mild or moderate infusion reactions occur; discontinue if severe or life-threatening. Monitor for abnormal liver tests, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism. Monitor for transplant-related complications (eg, hyperacute or Grade 3/4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease) and treat promptly. Moderate or severe hepatic impairment: not studied. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for ≥5 months after final dose. Pregnancy (esp. during 2nd & 3rd trimesters), nursing mothers: not recommended.

Adverse reactions: Fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper RTI; also with Ipilimumab: pyrexia, vomiting; immune-mediated reactions (may be fatal).

How supplied: Single-use vial (4mL, 10mL)—1

PROLEUKIN Prometheus

℞

Interleukin-2, recombinant. Aldesleukin 22 million IU/vial; pwd for IV infusion after reconstitution and dilution; contains mannitol; preservative-free.

Indications: Metastatic melanoma.

Adults: ≥18yrs: 600,000 IU/kg (0.037mg/kg) every 8 hours by IV infusion over 15 minutes for a max of 14 doses, followed by 9 days rest, then repeat for another 14 doses (max 28 doses/course), as tolerated. Retreatment and dose adjustments: see literature.

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DRUG MONOGRAPHS

SKIN CANCER Children: <18yrs: not established.

Contraindications: Abnormal thallium stress test or pulmonary function tests. Organ allografts.

Previous drug related toxicity (eg, sustained ventricular tachycardia [≥5 beats], uncontrolled or unresponsive arrhythmias, chest pain with ECG changes consistent with angina, or MI, cardiac tamponade, intubation >72hrs, renal failure requiring dialysis >72hrs, coma or toxic psychosis >48hrs, repetitive or difficult seizures, bowel ischemia or perforation, GI bleeding requiring surgery).

Warnings/Precautions: See literature. History of cardiac or pulmonary disease. Renal, hepatic, or CNS impairment. Seizure disorder. Bacterial infections (treat prior to starting therapy; esp. patients with indwelling central lines). Withhold dose if organ perfusion is not maintained, urine output is reduced, systolic BP <90mmHg, CHF, cardiac ischemia or arrhythmias occur; or if moderate-to-severe lethargy or somnolence (continuing may result in coma) develops. Evaluate and treat CNS metastases; obtain negative scan before starting treatment. Do thallium stress test; monitor vital signs, weight, fluid intake and output daily. Correct hypovolemia or fluid accumulations if occur. Obtain CBCs, differential and platelets, blood chemistries (electrolytes, renal and hepatic function tests), chest X-rays, serum creatinine (should be ≤1.5mg/dL before starting therapy), pulmonary function tests, arterial blood gases.

Monitor for capillary leak syndrome, mental status changes, thyroid changes, diabetes onset.

Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Psychotropics may increase CNS toxicity. Increased toxicity with other nephrotoxic, hepatotoxic, myelotoxic, or cardiotoxic drugs. Hypersensitivity reactions with other antineoplastics. Myocardial injury and rhabdomyolysis risk increased with interferonalfa. Antagonized by glucocorticoids (avoid). β-blockers and other antihypertensives may potentiate hypotension. Delayed reactions to iodinated contrast media. May increase risk of allograft rejection.

Adverse reactions: Hypotension, GI upset, oliguria, flu-like syndrome, respiratory disorders (eg, dyspnea), CNS effects (eg, confusion, somnolence), rash, metabolic and nutritional disorders (eg, bilirubinemia, increased creatinine), hyperglycemia, thyroid disorder, thrombocytopenia, anemia, impaired neutrophil function, capillary leak syndrome, cardiotoxicity, exacerbation of autoimmune and inflammatory disease, eosinophilia, possible antibody formation; others.

How supplied: Single-use vials—1

SYLATRON Merck

℞

Alpha interferon. Peginterferon alfa-2b 296mcg, 444mcg, 888mcg; per vial; lyophilized pwd for SC inj after reconstitution.

Indications: Adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy.

Adults: Give by SC inj. Rotate inj sites.

Premedicate with acetaminophen. ≥18yrs: 6mcg/kg/week for 8 doses, followed by 3mcg/kg/week for up to 5yrs. Renal impairment (moderate): initially 4.5mcg/kg/week for 8 doses, followed by 2.25mcg/kg/week for up to 5yrs; (severe or ESRD on dialysis): initially 3mcg/kg/week for 8 doses, followed by 1.5mcg/kg/week for up to 5yrs. Withhold dose if ANC <0.5x109/L, platelets <50x109/L, ECOG PS ≥2, or for non-hematologic toxicity ≥ Grade 3. Resume at reduced dose (see full labeling) when: ANC ≥0.5x109/L, platelets ≥50x109/L, ECOG PS 0–1, and non-hematologic toxicity has completely resolved or improved to Grade 1.

Children: <18yrs: not established.

Contraindications: Anaphylaxis to peginterferon alfa-2b or interferon alfa-2b.

Autoimmune hepatitis. Hepatic decompensation (Child-Pugh score >6 [Class B and C]).

Warnings/Precautions: Increased risk of serious depression, suicidal ideation, and other neuropsychiatric disorders. Permanently discontinue for: persistent severe or worsening neuropsychiatric disorders (eg, depression, psychosis, encephalopathy); new onset ventricular arrhythmia or cardiovascular decompensation; new or worsening retinopathy; Grade 4 non-hematologic toxicity; severe (Grade 3) hepatic injury or hepatic decompensation; hypothyroidism, hyperthyroidism, or diabetes mellitus that cannot be effectively managed; or if unable to tolerate a dose of 1mcg/kg/week. Monitor for signs/symptoms of depression/psychosis every 3 weeks during first 8 weeks, then every 6 months, continue for at least 6 months after last dose. Perform eye exam in patients with retinopathy and those with vision changes during therapy. Monitor hepatic function with serum bilirubin, ALT/AST, alkaline phosphate, and LDH at 2 and 8 weeks, and 2 and 3 months following initiation, then every 6 months. Obtain TSH levels within 4 weeks prior to initiation, at 3 and 6 months following initiation, then every 6 months. Moderate-to-severe renal impairment (monitor). Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Potentiates CYP1A2 (eg, caffeine) or CYP2D6 (eg, desipramine) substrates.

Concomitant drugs with narrow therapeutic range metabolized by CYP1A2 or CYP2D6; monitor for increased toxicities.

Adverse reactions: Fatigue, increased ALT/AST, pyrexia, headache, anorexia, myalgia, nausea, chills, inj site reactions; neuropsychiatric disorders.

How supplied: Single-use vial—1 (w. diluent)

TAFINLAR GlaxoSmithKline

℞

Kinase inhibitor. Dabrafenib 50mg, 75mg; caps.

Indications: As monotherapy for the treatment of unresectable or metastatic melanoma with BRAF V600E mutation, as detected by an FDAapproved test. In combination with trametinib for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test.

Limitation of use: not indicated for the treatment of wild-type BRAF melanoma.

Adults: Confirm presence of BRAF V600E or V600K mutation prior to initiation. Swallow whole.

Take at least 1hr before or 2hrs after a meal.

Monotherapy or in combination with trametinib: 150mg twice daily (about 12hrs apart); continue until disease progression or unacceptable toxicity occurs. Dose modifications or reductions: see full labeling.

Children: Not established.

Warnings/Precautions: See full labeling for trametinib prior to starting combination therapy.

Increased incidence of new primary cutaneous malignancies; perform skin evaluation prior to initiation, every 2 months during therapy, and up to 6 months after discontinuation. Withhold if fever ≥101.3°F or any serious febrile drug reaction occurs and evaluate for infection; prophylaxis with antipyretics may be needed when resuming.

Pre-existing diabetes or hyperglycemia; monitor serum glucose levels. Monitor for visual signs/symptoms of uveitis. Closely monitor patients with G6PD deficiency for signs of hemolytic anemia. Males (risk of infertility).

Embryo-fetal toxicity. Females of reproductive potential should use highly effective nonhormonal contraception during and for 4 weeks after treatment. Pregnancy (Cat. D). Nursing mothers: not recommended.

Interactions: Concomitant strong inhibitors (eg, ketoconazole, nefazodone, clarithromycin, gemfibrozil) or inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital, St John’s wort) of CYP3A4 or CYP2C8: not recommended; if unavoidable, monitor closely. Drugs that affect

Access Cancer Therapy Advisor treatment regimens in a user-friendly format.

CancerTherapyAdvisor.com/TreatmentRegimens.

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DRUG MONOGRAPHS

SKIN CANCER gastric pH (eg, PPIs, H2-blockers, antacids) may decrease dabrafenib exposure. May antagonize effects of CYP3A4, CYP2B6, CYP2C8, CYP2C9, CYP2C19, UGT, transporters, or other substrates (eg, midazolam, warfarin, dexamethasone, hormonal contraceptives).

Adverse reactions: Hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, palmarplantar erythrodysesthesia syndrome; combination with trametinib: chills, fatigue, rash, nausea, vomiting, diarrhea, constipation, abdominal pain, peripheral edema, cough, night sweats, decreased appetite, myalgia; hemorrhage, thromboembolic events.

How supplied: Caps—120

YERVOY Bristol-Myers Squibb

mediated reactions. Withhold dose for moderate immune-mediated adverse reactions until return to baseline, improvement to mild severity, or complete resolution, and patient is receiving <7.5mg prednisone or equivalent per day. Monitor for enterocolitis, hepatitis, dermatitis, neuropathy, endocrinopathy, and others including ocular manifestations; perform clinical chemistries including LFTs, ACTH levels, and thyroid tests at baseline and before each dose. Moderate or severe hepatic impairment. Pregnancy; avoid. Use effective contraception during therapy and for 3 months after final dose. Nursing mothers: not recommended (during therapy and for 3 months after final dose).

Adverse reactions: Fatigue, diarrhea, pruritus, rash, colitis, headache, weight loss, nausea, pyrexia, decreased appetite, vomiting, insomnia.

How supplied: Single-use vial (50mg, 200mg)—1

℞

Cytotoxic T-lymphocyte antigen 4 (CTLA-4)blocking antibody. Ipilimumab 5mg/mL; soln for IV infusion; preservative-free.

Indications: Treatment of unresectable or metastatic melanoma. Adjuvant treatment of cutaneous melanoma in patients with pathologic involvement of regional lymph nodes >1mm who have undergone complete resection, including total lymphadenectomy.

Adults: Give by IV infusion over 90 mins.

Unresectable, metastatic: 3mg/kg every 3 weeks for a maximum of 4 doses; may delay doses if toxicity occurs, but all treatment must be given within 16 weeks of the first dose. Adjuvant: 10mg/kg every 3 weeks for 4 doses, followed by 10mg/kg every 12 weeks for up to 3 years; may omit doses if toxicity occurs. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Severe and fatal immune-mediated adverse reactions can develop. Permanently discontinue therapy and initiate systemic high-dose corticosteroids for severe, persistent, or recurring immune-

ZELBORAF Genentech

℞

Kinase inhibitor. Vemurafenib 240mg; tabs.

Indications: Treatment of unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. Limitation of use: not for treatment of wild-type BRAF melanoma.

Adults: Swallow whole. ≥18yrs: 960mg every 12hrs; until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions: see full labeling.

Children: <18yrs: not established.

Warnings/Precautions: Confirm BRAF V600E mutation-positive melanoma with FDAapproved test before initiating. Risk of cutaneous squamous cell carcinoma (cuSCC): ≥65yrs, prior skin cancer, chronic sun exposure; if occurs, do excision and evaluate. Perform dermatologic evaluation before therapy, every 2 months during, and consider monitoring 6 months after discontinuation. Monitor for signs/symptoms of

new non-cutaneous SCC and other malignancies.

Long QT syndrome or QTc >500ms, uncorrectable electrolyte abnormalities, or concomitant drugs that prolong the QT interval: not recommended.

Prior to and following initiation or after dose adjustment for QTc prolongation, evaluate ECG and electrolytes after 15 days, monthly during the 1st 3 months, then every 3 months thereafter, or more as clinically indicated. Severe hepatic or renal impairment. Monitor liver enzymes, bilirubin before initiating and monthly during treatment, or as needed. Measure SCr before initiating and periodically during treatment. Monitor for ophthalmologic reactions routinely. Avoid sun exposure. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during therapy and for at least 2 weeks after final dose. Pregnancy. Nursing mothers: not recommended (during and for 2 weeks after final dose).

Interactions: Avoid concomitant strong CYP3A4 inhibitors (eg, azole antifungals, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir) or strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital); consider alternatives. Avoid concomitant CYP1A2 (eg, tizanidine) and P-gp (eg, digoxin) substrates with narrow therapeutic indices; if unavoidable, consider dose reduction of substrates and monitor. Increased transaminase and bilirubin with concomitant ipilimumab. Concomitant or sequential administration with radiation treatment; monitor closely.

Adverse reactions: Arthralgia, rash, alopecia, fatigue, photosensitivity, nausea, pruritus, skin papilloma; severe hypersensitivity or dermatologic reactions (permanently discontinue if occur), QT prolongation, hepatotoxicity, uveitis, blurry vision, photophobia, other malignancies, radiation sensitization and recall, renal failure.

How supplied: Tabs—112, 120

LIVER FUNCTION ASSESSMENT Child-Pugh Score is used to assess residual liver function and injury severity in cirrhosis patients.

CHILD-PUGH SCORES Criteria

1 point

2 points

3 points

Total serum bilirubin (mg/dL)

<2

2–3

>3

Serum albumin (g/dL)

>3.5

2.8–3.5

<2.8

INR

<1.70

1.71–2.20

>2.20

Ascites

No ascites

Ascites controlled

Ascites not controlled

Encephalopathy

No encephalopathy

Encephalopathy controlled

Encephalopathy not controlled

INTERPRETATION OF CHILD-PUGH SCORES Class A

Class B

Class C

Points

5–6

7–9

10–15

Life expectancy

15–20 years

Candidate for liver transplant

1–3 years

Perioperative mortality

10%

30%

82%

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DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS Anemias

ANADROL-50 Meda

CIII

Androgen. Oxymetholone 50mg; scored tabs.

Indications: Anemia caused by deficient red cell production. Acquired aplastic anemia, congenital anemia, myelofibrosis, and hypoplastic anemias due to myelotoxic drugs.

Adults and Children: Individualized. 1–5mg/kg per day for at least 3–6 months; may attempt to lower dose or discontinue after remission.

Congenital aplastic anemia: may need continued maintenance dose.

