VOl 5, NO 6
SIDE EFFECT MANAGEMENT
CANCER CENTER PROFILE
Indiana University Health Simon Cancer Center Addressing the Needs of the Patient
Mucositis Management to Become More Personalized By Caroline Helwick
new appreciation of the pathobiological foundation of mucositis, and the application of genomics to risk assessment, heralds an individualized and more effective approach to intervention for this costly, often disabling, toxicity, according to specialists who spoke at a session on mucosal injury during the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO).
By Alice Goodman
New Mechanistic Understanding Old concepts are being replaced by a
pathobiological paradigm that better captures the underlying mechanism and allows for more effective interventions. Mucositis is now “about bioinformatics, targeted treatment, risk prediction, and other exciting frontiers,” said Douglas Peterson, DMD, PhD, of the University of Connecticut Health Center in Farmington. Stephen T. Sonis, DMD, DMSc, of Biomodels in Watertown, Massachusetts, described the biological cascade leading to mucosal injury as one involving the mesContinued on page 36
THE PATIENT’S VOICE
Popping Pills and Shooting Up
The oncology pharmacy team at the Indiana University Health Simon Cancer Center. Photo courtesy of Indiana University Health.
he Indiana University Health Simon Cancer Center was established in 1992 under the leadership of Stephen D. Williams, MD, and in 1999, the center was designated by the National Cancer Institute as a clinical cancer center. The Indiana University Research Institute was opened in 1997, financed in part by federal funding. The name of the center was changed in 2006 to honor the philanthropic support of Melvin and Bren Simon. The Simon Cancer Center is a patient care, research, and educational institution within the Indiana University (IU) School of Medicine on the main campus in Indianapolis. The physicians and scientists
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must admit that I am not a fan of medications. I had 4 beautiful children medication-free with midwives. I drink green tea to get rid of a cold. I eat chocolate to calm a headache. I microwave rice in a sock and place it on sore muscles. Perhaps that is why I resent (yes, I said it, “resent!”) that I have been sent home with 2 medications I must in-
ject into myself twice a day for a total of 4 daily injections. When I got sent home from the hospital after my fourth chemotherapy session with both my regular white bag packed full of pills plus new injections of blood thinners and stem cell stimulators (I am preparing for a stem cell transplant), I felt nervous. Certainly, since the start of my Continued on page 16
By Alice Goodman
Surgery Versus Observation for Localized Prostate Cancer For men with localized prostate cancer detected by prostate-specific antigen (PSA) level, treatment with radical prostatectomy did not significantly reduce mortality compared with observation, according to overall results of the large, randomized, controlled PIVOT trial (Wilt TJ, et al. N Engl J Med. 2012; 367:203-213). All-cause mortality and prostate-specific mortality were similar
The GrowTh of SpecialTy pharmacy . . . . . . . . . . . . . . . . . . . . . .
for the surgery and observation groups over a 12-year follow-up. Results suggest that surgery may be a better option than observation for men with intermediate- and high-risk localized prostate cancer, but low-risk localized prostate cancer can be safely managed with observation. Overall, absolute differences in mor-
What Is the Impact on Patient Relationships? proSTaTe cancer
Progress in Treating Prostate Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Team Approach Enhances Choice of Observation . . . . . . . . . . . 23
Continued on page 4 ©2012 Green Hill Healthcare Communications, LLC
Side effecT manaGemenT
Chemotherapy-Induced Peripheral Neuropathy Increases Risk of Falls and Physical and Functional Problems immune ThrombocyTopenia
Considerations for Treatment complimenTary ce
Considerations in Lymphoma—Ask the Experts: Follicular Lymphoma
IV R FO AND ED US ION V T O O A PR ANE ST R P A UT INI C M B SU AD
If you define value as an overall survival advantage: VELCADE® (bortezomib) DELIVERED A >13-MONTH OVERALL SURVIVAL ADVANTAGE At 5-year median follow-up, VELCADE (bortezomib)+MP* provided a median overall survival of 56.4 months vs 43.1 months with MP alone (HR=0.695 [95% CI, 0.57-085]; p<0.05)† At 3-year median follow-up, VELCADE+MP provided an overall survival advantage over MP that was not regained with subsequent therapies
If you define value as defined length of therapy: Results achieved using VELCADE twice-weekly followed by weekly dosing for a median of 50 weeks (54 planned)1
If you define value as medication cost: Medication cost is an important factor when considering overall drug spend. The Wholesale Acquisition Cost for VELCADE is $1,471 per 3.5-mg vial as of January 2012 Health plans should consider medication cost, length of therapy, and dosing regimens when determining the value of a prescription drug regimen. This list of considerations is not meant to be all-inclusive; there are multiple other factors to consider when determining value for a given regimen
VELCADE Indication and Important Safety Information INDICATION VELCADE is indicated for the treatment of patients with multiple myeloma.
CONTRAINDICATIONS VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol. VELCADE is contraindicated for intrathecal administration.
