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VOL 3, NO 5
der a e L d The ews an in N eeting e M erag Cov
ASCO: BREAST CANCER
CANCER CENTER PROFILE
Albert Einstein Cancer Center Joins the NCCCP By Dawn Lagrosa
Novel Agents Improve Survival in Refractory Metastatic Breast Cancer By Caroline Helwick
CHICAGO—Several new agents elicited excitement for the treatment of women with advanced breast cancer, including a novel cytotoxic agent that is the first to improve survival as monotherapy in this challenging patient population. In an international phase 3 study, patients with metastatic breast cancer refractory to numerous treatments lived 2.5 months longer when treated with eribulin mesylate, a synthetic analog of the novel halichondrin B family, versus
single agents alone. According to Principal investigator Christopher Twelves, MD, of the University of Leeds in the United Kingdom, “The improvement is statistically significant and clinically meaningful for these women with a poor prognosis.” The Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice versus Eribulin (EMBRACE) was a global, randomized, open-label phase 3 trial involving 762 metastatic breast cancer patients Continued on page 10
Left to right: Tiffany Raroha, MSW; William J. Tester, MD, FACP; Lisa Jablon, MD, FACS; and Lawrence J. Solin, MD, FACR, FASTRO.
his past April, Albert Einstein Cancer Center was selected to join the National Cancer Institute Community Cancer Centers Program (NCCCP), which in the words of William J. Tester, MD, FACP, medical director of Einstein’s Cancer Center offers “an opportunity to bring more resources to our patients.” NCCCP is designed to create new research opportunities across the cancer continuum from screening and treatment to follow-up and survivorship care. NCCCP cancer centers are also tasked to reduce healthcare disparities and improve the quality of care at community hospitals.
Reducing disparities With its mission of delivering high-quality care, Albert Einstein Cancer Center (Einstein) has already been working to overcome those barriers that contribute to healthcare disparities. Located in north Philadelphia, Einstein serves a diverse population that includes large African-American, Hispanic, and Asian subpopulations. In this urban setting, Einstein delivers care to patients from multiple socioeconomic Continued on page 26
PHARMACY EDUCATION AND TRAINING
Time Out for Teaching: Keys to a Successful Preceptor– Learner Experience By John M. Valgus, PharmD, BCOP
any of us practice oncology pharmacy in academic medical centers, in schools of pharmacy, and in practices that actively train various learners, such as interns, students, and residents. Most data surveying preceptors suggest that the majority of preceptor time is spent on imparting clinical knowledge. Much less time is dedicated to the preparative work of defining baseline expectations, individualizing learning plans, delivering feedback, and mentoring young
learners. When thinking about your preceptorship, ask yourself: • Are baseline expectations well defined at the beginning of the learning experience? • Are these expectations individualized to each learner? • Have I been giving the learner consistent and constructive feedback throughout the learning experience? • Is the learner in a position to achieve the baseline expectations? Continued on page 24
ASCO: Pain Management Fentanyl Nasal Spray for Control of Breakthrough Cancer Pain
Perspectives on Idiopathic Thrombocytopenia Purpura
Gastrointestinal Cancers Nab-paclitaxel Plus Gemcitabine May Help Patients with Advanced Pancreatic Cancer
ASCO: Hematologic Cancers In CML, Longer Follow-up Conﬁrms Superiority of Nilotinib Over Imatinib Page 10
ASCO: Skin Cancer New Monoclonal Antibody Treatment Oﬀers Hope Page 13
Pharmacy Careers LeAnn Norris Wins New Practitioner Award Page 18
©2010 Green Hill Healthcare Communications, LLC
Fostering a Dialogue to Improve Patient Care & Outcomes
Submit your cases online today at www.myelomacases.com
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ARE YOU PREPARED?
TWO PRICE OPTIONS AVAILABLE
Totect® Kit (dexrazoxane) for injection is for intravenous infusion only. Totect is indicated for the treatment of extravasation resulting from intravenous anthracycline chemotherapy.
First and only FDA approved treatment for anthracycline extravasation. Supplied as a convenient and accessible complete three day treatment kit for single patient use, which should be proactively stocked on-site and infused as soon as possible and within 6 hours of an anthracycline extravasation. Demonstrates 98% overall efficacy based on two biopsy-confirmed clinical trials1,2 in reducing or avoiding surgical intervention (i.e., surgical debridement, plastic surgery and their related costs), thereby reducing postponement of a patient’s chemotherapy treatments and the avoidance of long-term consequences. Cited in nursing guidelines.3,4 Extravasation management is now a chemotherapy administration safety standard.5
For more information, call 866-478-8274 or visit our website at www.totect.com To order Totect®, contact one of our authorized distributors. ASD Healthcare Cardinal Specialty McKesson/OTN Oncology Supply US Oncology (800) 482-6700 (800) 633-7555 (888) 987-6679 (800) 746-6273 (866) 677-4844 1
Mouridsen HT et al. Treatment of anthracycline extravasation with savene (dexrazoxane). Results from two prospective clinical multicentre studies. Ann Oncol 2007; 18:546-550. 2 Totect® package insert. 3 Polovich M, White JM, Olsen, M (eds.). Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (ed 3). Pittsburgh, PA, Oncology Nursing Society, 2009. 4 Alexander M, Corrigan A, Gorski L, Hankins J, Perucca R. (eds). Infusion Nurses Society Infusion Nursing an Evidence-Based Approach (ed 3). Boston, MA, Infusion Nurses Society, 2009. 5 Jacobsen J., et al. American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards. Oncology Nursing Forum, 2009; 36:651-658. © 2010 Topotarget USA. All rights reserved. TOT0111/7-10 Totect and its logo mark are registered trademarks of Topotarget A/S Image is copyright © Photo Researchers, Inc. Pharma Chemo Ad 11x14FINAL 4 26 10 indd 1
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Totect® – Brief prescribing information Please refer to the package insert for full prescribing information. Each Totect carton contains 10 vials of Totect® (dexrazoxane for injection) 500 mg and 10 vials of 50 mL diluent. Indication: Treatment of extravasation resulting from IV anthracycline chemotherapy. Dosage and administration: Totect is a cytotoxic drug. Vial contents must be mixed and diluted before use. Totect should not be mixed or administered with any other drug during the infusion. Administration of Totect should begin as soon as possible and within 6 hours following the anthracycline extravasation. Totect should be given as an intravenous (IV) infusion once daily for 3 consecutive days. The dose of Totect is based on the patient’s body surface area: day one, 1000 mg/m2; day two, 1000 mg/m2; day three, 500 mg/m2. For patients with a body surface area of > 2 m2, a dose of 2000 mg should be given on days 1 and 2, and a dose of 1000 mg should be given on day 3. Treatment on Day 2 and Day 3 should start at the same hour (+/- 3 hours) as on the first day. The Totect dose should be reduced 50% for patients with creatinine clearance values of <40 mL/minute. Cooling procedures such as ice packs should be removed from the affected area at least 15 minutes prior to Totect administration. Totect (dexrazoxane for injection) must be reconstituted with diluent supplied in the carton. The patient’s Totect dose is diluted in 0.9% 1000 mL NaCl prior to administration. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.3-5 Direct contact of Totect® with the skin or mucous membranes prior to and following reconstitution should be avoided. If contact occurs, wash immediately and thoroughly with water. Contraindications: None. Warnings and Precautions: Myelosuppression: treatment with Totect is associated with leukopenia, neutropenia, and thrombocytopenia. Hematological monitoring should be performed. Use in Pregnancy: Pregnancy Category D. Totect can cause fetal harm when administered to a pregnant woman. There is no adequate information about the use of Totect in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Adverse reactions: The most common adverse reactions (≥ 16%) are nausea, pyrexia, injection site pain and vomiting.
Totect® is a registered trademark of Topotarget A/S US Patent No. 6,727,253B2 NDC 38423-110-01
Drug Interactions: No drug interactions have been identified. Based on anecdotal reports concurrent use of topical dimethyl sulfoxide (DMSO) at the site of tissue injury may reduce the benefit of Totect. Additionally, nonclinical studies using a mouse model that simulates extravasation of anthracyclines has shown that concomitant treatment with topical DMSO decreases the efficacy of systemic dexrazoxane. Use in Specific Populations: Nursing Mothers: Discontinue drug or nursing, taking into consideration the importance of drug to the mother. Renal Impairment: Reduce the Totect dose by 50% In patients with creatinine clearance values <40 mL/min. Pediatric Use: The safety and effectiveness of Totect in pediatric patients have not been established. Geriatric Use: This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Overdosage: There are no data on overdosage. There is no known antidote for dexrazoxane. Carcinogenesis, Mutagenesis, Impairment of Fertility: The carcinogenic potential of dexrazoxane has not been investigated. Nevertheless, a study by the National Cancer Institute has reported that long term dosing with razoxane (the racemic mixture of dexrazoxane, ICRF-187, and its enantiomer ICRF-186) is associated with the development of malignancies in rats and possibly in mice. Dexrazoxane was not mutagenic to bacteria in vitro (Ames assay), but caused significant chromosomal aberrations in mammalian cells in vitro. It also increased the formation of micronucleated polychromatic erythrocytes in mice. Thus, dexrazoxane is mutagenic and clastogenic. The possible adverse effects of Totect on the fertility of humans and experimental animals, male or female, have not been adequately studied. Testicular atrophy was seen with dexrazoxane administration at doses as low as 30 mg/kg weekly for 6 weeks in rats (about 1/5 the human dose on a mg/m2 basis) and as low as 20 mg/kg weekly for 13 weeks in dogs (about half the human dose on a mg/m2 basis).