Contraindications: Male breast or prostate carcinoma. Breast cancer in females with hypercalcemia. Nephrosis or the nephrotic phase of nephritis. Severe hepatic dysfunction.

Pregnancy (Cat.X).

Warnings/Precautions: Not a replacement for other supportive treatments (eg, transfusion; iron, folic acid, Vit. B12, Vit. B6 replacement). Discontinue if jaundice, abnormal liver function, hypercalcemia, or edema occurs. Cardiac, hepatic, or renal dysfunction.

Monitor hepatic function, blood, and bone age.

Elderly. Young children. Nursing mothers: not recommended.

Interactions: May potentiate oral anticoagulants. May alter insulin needs.

Adverse reactions: Peliosis hepatis, premature epiphyseal closure in adolescents, edema, hepatic carcinoma, prostatic hypertrophy or carcinoma, gynecomastia, priapism, oligospermia, nausea, jaundice, hirsutism, virilization, male pattern baldness, acne, polycythemia, headache, CNS excitation, insomnia, altered libido, fluid and electrolyte disturbances, suppression of clotting factors, increased serum cholesterol.

How supplied: Tabs—100

ARANESP Amgen

℞

Erythropoiesis stimulating protein. Darbepoetin alfa 25mcg/mL, 40mcg/mL, 60mcg/mL, 100mcg/mL, 150mcg/0.75mL, 200mcg/mL, 300mcg/mL, 500mcg/mL; for IV or SC inj; preservative-free; contains polysorbate 80. ℞ Also: ARANESP SINGLEJECT Darbepoetin alfa 10mcg/0.4mL, 25mcg/0.42mL, 40mcg/0.4mL, 60mcg/0.3mL, 100mcg/0.5mL, 150mcg/0.3mL, 200mcg/0.4mL, 300mcg/0.6mL, 500mcg/mL; per prefilled syringe; for IV or SC inj; preservative-free; contains polysorbate 80.

Indications: Anemia of chronic kidney disease (CKD), including patients on and not on dialysis.

Chemotherapy-induced anemia in patients with non-myeloid malignancies.

Adults: Initiate only when hemoglobin (Hgb) <10g/dL. CKD (on dialysis): initially 0.45mcg/kg IV or SC once weekly; or 0.75mcg/kg IV or SC once every 2 weeks. Patients on hemodialysis: IV route is recommended. CKD (not on dialysis): initially 0.45mcg/kg SC or IV given once at 4 week intervals. Reduce or interrupt dose if Hgb >10g/dL (not on dialysis) or >11g/dL (on dialysis).

Cancer: initially 2.25mcg/kg SC once weekly or 500mcg SC once every 3 weeks. Discontinue after completion of chemotherapy course. Use lowest dose sufficient to avoid red blood cell transfusion. Converting from epoetin alfa, and for dose adjustments: see full labeling.

Children: Initiate only when hemoglobin (Hgb) <10g/dL. CKD: initially 0.45mcg/kg SC or IV once weekly; patients with CKD (not on dialysis): may also initiate at 0.75mcg/kg once every 2 weeks.

Reduce or interrupt dose if Hgb >12g/dL. Cancer: not established.

Contraindications: Uncontrolled hypertension.

Do not use in patients with pure red cell aplasia due to erythropoietin antibodies.

Warnings/Precautions: See full labeling.

Increased risk of death, MI, stroke, venous thromboembolism, vascular thrombosis with Hgb >11g/dL in CKD. Increased risk of tumor progression or recurrence in breast, NSCLC, head and neck, lymphoid, cervical cancers. Evaluate serum iron, ferritin, transferrin saturation before and during therapy; most patients will need iron supplementation. Monitor hemoglobin weekly for 4 weeks after start and dose changes, until stabilized, then periodically; reduce dose if hemoglobin increases >1g/dL in any 2-week period. Monitor BP (reduce or withhold dose if hypertension occurs), folate, Vit. B12, renal function, electrolytes, fluid balance, and for premonitory neurological symptoms. Seizure, cardiovascular, or hematologic disorders.

Infection, inflammation, malignancy, occult blood loss, bone marrow fibrosis may reduce effectiveness; consider other etiologies in treatment failures. Adjust dialysis ℞ as needed.

Latex allergy. Pregnancy (Cat.C). Nursing mothers.

Adverse reactions: CKD: hypertension, dyspnea, peripheral edema, cough, procedural hypotension. Cancer: abdominal pain, edema, thrombovascular events.

How supplied: Single-dose vials (25, 40, 60, 100, 150mcg)—4; Single-dose vial (200, 300mcg)—1; Single-dose prefilled syringes (10, 25, 40, 60, 100, 150mcg)—4; Single-dose prefilled syringes (200, 300, 500mcg)—1

ATGAM Pfizer

℞

Immune globulin. Lymphocyte immune globulin, anti-thymocyte globulin [equine] 50mg/mL; soln for IV infusion after dilution.

Indications: Treatment of moderate to severe aplastic anemia in patients who are unsuitable for bone marrow transplantation.

Adults: Perform intradermal test dose before initiating therapy (see literature). Do not dilute in dextrose injection or highly acidic infusion solutions.

Give by IV infusion over >4hrs. 10–20mg/kg daily for 8–14 days. Additional alternate-day therapy up to a total of 21 doses can be administered. May need prophylactic platelet transfusions to maintain platelets.

Children: Limited experience (see literature).

Warnings/Precautions: To be administered by physicians with experience in immunosuppressive therapy and in facilities equipped with adequate lab and supportive medical resources.

Discontinue if symptoms of anaphylaxis develop.

Contains human plasma; monitor for possible infection transmission. Monitor for leukopenia, thrombocytopenia, or infection esp. with concomitant corticosteroids and antimetabolites.

Pregnancy (Cat.C): not recommended. Nursing mothers.

Interactions: Previously masked reactions may occur when corticosteroids and other immunosuppressant doses are reduced.

Adverse reactions: Fever, skin reactions, chills, arthralgia, headache, myalgia, GI upset, chest pain, phlebitis, diaphoresis, joint stiffness, edema, muscle ache, vomiting, agitation/lethargy, listlessness, light-headedness, seizures, bradycardia, myocarditis, cardiac irregularity, hepatosplenomegaly, possible encephalitis or post viral encephalopathy, hypotension, CHF, hypertension, burning soles/palms, foot sole pain, lymphadenopathy, post-cervical lymphadenopathy, tender lymph nodes, bilateral pleural effusion, respiratory distress, anaphylactic reaction, proteinuria, abnormal LFTs and renal function, serum sickness.

How supplied: Ampules (5mL)—5

BIFERA Meda

OTC

Iron (as polysaccharide iron complex [PIC] 22mg + heme iron polypeptide [HIP] as Proferrin bovine source 6mg) 28mg; gluten-free tabs.

Indications: Iron supplement. Iron deficiency.

Adults: 1 tab once daily.

Children: Not recommended.

Contraindications: Hemochromatosis.

Hemosiderosis.

Take advantage of our free online medical calculators at CancerTherapyAdvisor.com/MedicalCalculators.

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DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS Warnings/Precautions: May mask pernicious anemia. Monitor hemoglobin, hematocrit, ferritin levels periodically. Pregnancy. Nursing mothers.

Adverse reactions: Allergic sensitization.

How supplied: Tabs—30

BIFERARx Meda

℞

Iron (as polysaccharide iron complex [PIC] 22mg + heme iron polypeptide [HIP] as Proferrin bovine source 6mg) 28mg, folic acid 1mg, Vit. B12 25mcg; tabs.

Indications: Iron supplement. Iron deficiency.

Adults: 1 tab once daily.

Children: Not recommended.

Contraindications: Hemochromatosis.

Hemosiderosis.

Warnings/Precautions: May mask pernicious anemia. Monitor hemoglobin, hematocrit, ferritin levels periodically. Pregnancy. Nursing mothers.

Adverse reactions: Allergic sensitization.

How supplied: Tabs—90

DEXFERRUM American Regent

℞

Hematinic. Iron (as dextran complex) 50mg/mL; soln for IV inj.

Indications: Iron deficiency where oral therapy is unsatisfactory or impossible.

Adults and Children: <4months: not recommended. Give by IV inj. Administer 0.5mL test dose first; if no signs/symptoms of anaphylactic-type reactions, may give full therapeutic dose. ≥4months: Iron deficiency anemia: determine total dose based on hemoglobin and body weight (see literature). Iron replacement for blood loss: Replacement iron (in mg) = blood loss (in mL) X hematocrit. Max daily doses: <5kg: 0.5mL (25mg), <10kg: 1mL (50mg), ≥10kg: 2mL (100mg).

Contraindications: Anemia not associated with iron deficiency.

Warnings/Precautions: Monitor for signs/symptoms of anaphylactic-type reactions, esp. in patients with history of allergies, asthma; have epinephrine available.

Hepatic impairment. Avoid during acute phase of infectious kidney disease. Cardiovascular disease. Avoid large IV doses: higher incidence of adverse events. Iron overload more likely with hemoglobinopathies or refractory anemias.

Rheumatoid arthritis. Neonates. Pregnancy (Cat.C). Nursing mothers.

Interactions: Concomitant ACE inhibitors may increase the risk for anaphylactic-type reactions.

May falsely elevate serum bilirubin and decrease serum calcium.

Adverse reactions: See literature. Anaphylactic reactions (may be fatal, even in patients who tolerated test dose), cardiovascular events, pruritus, GI upset, arthralgia, arthritis, inj site reactions, others.

How supplied: Single-dose vials (1mL, 2mL)—10

DROXIA Bristol-Myers Squibb

℞

Antimetabolite. Hydroxyurea 200mg, 300mg, 400mg; caps.

Indications: To reduce the frequency of painful crises and to reduce the need for blood transfusions in adults with sickle cell anemia with recurrent moderate-to-severe painful crises.

Adults: Base dose on ideal or actual weight, whichever is less. Initially 15mg/kg/day as a single dose. May increase dose by 5mg/kg/day every 12 weeks to maximum tolerated dose or 35mg/kg/day achieved; do not increase dose if blood counts are between acceptable and toxic range. If blood counts toxic, discontinue until hematologic recovery, see full labeling for dosage adjustments. Renal impairment (CrCl <60mL/min or ESRD): initially 7.5mg/kg/day; give dose following dialysis (monitor).

Children: Not established.

Warnings/Precautions: Risk of severe myelosuppression. Monitor blood counts at baseline and during therapy; interrupt or reduce dose if necessary. Markedly depressed bone marrow function: do not initiate. Monitor for malignancies. Avoid sun exposure. Macrocytosis may mask folic acid deficiency; prophylactic folic acid is recommended. Myeloproliferative disorders; discontinue if cutaneous vasculitic ulcerations occur. Obtain fetal hemoglobin (HbF) levels every 3–4 months; may be used to assess efficacy. Renal or hepatic impairment.

Elderly. Embryo-fetal toxicity. Pregnancy; avoid. Exclude pregnancy prior to initiating; use effective contraception during and for ≥6 months (females) or ≥1 year (males) after therapy.

Nursing mothers: not recommended.

Interactions: Avoid concomitant didanosine, with or without stavudine, or other antiretrovirals (may cause pancreatitis [monitor], fatal hepatotoxicity, peripheral neuropathy). Avoid live vaccines. Increased risk of vasculitic toxicities with interferon therapy. May cause falsely elevated results in urea, uric acid, and lactic acid assays.

Adverse reactions: Leukopenia, thrombocytopenia, anemia, neutropenia, GI upset, anorexia, hair loss, macrocytosis, bleeding, melanonychia; secondary malignancies.

Note: Wear disposable gloves when handling caps or bottle.

How supplied: Caps—60

EPOGEN Amgen

℞

Erythropoietin (human, recombinant). Epoetin alfa 2000 Units, 3000 Units, 4000 Units, 10000 Units, 40000 Units; per mL; soln for IV or SC inj; contains albumin (human); preservativefree. ℞ Also: EPOGEN MULTIDOSE Epoetin alfa 10000 Units, 20000 Units; per mL; soln for IV or SC inj; contains albumin (human) and benzyl alcohol.

Indications: Anemia in chronic renal failure (CRF). Anemia related to zidovudine in HIVinfected patients. Chemotherapy-induced anemia in patients with non-myeloid malignancies (serum erythropoietin ≤200 mUnits/mL). To reduce need for allogeneic blood transfusions in anemic (hemoglobin >10 to ≤13g/dL) patients scheduled for elective, noncardiac, nonvascular surgery.

Adults: Individualize (see literature for titration). CRF: initially 50–100 Units/kg 3 times per week IV (dialysis or non dialysis) or SC (non dialysis); usual max (non dialysis) 150 Units/kg 3 times per week; (dialysis) 200 Units/kg 3 times per week; target hemoglobin 10–12g/dL. Zidovudine-treated HIV patients: if serum erythropoietin ≤500 mUnits/mL and zidovudine dose ≤4.2 g/wk: initially 100 Units/kg IV or SC 3 times per week for 8 weeks; usual max 300 Units/kg 3 times per week. Chemotherapyinduced: initially 150 Units/kg SC 3 times per week; may increase to 300 Units/kg 3 times per week after 8 weeks. Or, initially 40000 Units SC once weekly; may increase to 60000 Units once weekly after 4 weeks. Discontinue after completion of chemotherapy course. Surgery: If ≥21 days until surgery: 600 Units/kg once weekly SC at 21, 14 and 7 days before surgery, and a 4th dose on day of surgery. If <21 days until surgery: 300 Units/kg per day SC for 10 days before, on day of, and for 4 days after surgery. All: adjust dose to maintain the lowest hemoglobin level (target max 12g/dL) sufficient to avoid red blood cell transfusion; see literature.

Children: Individualize (see literature for monitoring). CRF (dialysis): <1 month: not recommended. ≥1 month of age: initially 50 Units/kg three times per week IV or SC. Target hemoglobin: 10–12g/dL. Chemotherapy-induced: ≥5yrs: 600 Units/kg IV weekly (max 40,000 Units); may increase to 900 Units/kg IV weekly (max 60,000 Units) after 4 weeks. Discontinue after completion of chemotherapy course. Other uses: see literature.

Contraindications: Uncontrolled hypertension.

Warnings/Precautions: See literature. Evaluate serum iron, ferritin, transferrin saturation before therapy; all patients will need iron supplementation. Monitor hemoglobin (measure twice weekly for 2–6 weeks after any dosage adjustment; reduce dose if hemoglobin increases >1g/dL in any 2-week period; withhold dose if hemoglobin exceeds 12g/dL), blood pressure, renal function, iron levels, clotting times, serum chemistry, CBC, and for premonitory neurological symptoms. Seizure disorders. Cardiovascular or hematologic disorders. Hypertension (esp. in renal failure). Porphyria. Concurrent infection, inflammation, increased zidovudine dose, or other factors may reduce effectiveness.