WARNINGS, PRECAUTIONS AND DRUG INTERACTIONS Peripheral neuropathy, including severe cases, may occur — manage with dose modification or discontinuation. Patients with preexisting severe neuropathy should be treated with VELCADE only after careful risk-benefit assessment Hypotension can occur. Use caution when treating patients receiving antihypertensives, those with a history of syncope, and those who are dehydrated Closely monitor patients with risk factors for, or existing heart disease Acute diffuse infiltrative pulmonary disease has been reported Nausea, diarrhea, constipation, and vomiting have occurred and may require use of antiemetic and antidiarrheal medications or fluid replacement Thrombocytopenia or neutropenia can occur; complete blood counts should be regularly monitored throughout treatment Tumor Lysis Syndrome, Reversible Posterior Leukoencephalopathy Syndrome, and Acute Hepatic Failure have been reported Women should avoid becoming pregnant while being treated with VELCADE. Pregnant women should be apprised of the potential harm to the fetus Closely monitor patients receiving VELCADE in combination with strong CYP3A4 inhibitors. Concomitant use of strong CYP3A4 inducers is not recommended
ADVERSE REACTIONS Most commonly reported adverse reactions (incidence ≥30%) in clinical studies include asthenic conditions, diarrhea, nausea, constipation, peripheral neuropathy, vomiting, pyrexia, thrombocytopenia, psychiatric disorders, anorexia and decreased appetite, neutropenia, neuralgia, leukopenia, and anemia. Other adverse reactions, including serious adverse reactions, have been reported Please see Brief Summary for VELCADE on the next page of this advertisement. To contact a reimbursement specialist: Please call 1-866-VELCADE, Option 2 (1-866-835-2233). *Melphalan+prednisone. † VISTA: a randomized, open-label, international phase 3 trial (N=682) evaluating the efficacy and safety of VELCADE administered intravenously in combination with MP vs MP in previously untreated multiple myeloma. The primary endpoint was TTP. Secondary endpoints were CR, ORR, PFS, and overall survival. At a pre-specified interim analysis (median follow-up 16.3 months), VELCADE+MP resulted in significantly superior results for TTP (median 20.7 months with VELCADE+MP vs 15.0 months with MP [p=0.000002]), PFS, overall survival, and ORR. Further enrollment was halted and patients receiving MP were offered VELCADE in addition. Updated analyses were performed. Reference: 1. Mateos M-V, Richardson PG, Schlag R, et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol. 2010;28(13):2259-2266.
News Briefs Surgery Versus Observation... Continued from cover
tality favoring surgery were less than 3 percentage points, explained lead author Timothy J. Wilt, MD, Minneapolis Veterans Affairs Health Care System, Minnesota. “Surgery might reduce mortality for men with higher PSA values and possibly among men with higher-
risk tumors, but not among men with PSA levels of ≤10 ng/mL or low-risk tumors,” Wilt wrote. He noted that PIVOT was conducted in the early era of PSA testing, and that in the current era men suspected of having prostate cancer undergo repeated PSA testing and sometimes repeat biopsies, which detect more indolent cancers. These factors increase the likelihood of overdiagnosis and overtreatment. “Our findings support observation for men
Brief Summary INDICATIONS: VELCADE® (bortezomib) for Injection is indicated for the treatment of patients with multiple myeloma. VELCADE is indicated for the treatment of patients with mantle cell lymphoma who have received at least 1 prior therapy. CONTRAINDICATIONS: VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol. VELCADE is contraindicated for intrathecal administration. WARNINGS AND PRECAUTIONS: VELCADE should be administered under the supervision of a physician experienced in the use of antineoplastic therapy. Complete blood counts (CBC) should be monitored frequently during treatment with VELCADE. Peripheral Neuropathy: VELCADE treatment causes a peripheral neuropathy that is predominantly sensory. However, cases of severe sensory and motor peripheral neuropathy have been reported. Patients with pre-existing symptoms (numbness, pain or a burning feeling in the feet or hands) and/or signs of peripheral neuropathy may experience worsening peripheral neuropathy (including ≥ Grade 3) during treatment with VELCADE. Patients should be monitored for symptoms of neuropathy, such as a burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain or weakness. In the Phase 3 relapsed multiple myeloma trial comparing VELCADE subcutaneous vs. intravenous the incidence of Grade ≥ 2 peripheral neuropathy events was 24% for subcutaneous and 41% for intravenous. Grade ≥ 3 peripheral neuropathy occurred in 6% of patients in the subcutaneous treatment group, compared with 16% in the intravenous treatment group. Starting VELCADE subcutaneously may be considered for patients with pre-existing or at high risk of peripheral neuropathy. Patients experiencing new or worsening peripheral neuropathy during VELCADE therapy may benefit from a decrease in the dose and/or a less dose-intense schedule. In the single agent phase 3 relapsed multiple myeloma study of VELCADE vs. Dexamethasone following dose adjustments, improvement in or resolution of peripheral neuropathy was reported in 51% of patients with ≥ Grade 2 peripheral neuropathy in