Manufactured by: Ben Venue Laboratories, Inc. Bedford, OH 44146 Hameln Pharmaceuticals GmbH 31789 Hameln Germany
Manufactured for: Topotarget A/S Fruebjergvej 3 DK-2100 Copenhagen Denmark
TOT0111/7-10 © 2010 Topotarget USA
Pharma Chemo Ad 11x14FINAL 4 26 10 indd 2
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Editorial Board EDITOR-INCHIEF Patrick Medina, PharmD, BCOP Oklahoma University College of Pharmacy Tulsa, OK
Beth Faiman, RN, MSN, APRN, BC, AOCN Cleveland Clinic Taussig Cancer Institute Cleveland, OH
Jim Koeller, MS University of Texas at Austin San Antonio, TX
Timothy G. Tyler, PharmD, FCSHP Desert Regional Medical Center Palm Springs, CA
Christopher Fausel, PharmD
Christopher J. Lowe, PharmD
John M. Valgus, PharmD, BCOP
Indiana University Simon Cancer Center Indianapolis, IN
Novant Health Winston-Salem, NC
University of North Carolina Hospitals and Clinics Chapel Hill, NC
David Baribeault, RPh, BCOP
Rebecca S. Finley, PharmD, MS
Emily Mackler, PharmD, BCOP
Boston Medical Center Boston, MA
Jefferson School of Pharmacy Philadelphia, PA
University of Michigan Health System & College of Pharmacy Ann Arbor, MI
Gary C. Yee, PharmD, FCCP, BCOP
Betty M. Chan, PharmD, BCOP
David C. Gammon, BS Pharm
Laura Boehnke Michaud, PharmD, BCOP, FASHP
John F. Aforismo, BSc Pharm, RPh, FASCP RJ Health Systems International, LLC Wethersfield, CT
USC/Norris Cancer Hospital Los Angeles, CA
University of Massachusetts Memorial Hospital Worcester, MA
University of Nebraska College of Pharmacy Omaha, NE
Burt Zweigenhaft, BS BioPharma Partners LLC New York, NY
The University of Texas M. D. Anderson Cancer Center Houston, TX
Marlo Blazer, RPh, PharmD 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
James Cancer Hospital & Solove Research Institute Columbus, OH
Heidi D. Gunderson, PharmD, BCOP Mayo Clinic Cancer Center Rochester, MN
Anjana Elefante, PharmD, BSc, BSc Pharm, RPh
Dwight Kloth, PharmD, FCCP, BCOP
Steve Stricker, PharmD, MS, BCOP
Roswell Park Cancer Institute Buffalo, NY
Fox Chase Cancer Center Philadelphia, PA
Samford University McWhorter School of Pharmacy Birmingham, AL
AugusT 2010 I VOL 3, NO 5
Kamakshi V. Rao, PharmD, BCOP University of North Carolina Hospitals and Clinics Chapel Hill, NC
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his issue of The Oncology Pharmacist spotlights the work of two of our board members—John Valgus and LeAnn Norris. Both of them have chosen to combine clinical and academic work in their own careers and serve as role models for pharmacy students and residents while providing the excellent clinical services of their institutions. Patrick Medina, John’s article, based on a presPharmD, BCOP entation at the 2009 American Editor-in-Cheif Society of Health-System Pharmacists’ midyear clinical meeting, provides excellent, practical suggestions for how preceptors can improve the learning experience for their trainees. As LeAnn discusses in an interview, her own decision to specialize in oncology was partly the result of working with Lew Iacovelli, another one of our board members, who was her role model and mentor. LeAnn won the New Practitioner Award at this year’s meeting of the
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241 Forsgate Drive, Suite 205C Monroe Twp, NJ 08831 The Oncology Pharmacist®, ISSN 1944-9607 (print); ISSN 1944-9593 (online) is published 8 times a year by Green Hill Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. Telephone: 732.656.7935. Fax: 732.656.7938. Copyright ©2010 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®, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. 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, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. 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.
August 2010 I Vol 3, No 5
CONTENTS FEATURE ARTICLES 6 ASCO: Prostate Cancer Denosumab prevents more skeletal events than zoledronic acid in men with prostate cancer and bone metastases Cabazitaxel improves overall survival in patients with hormone-refractory prostate cancer
8 ASCO: Pain Management Fentanyl nasal spray beats oral opioid for control of breakthrough cancer pain Naproxen reduces bone pain after pegfilgrastim injection
10 ASCO: Hematologic Cancers In CML, longer follow-up confirms superiority of nilotinib over imatinib
13 ASCO: Skin Cancer New monoclonal antibody treatment offers hope for treatment of metastatic melanoma
14 Continuing Education
Hematology/Oncology Pharmacy Association, a tribute to her own hard work and Lew’s excellence as a teacher and practitioner. This issue also features reports from the recent annual meeting of the American Society of Clinical Oncology. The thousands of studies presented there in just a few days is ample evidence of the enormous strides being made in basic and clinical research in oncology. To help readers keep up with the daunting amount of cancerrelated information released daily, we are adding daily news updates and other new features to The Oncology Pharmacist website (www.theoncologypharmacist.com). We hope you will visit the website and share your thoughts on the issues of the day. For those involved in research themselves, we invite contributions of original research as well as review articles, case reports, and articles on oncology pharmacy practice to our upcoming peer-reviewed publication, the Journal of Hematology/Oncology Pharmacy, which will provide a new outlet for oncology pharmacists to share their findings with their peers. Please send inquiries about manuscript preparation to editorial@ greenhillhc.com. ●
August 2010 • Vol 3, No 5 18 Gastrointestinal Cancers Nab-paclitaxel plus gemcitabine may help patients with advanced pancreatic cancer
22 Breast Cancer Postmenopausal women with breast cancer receiving letrozole or anastrozole may be at increased risk for bone loss
DEPARTMENTS 20 Oncology Drug Codes Colorectal cancer
27 Financial Planning Investment advisor or financial planner for your investments: who is right for you?
27 News Notes 28 International News 25th Anniversary EAU Annual Congress; 15th Congress of the EHA
Perspectives on idiopathic thrombocytopenia purpura: ASH 2009
18 Pharmacy Careers LeAnn Norris Wins New Practitioner Award
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Exploring uncharted territories — bringing advances in oncology to light
At Genentech BioOncology, we’re transforming the way cancer is treated by gaining a broad understanding of cancer biology and following a comprehensive approach to drug discovery. A robust pipeline — We currently have 22 new molecules in clinical development across a range of pathways, from angiogenesis to apoptosis. Innovative molecules — Our new molecular entities target the fundamental mechanisms of cancer growth and include antibody-drug conjugates, a HER2 dimerization inhibitor, a potent and specific B-Raf inhibitor, a Hedgehog pathway inhibitor, and antibodies targeting cancer cell-surface antigens. Extensive clinical trial program — We and our partners are currently enrolling patients in over 750 ongoing trials for both postapproval and pipeline products in dozens of tumor types. Our goal is to fundamentally change the way that cancer is treated — not just with incremental advances, but with new standards of care.
© 2010 Genentech USA, Inc. All rights reserved. 10201500 Printed in USA.
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ASCO Highlights The following articles are based on presentations at the 46th annual meeting of the American Society of Clinical Oncology held June 4-8, 2010, in Chicago. PROSTATE CANCER
Denosumab Prevents More Skeletal Events than Zoledronic Acid in Men with Prostate Cancer and Bone Metastases By Wayne Kuznar
CHICAGO—Denosumab delayed or prevented more skeletal-related adverse events than zoledronic acid in men with hormone-refractory prostate cancer and bone metastases. The superior efficacy of denosumab on this end point along with its ease of administration—subcutaneous rather than intravenous—gives it an edge over zoledronic acid, said Karim Fizazi, MD, PhD, lead investigator of a study comparing the two treatments. Earlier this year, denosumab was granted US Food and Drug Administration approval for the treatment of postmenopausal women who have a high risk for osteoporotic fractures, including those with a history of fracture or multiple risk factors for fracture, or those who have failed or are intolerant to other osteoporosis therapy. Denosumab specifically targets RANK ligand, a central mediator of the “vicious cycle” of bone destruction in metastatic cancer, said Fizazi, head, Department of Medical Oncology, Institut Gustave-
Roussy, Villejuif, France. In the trial, 1901 patients with hormone-refractory (castration-resistant) prostate cancer with bone metastases were randomized to denosumab given
Denosumab specifically targets RANK ligand, a central mediator of the “vicious cycle” of bone destruction in metastatic cancer. subcutaneously every 4 weeks, or zoledronic acid given intravenously every 4 weeks. Eighty percent of patients in each study arm discontinued therapy, mainly due to death or cancer progression, and rarely because of side effects, he said. The time to a first skeletal-related event—the primary efficacy end point —was delayed by 18% with denosumab compared with zoledronic acid. The
median time to first on-study skeletalrelated event was 20.7 months for denosumab compared with 17.1 months for zoledronic acid. The time to all on-study skeletalrelated events was also delayed by 18% in patients assigned to denosumab versus those on zoledronic acid. There was no significant difference in cancer progression and no significant difference in overall survival between the two treatment arms. Some 97% of patients in each group had adverse events, most of which were related to the underlying cancer: • The rates of infectious adverse events were 42.6% in the denosumab group and 39.7% in the zoledronic acid group. • Infectious serious adverse events occurred in 13.8% of patients assigned to denosumab compared with 11.4% of those assigned to zoledronic acid. • Acute-phase reactions occurred in about twice as many patients
assigned to zoledronic acid versus denosumab (17.8% vs 8.4%). • Hypocalcemia was more common in the denosumab arm than in the zoledronic acid arm (12.8% vs 5.8%). • There were 22 cases of osteonecrosis of the jaw in the denosumab group (2.3%) compared with 12 in the zoledronic acid group (1.3%). About 80% of patients in each treatment group who experienced osteonecrosis of the jaw had risk factors for it at baseline, such as tooth extraction, dental appliances, or poor oral hygiene. In addition to its subcutaneous route of delivery instead of intravenous infusion, Fizazi said that no renal monitoring or dose adjustment is needed with denosumab as opposed to zoledronic acid, nor is there a need to manage acute-phase reactions. To date, more than 11,000 patients have been exposed to denosumab in clinical trials of patients with cancer or bone loss. ●
Cabazitaxel Improves Overall Survival in Patients with Hormone-refractory Prostate Cancer
© ASCO/Todd Buchanan 2010
CHICAGO—Cabazitaxel is the first ly for palliation,” said Johann Sebastian treatment to show a survival benefit in De Bono, MD, PhD, who presented the patients with metastatic castration-resis- final and updated results of the multinatant prostate cancer (mCRPC), accord- tional trial. ing to data from a phase 3 trial. Cabazitaxel is a tubulin-binding drug On June 17, cabazitaxel became the developed specifically to overcome the first drug approved by the US Food and emergence of resistance to established Drug Administration (FDA) for the taxanes, including docetaxel. treatment of hormone-refractoFor this multinational ry prostate cancer. Results from trial, conducted in 146 the phase 3 trial delivered at centers in 26 countries, ASCO were included in the 755 patients with mCRPC FDA review. were randomized to re“The standard of care for ceive either prednisone treating mCRPC is docetaxel, (10 mg/day) in combinawhich improves both overall tion with either mitoxsurvival and quality of life. At antrone (12 mg/m2) or cabazitaxel (25 mg/m2) adprogression following docetax- Johann Sebastian el, however, there is currently De Bono, MD, PhD ministered three times weekly. Patients enrolled no standard of care for treating these patients, although there are a num- had received prior hormone therapy, ber of investigational drugs being stud- chemotherapy, and radiotherapy, but had ied, and treatment in this setting is large- progressive disease during or after treat-
August 2010 I VOL 3, NO 5
ment with docetaxel (cumulative dose ≥225 mg/m2). Upon primary intent-to-treat analysis, overall survival in the cabazitaxel combination arm was significantly higher compared with that in the mitoxantrone arm (15.1 months vs 12.7 months, respectively; P <.0001). Recently updated results of overall survival showed that the combination of cabazitaxel and prednisone significantly reduced the risk of death by 28% (P <.0001). Pain-free survival, response rates, and time to progression also significantly favored the cabazitaxel arm. “The safety profile of this drug was manageable, but proactive management of side effects associated with this drug, particularly febrile neutropenia and diarrhea, has to be carefully considered when treating a patient with this drug,” said De Bono, senior lecturer at Royal Marsden Hospital, London.