Perisurgery: consider DVT prophylaxis. Consider other etiologies in treatment failures. Adjust anticoagulant dose in dialysis patients. Menses

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DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS may resume. Pregnancy (Cat.C). Nursing mothers.

Adverse reactions: Iron deficiency, hypertension, headache, arthralgia, GI disturbances, edema, local reaction, rash, paresthesia, dizziness, clotted vascular access (A-V shunt), pyrexia, respiratory congestion, seizures. Increased risk of death, cardiovascular or thrombotic events if hemoglobin >12g/dL. May stimulate tumor growth, shorten time to tumor progression or overall survival if hemoglobin ≥12g/dL. Children: also abdominal pain, upper respiratory infection, cough, pharyngitis, constipation.

How supplied: Single-use 1mL vials (all)—10; Multidose 2mL vials (10000 Units/mL)—10; Multidose 1mL vials (20000 Units/mL)—10

FERAHEME AMAG

℞

Hematinic. Elemental iron 30mg/mL (as ferumoxytol 510mg/17mL); colloidal iron for IV infusion after dilution; contains mannitol 44mg/mL; preservative-free.

Indications: Iron deficiency anemia in adult patients with chronic kidney disease.

Adults: Give by IV infusion over at least 15 mins.

Initially 510mg, followed by a second 510mg dose 3–8 days later. May repeat in persistent or recurrent iron deficiency anemia. Hemodialysis: give at least 1 hour after starting hemodialysis and after BP is stable.

Children: <18yrs: not established.

Contraindications: History of any IV iron product allergy.

Warnings/Precautions: Iron overload: do not administer. Monitor for severe hypotension, and for hypersensitivity for at least 30 minutes after each infusion. Evaluate hemoglobin, ferritin, iron, transferrin saturation at least 1 month after 2nd infusion. Have equipment/personnel available to treat hypersensitivity reactions.

Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: May reduce absorption of concomitantly administered oral iron preparations. May transiently (up to 3 months) affect diagnostic ability of MRI (see full labeling).

Concomitant chemotherapy or monoclonal antibodies: separate dosing by at least 30 mins.

Adverse reactions: Diarrhea, nausea, hypotension (may be significant), dizziness, constipation, peripheral edema; infusion reactions, anaphylactic reactions (may be fatal), other hypersensitivity reactions (eg, rash, pruritus, urticaria, wheeze).

How supplied: Single-use vials (17mL)—1, 10

FERRALET 90 Mission

℞

Iron (as carbonyl) 90mg, folic acid 1mg, Vit.B12 12mcg, Vit.C 120mg, docusate sodium 50mg; tabs; contains tartrazine.

Indications: Iron deficiency anemia.

Adults: Swallow whole. Take 2hrs after meals.

1 tab once daily.

Children: Not recommended.

Contraindications: Hemolytic anemia.

Hemochromatosis. Hemosiderosis.

Warnings/Precautions: May mask pernicious anemia. Monitor hemoglobin, hematocrit, reticulocyte count periodically. Elderly.

Interactions: Inhibits tetracycline, fluoroquinolone absorption. Aluminum- or magnesium-containing antacids inhibit iron absorption.

Adverse reactions: GI upset or irritation, constipation, dark stools, allergic sensitization.

How supplied: Tabs—90

FERRLECIT Sanofi Aventis

℞

Hematinic. Iron (as sodium ferric gluconate complex in sucrose) 12.5mg/mL; soln for IV inj or infusion; contains benzyl alcohol.

Indications: Iron deficiency anemia in patients on chronic hemodialysis receiving epoetin therapy.

Adults: Give by IV infusion (diluted) or slow IV inj (undiluted). 125mg infused over 1 hour or by slow IV inj (at a rate of up to 12.5mg/min). Minimum cumulative dose: 1g given over 8 sequential dialysis sessions; usual max: 125mg/dose.

Children: <6 yrs: not recommended. Give by IV infusion (diluted) over 1 hour. ≥6yrs: 1.5mg/kg per dose at 8 sequential dialysis sessions; max: 125mg/dose.

Contraindications: Anemias not caused by iron deficiency. Iron overload. Neonates.

Warnings/Precautions: Hemoglobinopathies.

Refractory anemias. Pregnancy (Cat. B). Nursing mothers.

Interactions: May reduce absorption of concomitant oral iron preparations.

Adverse reactions: Hypotension, hypertension, GI upset, chest pain, back pain, abdominal pain, pruritus, inj site reaction, headache, dizziness, syncope, fatigue, fever, cramps, dyspnea, tachycardia; rare: hypersensitivity reactions.

How supplied: Ampules (5mL)—10

Folic acid (various)

℞

Hematinic. Folic acid 1mg; tabs.

Also: Folic acid injection Folic acid 5mg/mL; soln for IV, IM or SC inj; contains benzyl alcohol and aluminum.

℞

Indications: Megaloblastic anemias of folic acid deficiency. Anemias of nutritional origin, pregnancy, infancy or childhood.

Adults and Children: Usual dose: up to 1mg daily; may need higher dose if resistant disease.

Maintenance: infants: 0.1mg/day; <4yrs: 0.3mg/day; ≥4yrs: 0.4mg/day. Pregnant or lactating: 0.8mg/day. Alcoholism, hemolytic anemia, anticonvulsant therapy or chronic infection: may require higher dose.

Warnings/Precautions: Use injectable form if disease is severe or GI absorption impaired.

Rule out or treat vitamin B12 deficiency prior to treatment. May obscure diagnosis of pernicious anemia. Pregnancy (Cat. A).

Interactions: May antagonize phenytoin. False low serum and red cell folate levels may occur with antibiotics (eg. tetracycline).

Adverse reactions: Allergic sensitization.

How supplied: Contact supplier.

INFED Allergan

℞

Hematinic. Iron (as dextran complex) 50mg/mL; soln for IV or IM inj.

Indications: Iron deficiency where oral therapy is unsatisfactory or impossible.

Adults and Children: Give by IV or by deep IM (into upper outer quadrant of buttock only) inj. Administer 0.5mL test dose first; if no signs/symptoms of anaphylactic-type reactions, may give full therapeutic dose. Iron deficiency anemia: determine total dose based on hemoglobin and body weight (see literature). Iron replacement for blood loss: Replacement iron (in mg) = blood loss (in mL) X hematocrit. Max daily doses: <5kg: 0.5mL (25mg), <10kg: 1mL (50mg), ≥10kg: 2mL (100mg).

Contraindications: Anemias not associated with iron deficiency.

Warnings/Precautions: Monitor for signs/symptoms of anaphylactic-type reactions, esp. in patients with history of drug allergies, asthma; have epinephrine available. Avoid large IV doses: higher incidence of adverse events. Severe hepatic impairment. Avoid during acute phase of infectious kidney disease.

Dialysis. Cardiovascular disease. May reactivate quiescent rheumatoid arthritis. Neonates (avoid during first 4 months). Pregnancy (Cat. C).

Nursing mothers.

Interactions: Concomitant ACE inhibitors may increase the risk for anaphylactic-type reactions.

May falsely elevate serum bilirubin or decrease serum calcium levels.

Adverse reactions: See literature. Anaphylactic reactions (may be fatal; even if test dose was

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DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS Adverse reactions: Leukopenia, thrombocytopenia, infection, GI upset, stomatitis, constipation, lethargy, malaise, fatigue, alopecia, dermatitis, anorexia; seizures, syncope.

How supplied: Single-use vials—1

tolerated), cardiovascular events, pruritus, GI upset, arthralgia, arthritis, inj site reactions, others; possible IM inj site tumors, sepsis in neonates.

How supplied: Vials (2mL)—10

INJECTAFER American Regent

℞

Hematinic. Iron (as ferric carboxymaltose) 50mg/mL; soln for IV inj or infusion; preservativefree.

Indications: Iron deficiency anemia in adults who have intolerance or insufficient response to oral iron; or have non-dialysis-dependent chronic kidney disease.

Adults: Give by slow IV push (undiluted) at rate of approx. 100mg (2mL)/min; or by IV infusion (diluted) administered over at least 15 mins. When giving via IV infusion, dilute to concentration not less than 2mg iron/mL. Give in 2 doses separated by >7 days. <50kg: 15mg/kg/dose. ≥50kg: 750mg/dose. Total cumulative dose per course: max 1500mg. May repeat treatment if condition reoccurs.

Children: Not established.

Warnings/Precautions: Have epinephrine inj (1:1000) available. Monitor for serious hypersensitivity reactions during and after administration for >30 mins and until clinically stable. Monitor for signs/symptoms of hypertension after each administration. Avoid extravasation. Pregnancy (Cat. C). Nursing mothers.

Interactions: Lab assays may result in overestimating serum iron and transferrin bound iron within 24hrs after administration.

Adverse reactions: Nausea, hypertension, flushing, hypophosphatemia, dizziness; rare: hypersensitivity reactions.

How supplied: Single-use vial (15mL)—1, 2

Leucovorin Teva

℞

Folic acid derivative. Leucovorin calcium 100mg/vial, 350mg/vial; lyophilized pwd for IV or IM inj after reconstitution; preservativefree.

Indications: Megalobastic anemia due to folic acid deficiency when oral therapy is not feasible.

Adults: Up to 1mg daily.

Children: See literature.

Contraindications: Pernicious anemia and other megaloblastic anemias due to Vit. B12 deficiency.

Warnings/Precautions: Do not administer intrathecally. CNS metastases. Monitor CBCs with differential, platelets, electrolytes, liver function tests prior to each treatment, then periodically.

Elderly. Debilitated. Pregnancy (Cat.C). Nursing mothers.

Interactions: Potentiates toxicity of 5-fluorouracil; use lower 5-fluorouracil dose.

May antagonize phenobarbital, phenytoin, and primidone. Caution with trimethoprimsulfamethoxazole.

LUPRON DEPOT 3.75mg

℞

AbbVie

GnRH analogue. Leuprolide acetate 3.75mg; depot susp for IM inj; preservative-free.

Indications: Presurgical treatment of patients with anemia due to uterine leiomyomata (fibroids), with iron therapy if iron therapy alone is inadequate.

Adults: ≥18yrs: 3.75mg IM once per month for up to 3 months.

Children: <18yrs: not applicable.

Also: LUPRON DEPOT-3 MONTH 11.25mg ℞ Leuprolide acetate 11.25mg; depot susp for IM inj; preservative-free.

Adults: ≥18yrs: 11.25mg IM once every 3 months (1 injection). Do not split doses.

Children: <18yrs: not applicable.

Contraindications: Undiagnosed abnormal vaginal bleeding. Pregnancy (Cat.X). Nursing mothers.

Warnings/Precautions: Exclude pregnancy before starting; use nonhormonal contraception during therapy; discontinue if pregnancy occurs.

Risk factors for decreased bone mineral density (eg, chronic alcohol, tobacco, anticonvulsants, corticosteroids). Missing successive doses may cause breakthrough bleeding or ovulation.

Elderly.

Adverse reactions: Hot flashes, headache, vaginitis, depression, emotional lability, pain, decreased libido, breast changes, amenorrhea, mastodynia, joint disorder, asthenia, GI upset, edema, bone density loss, local reactions, acne, memory disorders, others; rarely: anaphylaxis, asthma, increased serum transaminases or lipids.

How supplied: Kit—1 (single-dose syringe w. diluent, supplies)

NASCOBAL Endo

℞

Cyanocobalamin 500mcg/spray; soln for nasal spray; contains benzalkonium chloride.

Indications: Maintenance of normal hematologic status in pernicious anemia patients who are in remission after intramuscular Vit. B12 therapy and who have no nervous system involvement. Supplementation for other Vit. B12 deficiencies.

Adults: Hematological parameters must be within normal range before beginning therapy.

Allow at least 1hr before or after hot foods or liquids. Initial dose: One spray (500mcg) in one nostril once weekly. Monitor response, may increase dose if serum B12 levels decline.

Children: Not recommended.

Warnings/Precautions: Confirm diagnosis.

May need supplemental folate. Risk of hypokalemia or sudden death in severe

megablastic anemia. Leber’s disease. Defer dose if nasal congestion, rhinitis, or upper respiratory infections occur. Reevaluate if low levels of Vit. B12 persist despite treatment.

Do not use for Schilling Test. Infection, uremia, and iron or folic acid deficiency may reduce response. Increased risk of stomach carcinoma in those with pernicious anemia; perform tests when indicated. May unmask polycythemia vera. Monitor B12 blood levels 1 month after starting therapy, 1 month after any dose increase, and regularly at 3–6 month intervals. Monitor serum potassium, platelet counts. Pregnancy (Cat.C).

Interactions: Antibiotics, methotrexate, pyrimethamine may interfere with lab tests.

Colchicine, chronic heavy alcohol use may impair Vit. B12 absorption. Reduced response with bone marrow suppressants (eg, chloramphenicol).

Adverse reactions: Headache, nausea, rhinitis.

How supplied: Single-use nasal spray (0.125mL)—4

NULECIT Actavis

℞

Hematinic. Iron (as sodium ferric gluconate complex in sucrose) 12.5mg/mL; soln for IV inj or infusion; contains benzyl alcohol.

Indications: Iron deficiency anemia in patients on chronic hemodialysis receiving epoetin therapy.

Adults: Give by IV infusion (diluted) or slow IV inj (undiluted). 125mg infused over 1 hour or by slow IV inj (at a rate of up to 12.5mg/min). Minimum cumulative dose: 1g given over 8 sequential dialysis sessions; usual max: 125mg/dose.

Children: <6yrs: not recommended. Give by IV infusion (diluted) over 1 hour. ≥6yrs: 1.5mg/kg per dose at 8 sequential dialysis sessions; max: 125mg/dose.

Contraindications: Anemias not caused by iron deficiency. Iron overload.

Warnings/Precautions: Hemoglobinopathies.

Refractory anemias. Avoid in neonates. Pregnancy (Cat. B). Nursing mothers.

Interactions: May reduce absorption of concomitant oral iron preparations.

Adverse reactions: Hypotension, hypertension, GI upset, chest pain, back pain, abdominal pain, pruritus, inj site reaction, cramps, headache, dizziness, syncope, fatigue, fever, dyspnea, tachycardia; rare: hypersensitivity reactions.