the relapsed multiple myeloma study. Improvement in or resolution of peripheral neuropathy was reported in 73% of patients who discontinued due to Grade 2 neuropathy or who had ≥ Grade 3 peripheral neuropathy in the phase 2 multiple myeloma studies. The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma. Hypotension: The incidence of hypotension (postural, orthostatic, and hypotension NOS) was 13%. These events are observed throughout therapy. Caution should be used when treating patients with a history of syncope, patients receiving medications known to be associated with hypotension, and patients who are dehydrated. Management of orthostatic/postural hypotension may include adjustment of antihypertensive medications, hydration, and administration of mineralocorticoids and/or sympathomimetics. Cardiac Disorders: Acute development or exacerbation of congestive heart failure and new onset of decreased left ventricular ejection fraction have been reported, including reports in patients with no risk factors for decreased left ventricular ejection fraction. Patients with risk factors for, or existing heart disease should be closely monitored. In the relapsed multiple myeloma study of VELCADE vs. dexamethasone, the incidence of any treatment-emergent cardiac disorder was 15% and 13% in the VELCADE and dexamethasone groups, respectively. The incidence of heart failure events (acute pulmonary edema, cardiac failure, congestive cardiac failure, cardiogenic shock, pulmonary edema) was similar in the VELCADE and dexamethasone groups, 5% and 4%, respectively. There have been isolated cases of QT-interval prolongation in clinical studies; causality has not been established. Pulmonary Disorders: There have been reports of acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration and Acute Respiratory Distress Syndrome (ARDS) in patients receiving VELCADE. Some of these events have been fatal. In a clinical trial, the first two patients given high-dose cytarabine (2 g/m2 per day) by continuous infusion with daunorubicin and VELCADE for relapsed acute myelogenous leukemia died of ARDS early in the course of therapy. There have been reports of pulmonary hypertension associated with VELCADE administration in the absence of left heart failure or significant pulmonary disease. In the event of new or worsening cardiopulmonary symptoms, a prompt comprehensive diagnostic evaluation should be conducted. Reversible Posterior Leukoencephalopathy Syndrome (RPLS): There have been reports of RPLS in patients receiving VELCADE. RPLS is a rare, reversible, neurological disorder which can present with seizure, hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances. Brain imaging, preferably MRI (Magnetic Resonance Imaging), is used to confirm the diagnosis. In patients developing RPLS, discontinue VELCADE. The safety of reinitiating VELCADE therapy in patients previously experiencing RPLS is not known. Gastrointestinal Adverse Events: VELCADE treatment can cause nausea, diarrhea, constipation, and vomiting sometimes requiring use of antiemetic and antidiarrheal medications. Ileus can occur. Fluid and electrolyte replacement should be administered to prevent dehydration. Thrombocytopenia/Neutropenia: VELCADE is associated with thrombocytopenia and neutropenia that follow a cyclical pattern with nadirs occurring following the last dose of each cycle and typically recovering prior to initiation of the subsequent cycle. The cyclical pattern of platelet and neutrophil decreases and recovery remained consistent over the 8 cycles of twice weekly dosing, and there was no evidence of cumulative thrombocytopenia or neutropenia. The mean platelet count nadir measured was approximately 40% of baseline. The severity of thrombocytopenia was related to pretreatment platelet count. In the relapsed multiple myeloma study of VELCADE vs. dexamethasone, the incidence of significant bleeding events (≥Grade 3) was similar on both the VELCADE (4%) and dexamethasone (5%) arms. Platelet counts should be monitored prior to each dose of VELCADE. Patients experiencing thrombocytopenia may require change in the dose and schedule of VELCADE. There have been reports of gastrointestinal and intracerebral hemorrhage in association with VELCADE. Transfusions may be considered. The incidence of febrile neutropenia was <1%. Tumor Lysis Syndrome: Because VELCADE is a cytotoxic agent and can rapidly kill malignant cells, the complications of tumor lysis syndrome may occur. Patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken. Hepatic Events: Cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions. Other reported hepatic events include increases in liver enzymes, hyperbilirubinemia, and hepatitis. Such changes may be reversible upon discontinuation of VELCADE. There is limited re-challenge information in these patients. Hepatic Impairment: Bortezomib is metabolized by liver enzymes. Bortezomib exposure is increased in patients with moderate or severe hepatic impairment; these patients should be treated with VELCADE at reduced starting doses and closely monitored for toxicities. Use in Pregnancy: Pregnancy Category D. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE. Bortezomib administered to rabbits during organogenesis at a dose approximately 0.5 times the clinical dose of 1.3 mg/m2 based on body surface area caused post-implantation loss and a decreased number of live fetuses.