The most frequent grade 3/4 hematologic adverse events in the cabazitaxel arm were neutropenia (81.7%), leukopenia (69.2%), anemia (10.5%), and febrile neutropenia (7.5%). Discontinuation of treatment due to adverse events oc curred in 18.3% of patients in the cabazitaxel arm, and 8.4% of those in the mitoxantrone arm. Deaths due to adverse events were 4.9% in the cabazitaxel arm (predominantly caused by neutropenia and its complications) versus 1.9% in the mitoxantrone arm. “Cabazitaxel demonstrates a statistically and clinically significant improvement in overall survival—evident across all subgroups—compared with mitoxantrone in this study population. Cabazitaxel also improved secondary end points of progression-free survival, response rate, and time to progression,” he concluded. ● —WK
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Request a Complimentary CE Program in Your Area:
Case Studies in the Proactive Management of Indolent and Mantle Cell Lymphomas Continuing Education Series for Nurses and Pharmacists To request a free CE presentation in your area, please visit us at www.avid-ed.com/when.html. Alternatively, you can e-mail us at email@example.com. The request must come from a medical institution (office, clinic, hospital, organization), or a nurse or pharmacist, and a contact must be designated. This individual will serve as the primary contact for all communications.
TARGET AUDIENCE This activity is designed for oncology nurses and pharmacists interested in learning more about indolent and
mantle cell lymphomas and the results of the latest research that promise to improve clinical outcomes.
STATEMENT OF NEED The American Cancer Society (ACS) estimates that in 2009 there will be 65,900 new cases of non-Hodgkin’s lymphoma (NHL) and 19,500 deaths due to NHL, making NHL one of the leading causes of cancer and cancerrelated deaths in the United States. NHL has been classified into two types, indolent and aggressive. Two types are difficult to treat: indolent and mantle cell. Indolent lymphoma makes up 70% of NHL and generally presents with slowly progressive disease and painless peripheral lymphadenopathy. Characterized by a relatively slow rate of growth, indolent lymphomas have a low potential for cure with currently available treatments. The majority of indolent lymphoma patients are diagnosed with advanced-stage disease, and the median survival is approximately 8 to 10 years. Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma that comprises 6% of NHLs. Patients with MCL typically present in an advanced stage with widespread lymphadenopathy, involvement of the bone marrow, and a predilection for gastrointestinal infiltration. Although the majority of MCL patients are able to achieve response, relapse almost always occurs. Currently, MCL has no standard therapy at diagnosis or relapse, and no curative options exist. The aggressive clinical course of MCL has resulted in a median overall survival of 3 to 4
years with fewer than 15% of patients alive at 5 years. Treatments of indolent lymphoma and MCL are areas of ongoing research, and promising results with combination therapy and novel agents were recently presented at the 2009 American Society of Hematology (ASH) meeting in New Orleans. Due to the high incidence rate of indolent lymphomas, community practice oncology nurses and pharmacists need to understand patient management issues associated with the “watch-and-wait” treatment strategy for asymptomatic patients as well as available treatment options for symptomatic disease. Community practice oncology healthcare professionals (HCPs) may not be familiar with MCL due to the relatively few cases diagnosed per year. However, the aggressive nature of MCL makes appropriate management more intense and treatment more difficult than that of indolent lymphomas. Clinical trials in indolent lymphoma and MCL are generally conducted in academic institutions, and it becomes challenging for oncology nurses and pharmacists not directly involved in the trials to keep abreast of the latest data. Through discussion of case studies in these lymphomas, from diagnosis through recurrence, oncology HCPs will have a better understanding of newer treatments and research, as well as their potential impact on managing lymphoma patients.
LEARNING OBJECTIVES At the end of each program participants will be able to: • Describe the typical clinical presentation of indolent and mantle cell lymphomas • Discuss the pharmacology of treatment regimens This activity is jointly sponsored by Medical Learning Institute, Inc. and Avid Education Partners, LLC.
ACCREDITATION Medical Learning Institute, Inc. (MLI) is an approved provider of continuing nursing education by the California Board of Registered Nursing, Provider Number 15106, for 1.0 contact hour.
Supported by an educational grant from Millennium Pharmaceuticals, Inc. and Cephalon Oncology.
• Identify the side effects seen with therapies • Enact interventions for symptom management of frequently occurring side effects of bio-/chemotherapy
MLI is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This CE activity provides 1.0 contact hour. The universal program number for this activity is 0468-9999-09-044-L01-P.
Faculty Disclosure: It is the policy of MLI and Avid Education Partners, LLC (AEP) to ensure balance, independence, objectivity, and scientific rigor in all its educational activities. All faculty will disclose the existence of any financial interest and/or relationship(s) they might have with the manufacturer(s) of any commercial product(s) to be discussed during their presentation(s). Presenters will inform participants of any offlabel discussions. The associates of MLI and AEP have no financial relationships to disclose.
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ASCO Highlights PAIN MANAGEMENT
Fentanyl Nasal Spray Beats Oral Opioid for Control of Breakthrough Cancer Pain By Wayne Kuznar
CHICAGO—A fentanyl pectin nasal spray provides analgesia faster than immediate-release morphine in the treatment of breakthrough cancer pain, said Andrew Davies, MD, MSc. Breakthrough cancer pain is a transient exacerbation of pain that occurs despite relatively stable and adequately controlled background pain and has a significant impact on quality of life. Forty percent to 80% of patients with cancer pain have breakthrough pain, which tends to be rapid in onset, often peaking at approximately 3 minutes, and short in duration, lasting a median of 30 minutes, Davies explained. “For most patients, the mainstay of treatment is the use of so-called ‘rescue medications,’” he said. “Throughout the world, an oral opioid [oral immediate-release morphine] is the standard of care.” Unfortunately, said Davies, the pharmacokinetic/pharmacodynamic profile of oral immediate-release morphine does not fit the temporal characteristics of breakthrough cancer pain. It takes 20 to 30 minutes to start to work
and 60 minutes for its peak effect. In contrast, fentanyl pectin nasal spray has pharmacokinetics that enable rapid onset of pain relief, which facilitates rapid but controlled absorption of fentanyl across the nasal mucosa. In a phase 3, double-blind, doubledummy, multiple-crossover study, patients who had one to four episodes of breakthrough cancer pain per day while taking at least 60 mg/day of morphine sulfate were randomized to fentanyl nasal spray or morphine sulfate. Seventy-nine patients who completed the treatment phase were included in the efficacy and safety analysis, representing 740 pain episodes. In the double-blind, double-dummy phase, 10 episodes of breakthrough cancer pain were randomly treated with fentanyl nasal spray and oral placebo or immediate-release morphine sulfate and nasal spray placebo. Pain intensity on an 11-point scale was measured up to 60 minutes. Pain intensity from baseline to 15 minutes, the primary end point of the study, was
Fentanyl pectin nasal spray has pharmacokinetics that enable rapid onset of pain relief, which facilitates rapid but controlled absorption of fentanyl across the nasal mucosa. improved by 3.02 points in patients assigned to fentanyl nasal spray compared with 2.69 for immediate-release morphine (P <.05). “This difference was maintained throughout the 60minute period of study,” said Davies, consultant in palliative medicine, The Royal Marsden Foundation Trust, Surrey, United Kingdom. Clinically meaningful pain relief, defined as a two-point or greater decrease in pain intensity, was superior at both 10 and 15 minutes in the
fentanyl nasal spray group. At 10 minutes, clinically meaningful pain relief was achieved by 52.4% of patients randomized to fentanyl nasal spray compared with 45.4% of those randomized to immediate-release morphine (P <.05), and at 15 minutes, 75.5% of the fentanyl nasal spray group versus 69.3% of the immediaterelease morphine group had clinically meaningful pain relief (P <.05). Patients were either satisfied or very satisfied with fentanyl nasal spray for 81.5% of pain episodes versus 71.2% with immediate-release morphine (P <.05). The most common adverse effects attributed to fentanyl nasal spray were typical opioid adverse effects, such as vomiting and somnolence; these were more common than with oral immediate-release morphine. Most side effects with fentanyl nasal spray were mild to moderate and none were dose-related. Only 4.7% of patients withdrew from titration (2.4% in double-blind, doubledummy phase) due to adverse events; no significant nasal effects were reported. ●
Naproxen Reduces Bone Pain after Pegfilgrastim Injection CHICAGO—Twice-daily dosing of naproxen can reduce the incidence and severity of bone pain in cancer patients being treated with pegfilgrastim, according to data presented by New York researchers. As such, “naproxen…should be considered for patients beginning pegfilgrastim, providing there are no contraindications,” concluded principal investigator Jeffrey J. Kirshner, MD, director of research and the Community Clinical Oncology Program, Hematology-On cology Associates of Central New York, East Syracuse. “However, a significant percentage of patients still will experience pegfilgrastim-induced pain, and there is a need to develop even more effective preventive treatments.” By stimulating bone marrow production of neutrophils, pegfilgrastim, an immunostimulator, functions as a pegylated granulocyte colony-stimulating factor. It is indicated for reducing the risk of infection in patients with certain types of tumors who require strong chemotherapy. Pegfilgrastim-induced bone pain, however, is a significant clinical problem, which may result in discontinuation of
August 2010 I VOL 3, NO 5
treatment and lead to less effective chemotherapy dosing. For this randomized, double-blind, placebo-controlled trial, 510 patients from 17 sites were randomized to receive either naproxen (500 mg twice daily) or placebo on the day of pegfilgrastim administration, and for 5 to 8 days thereafter. Eighty-six percent of the patients enrolled were women; 67% of enrollees had breast cancer.