How supplied: Vials (5mL)—10

BRAND NAME The main name under which the product and all other dosage forms in the monograph are marketed.

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DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS PROCRIT Janssen Biotech

℞

Erythropoietin (human, recombinant). Epoetin alfa 2000 Units, 3000 Units, 4000 Units, 10000 Units, 40000 Units; per mL; soln for IV or SC inj; contains albumin (human); preservativefree. ℞ Also: PROCRIT MULTIDOSE Epoetin alfa 10000 Units, 20000 Units; per mL; soln for IV or SC inj; contains albumin (human) and benzyl alcohol.

Indications: Anemia in chronic renal failure (CRF). Anemia related to zidovudine in HIVinfected patients. Chemotherapy-induced anemia in patients with non-myeloid malignancies (serum erythropoietin ≤200 mUnits/mL). To reduce need for allogeneic blood transfusions in anemic (hemoglobin >10 to ≤13g/dL) patients scheduled for elective, noncardiac, nonvascular surgery.

Adults: Individualize (see literature for titration).

CRF: initially 50–100 Units/kg 3 times per week IV (dialysis or non dialysis) or SC (non dialysis); usual max (non dialysis) 150 Units/kg 3 times per week; (dialysis) 200 Units/kg 3 times per week; target hemoglobin: 10–12g/dL. Zidovudinetreated HIV patients: if serum erythropoietin ≤500 mUnits/mL and zidovudine dose ≤4.2g/wk: initially 100 Units/kg IV or SC 3 times per week for 8 weeks; usual max 300 Units/kg 3 times per week. Chemotherapy-induced: initially 150 Units/kg SC 3 times per week; may increase to 300 Units/kg 3 times per week after 8 weeks.

Or, initially 40000 Units SC once weekly; may increase to 60000 Units once weekly after 4 weeks. Discontinue after completion of chemotherapy course. Surgery: If ≥21 days until surgery: 600 Units/kg once weekly SC at 21, 14 and 7 days before surgery, and a 4th dose on day of surgery. If <21 days until surgery: 300 Units/kg per day SC for 10 days before, on day of, and for 4 days after surgery. All: adjust dose to maintain the lowest hemoglobin level (target max 12g/dL) sufficient to avoid red blood cell transfusion; see literature.

Children: Individualize (see literature for monitoring). CRF (dialysis): <1 month: not recommended. ≥1 month of age: initially 50 Units/kg three times per week IV or SC. Target hemoglobin: 10–12g/dL. Chemotherapy-induced: ≥5yrs: 600 Units/kg IV weekly (max 40,000 Units); may increase to 900 Units/kg IV weekly (max 60,000 Units) after 4 weeks. Discontinue after completion of chemotherapy course. Other uses: see literature.

Contraindications: Uncontrolled hypertension.

Warnings/Precautions: See literature. Evaluate serum iron, ferritin, transferrin saturation

before therapy; all patients will need iron supplementation. Monitor hemoglobin (measure twice weekly for 2–6 weeks after any dosage adjustment; reduce dose if hemoglobin increases >1g/dL in any 2-week period; withhold dose if hemoglobin exceeds 12g/dL), blood pressure, renal function, iron levels, clotting times, serum chemistry, CBC, and for premonitory neurological symptoms. Seizure disorders. Cardiovascular or hematologic disorders. Hypertension (esp. in renal failure). Porphyria. Concurrent infection, inflammation, increased zidovudine dose, or other factors may reduce effectiveness.

Perisurgery: consider DVT prophylaxis. Consider other etiologies in treatment failures. Adjust anticoagulant dose in dialysis patients. Menses may resume. Pregnancy (Cat.C). Nursing mothers.

Adverse reactions: Iron deficiency, hypertension, headache, arthralgia, GI disturbances, edema, local reaction, rash, paresthesia, dizziness, clotted vascular access (A-V shunt), pyrexia, respiratory congestion, seizures. Increased risk of death, cardiovascular or thrombotic events if hemoglobin >12g/dL. May stimulate tumor growth, shorten time to tumor progression or overall survival if hemoglobin ≥12g/dL. Children: also abdominal pain, upper respiratory infection, cough, pharyngitis, constipation.

How supplied: Single-use 1mL vials (2000 Units/mL, 3000 Units/mL, 4000 Units/mL, 10000 Units/mL)—6, 25; Single-use 1mL vials (40000 Units/mL)—4; Multidose 2mL vials (10000 Units/mL)—4, 6; Multidose 1mL vials (20000 Units/mL)—4, 6

PROMACTA GlaxoSmithKline

℞

Thrombopoietin receptor agonist. Eltrombopag (as olamine) 12.5mg, 25mg, 50mg, 75mg; tabs.

Indications: Severe aplastic anemia in adults who have had insufficient response to immunosuppressive therapy.

Adults: Take on empty stomach. Initially 50mg once daily. Hepatic impairment or East Asian ancestry: initially 25mg once daily.

Titrate dose by 50mg every 2 weeks as needed to maintain platelet count ≥50x109/L; max 150mg daily. Monitoring, dose adjustment, and discontinuation: see full labeling.

Children: Not established.

Warnings/Precautions: Increased risk of hepatic decompensation in patients with chronic hepatitis C in combination with interferon and ribavirin; discontinue Promacta if antiviral therapy is discontinued. Monitor liver function

prior to initiation, every 2 weeks during dose adjustments, and monthly after stabilized (see full labeling); discontinue if ALT ≥3xULN and is progressive or persistent for ≥4 weeks, or if occurs with increased bilirubin, or evidence of hepatic injury/decompensation; reinitiate therapy if benefit outweighs risk; if restarted, monitor carefully. Increased risk of thromboembolism; do not use to normalize platelet counts. Do baseline eye exam; monitor for cataracts. Renal impairment. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Potentiates substrates of OATP1B1 (eg, most statins, bosentan, ezetimibe, glyburide, olmesartan, valsartan, repaglinide, rifampin) or BCRP (eg, imatinib, irinotecan, lapatinib, methotrexate, mitoxantrone, sulfasalazine, topotecan); monitor and consider reducing their doses. Antagonized by lopinavir/ritonavir.

Separate dosing by at least 2hrs before or 4hrs after food/drugs containing polyvalent cations (eg, Fe+2, Ca+2, Al+3, Mg+2, Se+2, Zn+2).

Adverse reactions: Nausea, diarrhea, fatigue, cough, headache, pain, dyspnea, pyrexia, dizziness, febrile neutropenia, ecchymosis, muscle spasms, arthralgia, rhinorrhea; hepatotoxicity, hemorrhage, thrombotic/thromboembolic complications, cataracts.

How supplied: Tabs—30

REVLIMID Celgene

℞

Immunomodulator. Lenalidomide 2.5mg, 5mg, 10mg, 15mg, 20mg, 25mg; caps; contains lactose.

Indications: Transfusion-dependent anemia due to Low- or Intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality.

Adults: Swallow whole with water. ≥18yrs: initially 10mg per day; adjust dose based on response. Renal impairment: Moderate (CrCL 30–60mL/min): 5mg per day. Severe (CrCL <30mL/min without dialysis): 2.5mg per day.

ESRD (CrCL <30mL/min with dialysis): 2.5mg once daily; administer after dialysis (on dialysis days). Dose adjustments if thrombocytopenia or neutropenia develops: see full labeling.

Children: <18yrs: not established.

Contraindications: Pregnancy (Cat. X).

Warnings/Precautions: Must register patient in Revlimid REMS program; patient must understand toxicity with fetal exposure. Counsel patient on need for contraception; females: use 2 forms of contraception 1 month before, during therapy, during dose interruptions, and 1 month after therapy; males: use condom during

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ASSOCIATED HEMATOLOGICAL DISORDERS and 1 month after therapy; obtain 2 negative pregnancy tests (one within 10–14 days, and then another within 24hrs prior to starting therapy), repeat at least weekly for 1st month then every 4 weeks (regular menstrual cycles) or every 2 weeks (irregular cycles); get informed consent. Do not donate blood during and for 1 month after therapy. Monitor for signs/symptoms of thromboembolic events; base thromboprophylaxis on patient’s risks. Obtain CBCs weekly for first 8 weeks, then monthly; dose interruption and/or reduction may be needed.

May require blood product support and/or growth factors. Renal impairment (monitor). Monitor for tumor lysis syndrome in those with high tumor burden. Monitor liver enzymes; discontinue if elevation occurs. Lactose intolerance.

Maximum 1 month per ℞. Nursing mothers: not recommended.

Interactions: Monitor digoxin. Concomitant warfarin; monitor PT, INR. May increase risk of thrombosis with dexamethasone, erythropoietic agents, or estrogen containing therapies.

Adverse reactions: Birth defects, thrombocytopenia, neutropenia, anemia, leukopenia, constipation, diarrhea, nausea, vomiting, pruritus, rash, fatigue, arthralgia, pyrexia, back pain, cough, dizziness, headache, dyspnea, nasopharyngitis, epistaxis, upper respiratory tract infection, tremor, blurred vision, muscle cramp, decreased appetite, peripheral edema; thrombosis/embolism, allergic reactions (discontinue if occurs; do not resume), tumor flare reaction (monitor; esp. in treating MCL), hepatotoxicity.

Note: Available only through Revlimid REMS program. Report any suspected fetal exposure to the FDA at (800) FDA-1088 and Celgene at (888) 423-5436.

How supplied: Caps 2.5mg, 5mg, 10mg—28, 100; 15mg, 20mg, 25mg—21, 100

SOLIRIS Alexion

℞

Complement inhibitor. Eculizumab 10mg/mL; soln for IV infusion after dilution; preservative-free.

Indications: Treatment of paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.

Treatment of atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy. Limitation of use: not for treating Shiga toxin E. coli-related HUS. Adults: Give by IV infusion over 35 mins; monitor for ≥1hr after completion. ≥18yrs: PNH: initially 600mg weekly for the first 4 weeks, followed by 900mg for the fifth dose 1 week later, then 900mg every 2 weeks thereafter. aHUS: initially 900mg weekly for the first 4 weeks, followed by 1200mg for the fifth dose 1 week later, then 1200mg every 2 weeks thereafter. Supplemental dosing after PE/PI: see full labeling.

Children: <18yrs: PNH: not established. aHUS: Give by IV infusion over 1–4hrs via gravity feed, syringe-type pump, or infusion pump; monitor for ≥1hr after completion. 5–<10kg: induction:

300mg weekly for 1 dose; maintenance: 300mg at Week 2, then 300mg every 3 weeks; 10–<20kg: induction: 600mg weekly for 1 dose; maintenance: 300mg at Week 2, then 300mg every 2 weeks; 20–<30kg: induction: 600mg weekly for 2 doses; maintenance: 600mg at Week 3, then 600mg every 2 weeks; 30–<40kg: induction: 600mg weekly for 2 doses; maintenance: 900mg at Week 3, then 900mg every 2 weeks; ≥40kg: induction: 900mg weekly for 4 doses; maintenance: 1200mg at Week 5, then 1200mg every 2 weeks. Supplemental dosing after PE/PI: see full labeling.

Contraindications: Unresolved serious Neisseria meningitidis infection. Individuals not vaccinated against Neisseria meningitidis.

Warnings/Precautions: Increased risk of meningococcal infection. Give meningococcal vaccine at least 2 weeks prior to treatment.

Monitor for early signs of meningococcal infection; evaluate and treat if an infection develops. Discontinue eculizumab if undergoing treatment for meningococcal infections.

Administering eculizumab treatment with any other systemic infection (eg, S. pneumoniae, H. influenza). PNH: risk of hemolysis after treatment discontinuation; monitor for at least 8 weeks. aHUS: risk of thrombotic microangiopathy (TMA) after treatment discontinuation; monitor for at least 12 weeks; if TMA occurs, consider reinitiating eculizumab, plasma therapy [plasmapheresis, plasma exchange, or fresh frozen plasma infusion (PE/PI)], or appropriate organ-specific supportive measures. Monitor platelets, serum LDH, and creatinine during and after therapy. Pregnancy (Cat.C). Nursing mothers.

Adverse reactions: Headache, nasopharyngitis, back pain, nausea, diarrhea, vomiting, abdominal pain, hypertension, upper respiratory tract infection, anemia, cough, peripheral edema, UTI, pyrexia; meningococcal infection (may be fatal), hypersensitivity reactions.

How supplied: Single-use vials (30mL)—1

TRINSICON UCB

℞

Iron (as fumarate) 110mg, Vit. B12 15micrograms, folic acid 0.5mg, Vit. C 75mg, liver-stomach concentrate 240mg; caps.

Indications: Megaloblastic anemias. Iron deficiency anemia.

Adults: 1 cap twice daily.

Children: <10 yrs: not recommended.

Contraindications: Hemochromatosis.

Hemosiderosis.

Warnings/Precautions: For pernicious anemia, parenteral cyanocobalamin is preferred.

Resistance to exogenous intrinsic factor may develop. Folic acid may mask pernicious anemia.

Monitor blood parameters. Hepatitis. Pancreatitis.

Peptic ulcer or GI inflammation. Achlorhydria.

Repeated blood transfusions. Pregnancy (Cat.C).

Nursing mothers. Elderly.

Interactions: Inhibits tetracycline absorption.

Adverse reactions: Nausea, abdominal discomfort and pain, constipation, diarrhea, masks occult bleeding, black stools, rash.

How supplied: Caps—60, 100

VENOFER American Regent

℞

Hematinic. Iron (as sucrose) 20mg/mL; soln for IV inj or infusion; preservative-free.

Indications: Iron deficiency anemia in chronic kidney disease.

Adults: Give by slow IV inj (undiluted) or infusion (diluted). Usual total cumulative dose: 1000mg.

Hemodialysis dependent: 100mg slow IV inj over 2–5 mins or infuse 100mg over at least 15 mins per consecutive session. Non-dialysis dependent: 200mg slow IV inj over 2–5 mins on 5 different occasions within a 14-day period; limited experience with IV infusion (see full labeling).

Peritoneal dialysis dependent: Two infusions of 300mg over 1.5hrs 14 days apart, then one 400mg infusion over 2.5hrs 14 days later.

Children: Not recommended.

Contraindications: Anemia not caused by iron deficiency. Iron overload.

Warnings/Precautions: Withhold therapy if tissue iron overload suspected. Monitor hemoglobin, hematocrit, serum ferritin, transferrin saturation; obtain serum iron values 48 hours after dosing. Pregnancy (Cat. B). Nursing mothers.

Interactions: May reduce absorption of concomitant oral iron preparations.