with localized prostate cancer, especially those who have low-risk disease,” he wrote. PIVOT randomized 364 men to radical prostatectomy and 367 to observation alone. All participants were suspected of having prostate cancer based on PSA testing and had histologically confirmed localized prostate cancer diagnosed within the previous year. Mean age was 67 years, about one-third were black, and median PSA value was 7.8
ADVERSE EVENT DATA: Safety data from phase 2 and 3 studies of single-agent VELCADE (bortezomib) 1.3 mg/m2/dose administered intravenously twice weekly for 2 weeks followed by a 10-day rest period in 1163 patients with previously treated multiple myeloma (N=1008, not including the phase 3, VELCADE plus DOXIL® [doxorubicin HCI liposome injection] study) and previously treated mantle cell lymphoma (N=155) were integrated and tabulated. In these studies, the safety profile of VELCADE was similar in patients with multiple myeloma and mantle cell lymphoma. In the integrated analysis, the most commonly reported adverse events were asthenic conditions (including fatigue, malaise, and weakness); (64%), nausea (55%), diarrhea (52%), constipation (41%), peripheral neuropathy NEC (including peripheral sensory neuropathy and peripheral neuropathy aggravated); (39%), thrombocytopenia and appetite decreased (including anorexia); (each 36%), pyrexia (34%), vomiting (33%), anemia (29%), edema (23%), headache, paresthesia and dysesthesia (each 22%), dyspnea (21%), cough and insomnia (each 20%), rash (18%), arthralgia (17%), neutropenia and dizziness (excluding vertigo); (each 17%), pain in limb and abdominal pain (each 15%), bone pain (14%), back pain and hypotension (each 13%), herpes zoster, nasopharyngitis, upper respiratory tract infection, myalgia and pneumonia (each 12%), muscle cramps (11%), and dehydration and anxiety (each 10%). Twenty percent (20%) of patients experienced at least 1 episode of ≥Grade 4 toxicity, most commonly thrombocytopenia (5%) and neutropenia (3%). A total of 50% of patients experienced serious adverse events (SAEs) during the studies. The most commonly reported SAEs included pneumonia (7%), pyrexia (6%), diarrhea (5%), vomiting (4%), and nausea, dehydration, dyspnea and thrombocytopenia (each 3%). In the phase 3 VELCADE + melphalan and prednisone study in previously untreated multiple myeloma, the safety profile of VELCADE administered intravenously in combination with melphalan/prednisone is consistent with the known safety profiles of both VELCADE and melphalan/prednisone. The most commonly reported adverse events in this study (VELCADE+melphalan/prednisone vs melphalan/prednisone) were thrombocytopenia (52% vs 47%), neutropenia (49% vs 46%), nausea (48% vs 28%), peripheral neuropathy (47% vs 5%), diarrhea (46% vs 17%), anemia (43% vs 55%), constipation (37% vs 16%), neuralgia (36% vs 1%), leukopenia (33% vs 30%), vomiting (33% vs 16%), pyrexia (29% vs 19%), fatigue (29% vs 26%), lymphopenia (24% vs 17%), anorexia (23% vs 10%), asthenia (21% vs 18%), cough (21% vs 13%), insomnia (20% vs 13%), edema peripheral (20% vs 10%), rash (19% vs 7%), back pain (17% vs 18%), pneumonia (16% vs 11%), dizziness (16% vs 11%), dyspnea (15% vs 13%), headache (14% vs 10%), pain in extremity (14% vs 9%), abdominal pain (14% vs 7%), paresthesia (13% vs 4%), herpes zoster (13% vs 4%), bronchitis (13% vs 8%), hypokalemia (13% vs 7%), hypertension (13% vs 7%), abdominal pain upper (12% vs 9%), hypotension (12% vs 3%), dyspepsia (11% vs 7%), nasopharyngitis (11% vs 8%), bone pain (11% vs 10%), arthralgia (11% vs 15%) and pruritus (10% vs 5%). In the phase 3 VELCADE subcutaneous vs. intravenous study in relapsed multiple myeloma, safety data were similar between the two treatment groups. The most commonly reported adverse events in this study were peripheral neuropathy NEC (38% vs 53%), anemia (36% vs 35%), thrombocytopenia (35% vs 36%), neutropenia (29% vs 27%), diarrhea (24% vs 36%), neuralgia (24% vs 23%), leukopenia (20% vs 22%), pyrexia (19% vs 16%), nausea (18% vs 19%), asthenia (16% vs 19%), weight decreased (15% vs 3%), constipation (14% vs 15%), back pain (14% vs 11%), fatigue (12% vs 20%), vomiting (12% vs 16%), insomnia (12% vs 11%), herpes zoster (11% vs 9%), decreased appetite (10% vs 9%), hypertension (10% vs 4%), dyspnea (7% vs 12%), pain in extremities (5% vs 11%), abdominal pain and headache (each 3% vs 11%), abdominal pain upper (2% vs 11%). The incidence of serious adverse events was similar for the subcutaneous treatment group (36%) and the intravenous treatment group (35%). The most commonly reported SAEs were pneumonia (6%) and pyrexia (3%) in the subcutaneous treatment group and pneumonia (7%), diarrhea (4%), peripheral sensory neuropathy (3%) and renal failure (3%) in the intravenous treatment group. DRUG INTERACTIONS: Bortezomib is a substrate of cytochrome P450 enzyme 3A4, 2C19 and 1A2. Co-administration of ketoconazole, a strong CYP3A4 inhibitor, increased the exposure of bortezomib by 35% in 12 patients. Therefore, patients should be closely monitored when given bortezomib in combination with strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir). Co-administration of omeprazole, a strong inhibitor of CYP2C19, had no effect on the exposure of