Mean AUC for pain was significantly reduced from 7.71 in the placebo group to 6.04 in the naproxen group (P = .037).
Eligible patients included those with a diagnosis of nonmyeloid malignancy who were scheduled to receive chemotherapy and a first dose of pegfilgrastim on day 2, 3, or 4 of the chemotherapy cycle. Patients could have no history of
active or past gastrointestinal bleeding, have no allergies to nonsteroidal antiinflammatory drugs (NSAIDs) or be currently taking NSAIDs or any medication for preexisting chronic pain, or have undergone heart surgery within the previous 6 months. Patients were asked to record pain duration and severity and were assessed using the University of Rochester Cancer Center Symptom Inventory Assessment. The primary outcome measure was the area under the curve (AUC) for pain during days 1 through 5. In both the placebo and naproxen groups, pain peaked at approximately 3 days after pegfilgrastim administration. Mean AUC for pain was significantly reduced from 7.71 in the placebo group to 6.04 in the naproxen group (P = .037). Naproxen was associated with significant reductions in maximum pain (from 3.40 in the placebo group to 2.59 in the naproxen group; P = .005), the overall incidence of pain (from 76.3% to 65.6%, respectively; P = .01), and the duration of pegfilgrastim-induced bone pain (from 2.40 to 1.92 days, respectively; P = .005). A reduction in severe pain, defined as >5
on a 1 to 10 scale, was of borderline significance, with a reduction from 24.5% in the placebo group to 17.6% in the naproxen group (P = .0643). No significant adverse events occurred in either group. Associations between the incidence, severity, or preventability of pegfilgrastim-induced bone pain and specific risk factors could not be found. “There was a suggestion that pegfilgrastim-induced pain may be more frequent in African Americans, with an AUC of 12.88 as opposed to 6.48 in the non–African Americans. But there were only 33 African Americans [in this study], so I’m not sure what to make of this,” Kirshner noted. ● —WK
Did You Know? People diagnosed with breast, bowel, and ovarian cancers and non-Hodgkin’s lymphoma today are twice as likely as they were 10 years ago to survive at least 10 years, according to new data from Cancer Research UK.
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ASCO Highlights BREAST CANCER
Novel Agents Improve Survival in Refractory... Continued from cover who had received a median of four prior chemotherapy regimens. Most were estrogen receptor–positive and human epidermal growth factor receptor type 2 (HER2)-negative, and about half had two or more metastatic sites. Patients were randomized 2:1 to eribulin given intravenously twice a month every 3 weeks or to a treatment
restrict the options. This was a real-life comparison,” Twelves noted. Overall survival improved by 2.5 months Median overall survival (OS), the primary end point, improved from 10.65 months with standard single-agent therapy to 13.12 months with eribulin, repre-
© ASCO/Todd Buchanan 2010
“The 2.5-month improvement in median survival represented a 23% benefit. We see these findings as potentially establishing eribulin as a new option.” —Christopher Twelves, MD
of physician’s choice (TPC), which could be any single agent—cytotoxic, endocrine, or biologic—approved for the treatment of cancer. “We allowed physician’s choice because there is no single established standard and we felt it was inappropriate to
senting a 19% reduction in mortality risk (P = .04). One-year survival was 53.9% with eribulin and 43.7% in the TPC arm. “The benefits were achieved with a manageable toxicity,” Twelves announced. Serious adverse events (AEs) were observed in 25% of each arm, and
AEs leading to treatment interruption, dose delays, and interruptions and discontinuations were similar. “EMBRACE is the first phase 3 singleagent study in heavily pretreated metastatic breast cancer to meet its primary end point of prolonged overall survival, so these are striking findings,” Twelves concluded. “The 2.5-month improvement in median survival represented a 23% benefit. We see these findings as potentially establishing eribulin as a new option.” Eric P. Winer, MD, head of medical oncology at Dana-Farber Cancer Center, Boston, commented at a press briefing that a 2.5-month improvement is “a difference that is sufficient to make one look seriously at this agent.” T-DM1 effective after trastuzumab A small phase 1 trial found that trastuzumab conjugated to DM-1 (TDM1), with or without the monoclonal antibody pertuzumab, was efficacious in women with advanced HER2positive breast cancers who were previously treated with trastuzumab. T-DM1 is a HER2-targeted antibody drug con-
See also page 22. jugate composed of the cytotoxic agent DM1 (an antimicrotubule agent) conjugated to the monoclonal antibody trastuzumab. Pertuzumab is a monoclonal antibody that binds to a different HER2 receptor than T-DM1. The theory is that the use of these agents in combination will offer complementary modes of action that will more fully cover the HER receptors and thus be more effective in treating HER2overexpressing tumors. The study has so far enrolled 44 patients with advanced or metastatic HER2-positive breast cancers; all those enrolled had previously received trastuzumab. Outcomes were reported for 28 of the participants, 10 of whom had partial responses, for a 36% response rate, when treated with T-DM1 and pertuzumab, according to Kathy Miller, MD, of Indiana University, Indianapolis. Edith Perez, MD, the Serene M. and Frances C. Durling Professor of Medicine at the Mayo Clinic, Jackson ville, commented, “The use of two targeted agents in these advanced breast cancer patients is a reasonable ap proach to therapy.” ●
In Chronic Myeloid Leukemia, Longer Follow-up Confirms Superiority of Nilotinib Over Imatinib By Walter Alexander
CHICAGO—Among patients with chronic myeloid leukemia (CML) in the Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study, major molecular response (MMR) rates with nilotinib remain superior to those with imatinib after follow-up extended to a median of 18.5 months. The finding suggests that nilotinib should be “a new standard of care” in this population, according to lead investigator Richard Larson, MD, director of the leukemia program at the University of Chicago Medical Center in Chicago, Illinois. He noted that although nilotinib is the most selective inhibitor of BCR-ABL, imatinib is the current standard of care for CML. ENESTnd included 846 patients, all diagnosed with Philadelphia chromosome–positive (Ph+ CML) in chronic phase within the previous 6 months. They were randomized to receive nilotinib 300 mg twice daily (n = 282), nilotinib 400 mg twice daily (n = 281), or imatinib 400 mg once daily (n = 283), with planned 5-year follow-up and a primary end point of MMR re-
August 2010 I VOL 3, NO 5
sponse (MMR, ≤0.1% BCR-ABLIS) at 12 months and 24 months. In prior reporting of 12-month followup, MMRs were achieved by 44% of patients taking nilotinib 300 mg twice daily, 43% of patients taking nilotinib 400 mg twice daily, and 22% of patients taking imatinib 400 mg once daily (P <.0001 for both nilotinib groups vs imatinib). After median follow-up of 18.5 months in 525 patients, MMRs were achieved by 69% of those taking nilotinib 300 mg twice daily (n = 178), 63% of those taking nilotinib 400 mg twice daily (n = 175), and 36% of those taking imatinib 400 mg once daily (n = 172). Among 145 patients with follow-up out to 24 months, MMR rates were 86% for nilotinib 300 mg twice daily (n = 49), 88% for nilotinib 400 mg twice daily (n = 48), and 48% for imatinib 400 mg once daily (n = 48). Similar percentages of patients remain on treatment in all groups (80% nilotinib 300 mg twice daily; 81% nilotinib 400 mg twice daily; 75% imatinib 400 mg once daily). Although dose escalation was not permitted in the nilotinib arms,
imatinib dose escalation to 800 mg/day for suboptimal response or treatment failure was allowed and occurred in 24%. Progression to accelerated phase or blast crisis was reported in <1% of nilotinib patients (0.7% nilotinib 300 mg twice daily; 0.4% nilotinib 400 mg twice daily) and in 4.2% of imatinib 400-mg once-daily patients (P = .006/.003 for nilotinib 300/400 mg twice daily vs imatinib 400 mg once daily).
Longer follow-up supports nilotinib as a new standard of care in patients with newly diagnosed CML. Edema was more common among patients receiving imatinib. Grade 3 to 4 adverse events were rare (<1%) across all treatments. No clinically relevant prolongations of QT interval or left ventricular ejection fraction were reported. CML-related deaths were significantly
(P = .03) less common for nilotinib 400 mg twice daily compared with imatinib (1 vs 8; 2 with nilotinib 300 mg twice daily, P = .28). Larson concluded, “With longer follow-up, rates of MMR and CCyR [complete cytogenetic response] remain superior for nilotinib versus imatinib. Molecular responses are continuing to deepen over time.” He added, “Longer follow-up supports nilotinib as a new standard of care in patients with newly diagnosed CML.” In response to a question about the implications of the dose findings, Larson commented, “The data from this trial show that while the efficacy of the 300mg twice-daily dose is equivalent to that of the 400-mg, the side effect profile favors the lower dose—so that is probably the dose that will go forward.” The US Food and Drug Administration granted nilotinib priority review status for newly diagnosed CML in February 2010, and, based on the ENESTnd results, approved the drug for adults with newly diagnosed Ph+ CML in chronic phase in June 2010. ●
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Presents the Third Annual Curriculum for
CONSIDERATIONS IN MULTIPLE MYELOMA A Newsletter Series for Cancer Care Professionals Center of Excellence Media, along with Editor-in-Chief Sagar Lonial, MD, of Emory University, are pleased to offer your multidisciplinary cancer team this series of newsletters focusing on the challenges of treating patients with multiple myeloma.