Adverse reactions: Hypotension (esp. by IV infusion), hypertension, muscle cramps, GI upset, headache, dizziness, chest pain, graft complications, dysgeusia, pruritus, edema, constipation; rare: hypersensitivity reactions (may be severe).

How supplied: Single-dose vials (100mg/5mL)—1, 10, 25; 200mg/10mL—1, 5,10

GENERIC NAME The active ingredients and strengths are listed under the name of each dosage form. If the product contains tartrazine, alcohol, flavors, or is alcohol-, sugar-, or dye-free, it is noted. Abbreviations are used to describe the dosage form and its formulation, e.g.: tabs = tablets caps = capsules e-c = enteric coated sust rel = sustained-release ext rel = extended-release

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DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS Bleeding disorders

AMICAR TABLETS Clover

℞

Hemostatic (plasmin and plasminogen activator inhibitor). Aminocaproic acid 500mg, 1000mg; scored tabs. ℞ Also: AMICAR ORAL SOLUTION Aminocaproic acid 250mg/mL; raspberry-flavor.

Indications: Bleeding associated with fibrinolysis.

Adults: Initially 5g during 1st hour, then 1g/hour for 8 hours or until bleeding is controlled.

Children: Not recommended.

Also: Aminocaproic Acid Injection (various) ℞ Aminocaproic acid 250mg/mL; soln for IV infusion after dilution; contains benzyl alcohol.

Adults: 4–5g (in 250mL of diluent) by IV infusion during the 1st hour, then 1g/hour (in 50mL of diluent) for 8 hours or until bleeding is controlled.

Children: Not recommended.

Contraindications: Active intravascular clotting process. Disseminated intravascular coagulation without concomitant heparin.

Warnings/Precautions: Upper urinary tract bleeding: not recommended. Cardiac, hepatic or renal disease. Risk of myopathy with longterm use; monitor creatine phosphokinase (CPK); discontinue if CPK rises. Avoid rapid IV administration. Neonates. Pregnancy (Cat.C).

Nursing mothers.

Interactions: Avoid concomitant Factor IX complex or Anti-inhibitor Coagulant concentrates; may increase thrombosis risk.

Adverse reactions: Inj site reactions, bradycardia, hypotension, GI upset, edema, headache, malaise, CNS effects, thrombosis, others; rare: myopathy.

How supplied: Tabs—100; Oral soln—473mL; Inj—contact supplier

CARIMUNE NF CSL Behring

℞

Immune globulin. Immune globulin (human) 3g, 6g, 12g; per vial; pwd for IV infusion after reconstitution; contains sucrose and NaCl; preservative-free.

Indications: Immune thrombocytopenic purpura (ITP).

Adults and Children: Induction: give by IV infusion at a rate of 0.5mg/kg/min for first 30mins, if tolerated may increase to 1mg/kg/min up to max 3mg/kg/min in a stepwise manner.

0.4g/kg on 2–5 consecutive days. Use of 6% immunoglobulin solution is recommended. Acute childhood ITP: discontinue therapy after second day of 5 day course if platelet count response to

first two doses is 30–50000/μL. Maintenance: If platelet count falls to <30000/μL and/or clinically significant bleed: give 0.4g/kg as a single infusion, may increase to 0.8–1g/kg as single infusion if inadequate response. Risk of renal dysfunction/failure or thrombosis: max infusion rate <2mg/kg/min.

Contraindications: IgA-deficiency with antibodies against IgA. Previous severe reaction to human immune globulin.

Warnings/Precautions: Advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, cardiovascular risk factors: increased risk of thrombosis. Monitor for signs/symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Pre-existing renal insufficiency, diabetes, >65yrs, hypovolemia, sepsis, paraproteinemia: increased risk of renal dysfunction or acute renal failure. Correct volume depletion; assess renal function, BUN, serum creatinine, urine output before and during therapy; discontinue if renal function deteriorates.

Monitor for aseptic meningitis, hemolysis and delayed hemolytic anemia. Monitor for pulmonary dysfunction; perform test for anti-neutrophil antibodies if transfusion-related acute lung injury (TRALI) suspected. Contains human plasma; monitor for possible infection transmission. Have epinephrine inj available. Elderly. Pregnancy (Cat.C).

Interactions: Concomitant nephrotoxic drugs: increased risk of renal toxicity. May affect response to live virus vaccines.

Adverse reactions: Headache, arthralgia, myalgia, transient skin reactions, infusion reactions (eg, flushing, chills, fever), renal toxicities; aseptic meningitis syndrome (esp. high dose 2g/kg), TRALI, thrombosis.

How supplied: Single-use vial—1

CORIFACT CSL Behring

℞

Clotting factor. Factor XIII concentrate (human); 1000–1600 units; per vial; powder for IV injection after reconstitution; preservative-free.

Indications: Routine prophylactic treatment and peri-operative management of surgical bleeding in patients with congenital Factor XIII (FXIII) deficiency.

Adults and Children: Give by slow IV injection at a rate of ≤4mL/min. Initially 40units/kg. Adjust ±5units/kg to maintain 5–20% trough FXIII activity levels using Berichrom Activity Assay: One trough level of <5%: increase by 5units/kg;

trough level of 5–20%: no change; two trough levels of >20%: decrease by 5units/kg; one trough level of >25%: decrease by 5units/kg.

Routine prophylaxis: give every 28 days. Perioperative management: individualized based on patient’s FXIII activity level, surgery type, and clinical response; dose adjustment: see full labeling.

Warnings/Precautions: Contains human plasma; monitor for possible infection transmission. Long-term therapy: consider appropriate vaccination (hepatitis A and B virus).

Monitor FXIII activity levels during and after surgery. Monitor for development of inhibitory antibodies, thromboembolic events. Pregnancy (Cat. C). Nursing mothers.

Adverse reactions: Joint inflammation, hypersensitivity, rash, pruritus, erythema, hematoma, arthralgia, headache, elevated thrombin-antithrombin levels, increased blood lactate dehydrogenase; acute ischemia, neutralizing antibodies.

How supplied: Single-use vial—1

CYKLOKAPRON Pfizer

℞

Plasminogen activation inhibitor. Tranexamic acid 100mg/mL; soln for IV inj.

Indications: Short-term use in hemophilia to reduce or prevent hemorrhage, and reduce the need for replacement therapy during and following tooth extraction.

Adults and Children: Give by IV inj. Max injection rate: 1mL/min. Pre-extraction: 10mg/kg; post-op: 10mg/kg 3–4 times daily for 2–8 days. Renal impairment: serum creatinine 1.36–2.83mg/dL: 10mg/kg twice daily; 2.83– 5.66mg/dL: 10mg/kg once daily; >5.66mg/dL: 10mg/kg every 48hrs or 5mg/kg every 24 hours.

Contraindications: Acquired defective color vision. Subarachnoid hemorrhage. Active intravascular clotting.

Warnings/Precautions: Therapy longer than several days: do ophthalmologic exam (before and during); discontinue if visual changes occur. Renal insufficiency; reduce dose. History of thromboembolic disease. Disseminated intravascular coagulation. Upper urinary tract bleeding. Pregnancy (Cat.B). Nursing mothers.

Interactions: Avoid concomitant Factor IX complex concentrates or Anti-inhibitor Coagulant concentrates; increased risk of thrombosis. Do not mix with solutions containing penicillin.

Adverse reactions: GI upset, giddiness, hypotension, visual abnormalities; rare: thromboembolic events.

How supplied: Amps (10mL)—10

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ASSOCIATED HEMATOLOGICAL DISORDERS ETHAMOLIN QOL Medical

℞

Sclerosing agent. Ethanolamine oleate 50mg/mL; soln for IV inj; contains benzyl alcohol 2%.

Indications: For the treatment of esophageal varices that have recently bled, to prevent rebleeding.

Adults: Usual IV dose: 1.5–5mL per varix. Max dose per treatment session: 20mL. Child Class C or concomitant cardiopulmonary disease: give less than the recommended max dose. To obliterate the varix, may give injections at the time of the acute bleeding episode and then after one week, six weeks, three months, and six months as indicated.

Children: Not recommended.

Warnings/Precautions: Should be performed by physician familiar with technique. Submucosal inj: not recommended. Cardiorespiratory disease; monitor. Child Class C (more likely to develop esophageal ulceration). Elderly, critically ill (increased risk of fatal aspiration pneumonia).

Pregnancy (Cat.C). Nursing mothers.

Adverse reactions: Pleural effusion/infiltration, esophageal ulcer, pyrexia, retrosternal pain, esophageal stricture, pneumonia, rare: anaphylactic reaction (may be fatal), acute renal failure.

How supplied: Ampules (2mL)—10

FEIBA Baxter

℞

Clotting factor. Anti-inhibitor Coagulant Complex (AICC) 500 units, 1000 units, 2500 units; per vial; lyophilized pwd for IV infusion after reconstitution; contains Factors II, IX, X (nonactivated); Factor VII (activated); Factor VIII inhibitor bypassing activity; Prothrombin Complex Factors; heparin-free.

Indications: To control and prevent bleeding episodes, perioperative management, or as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in Hemophilia A and B with inhibitors (see full labeling). Not for treating bleeding episodes due to coagulation factor deficiencies in the absence of inhibitors to factor VIII or IX. Adults and Children: Infusion rate: ≤2units/kg/min.

Joint hemorrhage: 50–100units/kg every 12hrs until improved. Mucous membrane bleeding: 50–100units/kg every 6hrs for at least 1 day or until resolved. Soft tissue hemorrhage: 100units/kg every 12hrs until resolved. Other severe hemorrhage (eg, CNS bleeds): 100units/kg every 6–12hrs until resolved. Preoperative: 50– 100units/kg once immediately prior to surgery.

Postoperative: 50–100units/kg every 6–12hrs until resolved and healed. Routine prophylaxis: 85units/kg every other day. All: Max 200units/kg per day (100units/kg per dose).

Contraindications: Hypersensitivity to factors of the kinin generating system. Disseminated intravascular coagulation (DIC). Acute thrombosis or embolism (including myocardial infarction).

Warnings/Precautions: Increased risk of thromboembolic events esp. after

high-doses (>200units/kg/day) and/or in patients with thrombotic risk factors (eg, DIC, atherosclerosis, crush injury, septicemia, concomitant recombinant factor VIIa). Monitor patients receiving doses >100units/kg for DIC development, acute coronary ischemia, and signs/symptoms of other thromboembolic events; discontinue if occurs and treat. Discontinue if hypersensitivity reactions occur. Contains human plasma; monitor for possible infection transmission. Elderly. Neonates. Pregnancy (Cat.C). Nursing mothers.

Interactions: Separate systemic antifibrinolytics by 12hrs.

Adverse reactions: Anemia, diarrhea, hemarthrosis, hep B surface antibody positive, nausea, vomiting; hypersensitivity, thromboembolic events (eg, stroke, DVT, PE).

Note: Report all infections suspected to be transmitted by Feiba to (800) 423-2862.

How supplied: Single-dose vials—1 (w. diluent, transfer device)

GAMUNEX-C Grifols Biologicals

℞

Immune globulin. Immune Globulin (human) 1g/10mL, 2.5g/25mL, 5g/50mL, 10g/100mL, 20g/200mL; soln for IV or SC infusion; preservative- and sucrose-free.

Indications: Idiopathic thrombocytopenic purpura (ITP).

Adults and Children: Give by IV infusion at a rate of 1mg/kg/min for first 30mins, if tolerated may increase to max 8mg/kg/min. 1g/kg once daily given on 2 consecutive days or 0.4g/kg once daily given on 5 consecutive days. If adequate response after first 1g/kg dose, may withhold second dose. Risk of renal dysfunction or thrombosis: give at minimum practicable infusion rate (<8mg/kg/min). Expanded fluid volumes: high dose regimen not recommended.

Contraindications: IgA deficiency with antibodies against IgA. Previous severe reaction to human immune globulin.

Warnings/Precautions: Advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, cardiovascular risk factors: increased risk of thrombosis. Monitor for signs/symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Pre-existing renal insufficiency, diabetes, >65yrs, hypovolemia, sepsis, paraproteinemia: increased risk of renal dysfunction or acute renal failure. Correct volume depletion; assess renal function, BUN, serum creatinine, urine output before and during therapy; discontinue if renal function deteriorates.

Monitor for aseptic meningitis, hemolysis, hemolytic anemia. Monitor for pulmonary dysfunction; perform test for anti-neutrophil antibodies if transfusion-related acute lung injury (TRALI) suspected. Contains human plasma; monitor for possible infection transmission. Have

epinephrine inj available. Pregnancy (Cat.C).

Nursing mothers: not evaluated.

Interactions: May affect response to live virus vaccines. Concomitant nephrotoxic drugs: increased risk of acute renal failure. May cause false positive direct or indirect Coombs’ test.

Adverse reactions: Headache, vomiting, fever, nausea, back pain, rash; renal dysfunction (may be fatal), hypersensitivity reactions; rare: hemolytic anemia, aseptic meningitis syndrome (esp. high dose of 2g/kg and/or rapid infusion), TRALI, thrombosis, hyperproteinemia.

Note: Report all infections suspected to be transmitted by Gamunex-C to (800) 520-2807.

How supplied: Vials—1

KCENTRA CSL Behring

℞

Clotting factor. Prothrombin complex concentrate (human) 500 units, 1000 units; per vial; lyophilized pwd for IV infusion after reconstitution; contains non-activated coagulation Factors II, VII, IX, X, antithrombotic Proteins C and S; also, heparin, human albumin, antithrombin III; preservative-free; latex-free.

Indications: Urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA) therapy in adults with acute major bleeding or need for an urgent surgery/invasive procedure.

Adults: See full labeling. Administer concomitant Vitamin K. Individualize dosing based on patient’s baseline INR and weight. Potency (units) is defined

by Factor IX content. Give by IV Infusion at a rate of 0.12mL/kg/min (~3 units/kg/min); max rate of 8.4mL/min (~210 units/min). ≤100kg: Pre-treatment INR: (2–<4): 25 units of Factor IX/kg; max 2500 units; (4–6): 35 units of Factor IX/kg; max 3500 units; (>6): 50 units of Factor IX/kg; max 5000 units. >100kg: do not exceed max dose.

Repeat dosing: not recommended.

Children: Not established.

Contraindications: Severe hypersensitivity to heparin, Factors II, VII, IX, X, Proteins C and S, antithrombin III, human albumin. Disseminated intravascular coagulation (DIC). Known heparininduced thrombocytopenia (HIT).