bortezomib in 17 patients. Co-administration of rifampin, a strong CYP3A4 inducer, is expected to decrease the exposure of bortezomib by at least 45%. Because the drug interaction study (n=6) was not designed to exert the maximum effect of rifampin on bortezomib PK, decreases greater than 45% may occur. Efficacy may be reduced when VELCADE is used in combination with strong CYP3A4 inducers; therefore, concomitant use of strong CYP3A4 inducers is not recommended in patients receiving VELCADE. St. John’s Wort (Hypericum perforatum) may decrease bortezomib exposure unpredictably and should be avoided. Co-administration of dexamethasone, a weak CYP3A4 inducer, had no effect on the exposure of bortezomib in 7 patients. Co-administration of melphalan-prednisone increased the exposure of bortezomib by 17% in 21 patients. However, this increase is unlikely to be clinically relevant. USE IN SPECIFIC POPULATIONS: Nursing Mothers: It is not known whether bortezomib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from VELCADE, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use: The safety and effectiveness of VELCADE in children has not been established. Geriatric Use: No overall differences in safety or effectiveness were observed between patients ≥age 65 and younger patients receiving VELCADE; but greater sensitivity of some older individuals cannot be ruled out. Patients with Renal Impairment: The pharmacokinetics of VELCADE are not influenced by the degree of renal impairment. Therefore, dosing adjustments of VELCADE are not necessary for patients with renal insufficiency. Since dialysis may reduce VELCADE concentrations, VELCADE should be administered after the dialysis procedure. For information concerning dosing of melphalan in patients with renal impairment, see manufacturer’s prescribing information. Patients with Hepatic Impairment: The exposure of bortezomib is increased in patients with moderate and severe hepatic impairment. Starting dose should be reduced in those patients. Patients with Diabetes: During clinical trials, hypoglycemia and hyperglycemia were reported in diabetic patients receiving oral hypoglycemics. Patients on oral antidiabetic agents receiving VELCADE treatment may require close monitoring of their blood glucose levels and adjustment of the dose of their antidiabetic medication. Please see full Prescribing Information for VELCADE at VELCADEHCP.com.
VELCADE, MILLENNIUM and are registered trademarks of Millennium Pharmaceuticals, Inc. Other trademarks are property of their respective owners. Millennium Pharmaceuticals, Inc., Cambridge, MA 02139 Copyright © 2012, Millennium Pharmaceuticals, Inc. All rights reserved. Printed in USA
ng/mL. About 40% of the men had lowrisk prostate cancer, 34% intermediaterisk prostate cancer, and 21% high-risk prostate cancer. At a median follow-up of 10 years, mortality was 47% in the surgery group versus 49.9% in the observation group, an absolute reduction of 2.9% for surgery. The rates of prostate-specific mortality were 5.8% for surgery versus 8.4% for observation, an absolute risk reduction of 2.6%. The effect of treatment on all-cause mortality was similar according to age, race, coexisting illness, performance status, or histologic tumor features. Radical prostatectomy was associated with reduced all-cause mortality among men with PSA >10 ng/mL and for men with intermediate- or high-risk tumors. Perioperative adverse events (occurring within 30 days of surgery) were reported in 21.4% of men. Rates of urinary incontinence and erectile dysfunction were significantly higher in the radical prostatectomy group (P <.001 for both comparisons vs observation).
Older patients With Mantle Cell lymphoma R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) induction therapy followed by maintenance therapy with rituximab was more effective than R-FC (rituximab, fludarabine, and cyclophosphamide) followed by maintenance therapy with interferon alfa in older patients with mantle cell lymphoma, according to a recently published prospective, randomized, double-blind clinical trial (Kluin-Nelemans HC, et al. N Engl J Med. 2012;367:520-531). “The excellent results with rituximab administered as maintenance therapy are important. Maintenance therapy with rituximab showed not only a progression-free survival benefit but also a significant survival advantage among patients who were successfully pretreated with R-CHOP,” wrote the authors. The long-term prognosis is poor for older patients with mantle cell lymphoma. Treatment with chemotherapy achieves low rates of complete remission (CR), the authors wrote. Most older patients with mantle cell lymphoma will relapse, and better therapy is needed for this group of patients. When the trial was first initiated, the authors hoped that the fludarabine-containing regimen would perform better than it did in this trial. However, results showed that R-FC was not more effective than R-CHOP, and the fludarabine-containing regimen was more toxic. The study enrolled 560 patients aged 60 years or older with stage II to IV mantle cell lymphoma who were ranContinued on page 21
sEPTEmbER 2012 I VOL 5, NO 6
Editorial Board EDITOR-IN-CHIEF
Patrick Medina, PharmD, BCOP
Anjana Elefante, PharmD, BSc, BSc Pharm, RPh