SAGAR LONIAL, MD Associate Professor of Hematology and Oncology Emory University School of Medicine
★ Earn Continuing Education Credits ★ 8-part newsletter series
CASE STUDY DISCUSSIONS: • Front-line Therapy
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PARTICIPATE TODAY at www.COEXM.com For complete learning objectives and accreditation information, please refer to each activity.
Target Audience These activities were developed for physicians, nurses, and pharmacists.
These activities are jointly sponsored by
These activities are supported by an educational grant from Millennium Pharmaceuticals, Inc.
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OncoMed provided funding and editorial support for this article www.OncoMed.net
2 OF A SERIES PART
Oncology Practice Management
New Jersey Hematology and Oncology Center Partners with OncoMed Bayonne, NJ—As demand for their services grew and it became increasingly clear that their practice was becoming a regional center for patients battling cancer, the medical staff at Colanta Hematology & Oncology Center made the decision to build and open an outpatient infusion center that could adequately and comfortably serve their patients. The result was a state-of-the-art infusion center with 20 recliners in a patientfocused environment that is open to serve patients 7 days a week. The medical staff of 3 physicians and 4 nurses, led by practice administrator Romel Colanta, MD, now delivers a broad array of outpatient oncology services, including chemotherapy, albumin, antiemetic, and iron therapy infusions. Additionally, the infusion center staff provides supportive cancer care services, including therapeutic phlebotomy, antibiotic infusion, and electrolyte replacement. They also provide multidisciplinary infusion services for patients referred to the center by gastroenterologists, neurologists, and infectious disease specialists. With the high volume of oncology drugs required to treat their patient panel, the medical staff at Colanta had to make the decision as to how they would supply their patients with oncology medications. If they followed the traditional practice of hematology and oncology providers, they would “buy and bill” the
medications, meaning they would have the responsibility of sourcing and purchasing the medications, storing them, preparing and sometimes compounding them for patients, managing the inventory on an ongoing basis, and dealing with a bevy of insurance prior authorization and reimbursement procedures and requirements in order to get paid.
est clinical standards, deliver them just in time for treatment day (thereby eliminating waste), handle all the hassles of insurance prior authorization and reimbursement, and free the center from the challenges of safely storing and dispensing the drugs and the huge, capitalintensive “carry costs” that maintaining such an inventory requires.
“The partnership with OncoMed has enabled us to make better use of our capital.” —Romel Colanta, MD Practice Administrator Colanta Hematology & Oncology Center
Although buy and bill traditionally had its benefits, including a substantial margin paid by Medicare and other commercial payers, changes that resulted from the Medicare Modernization Act lowered a margin that sometimes paid physicians 40% over the cost of the drug to just 6%. The Colanta team decided there was a better way. They knew they could outsource the pharmacy function to a pharmacy that was highly specialized in oncology medications. This pharmacy would prepare the drugs under the high-
The outpatient infusion center at Colanta Hematology & Oncology Center comfortably serves patients.
Dr Colanta and his colleagues researched their options and chose OncoMed—The Oncology Pharmacy. OncoMed is an oncology pharmacy, meaning that its sole business is oncology medications. Its specially trained and certified oncology pharmacists work in a technologically advanced pharmacy built exclusively for oncology pharmaceutical prescription processing and dispensing, including a USP <797>-compliant class 5 clean room. To protect the supply chain and ensure a complete and full drug pedigree, all inventories are purchased directly from pharmaceutical manufacturers. The company’s “just-intime treatment-day” service means that oncologists and hematologists in any state in the nation are guaranteed delivery of medications and all therapyspecific administration supplies within 24 hours of placing the order. Given the Colanta Hematology & Oncology Center’s close proximity to one of OncoMed’s regional oncology pharmacy sites, they were eligible to get same day and even emergency stat dose delivery when needed. But what also set OncoMed apart from specialty pharmacies that concentrate on more than one class of pharmaceuticals is the OncoMed care management support team’s ability to work with insurers to get the authorizations that the Colanta Hematology & Oncology Center’s patients need. OncoMed’s team includes
patient care navigators and patient reimbursement specialists who have extensive experience working with insurers, oncology drug manufacturers, and medical foundations. These specialists always know where to go to search for needed funding for patients who are banking on that expertise for their recovery. OncoMed has become a pivotal partner to the Colanta Hematology & Oncology Center by owning the pharmaceutical worry and letting the physicians focus solely on guiding their patients to remission. We sat down with Dr Colanta and asked him about the new center and its partnership with OncoMed. Why did your infusion center choose to partner with OncoMed? The buy-and-bill model that oncologists have always worked under is no longer viable. Physicians can’t make an office run on a 6% margin. Under buy and bill, the average sales price (ASP) + 6% methodology can very quickly go to ASP + 4%, +2%, or -2% if we run into any obstacles in getting reimbursed. And with expensive drugs like chemotherapy, we cannot take that risk. Plus, OncoMed helps patients get funding for medication even after the patient’s insurer has denied coverage. In addition to this new center, you now have 2 additional sites in New Jersey. How has the partnership with OncoMed enabled you to successfully launch and grow the center? When we opened, 90% of what we infused in the clinic was oncolytics. As we have grown, we infuse a far broader array of medications. The backbone of our practice is still chemotherapy, but we have increased our nononcolytic infusions. For patients referred by gastrointestinal practitioners, we infuse infliximab, and for those referred by infectious disease physicians, we provide antibiotic infusions. Some of those drugs are still viable [under buy and bill], but not all. We have been able to devote money that has traditionally gone to purchasing medication and instead expand our services. The partnership with OncoMed has enabled us to make better use of our capital. Continued on next page
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EVOLUTION IN ONCOLOGY PRACTICE MANAGEMENT™ 22 Continued from page 12
How does the medication ordering and fulfillment process work with OncoMed? Having an efficient and focused process in place is very important. We have been able to institute a process where we have someone devoted to being our liaison with OncoMed. When a patient comes in and his or her benefits are precertified, we send the person’s case information to OncoMed, and the drugs are sent to us directly, along with all the administration supplies. We get them on a next-day basis, or sooner if needed, and everything is clearly labeled with patient-specific information. That makes a huge difference to us when dealing with OncoMed versus some specialty pharmacies that some insurers have imposed upon us to use, which get the drugs wrong, ship them late, and have no idea of the correct administration supplies. How does the relationship with OncoMed allow you and your team to
focus on what is important? I will give you a “before-and-after” example. Before we worked with OncoMed, 50% or more of our time was spent on managing drug costs and reimbursement. We had 5 people managing pharmacy at the 3 locations; we have been able to reduce that number of employees to 1. Before, we had to continually make sure that we were not underwater on drugs, as reimbursement rates and times fluctuated. OncoMed has made it possible to not devote time and effort on that. Based on your experience, what would you say about OncoMed to hematologists and oncologists considering such a move? It is definitely a relationship that every infusion center or oncologist has to explore. When dealing with narrowing reimbursement margins and delayed reimbursement, ultimately it will be beneficial to switch to OncoMed.
Pharmacists filling orders at the OncoMed facility.
THE LEADERSHIP OF ONCOMED – THE ONCOLOGY PHARMACY
Burt Zweigenhaft CEO, OncoMed
Kevin Askari, RPh President and Chief Clinical Pharmacist OncoMed
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To learn more about OncoMed or to request a presentation, contact OncoMed at 1-877-662-6633, extension 1298 or firstname.lastname@example.org, or go to www.oncomed.net.
ASCO Highlights SKIN CANCER
New Monoclonal Antibody Treatment Offers Hope for Treatment of Metastatic Melanoma By Wayne Kuznar
CHICAGO—A human monoclonal antibody that blocks a receptor that downregulates T-cell responses improves long-term survival in patients with previously treated advanced melanoma, according to the results of a phase 3 trial. “This is the first time we have shown a survival benefit in metastatic melanoma,” said Steven O’Day, MD, chief of research and director of the melanoma program at The Angeles Clinic and Research Institute in Los Angeles. “What is equally impressive is the near doubling in the 1-year and 2year landmark overall survival analyses.” The study was a head-to-head comparison of treatments in 676 patients with previously treated, unresectable stage III
www.TheOncologyPharmacist.com NO. 2
or IV melanoma. There were three treatment arms: monotherapy with ipilimumab (n = 137), gp100 peptide vaccine alone (n = 136), and the combination of these two agents (n = 403). Ipilimumab is a fully human monoclonal antibody that blocks the CTLA4 receptor (CTLA-4 is an antigen found on T cells that downregulates the T-cell response) and potentiates Tcell activation. gp100 is a vaccine that produces T-cell specific immune responses, and served as the active control arm for this study. “By blocking CTLA-4, ipilimumab keeps the T-cell potentiated and hopefully leads to antitumor immunity,” O’Day explained.