Warnings/Precautions: Risk of arterial and venous thromboembolic complications (may be fatal). History of thromboembolic events within the previous 3 months. Monitor for signs/symptoms of thromboembolic events during and after infusion. Discontinue immediately if hypersensitivity reactions occur.

Measure INR before, during, and after each treatment. Contains human plasma; monitor for possible infection transmission. Pregnancy (Cat.C). Nursing mothers.

Adverse reactions: Headache, nausea, vomiting, hypotension, anemia; hypersensitivity, thromboembolic events (eg, stroke, PE, DVT).

Note: Report all infections suspected to be transmitted by Kcentra to (866) 915-6958.

How supplied: Kit (500 units, 1000 units)—1 (single-use vial + diluent, supplies)

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ASSOCIATED HEMATOLOGICAL DISORDERS NEUMEGA Pfizer

℞

Thrombopoietic growth factor (Interleukin-11).

Oprelvekin 5mg/vial; lyophilized pwd for SC inj after reconstitution; preservative-free.

Indications: Prevention of severe thrombocytopenia. To reduce platelet transfusions following myelosuppressive chemotherapy in adults with non-myeloid malignancies who are at high risk of severe thrombocytopenia.

Adults: Initiate 6–24hrs after chemotherapy completion. Give by SC inj into abdomen, thigh, or hip; also upper arm if not self-injecting.

50micrograms/kg once daily until post-nadir platelet count is ≥50,000/microliter; max 21 days.

Discontinue ≥2days prior to next chemotherapy cycle. Severe renal impairment: CrCl <30mL/min: 25micrograms/kg. May give for ≤6 cycles following chemotherapy.

Children: Not recommended.

Warnings/Precautions: Not for use after myeloablative chemotherapy. Monitor fluid balance and electrolytes; increased risk of serious fluid retention with CHF, renal impairment, chronic diuretic or aggressive hydration therapy. Consider draining pre-existing fluid collections (eg, pericardial effusion, ascites).

Obtain CBCs before and during therapy; monitor platelet counts. Pre-existing papilledema or tumors involving the CNS. History of stroke, transient ischemic attack, or atrial arrhythmias.

Effectiveness unknown with chemotherapy regimens >5 days duration or with regimens associated with delayed myelosuppression (eg. nitrosoureas, mitomycin-C). Pregnancy (Cat.C).

Nursing mothers: not recommended.

Adverse reactions: Edema, dyspnea, tachycardia, conjunctival injection, palpitations, atrial arrhythmias, pleural effusions, neutropenic fever, syncope, atrial fibrillation, fever, pneumonia, CHF, pulmonary edema, dilutional anemia, blurred vision, paresthesia, dehydration, skin discoloration, exfoliative dermatitis, eye hemorrhage, stroke, papilledema, hypersensitivity reactions (permanently discontinue if occur).

How supplied: Single-use vials—7 (w. diluent)

NITROPRESS Hospira

℞

Vasodilator. Sodium nitroprusside 25mg/mL; soln for IV infusion after dilution.

Indications: To produce controlled hypotension to reduce surgical bleeding.

Adults and Children: Use infusion pump only. Monitor BP closely. Initially 0.3microgram/kg/min; may increase infusion rate every few minutes until desired effect;

max 10microgram/kg/min and no more than 10 minutes. Titrate infusion rate (see literature).

Contraindications: Compensatory hypertension due to aortic coarctation or arteriovenous shunting.

Inadequate cerebral circulation or moribund patients requiring emergency surgery. Congenital (Lebers) optic atrophy. Tobacco amblyopia. Acute CHF associated with reduced peripheral vascular resistance.

Warnings/Precautions: Use only when available equipment and personnel allow BP to be continuously monitored. Cyanide toxicity possible (esp. at infusion rates >2micrograms/kg/min); monitor acid-base disturbances and venous oxygen concentration. Elevated intracranial pressure.

Correct pre-existing anemia and hypovolemia, esp. during anesthesia. Poor surigical risk. Hepatic impairment. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Hypotensive effect potentiated by ganglionic blocking agents, negative inotropic agents, and inhaled anesthetics.

Adverse reactions: Excessive hypotension, cyanide toxicity, methemoglobinemia, abdominal pain, apprehension, diaphoresis, dizziness, headache, muscle twitch, nausea, palpitations, restlessness, rash, hypothyroidism, ileus, flushing, infusion site reactions.

How supplied: Single-dose vials (2mL)—100

NPLATE Amgen

℞

Thrombopoietin receptor agonist. Romiplostim (recombinant) 250mcg, 500mcg; per vial; lyophilized pwd for SC inj after reconstitution; contains sucrose and mannitol; preservative-free.

Indications: Thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Adults: Give by SC inj. To reduce risk of bleeding: use lowest effective dose to achieve and maintain platelets ≥50x109/L. ≥18yrs: initially: 1mcg/kg weekly; may increase by 1mcg/kg if platelets <50x109/L; max: 10mcg/kg weekly. May reduce by 1mcg/kg if platelets >200x109/L for 2 consecutive weeks. Do not dose if platelets >400x109/L; resume Nplate at a dose reduced by 1mcg/kg when platelets fall to <200x109/L. Discontinue if platelets have not increased after 4 weeks at max dose.

Children: <18yrs: not recommended.

Warnings/Precautions: Not for normalization of platelet counts or to treat thrombocytopenia due to MDS or any cause of thrombocytopenia other than chronic ITP. Risk of bone marrow fibrosis with cytopenias. Worsened

thrombocytopenia after discontinuation. Monitor CBCs, platelets, and peripheral blood smears before and weekly during dose adjustments then monthly after achieving stable dose; and weekly for 2 weeks after discontinuation of therapy.

Monitor after initial response for formation of neutralizing antibodies. Risk of hematologic malignancies (esp. myelodysplastic syndrome).

Renal or hepatic impairment. Elderly. Pregnancy (Cat.C). Nursing mothers.

Interactions: May increase bleeding risk with anticoagulants or antiplatelet agents.

Adverse reactions: Arthralgia, dizziness, insomnia, myalgia, pain in extremity, abdominal pain, shoulder pain, dyspepsia, paresthesia, headaches; bone marrow reticulin formation, worsening thrombocytopenia, risk of bleeding, thrombotic/thromboembolic complications, antibody formation.

How supplied: Single-use vial—1

PRIVIGEN CSL Behring

℞

Immune globulin. Immune globulin (human) 0.1g/mL; soln for IV infusion; contains L-proline; sucrose-, preservative-, and latex-free.

Indications: Chronic immune thrombocytopenic purpura (ITP).

Adults and Children: <15yrs: not established. ≥15yrs: Give by IV infusion at an initial rate of 0.5mg/kg/min, if tolerated may increase to 4mg/kg/min. Renal dysfunction, thrombosis risk: give at the minimum infusion rate practicable. Usual dose: 1g/kg once daily for 2 consecutive days for a total dose of 2g/kg. Increased risk of thrombosis, hemolysis, acute renal injury, or volume overload: consider carefully the relative risks and benefits before prescribing high dose regimen (2g/kg).

Contraindications: IgA-deficiency with antibodies against IgA and history of hypersensitivity. Hyperprolinemia. Previous severe reaction to human immune globulin.

Warnings/Precautions: Advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, cardiovascular risk factors: increased risk of thrombosis.

Monitor for signs/symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Pre-existing renal insufficiency, diabetes, >65yrs, obese, hypovolemia: increased risk of renal dysfunction and acute renal failure.

Correct volume depletion; assess renal function, BUN, serum creatinine, urine output before and during therapy; discontinue if renal function deteriorates. Monitor for aseptic meningitis,

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DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS hemolysis, delayed hemolytic anemia, transfusionrelated acute lung injury (eg, respiratory distress, pulmonary edema, hypoxemia). Antibody formation. Risk of transmission of viral diseases.

Have epinephrine inj available. Elderly. Pregnancy (Cat.C). Nursing mothers.

Interactions: Concomitant nephrotoxic drugs: increased risk of renal toxicity. May affect response to live virus vaccines. May interfere with serological test interpretation.

Adverse reactions: Headache, elevated body temperature, positive direct antiglobulin test, anemia, nausea, epistaxis, vomiting, hematocrit decreased, increase in blood bilirubin, blood total bilirubin and blood lactate dehydrogenase; hyperproteinemia, increased serum viscosity, hyponatremia; rare: aseptic meningitis syndrome (esp. high dose of 2g/kg), hemolysis, TRALI, thrombosis.

How supplied: Single-use vial (50mL, 100mL, 200mL, 400mL)—1

PROMACTA GlaxoSmithKline

℞

Thrombopoietin receptor agonist. Eltrombopag (as olamine) 12.5mg, 25mg, 50mg, 75mg; tabs.

Indications: Thrombocytopenia in adults with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Thrombocytopenia in adults with chronic hepatitis C to allow initiation and maintenance of interferon-based therapy.

Limitations of use: should be used only in ITP whose degree of thrombocytopenia and clinical condition increase the risk of bleeding; or, in chronic hepatitis C whose degree of thrombocytopenia prevents starting or limiting ability to maintain interferon-based therapy.

Safety and efficacy not established in combination with direct-acting antiviral agents without interferon for chronic hepatitis C infection.

Adults: Take on empty stomach. ITP: initially 50mg once daily. Hepatic impairment or East Asian ancestry: initially 25mg once daily. East Asian ancestry with hepatic impairment: consider initiating at 12.5mg once daily. Titrate to maintain platelet count ≥50x109/L; max 75mg once daily.

Chronic hepatitis C-associated thrombocytopenia: initially 25mg once daily. Titrate dose by 25mg every 2 weeks as needed to achieve target platelet counts; max 100mg/day. Monitoring, dose adjustment, and discontinuation: see full labeling.

Children: Not established.

Warnings/Precautions: Increased risk of hepatic decompensation in chronic hepatitis C, when concomitant with interferon and ribavirin; discontinue Promacta if antiviral therapy is discontinued. Monitor liver function prior to initiation, every 2 weeks during dose adjustments, and monthly after stabilized (see full labeling); discontinue if ALT ≥3xULN and is progressive or persistent for ≥4 weeks, or if occurs with increased bilirubin, or evidence of hepatic injury/decompensation; reinitiate therapy if benefit outweighs risk; if restarted, monitor

carefully. Increased risk of thromboembolism; do not use to normalize platelet counts. Do baseline eye exam; monitor for cataracts. Renal impairment. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Do not take within 4hrs of food/drugs containing polyvalent cations (eg, Fe+2, Ca+2, Al+3, Mg+2, Se+2, Zn+2). Potentiate substrates of OATP1B1 (eg, most statins, bosentan, ezetimibe, glyburide, olmesartan, valsartan, repaglinide, rifampin) or BCRP (eg, imatinib, irinotecan, lapatinib, methotrexate, mitoxantrone, sulfasalazine, topotecan); monitor and consider reducing their doses. Antagonized by lopinavir/ritonavir.

Adverse reactions: Nausea, diarrhea, vomiting, infections, increased ALT/AST, myalgia, pain, pharyngitis, paresthesia, rash, anemia, pyrexia, fatigue, headache, decreased appetite, asthenia, insomnia, cough, pruritus, chills, alopecia, peripheral edema; hepatotoxicity, hemorrhage, thrombotic complications from excessive increases in platelet counts, cataracts.

How supplied: Tabs—30

RECOTHROM ZymoGenetics

℞

Topical hemostatic. Thrombin [recombinant] 5000 IU, 20000 IU; per vial; pwd for topical use after reconstitution; preservative-free.

Indications: Aid to hemostasis for minor bleeding/oozing from capillaries and venules when standard surgical techniques are inadequate or ineffective. May use with absorbable gelatin sponge.

Adults: Apply directly to bleeding area, or soak into absorbable gelatin sponge and apply in a single layer.

Children: Not recommended.

Contraindications: Not for direct injection into circulatory system. Not for treatment of massive or brisk arterial bleeding. Hypersensitivity to hamster proteins.

Warnings/Precautions: Avoid systemic absorption (thrombosis may occur). Hypersensitivity to snake proteins. Pregnancy (Cat.C).

Adverse reactions: Incision site complication, infection, pain, bleeding, nausea/vomiting, cardiac events, thromboembolic events.

How supplied: Single-use vial (5000 IU, 20000 IU)—1 (w. diluent, supplies) 20000 IU Recothrom kit (co-packaged with ZymoGenetics Spray Applicator Kit)—1

REFACTO Pfizer

℞

Clotting factor. Antihemophilic Factor VIII (recombinant) 250 IU, 500 IU, 1000 IU, 2000 IU; per vial; lyophilized pwd for IV infusion after reconstitution; preservative-free.

Indications: Prevention and control of hemorrhagic episodes and for surgical prophylaxis in Hemophilia A. Short-term routine prophylaxis to reduce frequency of spontaneous bleeding episodes.

Adults and Children: Dosage Required (IU) = Body Weight (kg) × Desired % Factor VIII Increase × 0.5. Individualize. Infuse at rate comfortable to patient. Minor hemorrhage: obtain 20–40% FVIII increase; give every 12–24hrs for at least 1 day until resolved. Moderate hemorrhage and tooth extraction: obtain 30–60% FVIII increase; give every 12–24hrs for 3–4 days until adequate hemostasis; for tooth extraction: a single infusion plus oral antifibrinolytic therapy within 1hr may be sufficient. Major hemorrhage: obtain 60–100% FVIII increase; give every 8–24hrs until resolved; or, for surgery, until local hemostasis achieved.

Prophylaxis: give ≥2 times weekly; children may need shorter dosage intervals or higher doses.

Contraindications: Mouse or hamster protein sensitivity.

Warnings/Precautions: Not for von Willebrand’s disease. Confirm Factor VIII deficiency prior to treatment. Monitor for development of Factor VIII inhibitors. Pregnancy (Cat.C). Nursing mothers.

Adverse reactions: Allergic reactions, headache, fever, chills, flushing, nausea, vomiting, lethargy, pruritus, antibody formation.

How supplied: Single-use vial—1 (w. diluent, supplies)

RHOPHYLAC CSL Behring

℞

Rho (D) immune globulin human 1500 IU (300mcg)/2mL; syringe; for IV or IM inj; preservative- and latex-free; contains albumin (human); solvent/detergent treated.

Indications: Raising platelet counts in Rho (D) positive non-splenectomized patients with chronic immune thrombocytopenic purpura (ITP).

Adults: See full labeling. 250 IU (50mcg) per kg

by IV only at rate of 2mL per 15–60 secs.