Dwight Kloth, PharmD, FCCP, BCOP
Oklahoma University College of Pharmacy Tulsa, OK
Roswell Park Cancer Institute Buffalo, NY
Fox Chase Cancer Center Philadelphia, PA
Beth Faiman, PhD(c), MSN, APRN-BC, AOCN
Jim Koeller, MS
Steve Stricker, PharmD, MS, BCOP Samford University McWhorter School of Pharmacy Birmingham, AL
University of Texas at Austin San Antonio, TX
Cleveland Clinic Taussig Cancer Institute Cleveland, OH
Timothy G. Tyler, PharmD, FCSHP Desert Regional Medical Center Palm Springs, CA
John M. Valgus, PharmD, BCOP University of North Carolina Hospitals and Clinics Chapel Hill, NC
Christopher Fausel, PharmD
Christopher J. Lowe, PharmD
Indiana University Simon Cancer Center Indianapolis, IN
Indiana University Hospital Indianapolis, IN
David Baribeault, RPh, BCOP
Rebecca S. Finley, PharmD, MS
Emily Mackler, PharmD, BCOP
Burt Zweigenhaft, BS
Boston Medical Center Boston, MA
Jefferson School of Pharmacy Philadelphia, PA
University of Michigan Health System & College of Pharmacy Ann Arbor, MI
BioPharma Partners LLC New York, NY
Betty M. Chan, PharmD, BCOP
David C. Gammon, BSPh
USC/Norris Cancer Hospital Los Angeles, CA
OncologyPharmacist.net Warwick, RI
Laura Boehnke Michaud, PharmD, BCOP, FASHP
John F. Aforismo, BSc Pharm, RPh, FASCP RJ Health Systems International, LLC Wethersfield, CT
Gary C. Yee, PharmD, FCCP, BCOP University of Nebraska College of Pharmacy Omaha, NE
Marlo Blazer, PharmD, BCOP
The University of Texas MD Anderson Cancer Center Houston, TX
James Cancer Hospital & Solove Research Institute Columbus, OH
Heidi D. Gunderson, PharmD, BCOP Mayo Clinic Cancer Center Rochester, MN
Steven L. Dâ€™Amato, RPh, BCOP
Lew Iacovelli, BS, PharmD, BCOP, CPP
LeAnn Best Norris, PharmD, BCPS, BCOP
Maine Center for Cancer Medicine Scarborough, ME
Moses H. Cone Health System Greensboro, NC
South Carolina College of Pharmacy Columbia, SC
Kamakshi V. Rao, PharmD, BCOP University of North Carolina Hospitals and Clinics Chapel Hill, NC
sEPTEmbER 2012 I VOL 5, NO 6
From the Editors PUBLISHING STAFF Senior Vice President, Sales & Marketing Philip Pawelko email@example.com Publisher John W. Hennessy firstname.lastname@example.org Associate Publisher Joe Chanley email@example.com
Patrick Medina, PharmD, BCOP Editor-in-Chief
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n this month’s issue of The Oncology Pharmacist (TOP), we explore the growth of specialty pharmacies and the implications for our relationship with patients. Author Lea Ann Hansen discusses the evolution of specialty pharmacy and the function it serves in the treatment of cancer and how this affects patients. As Hansen points out in her article, “In many cases, the complicated nature of administration or possible adverse events with specialty drugs necessitate intensive patient monitoring.” The topic of The Patient’s Voice article revolves around a patient’s complicated relationship with her oncology drugs. MMA writes about “popping pills and shooting up” at home. While not directly acknowledging adherence,
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The Oncology Pharmacist®, ISSN 1944-9607 (print); ISSN 1944-9593 (online) is published 8 times a year by Green Hill Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. Telephone: 732.656.7935. Fax: 732.656.7938. Copyright ©2012 by Green Hill Healthcare Communications, LLC. All rights reserved. The Oncology Pharmacist® logo is a registered trademark of Green Hill Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the Publisher. Printed in the United States of America. EDITORIAL CORRESPONDENCE should be addressed to EDITORIAL DIRECTOR, The Oncology Pharmacist®, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. E-mail: firstname.lastname@example.org. YEARLY SUBSCRIPTION RATES: United States and possessions: individuals, $105.00; institutions, $135.00; single issues, $17.00. Orders will be billed at individual rate until proof of status is confirmed. Prices are subject to change without notice. Correspondence regarding permission to reprint all or part of any article published in this journal should be addressed to REPRINT PERMISSIONS DEPARTMENT, Green Hill Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. The ideas and opinions expressed in The Oncology Pharmacist® do not necessarily reflect those of the Editorial Board, the Editorial Director, or the Publisher. Publication of an advertisement or other product mention in The Oncology Pharmacist® should not be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturer with questions about the features or limitations of the products mentioned. Neither the Editorial Board nor the Publisher assumes any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this periodical. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosage, the method and duration of administration, or contraindications. It is the responsibility of the treating physician or other healthcare professional, relying on independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Every effort has been made to check generic and trade names, and to verify dosages. The ultimate responsibility, however, lies with the prescribing physician. Please convey any errors to the Editorial Director. BPA Worldwide membership applied for April 2011.