Patients in both ipilimumab arms achieved improvements in overall survival. In the gp100 vaccine plus placebo group, median overall survival was 6.4 months, which is comparable with results with placebo in previous studies. In each of the two arms receiving ipilimumab, median overall survival was 10.0 months. One-year survival was 44% in patients who received ipilimumab plus vaccine, and 46% in those treated with ipilimumab alone, compared with 25% in the gp100 vaccine group. Two-year survival was 22% and 24%, respectively, compared with 14% in patients in the vaccine group. Better disease control was also seen in both groups treated with ipilimum-
ab. After 6 months, melanoma progression was halted in approximately 30% of patients, compared with only 11% of those who received the gp100 vaccine alone. Serious adverse events were more common in both ipilimumab arms, at 17.4% and 22.9%, respectively, compared with 11.4% in the gp100 plus placebo arm. Of significance are the side effects with ipilimumab related to the immune system. These occurred in two thirds of the ipilimumab arm patients and in only one third of the gp100 vaccine group. In ipilimumab-treated patients, T cells began attacking normal tissue, the most common sites being dermatologic, gastrointestinal, endocrine, and hepatic tissue. ●
AugusT 2010 I VOL 3, NO 5
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CONTINUING EDUCATION PROGRAM P10031 • RELEASE DATE: JUNE 30, 2010 • EXPIRATION DATE: JUNE 30, 2011 ESTIMATED TIME TO COMPLETE: 1.0 HOUR
Perspectives on Idiopathic Thrombocytopenia Purpura: ASH 2009 By Gary C. Yee, PharmD, FCCP, BCOP Professor of Pharmacy Practice and Associate Dean, College of Pharmacy, University of Nebraska Medical Center, Omaha
This activity was developed for pharmacists and other healthcare professionals. LEARNING OBJECTIVES
Upon completion of this activity, participants will be able to: • Provide payers with a practical understanding of the key clinical, business, and regulatory factors, guidelines, and research advances involving idiopathic thrombocytopenia purpura (ITP) treatment that providers are using as the basis for their treatment decisions • Offer payers a multistakeholder commentary on this information, to identify the impact on different stakeholders of these changes to treatment • Illuminate the different perspectives and incentives of the various stakeholders involved in ITP treatment decisions— patients, providers, payers, purchasers, distributors, regulatory agencies, and manufacturers • Align incentives with providers and transform payer drug management policies into patient-centered, value-based models
diopathic thrombocytopenia purpura (ITP) is an autoimmune disorder mediated by platelet antibodies that accelerate platelet destruction and inhibit their production.1 Most cases of ITP are acquired (ie, primary), but ITP can also occur with other disorders (ie, secondary). Although the presenting signs and symptoms of ITP vary widely, the primary clinical manifestation is bleeding. Bleeding risk generally correlates with the severity of thrombocytopenia. Until recently, the primary goal of treatment was to interfere with the antibody-mediated platelet destruction. The primary treatment options were intravenous (IV) immune globulin and corticosteroids. Other treatment options were immunosuppressive agents (eg, cyclosporine, azathioprine, cyclophosphamide, and mycophenolate mofetil), rituximab, danazol, dapsone, and vinca alkaloids. Most patients with newly diagnosed (ie, acute) primary ITP respond without treatment or to first-line therapy with corticosteroids or IV immune globulin.
August 2010 I VOL 3, NO 5
Patients who fail first-line therapy are treated with splenectomy or other second-line therapies. Patients with ITP lasting for more than 12 months are considered to have chronic ITP. In 2008, two novel thrombopoietin receptor agonists (sometimes referred to as thrombopoietin mimetics) were US Food and Drug Administration (FDA)approved for the treatment of chronic ITP: romiplostim and eltrombopag. Both agents activate the receptor for thrombopoietin, which is the primary regulator of thrombopoiesis in humans. By stimulating platelet production, these agents provide clinicians with new treatment options for ITP. The availability of thrombopoietin receptor agonists has stimulated interest in the biology and treatment of ITP. An international working group recently published a report to standardize terminology, definitions, and outcome criteria in ITP,2 and another international group recently published an evidence-based guideline for the diagnosis and treatment of ITP.3 At the last annual meeting of the American Society of Hematology (ASH), more than 60 studies were presented on ITP. This report highlights the results of some of the major studies on ITP to provide decision makers with information on the clinical and economic implications of those studies. PHARMACISTS DESIGNATION
Medical Learning Institute, Inc., is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. Completion of this activity provides for 1.0 contact hour (0.1 CEU) of continuing education credit. The universal activity number for this activity is 468-9999-10-025-H01-P. INSTRUCTIONS FOR CREDIT
1. Read the article in its entirety 2. Go to www.TheOncologyPharmacist.com 3. Select “Continuing Education” 4. Click on this article’s title from the list shown 5. Select “Click here to complete the posttest and obtain a CE certificate online” 6. Complete and submit the CE posttest and CE Activity Evaluation and Request for Credit Form online 7. Print your Certificate of Credit This activity is provided free of charge to participants. Upon completion of the evaluation and
Role of rituximab as first-line treatment of ITP Although not FDA-approved for ITP, rituximab is sometimes used as second-line therapy in ITP patients, based on uncontrolled trials.4 Few studies have evaluated rituximab in previously untreated patients. In a recently published multicenter, open-label, randomized, controlled trial (ML18542), dexamethasone alone was compared with dexamethasone plus rituximab in 101 adults with newly diagnosed or persistent/chronic ITP.5 All patients received 40 mg of dexamethasone orally for 4 consecutive days (days 1-4); patients in the rituximab group received 375 mg/m2 of rituximab on days 7, 14, 21, and 28. Patients who received dexamethasone plus rituximab were more likely to achieve a sustained response, defined as a platelet count ≥50 ¥ 109/L at 6 months compared with those treated with dexamethasone alone (63% vs 36%; P = .004). A similar pattern was noted for higher platelet counts at 6 months (≥100 ¥ 109/L or 150 ¥ 109/L). Patients in the dexamethasone group who failed therapy were treated with salvage dexamethasone plus rituximab. Patients who received dexamethasone plus rituximab had a higher incidence of grades 3/4 adverse events (10% vs scoring 70% or better on the posttest, you will immediately receive your certificate online. If you do not achieve a score of 70% or better on the posttest, you will be asked to take it again. Please retain a copy of the certificate for your records. FACULTY DISCLOSURES
Before the activity, all faculty will disclose the existence of any financial interest and/or relationship(s) they might have with the manufacturer(s) of any commercial product(s) to be discussed during their presentation(s): honoraria, expenses, grants, consulting roles, speaker’s bureau membership, stock ownership, or other special relationships. Presenters will inform participants of any off-label discussions. The associates of Medical Learning Institute, Inc., and Center of Excellence Media, LLC, have no financial relationships to disclose. Gary C. Yee, PharmD, FCCP, BCOP, is on the Advisory Board of Amgen and Eisai.
2%; P = .082), but the incidence of serious adverse events was similar.5 At the ASH meeting, Zaja and colleagues reported on the long-term (>6 months) safety and efficacy of patients enrolled in the ML18542 trial.6 Patients were evaluated every 4 months during the planned 30-month observation period. Eighty patients were available for evaluation (median follow-up: 20 months); 54 of these 80 patients achieved a sustained response at 6 months and were evaluated for response duration. The rates of relapse, defined as platelets <50 ¥ 109/L, in the dexamethasone alone, dexamethasone plus rituximab, and salvage dexamethasone plus rituximab groups were 23%, 26%, and 14%, respectively. The only delayed adverse event was a case of herpes zoster reactivation in a patient who initially received dexamethasone alone, but later received salvage dexamethasone plus rituximab therapy.6 Although these results are interesting, higher response rates have been reported with 4 cycles of dexamethasone (40 mg/day for 4 days) given every 14 days.7 Some experts are concerned about the additional cost and potential toxicity of rituximab. Romiplostim in chronic ITP One of the most interesting abstracts was a randomized, open-label, phase 3b DISCLAIMER
The information provided in this CE activity is for continuing education purposes only and is not meant to substitute for the independent medical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition. SPONSOR
This activity is jointly sponsored by Medical Learning Institute, Inc., a nonprofit medical accreditation company, and Center of Excellence Media, LLC. COMMERCIAL SUPPORT ACKNOWLEDGMENT
This activity is supported by an educational grant from Amgen. FACULTY
Gary C. Yee, PharmD, FCCP, BCOP Professor, Department of Pharmacy Practice College of Pharmacy Universtiy of Nebraska Medical Center 986045 Nebraska Medical Center Omaha, NE 68198-6045
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www.TheOncologyPharmacist.com study of 234 adult nonsplenectomized patients with chronic ITP.8 Patients were randomized 2:1 to receive onceweekly subcutaneous romiplostim, with dose adjustments to maintain platelet counts between 50 ¥ 109/L and 200 ¥ 109/L, or medical standard of care for 52 weeks. Many of the patients in the romiplostim arm received their weekly injections at home.9 Coprimary end points were the incidence of splenectomy and the incidence of treatment failure, defined as platelet count ≤20 ¥ 109/L for 4 consecutive weeks at the highest recommended dose and schedule, major bleeding event, or change in therapy because of an intolerable side effect or bleeding symptoms.8 Patients who discontinued the study during the treatment period were counted as having had splenectomy or treatment failure. Standard-of-care treatments were administered according to standard institutional practices or therapeutic guidelines. Romiplostim was significantly better than medical standard of care for both of the primary end points (Table 1). Sensitivity analysis, which used the actual incidence of splenectomy or treatment failure, confirmed the primary end point results. The incidence of bleeding events with a worst grade score ≥3 was lower in the romiplostim group (3% vs 7%). Serious adverse events occurred in 23% of patients in the romiplostim group and 37% of patients in the standard-ofcare group. Six patients died—one (1%) in the romiplostim group and five (7%) in the standard-of-care group. No patients tested positive for neutralizing antibodies to romiplostim or thrombopoietin, and one romiplostim-treated patient showed an increase in bone marrow reticulin that was still within the normal range (grade 2).8 Romiplostim received FDA approval based on 2 clinical trials in which patients received romiplostim for 24 weeks. Bussel and colleagues presented
maintenance romiplostim doses and that more than 50% had platelet counts ≥50 ¥ 109/L on 95% of all study visits.10 Patients who received a stable romiplostim dose for 3 consecutive weeks were eligible to receive romiplostim at home by self-injection or by a caregiver; home administration was started by 75% of patients. The incidence and severity of bleeding events was low and did not increase over time. Bone marrow reticulin was present or increased in nine patients, with no evidence of progression to myelofibrosis. Thrombotic events occurred in 6% of patients, and the risk did not increase over time. Two patients developed neutralizing antibodies to romiplostim that were absent on retesting after drug withdrawal.10 The primary outcome in the pivotal clinical trials was platelet response, which is clinically important, because it correlates with the risk of bleeding and bleeding-related complications. Weitz and colleagues presented an evaluation of bleeding-related episodes in patients with chronic ITP who participated in the two phase 3 clinical trials of romiplostim.11 A bleeding-related episode was defined as an actual bleeding event or the use of rescue medication to treat or prevent bleeding. The rate of bleeding-related episodes was reduced by 55% in the patients receiving romiplostim compared with those receiving placebo.11 Bleeding-related episodes were associated with platelet counts <50 ¥ 109/L. Hospitalizations associated with bleeding-related episodes were less common in the romiplostim group compared with the placebo group.11 In another study, Buchanan and colleagues presented the results of a randomized, double-blind study of romiplostim in children with chronic ITP.12 That study confirmed the effectiveness and safety of romiplostim in children with chronic ITP.12
The primary outcome in the pivotal clinical trials was platelet response, which is clinically important, because it correlates with the risk of bleeding and bleeding-related complications.