Children: Not recommended.

Contraindications: Rho (D) positive patients.

IgA deficiency.

Warnings/Precautions: Monitor patients 20 mins after administration. Pregnancy (Cat.C).

Interactions: Do not give live vaccines within 3 months.

Adverse reactions: Local or infusion reactions, fever, chills, headache; see full labeling.

How supplied: Single-dose prefilled syringes—1, 10

RIASTAP CSL Behring

℞

Hemostatic. Fibrinogen concentrate (human) 900–1300mg; per vial; lyophilized pwd for IV inj after reconstitution; contains albumin; preservative-free.

Indications: Acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia.

Adults and Children: See literature. Give by slow IV inj at rate not exceeding 5mL/min. Individualize.

Calculate dose when baseline fibrinogen level is known: Dose (mg/kg body wt) = [Target level (mg/dL) – measured level (mg/dL)] / 1.7 (mg/dL per mg/kg body wt). When baseline fibrinogen level is not known: 70mg/kg. Monitor fibrinogen

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DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS Children: Not recommended.

Warnings/Precautions: Not for injection or use in large blood vessels. Antibody formation: do not re-expose, abnormalities in hemostasis (eg, severe bleeding or thrombosis) more likely with repeated use. Pregnancy (Cat.C). Nursing mothers.

Adverse reactions: Hypersensitivity reactions, antibody formation.

How supplied: Vials—1 (w. diluent) Pump Spray Kit (20000 IU)—1 (w. diluent) Syringe Spray Kit (20000 IU)—1 (w. diluent) Epistaxis Kit (5000 IU)—1 (w. diluent)

level during therapy. Maintain target fibrinogen level of 100mg/dL until hemostatis is obtained.

Warnings/Precautions: Not for use in dysfibrinogenemia. Monitor for allergic or hypersensitivity reactions; discontinue if occur. Risk of thrombosis (monitor). Contains human plasma; monitor for possible infection transmission. Labor & delivery. Pregnancy (Cat.C). Nursing mothers.

Adverse reactions: Fever, headache, chills, nausea, vomiting; thrombotic episodes (eg, pulmonary embolism, MI, DVT), anaphylactic reactions.

How supplied: Single-use vial—1

THROMBIN-JMI Pfizer

WINRHO SDF

℞

℞

Emergent BioSolutions

Topical hemostatic. Thrombin [bovine origin] 5000 IU, 20000 IU; per vial; pwd for topical use after reconstitution; preservative-free.

Indications: Aid to hemostasis for oozing blood and minor bleeding from accessible capillaries and small venules. Adjunct for surgical hemostasis with absorbable gelatin sponge.

Adults: For topical use only. See literature. Profuse bleeding (eg, abraided surfaces of liver or spleen): 1000 IU/mL. General use (eg. plastic surgery, dental extractions, skin grafting): 100 IU/mL. May dilute to prepare intermediate strengths, if needed.

Oozing surfaces: may use dry form.

Rho(D) immune globulin intravenous human 600IU (120mcg), 1500IU (300mcg), 2500IU (500mcg), 5000IU (1000mcg), 15000IU (3000mcg); per vial; lyophilized pwd or soln; for IV or IM inj after reconstitution; preservative-free.

Indications: Treatment of non-splenectomized, Rho(D) positive children with acute immune thrombocytopenic purpura (ITP); adults and children with chronic ITP and ITP secondary to HIV infection; in clinical situations requiring an increase in platelet count to prevent excessive hemorrhage.

Adults and Children: Give by IV inj only.

Confirm Rho(D) positive prior to treatment.

Initially: 250 IU/kg as single dose or 2 divided doses on separate days; if Hgb <10g/dL, reduce to 125–200 IU/kg. Maintenance: 125– 300 IU/kg; Hbg >10g/dL: 250–300 IU/kg; Hgb 8–10g/dL: 125–200 IU/kg; Hgb <8g/dL: use with caution. Base frequency and dose on clinical response.

Contraindications: IgA deficiency. Allergy to blood products. Treatment of immune globulin deficiency syndromes.

Warnings/Precautions: Not for use in Rho(D) negative or splenectomized patients; monitor for intravascular hemolysis, anemia, renal insufficiency; hemoglobin <10g/dL decrease dose, if <8g/dL use extreme caution. Pregnancy (Cat.C).

Interactions: Do not give live vaccines within 3 months.

Adverse reactions: Headache, chills, fever, local or infusion reactions; see literature.

Note: Report all infections suspected to be transmitted by WinRho SDF to (800) 423-2090.

How supplied: Single-dose vials (pwd) 600IU, 1500IU, 5000IU—1 (w. diluent); Single-dose vials (soln) 600IU, 1500IU, 2500IU, 5000IU, 15000IU—1

LIVER FUNCTION ASSESSMENT Child-Pugh Score is used to assess residual liver function and injury severity in cirrhosis patients.

CHILD-PUGH SCORES Criteria

1 point

2 points

3 points

Total serum bilirubin (mg/dL)

<2

2–3

>3

Serum albumin (g/dL)

>3.5

2.8–3.5

<2.8

INR

<1.70

1.71–2.20

>2.20

Ascites

No ascites

Ascites controlled

Ascites not controlled

Encephalopathy

No encephalopathy

Encephalopathy controlled

Encephalopathy not controlled

Class A

Class B

Class C

Points

5–6

7–9

10–15

Life expectancy

15–20 years

Candidate for liver transplant

1–3 years

Perioperative mortality

10%

30%

82%

INTERPRETATION OF CHILD-PUGH SCORES

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DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS White blood cell disorders

GRANIX Teva

℞

Granulocyte colony stimulating factor. Tbofilgrastim 300mcg/0.5mL, 480mcg/0.8mL; soln for SC inj; preservative-free.

Indications: To reduce the duration of severe neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

Adults: Administer the 1st dose no earlier than 24hrs following myelosuppressive chemotherapy. Do not administer within 24hrs prior to chemotherapy. Inject 5mcg/kg SC once daily until expected neutrophil nadir is passed and neutrophil count has recovered to normal range. Monitor CBC prior to chemotherapy and twice per week until recovery. Recommended inj sites: the abdomen (except for the 2-inch area around navel), the front of the middle thighs, the upper outer area of the buttocks, or the upper back portion of the upper arms; rotate inj site daily. Avoid injecting into an area that is tender, red, bruised or hard, or that has scars or stretch marks.

Children: <18yrs: not established.

Warnings/Precautions: Risk of splenic rupture; discontinue and evaluate if symptoms of enlarged spleen or rupture occur. Evaluate for acute respiratory distress syndrome if fever and lung infiltrates or respiratory distress develop after treatment; discontinue if acute respiratory distress syndrome is diagnosed. Permanently discontinue if serious allergic reactions occur.

Sickle cell disease: consider potential risks and benefits prior to treatment and discontinue if sickle cell crisis develops. Hepatic or moderateto-severe renal impairment. Pregnancy (Cat. C).

Nursing mothers.

Interactions: Caution with drugs that may potentiate release of neutrophils (eg, lithium).

May cause transient positive changes in boneimaging test results.

Adverse reactions: Bone pain; splenic rupture (may be fatal), acute respiratory distress syndrome, serious allergic reactions, sickle cell crisis, potential for tumor growth stimulatory effects on malignant cells.

How supplied: Single-use prefilled syringe (0.5mL, 0.8mL)—1, 10 (w. safety needle guard)

LEUKINE Genzyme Granulocyte-macrophage colony stimulating factor (recombinant). Sargramostim (recombinant human granulocyte-macrophage colony stimulating factor, or rhu GM-CSF) 250mcg; per vial; pwd for SC inj or IV infusion after reconstitution; preservative-free.

Indications: To speed neutrophil recovery and reduce infections after induction chemotherapy in treatment of acute myelogenous leukemia

℞

(AML) in patients >55 years of age. To mobilize hematopoietic progenitor cells into peripheral blood for collection by leukapheresis. To speed myeloid recovery in non-Hodgkin’s lymphoma, acute lymphoblastic leukemia (ALL), and Hodgkin’s disease in autologous bone marrow transplantation (BMT). To speed myeloid recovery in allogeneic BMT. Patients with BMT failure or engraftment delay.

Adults: See literature for timing and duration of dosing, and for repeat courses of therapy.

Individualize. Neutrophil recovery: 250mcg/m2 per day IV over 4 hrs. Mobilization or post peripheral blood progenitor cell transplantation: 250mcg/m2 per day IV over 24 hrs or SC once daily. Myeloid recovery after BMT: 250mcg/m2 per day IV over 2 hrs. BMT failure or engraftment delay: 250mcg/m2 per day IV over 2 hrs for 14 days.

Children: See literature.

Contraindications: Excessive leukemic myeloid blasts in bone marrow or peripheral blood (≥10%). Allergy to GM-CMF or yeastderived products. Concomitant (within 24 hrs) chemotherapy or radiotherapy.

Warnings/Precautions: Fluid retention, pleural or pericardial effusions. Pulmonary infiltrates. Respiratory disease or symptoms.

Hypoxia. Reduce infusion rate by ½ if dyspnea occurs; discontinue if dyspnea worsens.

Cardiac disease. CHF. Renal or hepatic dysfunction (monitor before and every other week during therapy). Monitor CBC and differential twice weekly. Reduce dose by ½ or discontinue if absolute neutrophil count exceeds 20,000cells/mm3 or if platelet count exceeds 500,000cells/mm3. Myeloid malignancies.

Monitor body weight and hydration. Pregnancy (Cat.C). Nursing mothers.

Interactions: Caution with lithium, corticosteroids, others that may enhance myeloproliferative effects.

May be antagonized by radiotherapy, myelotoxic drugs.

Adverse reactions: Flu-like symptoms, GI disturbances, edema, dyspnea, pharyngitis, rash, joint or bone or chest pain, eye hemorrhage, hypomagnesemia, anxiety, headache, pleural +/or pericardial effusion, arthralgia, myalgia, others.

How supplied: Vials—5

NEULASTA Amgen

℞

Granulocyte colony stimulating factor.

Pegfilgrastim (polyethylene glycol/filgrastim conjugate) 6mg/0.6mL; soln for SC inj; preservative-free.

Indications: To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with clinically significant incidence of febrile neutropenia. To increase survival in patients acutely exposed to myelosuppressive doses of radiation.

Adults and Children: See full labeling. ≥45kg: Chemotherapy-induced neutropenia: Do not

give between 14 days before and 24 hours after chemotherapy. 6mg SC once per chemotherapy cycle. Acute radiation syndrome: 2 doses, each of 6mg SC; give 1st dose as soon as possible after exposure to radiation levels >2 gray (Gy), then a 2nd dose one week later. Pediatrics weighing 31–44kg: 4mg; 21–30kg: 2.5mg; 10–20kg: 1.5mg; <10kg: 0.1mg/kg. Direct administration of prefilled syringe with doses <6mg is not recommended.

Warnings/Precautions: Monitor CBC and platelets before and during therapy. Monitor for splenomegaly, splenic rupture, acute respiratory distress syndrome (ARDS); evaluate if fever, lung infiltrates, or respiratory distress occurs; discontinue if ARDS diagnosed. Monitor for glomerulonephritis; consider dose reduction or interruption if treatment-related. Permanently discontinue if serious allergic reactions develop.

Sickle cell disease: may cause severe sickle cell crises. Myeloid malignancies. Myelodysplasia.

Acrylic adhesive allergy (On-body injector).

Pregnancy (Cat.C). Nursing mothers.

Interactions: May cause transient (+) changes in bone-imaging test results.

Adverse reactions: Bone or extremity pain; anaphylaxis, ARDS, splenic rupture, glomerulonephritis, leukocytosis, capillary leak syndrome (monitor closely if occurs).

How supplied: Prefilled syringe—1; Onpro Kit—1 (prefilled syringe + On-body injector)

NEUPOGEN Amgen

℞

Granulocyte colony stimulating factor.

Filgrastim 600mcg/mL; for SC inj or IV infusion; preservative-free. ℞ Also: NEUPOGEN VIALS Filgrastim 300mcg/mL; for SC or IV infusion; preservative-free.

Indications: See full labeling. To decrease incidence of infection in patients with nonmyeloid malignancies receiving certain myelosuppressive anti-cancer drugs. To reduce time to neutrophil recovery and fever duration after induction or consolidation chemotherapy treatment of adults with AML. To reduce duration of neutropenia and related sequelae in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bonemarrow transplantation (BMT). To mobilize hematopoietic progenitor cells (PBPC) into peripheral blood for collection by leukapheresis.

To reduce the incidence and duration of neutropenia sequelae in severe chronic neutropenia (SCN).

Adults: See full labeling. Do not give for at least 24hrs before or after cytotoxic chemotherapy dose. BMT: Give 1st dose at least 24hrs after bone marrow infusion. SCN: Give on a daily basis.

Children: See full labeling.

Contraindications: Hypersensitivity to E. coliderived products.

Warnings/Precautions: Monitor blood, including CBC and differential and platelets,

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DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS before and during therapy (myelosuppressive chemotherapy: monitor twice weekly; BMT: at least 3 times weekly; SCN: twice per week during initial 4 weeks of therapy and during 2 weeks after dose adjustment). Discontinue if post nadir absolute neutrophil count (ANC) reaches 10,000/mm3 for patients receiving myelosuppressive chemotherapy; other indications: see full labeling. Monitor for splenomegaly/splenic rupture and for acute respiratory distress syndrome (ARDS); suspend until ARDS resolves if fever or lung infiltrates occur. Confirm diagnosis and do appropriate pretreatment hematological workup in SCN. Preexisting cardiac or hyperplastic skin conditions. Sickle cell disease (may cause sickle cell crisis). Avoid simultaneous chemo- and radiation therapy. Pregnancy (Cat.C). Nursing mothers.

Interactions: Caution with mitomycin C, and with concomitant (same day) drugs that decrease platelets, or increase release of neutrophils (eg, lithium), or cause delayed myelosuppression, or with myelosuppressive doses of antimetabolites (eg, nitrosoureas, 5-FU).

Adverse reactions: Bone pain, cutaneous vasculitis, splenomegaly, others (see literature).

How supplied: Prefilled syringes (0.5mL, 0.8mL)—10; Vials (1mL, 1.6mL)—10

ZARXIO Sandoz

℞

Granulocyte colony stimulating factor. Filgrastimsndz 300mcg/0.5mL, 480mcg/0.8mL; for SC inj or IV infusion; preservative-free.