sEPTEmbER 2012 I VOL 5, NO 6
MMA shows us how difficult it is to ensure that patients take medications as prescribed. In our reader survey poll, we ask how you talk to patients about adherence. Go to www.TheOncologyPharmacist.com and tell us how you try to help patients like MMA overcome their emotional reactions to taking (or not taking) their medications. We continue our coverage of the news from the 2012 Annual Meeting of the American Society of Clinical Oncology by addressing the topic of mucositis—noting that the advent of personalized cancer medicine also means personalizing supportive care issues as well. As always, we want to hear from you about what you see in TOP. Contact us at email@example.com. ●
Recent FDA News
Editorial Contact: Telephone: 732-656-7935 Fax: 732-656-7938
Steve Stricker, PharmD, MS, BCOP Associate Editor-in-Chief
bosutinib for Chronic Myelogenous leukemia The US Food and Drug Administration (FDA) approved bosutinib tablets (Bosulif; Pfizer) for the treatment of adults with chronic, accelerated, or blast phase Philadelphia chromosome–positive chronic myelogenous leukemia (CML) who did not respond or were resistant to prior therapy. The September 4, 2012, approval was based on the results of a single-arm, open-label, multicenter trial in 546 adults (503 evaluable for efficacy) with chronic, accelerated, or blast phase CML. All patients had been previously treated with at least 1 tyrosine kinase inhibitor (TKI). The efficacy end points for patients with chronic phase CML were the rate of major cytogenetic response (MCyR) at week 24, and the duration of MCyR. The rate of confirmed complete hematologic response (CHR) and overall hematologic response (OHR) by week 48 were the efficacy end points for patients with accelerated or blast phase CML. For those with chronic phase CML, 33.8% of patients who had received 1 prior TKI (imatinib) achieved MCyR at week 24 while 26.9% of patients who received prior therapy with more than 1 TKI (imatinib followed by dasatinib and/or nilotinib) achieved MCyR by week 24. Among patients with accelerated or blast phase CML who had received 1 prior TKI, 30.4% and 15%, respectively, achieved CHR response by week 48, while 55.1% and 28.3%, respectively, achieved OHR by week 48. Diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue were the most common side effects in the safety population of patients. Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, noted, “With the approval of tyrosine kinase inhibitors, we are seeing improvements in the treatment of CML based on a better understanding of the molecular basis of the disease.” enzalutamide for Metastatic Castration-resistant prostate Cancer The FDA granted expedited approval for enzalutamide (Xtandi; Medivation and Astellas Pharma US) on August 31, 2012. Enzalutamide was approved for the treatment of
patients with metastatic castration-resistant prostate cancer (CRPC) who have previously received docetaxel. Approval was based on the results of a single randomized, placebo-controlled, multicenter trial of 1199 patients with metastatic CRPC. The study was designed to measure overall survival in men receiving enzalutamide compared with men receiving a placebo. The median overall survival for those patients who received enzalutamide was 18.4 months, compared with 13.6 months for those who received placebo. For more information about enzalutamide, please see page 22.
Carfilzomib for Multiple Myeloma On July 20, 2012, the FDA granted accelerated approval to carfilzomib injection (Kyprolis; Onyx Pharmaceuticals) for the treatment of patients with multiple myeloma who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent, and who have demonstrated disease progression on or within 60 days of the completion of their last therapy. The safety and effectiveness of carfilzomib was evaluated in a study of 266 patients participating in a single-arm, multicenter trial. Patients received carfilzomib intravenously for a 2- to 10-minute period on 2 consecutive days weekly for 3 weeks, followed by a 12-day rest period (a 28-day treatment cycle). Treatment was continued until disease progression, unacceptable toxicity, or completion of a maximum of 12 cycles. The overall response rate was 22.9% and consisted of 1 complete response, 13 very good partial responses, and 47 partial responses. The median response duration was 7.8 months. The most common side effects observed in more than 30% of patients in the study were fatigue, low blood cell count and blood platelet levels, shortness of breath, diarrhea, and fever. Serious side effects included heart failure and shortness of breath. As a condition of having received accelerated approval for carfilzomib, Onyx Pharmaceuticals will submit a complete analysis of an ongoing randomized phase 3 trial that compares lenalidomide plus low-dose dexamethasone to lenalidomide plus low-dose dexamethasone plus carfilzomib. ●
Cancer Center Profile Indiana University Health Simon Cancer Center... Continued from cover
What is the approach to treating cancer patients at the Simon Cancer Center? Patrick Kiel (PK): We are an NCIdesignated cancer center, and we employ a multidisciplinary approach. Physicians handle diagnosis and treatment, and the oncology pharmacists monitor treatments, develop symptom reports, and participate in developing treatment algorithms and standard operating procedures. Our nursing staff includes magnet-trained nurses, and we have case managers and social workers. There is a good dynamic between case managers and pharmacists at our center to ensure that patients get their treatments covered by insurance, or if not, by assistance programs from the phar-
maceutical company or the Simon Center to offset costs so that patients can afford their treatments.