the interim results of a 5-year open-label extension study evaluating the safety and efficacy of romiplostim.10 All of the 291 adult patients had participated in a previous romiplostim study. Romiplostim was administered once weekly by subcutaneous injection, with dose adjustments to maintain platelet counts between 50 ¥ 109/L and 200 ¥ 109/L. The results showed that about 80% of patients received stable weekly
Eltrombopag in chronic ITP The other FDA-approved thrombopoietin receptor agonist is eltrombopag. Saleh and colleagues presented the results of the Eltrombopag Extended Dosing Study (EXTEND), an openlabel extension study evaluating the safety and efficacy of eltrombopag.13 All of the 299 patients with chronic ITP had participated in a previous study of eltrombopag. The study is similar to the
Table 1. Comparison of Romiplostim and Medical Standard of Care in Adult Nonsplenectomized Patients with Chronic ITP Romiplostim (n = 157) N (%)
SOC (n = 77) N (%)
Treatment failure incidence
Treatment failure incidence
Primary end point
ITP indicates idiopathic thrombocytopenia purpura; SOC, standard of care.
Table 2. ITP-attributable Medical Resource Use and Cost in Patients with Chronic ITP Mean services used, Na
Mean resource cost, $a
Medical diagnostic/ treatment procedures
Other outpatient facility visits
Emergency department visits
Per patient, per year. ITP indicates idiopathic thrombocytopenia purpura.
romiplostim study, except for a shorter period of follow-up (only about 6% of patients had received eltrombopag for more than 24 months). Overall, 86% of patients treated with eltrombopag achieved a platelet count >50 ¥ 109/L, while median platelet counts remained >50 ¥ 109/L during the observation period. Patients on treatment for 6 or 12 months achieved platelet counts >50 ¥ 109/L for about 70% of the time on treatment.13 Eltrombopag appeared to be well-tolerated; most adverse events were mild to moderate in severity. Thirteen (4%) patients experienced 16 thromboembolic events. A total of 86 bone marrow biopsies were performed, and the authors reported that no “clinically relevant” effects of eltrombopag were detected.13 Results of bone marrow examinations in patients with chronic ITP who participated in several eltrombopag trials were presented in a study by Saleh and colleagues.14 Ninety-one patients had a bone marrow biopsy after eltrom-
bopag treatment, including 86 patients in the EXTEND study who were treated for a median of 12 months (range, 1-18 months).14 Reticulin fibers were mentioned in 83 of the reports; five patients had myelofibrosis grade 2 reticulin, with no clinical signs or symptoms of bone marrow dysfunction, and two reported collagen. Pretreatment bone marrow biopsies were available for comparison for a few patients. Treatment was discontinued in one patient who progressed from grade 1/3 to grade 2/3 after 15 months on study. A second, 81-year-old patient with a history of three cancers had no change in the degree of reticulin after 14 months on study, but collagen was noted on the second bone marrow biopsy. The authors concluded that there was no evidence of clinically relevant bone marrow abnormalities or clinical findings typically associated with myelofibrosis in patients treated for up to 18 months with eltrombopag.14 One of the differences between romiContinued on page 16
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Perspectives on Idiopathic Thrombocytopenia Purpura... plostim and eltrombopag is that eltrombopag has a black box warning about hepatotoxicity. Maddrey and colleagues presented the results of a detailed evaluation of the effects of eltrombopag on the liver in patients enrolled in one of five different clinical trials.15 The incidence of several hepatobiliary laboratory abnormalities was evaluated. The FDA draft guidance on drug-induced liver injury (DILI) was used to screen for abnormalities.15
home. Romiplostim would be considered for specialty pharmacy programs at most health plans. Eltrombopag is administered daily, orally, and utilization management tools used for other orally administered drugs could be used to ensure appropriate use. With both drugs, adherence is important to maintain platelet counts >50 ¥ 109/L. Expenditures for specialty pharmaceuticals are growing more rapidly than for conventional drugs, and it is
their efficacy without any new safety concerns. Results of the romiplostim trial in adult nonsplenectomized patients have the potential to change the treatment of ITP. Romiplostim can delay splenectomy, but the long-term results of romiplostim in this setting are not known. About 80% of patients respond to splenectomy, and response is sustained in 66% with no additional therapy for at least 5 years.3 Also, complications with laparoscopic splenectomy are low. ● References
Estimates of the prevalence of chronic ITP in the United States vary widely. Some analysts estimate that there are currently 60,000 patients with chronic ITP.
In the three placebo-controlled trials, 7% (9/128) of placebo patients and 11% (33/299) of eltrombopag-treated patients met at least one of the DILI screening criteria. A similar incidence of abnormalities in liver function tests was observed in the placebo and eltrombopag groups, with the exception of greater than threefold elevations in alanine aminotransferase. Twenty-four (8%) patients in the EXTEND study met at least one of the DILI screening criteria; five of these patients were withdrawn because of a hepatobiliary abnormality.15 Key issues for managed care Estimates of the prevalence of chronic ITP in the United States vary widely.16 Some analysts estimate that there are currently 60,000 patients with chronic ITP in the United States.17 However, a recently published study reported an annual prevalence of adult chronic ITP of 0.08% (ie, 80 persons in 100,000).18 The burden of chronic ITP is substantial, based on a retrospective analysis of claims data from more than 5 million adults enrolled from 2000 to 2004 (Table 2).18 Table 2 shows ITP-attributable resource use and cost in patients with chronic ITP; ITP-attributable resource use and cost accounted for a substantial proportion of all-cause resource use and cost. In another analysis of hospitalizations for ITP between 2003 and 2006, the average cost associated with all discharges was $16,476 (2008 dollars), with an average 6.4-day length of stay and inhospital mortality of 3.8%.19 Romiplostim and eltrombopag are expensive drugs, with annual costs of about $50,000 per patient. Romiplostim is administered weekly by subcutaneous injection, and many patients can be taught to self-inject the medication at
August 2010 I VOL 3, NO 5
predicted that specialty pharmaceuticals will account for the majority of drug sales by 2012.20 Self-administered pharmaceuticals, such as romiplostim, can be paid through the pharmacy benefit or medical benefit.21 Payers have developed various benefit plans and strategies to manage outpatient specialty pharmaceuticals.22,23 One widely used benefit design is to add a fourth copayment tier for specialty pharmaceuticals. In a survey of Blue Cross and Blue Shield plans, the most commonly used strategies were prior authorization, claims review, formulary management, and utilization review.22 Although paying for specialty pharmaceuticals through the pharmacy benefit offers more opportunities for utilization management, strategies must be carefully considered. When specialty pharmaceuticals are paid through the pharmacy benefit, outof-pocket spending can increase dramatically.24 In a retrospective analysis of pharmacy claims for specialty pharmaceuticals, per-claim out-of-pocket costs >$100 for tumor necrosis factor blockers and >$200 for multiple sclerosis biologic agents were associated with new prescription abandonment.25 These results suggest that insurers should consider the out-of-pocket burden on members and the potential impact of out-of-pocket cost on adherence and member satisfaction. Conclusions Studies presented at the ASH meeting provide new information about the role of rituximab and thrombopoietin receptor agonists in the treatment of ITP. The long-term safety and efficacy results with both of the recently approved thrombopoietin receptor agonists show that these agents maintain
1. Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002; 346:995-1008. 2. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009; 113:2386-2393. 3. Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115:168-186. Epub 2009 Oct 21. 4. Arnold DM, Dentali F, Crowther MA, et al. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med. 2007;146:25-33. 5. Zaja F, Baccarani M, Mazza P, et al. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Blood. 2010;115:2755-2762. 6. Zaja F, Baccarani M, Mazza P, et al. Long term follow up analysis following front line therapy with dexamethasone or dexamethasone plus rituximab in adults with primary immune thrombocytopenia. Presented at the American Society of Hematology Annual Meeting; December 6, 2009; New Orleans, LA. Abstract 2415. 7. Mazzucconi MG, Fazi P, Bernasconi S, et al. Therapy with high-dose dexamethasone (HSD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007; 109:1401-1407. 8. Kuter DJ, Rummel MJ, Boccia RV, et al. Comparison of splenectomy and treatment failure incidence in nonsplenectomized patients with immune thrombocytopenia (ITP) receiving romiplostim or medical standard of care: 1year treatment and 6-month safety follow-up. Presented at the American Society of Hematology Annual Meeting; December 7, 2009; New Orleans, LA. Abstract 679. 9. Lyons RM, Boccia RV, Macik G, et al. Home administration of romiplostim by patients with chronic immune thrombocytopenia (ITP). Presented at the American Society of Hematology Annual Meeting; December 7, 2009; New Orleans, LA. Abstract 3510. 10. Bussel JB, Kuter DJ, Newland A, et al. Longterm efficacy and safety of romiplostim for the treatment of patients with chronic immune thrombocytopenia (ITP): 5-year update from an open-label extension study. Presented at the American Society of Hematology Annual Meeting; December 7, 2009; New Orleans, LA. Abstract 681. 11. Weitz IC, Sanz MA, Henry DH, et al. Evaluation of bleeding-related episodes in patients with chronic immune thrombocytopenia (ITP) treated with romiplostim in two phase 3 placebo-controlled clinical trials. Presented at the American Society of