Indications: See full labeling. To decrease incidence of infection in patients with nonmyeloid malignancies receiving certain myelosuppressive anti-cancer drugs. To reduce time to neutrophil recovery and fever duration after induction or consolidation chemotherapy treatment of adults with AML. To reduce duration of neutropenia and related sequelae in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone-marrow transplantation (BMT). To mobilize hematopoietic progenitor cells (PBPC) into peripheral blood for collection by leukapheresis. To reduce the incidence and duration of neutropenia sequelae in severe chronic neutropenia (SCN).

Adults: See full labeling. Do not give for at least 24hrs before or after cytotoxic chemotherapy dose. BMT: Give 1st dose at least 24hrs after bone marrow infusion. SCN: Give on a daily basis.

Children: See full labeling.

Warnings/Precautions: Monitor blood, including CBC and differential and platelets, before and during therapy (myelosuppressive chemotherapy: monitor twice weekly; BMT: monitor frequently; SCN: monitor during initial

4 weeks of therapy and during 2 weeks after dose adjustment) then monthly for the 1st year.

Discontinue if post nadir absolute neutrophil count (ANC) reaches 10,000/mm3 for patients receiving myelosuppressive chemotherapy; other indications: see full labeling. Monitor for splenomegaly/splenic rupture and for acute respiratory distress syndrome (ARDS); discontinue if ARDS occurs. Confirm diagnosis and do appropriate pretreatment hematological workup in SCN. Permanently discontinue if serious allergic reactions occur. Sickle cell disease (may cause sickle cell crisis). Evaluate if glomerulonephritis is suspected; consider dose reduction or interruption if causality is likely. Abnormal cytogenetics or myelodysplastic syndrome. Chronic myeloid leukemia. Hold dose if cutaneous vasculitis occurs; resume at reduced dose after symptoms resolve and the ANC decreased. Avoid simultaneous chemo- and radiation therapy. Latex allergy. Pregnancy (Cat.C).

Nursing mothers.

Interactions: May cause transient (+) boneimaging results.

Adverse reactions: Pyrexia, pain, rash, cough, dyspnea, epistaxis, bone pain, headache, anemia, diarrhea, hypoesthesia, alopecia; capillary leak syndrome (monitor), thrombocytopenia.

How supplied: Single-use prefilled syringes (0.5mL, 0.8mL)—1, 10 (w. needle guard)

DOSAGES FOR THE ELDERLY Special caution is advised when prescribing drugs for elderly patients. Keep the following points in mind when prescribing drugs for patients of approximately 60 years or older:

1. Renal Function: Glomerular filtration rate, renal tubular secretion and blood flow tend to decrease with advancing age, while the incidence of renal pathology increases.

2. Drug Sensitivity: Elderly patients may show unusual sensitivity or paradoxical reactions to a number of drugs. Refer to the complete prescribing information.

3. Drug Distribution: The ratio of fat to lean body weight may increase in the elderly, which affects the volume of distribution of fat-soluble drugs. Plasma albumin concentrations may be decreased in the elderly. This potentiates plasma-protein bound drugs and increases the potential for drug interactions caused by plasma-protein displacement.

4. Polypharmacy: It is important to determine the patient’s current medication use, including nonprescription products, before adding any medication to determine any possible interactions.

5. Hepatic Function: Reduced function of metabolic enzymes in the liver may occur in the elderly.

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DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS Miscellaneous hematological agents

CINRYZE Shire

℞

C1 inhibitor. C1 inhibitor (human) 500 Units/vial; lyophilized pwd for IV infusion after reconstitution; preservative-free.

Indications: Routine prophylaxis against angioedema attacks in adolescent and adult patients with hereditary angioedema.

Adults: Give by IV infusion at a rate of 1mL/min (10mins). 1000 Units every 3–4 days.

Children: Not recommended.

Warnings/Precautions: Contains human plasma; monitor for possible infection transmission. Have epinephrine available to treat hypersensitivity reactions. Monitor patients with known risk factors for thrombotic events. Labor & delivery. Pregnancy (Cat.C). Nursing mothers.

Adverse reactions: Upper respiratory tract infection, sinusitis, rash, headache; thrombotic events, hypersensitivity reactions (may be severe); discontinue if occurs.

Note: To report infections that may have been transmitted by Cinryze, call CinryzeSolutions at (877) 945-1000.

How supplied: Single-use vial—1

EXJADE Novartis

℞

Iron chelating agent. Deferasirox 125mg, 250mg, 500mg; tabs for oral susp.

Indications: Chronic iron overload due to blood transfusions in patients ≥2yrs of age. Chronic iron overload in patients ≥10yrs of age with non-transfusion dependent thalassemia (NTDT) syndromes and with a liver iron concentration (LIC) of at least 5mg Fe per gram of dry weight and a serum ferritin >300 mcg/L. Adults and Children: Calculate dose to nearest whole tab. Take on empty stomach at least 30 mins before food. Do not chew or swallow tabs; disperse completely in water, orange juice or apple juice; drink immediately; resuspend remainder and drink.

Transfusional iron overload: <2yrs: not established. ≥2yrs: initially 20mg/kg once daily; may adjust dose by 5 or 10mg/kg every 3–6 months based on serum ferritin levels or response. If inadequate control at 30mg/kg, may consider increasing up to max 40mg/kg. Adjust dose if severe skin rashes occur; consider suspending therapy if serum ferritin <500mcg/L. NTDT syndromes: <10yrs: not established. ≥10yrs: initially 10mg/kg once daily; if baseline LIC>15mg Fe/g dw, consider increasing dose to 20mg/kg after 4 weeks. Suspend therapy if serum ferritin <300mcg/L and obtain LIC to determine whether it has fallen to <3mg Fe/g dw.

After 6 months, if LIC remains >7mg Fe/g dw, increase dose to max 20mg/kg/day. If after 6 months, LIC is 3–7mg Fe/g dw, continue with max 10mg/kg/day. When LIC is <3mg Fe/g dw, interrupt treatment and continue to monitor LIC. Restart when LIC rises again to >5mg Fe/g dw.

Adjustments based on serum creatinine: see full

labeling. Hepatic impairment: moderate: reduce dose by 50%; severe: avoid.

Contraindications: CrCl <40mL/min or serum creatinine >2x age-appropriate ULN. Poor performance status. High risk myelodysplastic syndromes. Advanced malignancies. Platelets <50x109/L. Warnings/Precautions: May cause renal or hepatic failure, GI hemorrhage; may be fatal (monitor). Hepatic or renal impairment. Advanced disease or co-morbid conditions. Obtain baseline serum ferritin level, monitor monthly and adjust dose accordingly. Measure serum creatinine and CrCl in duplicate before starting therapy; monitor weekly during 1st month then at least monthly thereafter; more frequently if creatinine levels increase. Monitor for proteinuria monthly.

Measure serum transaminases, bilirubin before initiating therapy then every 2 weeks during 1st month, then monthly. Monitor blood counts; interrupt therapy if cytopenias develop. For NTDT syndromes: obtain LIC by liver biopsy prior to starting therapy, monitor LIC every 6 months. Do baseline auditory and ocular exams, then every 12 months; if disturbances occur, adjust dose or suspend therapy. Elderly. Pregnancy (Cat.C).

Nursing mothers: not recommended.

Interactions: Avoid aluminum-containing antacids, bile acid sequestrants (eg, cholestyramine, colesevelam, colestipol), or UGT inducers (eg, rifampicin, phenytoin, phenobarbital, ritonavir); if co-administration necessary consider increasing initial Exjade dose by 50% and monitor serum ferritin levels and clinical responses. Caution with drugs that have ulcerogenic or hemorrhagic potential (eg, NSAIDs, corticosteroids, oral bisphosphonates, anticoagulants) or drugs metabolized by CYP3A4 (eg, cyclosporine, simvastatin, hormonal contraceptives). Potentiates repaglinide (consider reducing repaglinide dose); monitor blood glucose levels. Caution with other CYP2C8 substrates (eg, paclitaxel). Avoid concomitant theophylline or other CYP1A2 substrates with narrow therapeutic index. Concomitant other iron chelation therapy: not recommended.

Adverse reactions: Diarrhea, vomiting, nausea, abdominal pain, elevated serum creatinine, rash; renal or hepatic impairment/failure (may be fatal), GI hemorrhage, cytopenias (eg, agranulocytosis, neutropenia, thrombocytopenia, anemia), hypersensitivity reactions, severe skin reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme); discontinue if occurs and do not restart.

How supplied: Tabs—30

PHARMACOLOGIC CLASS The chemical/therapeutic class of the drug is listed in italics.

FERRIPROX ApoPharma

℞

Iron chelating agent. Deferiprone 500mg; scored tabs.

Indications: Treatment of transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate.

Limitations of use: not for use in treating other chronic anemias.

Adults: Individualize. Initially 25mg/kg three times daily (total dose 75mg/kg/day).

Max: 33mg/kg three times daily (total dose 99mg/kg/day). Round dose to the nearest 250mg (half-tablet). Adjust dose to individual response and therapeutic goals. Consider temporary dose interruption if serum ferritin falls consistently <500mcg/L. Children: Not established.

Warnings/Precautions: Risk of neutropenia or fatal agranulocytosis. Measure ANC before starting therapy and monitor weekly during.

Interrupt therapy if infection or neutropenia develops (ANC <1.5×109/L). If neutropenia occurs, obtain CBCs, WBCs, ANC, and platelets daily until recovery (ANC ≥1.5×109/L). Monitor serum ALT monthly; consider interruption if persistent increase in transaminase levels.

Monitor serum ferritin every 2–3 months.

Monitor plasma zinc, supplement if deficient.

Severe hepatic impairment. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended.

Interactions: Avoid concomitant use with other drugs associated with neutropenia or agranulocytosis. Allow at least 4-hour interval with antacids or mineral supplements containing polyvalent cations (eg, iron, aluminum, zinc).

Concomitant UGT 1A6 inhibitors: closely monitor and may need dose adjustments or interruptions.

Adverse reactions: Chromaturia, GI upset, abdominal pain, increased ALT, arthralgia, neutropenia; agranulocytosis.

Note: This product is available from Centric Health Resources (CHR). CHR is a specialty pharmacy specializing in orphan drugs and is the sole distributor of Ferriprox in the U.S. For more information, contact Ferriprox Total Care at (866) 758-7071.

How supplied: Tabs—100

FIRAZYR Shire

℞

Bradykinin B2 receptor antagonist. Icatibant 10mg/mL; soln for SC inj; preservative-free.

Indications: Treatment of acute attacks of hereditary angioedema.

Adults: ≥18yrs: 30mg SC in abdominal area; may give additional doses at intervals of at least 6 hours if response inadequate or symptoms recur. Max 3 doses/24hrs.

Children: <18yrs: not recommended.

Warnings/Precautions: Advise patients to seek medical attention after treating laryngeal

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DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS attack given the potential for airway obstruction.

Elderly. Labor & delivery. Pregnancy (Cat.C).

Nursing mothers.

Interactions: May attenuate the antihypertensive effect of ACE inhibitors.

Adverse reactions: Inj site reactions, pyrexia, transaminase increase, dizziness, rash.

How supplied: Single-use prefilled syringe (3mL)—1, 3

reactions. Labor & delivery. Pregnancy (Cat.C).

Nursing mothers.

Adverse reactions: Headache, nausea, diarrhea, pyrexia, inj site reactions, nasopharyngitis, fatigue, upper respiratory tract infection, pruritus, upper abdominal pain; anaphylaxis, antibody formation.

How supplied: Single-use vials—3

MOZOBIL Genzyme

KALBITOR Shire

℞

Plasma kallikrein inhibitor. Ecallantide 10mg/mL; soln for SC inj; preservative-free.

Indications: Treatment of acute attacks of hereditary angioedema.

Adults: Give 30mg SC in three 10mg (1mL) inj into abdomen, thigh, or upper arm. May give additional 30mg within 24hrs if attack persists.

Children: <12yrs: not established.

Warnings/Precautions: Have medical support available to manage anaphylaxis and hereditary angioedema. Monitor closely for hypersensitivity

℞

Hematopoietic stem cell mobilizer. Plerixafor 20mg/mL; soln for SC inj; preservative-free.

Indications: In combination with granulocyte colony stimulating factor (G-CSF): To mobilize hematopoietic stem cells to the peripheral blood for collection and autologous transplantation in patients with non-Hodgkin’s lymphoma or multiple myeloma.

Adults: Start after 4 days’ treatment with G-CSF. Give approximately 11hrs before starting apheresis. Repeat up to 4 consecutive days. Base dose on actual body weight.

0.24mg/kg SC; max 40mg/day. Renal

impairment (CrCl≤50mL/min): 0.16mg/kg; max 27mg/day.

Children: Not established.

Warnings/Precautions: Not for use in leukemia. May cause mobilization of tumor cells. Monitor blood and platelet counts (esp. neutrophils). Monitor for splenic rupture (eg, left upper quadrant/scapular or shoulder pain). Monitor for signs/symptoms of hypersensitivity during and after administration for at least 30mins. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended.

Interactions: May be potentiated by drugs that reduce renal function or compete for active tubular secretion.

Adverse reactions: Diarrhea, nausea, fatigue, injection site reactions, headache, arthralgia, dizziness, vomiting; anaphylactic shock, hypersensitivity reactions (may be serious), tumor cell mobilization, increased circulating neutrophils, decreased platelet counts, enlarged spleen, vasovagal reaction may occur.

How supplied: Single-use vials (1.2mL)—1

FDA PREGNANCY CATEGORIES When pregnancy appears as a contraindication or precaution to the use of a drug, it is usually qualified by a category as assigned by the FDA.

A: Adequate and well-controlled studies in pregnant women have failed to show a risk to the fetus in the first trimester of pregnancy and there is no evidence of risk in later trimesters.

B: Animal studies have failed to show a risk to the fetus and there are no adequate and well-controlled studies in pregnant women; or animal studies have shown an adverse effect but adequate and wellcontrolled studies in pregnant women have failed to demonstrate a risk to the fetus during the first trimester of pregnancy and there is no evidence of a risk in later trimesters.

C: Animal studies have shown an adverse effect on the fetus, there are no adequate and well-controlled studies in humans, and the potential benefits may outweigh the risks; or there are no animal studies and no adequate and well-controlled studies in humans.

D: Positive evidence of human fetal risk but the benefits may outweigh the risks.

X: Animal or human studies have shown fetal abnormalities or toxicity, or both, and the risks clearly outweigh any possible benefits.

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