Photo courtesy of Indiana University Health.
who work at the center are mainly from the faculty of the IU School of Medicine, the IU Schools of Nursing and Dentistry, and the Purdue University School of Science. The staff works with a team of other professionals to address the full spectrum of the needs of cancer patients, including physical, emotional, psychological, and spiritual needs. Over the past decade, many milestones have been reached, including launching of the Indiana Genomics Initiative, opening of the Biotechnology Research and Training Center, expanding research space for the Walther Oncology Center, breaking ground on a new research facility, dedication of a new 405,000 square foot patient care center, and dedication of the largest research building on the campus, the Joseph E. Walther Hall, at 238,371 square feet. The mission and goals of the Simon Cancer Center drive the staff to conduct better research, provide better education, and improve patient care. The Oncology Pharmacist spoke with Patrick Kiel, PharmD, BCPS, BCOP, Cancer Pharmacy Specialist, Hematology and Stem Cell Transplant, Indiana University Health Simon Cancer Center, about the approach to managing patients at the center and his role as an oncology pharmacy specialist.
Now the emphasis is on targeted treatments for subgroups and rarer diseases. Oncology pharmacists are becoming in-
“The most important aspect of your job is to talk to patients about their experiences on therapy and get their perspective.”
cell transplant patients and how we can improve upon safety.
How has the role of the oncology pharmacist changed over the past 5 years? PK: What has changed the most is going from having oncology pharmacists at large oncology centers to now having a demand for them from smaller hospitalassociated clinics and private practices. In these smaller practice settings, pharmacy is becoming integral to the management of chemotherapy-induced toxicities and monitoring associated side effects.
—Patrick Kiel, PharmD, BCPS, BCOP
Is cost becoming more of an issue with regard to treatment? PK: Yes, there is a push nationally as well as here at our center to contain costs to help doctors and nurses be aware of the direct and associated costs of treatment; for example, considerations as to whether a treatment can be given as inpatient versus outpatient and the amount and frequency of monitoring a treatment requires. How does this approach translate to better outcomes? PK: The benefit comes from the more eyes that are on the patient, and that includes the pharmacist’s eyes. Also, patient education is a multidisciplinary effort. The pharmacist reinforces physician’s education about treatments and their side effects. I tell patients, “You are not a car getting a type of oil. You are a person, and whenever you get a medication, you should ask what this medication is for, what the side effects are, and how they can help monitor for side effects.”
volved in clinical trials and bench research. I have just been given a grant to work with a physician scientist on studying PARP inhibition in leukemias and
What advice would you give an oncology pharmacist just entering the field? PK: The most important aspect of your job is to talk to patients about their experiences on therapy and get their perspective. Always see patients first, and then go to the computer to look up laboratory reports. The computer is important, but the patient should be the top priority. Indiana University Health Simon Cancer Center. Photo courtesy of Indiana University Health.
What are you excited about now in the field of oncology? PK: I am excited about new therapies. We have already covered the low-hanging fruit, that is, treatments that affect multiple disease states and benefit large numbers of patients. Those days are over.
What inspired you to become an oncology pharmacist? PK: I was always interested in genetics as well as pharmacotherapy of disease states. At Midwestern University Chicago College of Pharmacy, I studied with David Frame and Deb Drager (both PharmDs) who taught me how to evaluate clinical trials and the rationale behind them. I gravitated toward evidence-based medicine. Oncology is a field where you can establish long-term relationships with patients that can last for many years. The best experience is a routine visit from a patient who is doing well in his or her life after being treated for cancer.
lymphomas. Pharmacists are also involved in clinical outcomes research, for example, on potential treatments to address neurotoxicity of chemotherapy, or immune suppression outcomes in stem
What work would you be doing if you weren’t an oncology pharmacist? PK: I have always been interested in chemistry and food. If I weren’t a pharmacist, I would be a brewmaster or a food critic, as long as the food was for free! One of my favorite TV shows is Alton Brown’s “Good Eats.” ●
Take action: get YOUR cancer center profiled! We are looking to interview oncology pharmacists from cancer centers around the country. It’s an easy process—a short phone interview and you need to submit some photos.
Contact firstname.lastname@example.org for more information. www.TheOncologyPharmacist.com
sEPTEmbER 2012 I VOL 5, NO 6
TREANDA速 (bendamustine HCI) for Injection is his chemo.
This is his therapy.
Single-agent TREANDA tripled median PFS* TREANDA is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL). EfďŹ cacy relative to ďŹ rst-line therapies other than chlorambucil has not been established. PROGRESSION-FREE SURVIVAL (PFS): CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) Survival distribution function
1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1
18 months median PFS
6 months median PFS
P<.0001 HRâ€ =0.27 (95% CIâ€Ą: 0.17, 0.43)
Months *TREANDA (95% CI: 11.7, 23.5) vs chlorambucil (95% CI: 5.6, 8.6). â€ HR=hazard ratio. â€Ą CI=confidence interval.
s 42%!.$! WAS COMPARED WITH CHLORAMBUCIL IN A RANDOMIZED OPEN LABEL PHASE TRIAL IN TREATMENT NAĂ•VE PATIENTS WITH "INET STAGE "