Hematology Annual Meeting; December 8, 2009; New Orleans, LA. Abstract 891. 12. Buchanan GR, Bomgaars L, Bussel JB, et al. A randomized double-blind, placebo-controlled phase 1/2 study to determine the safety and efficacy of romiplostim in children with chronic immune (idiopathic) thrombocytopenic purpura (ITP). Presented at the American Society of Hematology Annual Meeting; December 7, 2009; New Orleans, LA. Abstract 680. 13. Saleh MN, Bussel JB, Cheng G, et al. Longterm treatment of chronic immune thrombocytopenic purpura with oral eltrombopag: results from the EXTEND study. Presented at the American Society of Hematology Annual Meeting; December 7, 2009; New Orleans, LA. Abstract 682. 14. Saleh MN, Bussel JB, Meyer O, et al. Results of bone marrow examinations in patients with chronic immune thrombocytopenic purpura treated with eltrombopag. Presented at the American Society of Hematology Annual Meeting; December 5, 2009; New Orleans, LA. Abstract 1326. 15. Maddrey WC, Cheng G, Khelif A, et al. Evaluation of hepatobiliary parameters during eltrombopag treatment in patients with chronic immune thrombocytopenic purpura. Presented at the American Society of Hematology Annual Meeting; December 6, 2009; New Orleans, LA. Abstract 2410. 16. Fogarty PF. Chronic immune thrombocytopenia in adults: epidemiology and clinical presentation. Hematol Oncol Clin North Am. 2009; 23:1213-1221. 17. Cines DB, Yasothan U, Kirkpatrick P. Romiplostim. Nat Rev Drug Discov. 2008;7:887-888. 18. Saleh MN, Fisher M, Grotzinger KM. Analysis of the impact and burden of illness of adult chronic ITP in the US. Curr Med Res Opin. 2009;25:2961-2969. 19. Danese MD, Lindquist K, Gleeson M, et al. Cost and mortality associated with hospitalizations in patients with immune thrombocytopenic purpura. Am J Hematol. 2009;84:631-635. 20. Goodman M. Market watch: specialty pharmaceuticals to provide majority of sales by 2012. Nat Rev Drug Discov. 2009;8:184. 21. McDonald RC. Managing the intersection of medical and pharmacy benefits. J Manag Care Pharm. 2008;14(suppl 4):S7-S11. 22. Mullins CD, Lavallee DC, Pradel FG, et al. Health plans’ strategies for managing outpatient specialty pharmaceuticals. Health Aff (Millwood). 2006;25:1332-1339. 23. Stern D. Benefit design innovations to manage specialty pharmaceuticals. J Manag Care Pharm. 2008;14(suppl 4):S12-S16. 24. Willey VJ, Pollack MF, Lednar WM, et al. Costs of severely ill members and specialty medication use in a commercially insured population. Health Aff (Millwood). 2008;27:824-834. 25. Gleason PP, Starner CI, Gunderson BW, et al. Association of prescription abandonment with cost share for high-cost specialty pharmacy medications. J Manag Care Pharm. 2009;15: 648-658.
October Highlights from ASCO 2010: An Update for Payers and Pharmacists on Breast Cancer
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value-focused www.ValueBasedCancer.com www.ValueBasedCancer.com
New NewTools ToolsArriving ArrivingtotoMeasure Measureand and NCCN NCCNRoundtable: Roundtable:Clinical Clinicaland and Manage Economic ManageChemotherapy ChemotherapyCare Care EconomicIssues IssuesImpacting Impacting Business, Cancer Business,clinical clinicalconcerns concernsnow nowconnected connectedinin CancerCare CareDelivery Delivery value-focused value-focusedapproach approach ByBy Daniel Denvir Daniel Denvir
Baltimore, MDâ€”A long-held business Baltimore, MDâ€”A long-held business truism is is that â€œifâ€œif you canâ€™t measure it, it, truism that you canâ€™t measure you it.â€?it.â€? The application youcanâ€™t canâ€™tmanage manage The application ofofthis thisbelief beliefto tothetheoncology oncologysetting setting was of of thethe wasdemonstrated demonstratedat ata session a session Association AssociationofofCommunity CommunityCancer Cancer Cen tersâ€™ 36th Annual National Cen tersâ€™(ACCC) (ACCC) 36th Annual National Meeting. Kimberly Bergstrom, PharmD, Meeting. Kimberly Bergstrom, PharmD, chief chiefclinical clinicalofficer officerforforMcKesson McKesson Specialty Care Solutions, told attendees Specialty Care Solutions, told attendees ofof thethe growing importance of of developing growing importance developing and andusing usingstandardized standardizedchemotherapy chemotherapy treatment regimens, and of of thethe tools that treatment regimens, and tools that
clinical practice guidelines
â€œCollision â€œCollisioncourseâ€? courseâ€?ininsight sight cancan benchmark performance andand foster benchmark performance foster compliance with treatment guidelines. Dr DrGoodman Audrey Andrews Goodman compliance with treatment guidelines. By By Audrey Andrews Public and private payers areare movalluded to atolevel Public and private payers movalluded a level ingingto tocontrol exploding healthcare thatthat control exploding healthcare Hollywood, Hollywood,FLâ€”Clinical FLâ€”Clinicalpractice practice of frustration of frustration costs, told attendees, issued by by thethe National never been guidelines issued National hashas never been costs,DrDrBergstrom Bergstrom told attendees, guidelines and control in in cancer andbecause becauseincreased increasedcost cost control Comprehensive ComprehensiveCancer CancerNetwork Network higher higher cancer â€œToo many was areare followed by by conscienwasinevitable, inevitable,it itis isin inprovidersâ€™ providersâ€™ (NCCN) (NCCN) followed conscien- care. care. â€œToo many interest to get a seat at the table. tious oncologists in their everyday patients are still interest to get a seat at the table. tious oncologists in their everyday patients are still areare developed young. WeWe â€œItâ€œIt is is anan important topic, because dying young. important topic, because practice, practice,butbutthey they developed dying this is one of of those things, if we donâ€™t on on clinical efficacy andand without innovations andand a cure,â€? he said. this is one those things, if we donâ€™t based based clinical efficacy without need need innovations a cure,â€? he said. getget a handle on it, itâ€™s going to happen regard to to costs. At At a roundtable held thethe inadequacy of current treata handle on it, itâ€™s going to happen regard costs. a roundtable held ButBut inadequacy of current treatments for cancer is no the the main to to us,â€? she said. â€œPeople and groups during the NCCNâ€™s 15th Annual us,â€? she said. â€œPeople and groups during the NCCNâ€™s 15th Annual ments for cancer is longer no longer main and organizations areare going to to start Equally challenging, he sugproblem. Equally challenging, he sugand organizations going start Conference, Conference, moderator moderator Clifford Clifford problem. is finding a means to pay for for dictating how wewe provide cancer care, PhD, Senior Vice President dictating how provide cancer care, Goodman, Goodman, PhD, Senior Vice President gested, gested, is finding a means to pay and we canâ€™t let that happen.â€? at The Lewin Group, predicted, â€œThe the ever-costlier care that threatens to and we canâ€™t let that happen.â€? at The Lewin Group, predicted, â€œThe the ever-costlier care that threatens to appropriate use of evidence-based bankrupt the healthcare system. Continued on page 8 appropriate use of evidence-based bankrupt the healthcare system. Continued on page 8 guidelines is on a collision course As society struggles to find soluAs society struggles to find soluguidelines is on a collision course with the financial nonsustainability of tions, â€œthe ground is shaking beneath with the financial nonsustainability of tions, â€œthe ground is shaking beneath the healthcare system.â€? us,â€? Dr Goodman commented. the healthcare system.â€? us,â€? Dr Goodman commented.
Value-Based Value-BasedCancer CancerCare Care will willbebeatatthe theASCO ASCOAnnual Annual Meeting, June 4-8, in Chicago. Meeting, June 4-8, in Chicago.
Continued on page 19 Continued on page 19
Please visit usus atat booth 18121 Please visit booth 18121
SEER-Medicare SEER-MedicareDatabase DatabaseAnalysis Analysis Confirms Expensive Prostate Confirms Expensive Prostate Breast BreastCancer CancerSurvival SurvivalImproves, Improves, Cancers CancersGaining GainingSupremacy Supremacy Photo by ÂŠ ASCO/Todd Buchanan 2009 Photo by ÂŠ ASCO/Todd Buchanan 2009
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Breast Cancer Conference (EBCC7). Breast Cancer Conference (EBCC7). This improvement, the researchers By Rosemary Frei, MSc This improvement, the researchers By Rosemary Frei, MSc Barcelonaâ€”Survival for patients with suggest, is due to increased use of The 2010 Genitourinary Cancers Barcelonaâ€”Survival with anthracyclines suggest, is due to rise increased use of San Francisco, CAâ€”The popularity of The 2010 Progress Genitourinary Cancers metastatic breast cancerfor haspatients improved and the of targeted Symposium: in Multi San Francisco, CAâ€”The metastatic breast has improved anthracyclines and the rise of targeted minimally Symposium: Progresswas in held Multidramatically in the cancer last 20 years, espe- therapies. Management invasive radical popularity prostatec- of disciplinary minimally invasive radical prostatecdramatically in the last 20 years, espetherapies. disciplinary Management cially in the subgroup of patients with â€œThere is no doubt that trastuzu- tomy (MIRP), intensity-modulated March 5-7 in San Francisco. Allwas ses-held tomy (MIRP), intensity-modulated cially in the subgroup of patients with â€œThere is no doubt that trastuzu March 5-7 in San Francisco. All HER2-positive tumors, according to mab (Herceptin), which targets the radiation therapy (IMRT), and of sions emphasized a multidisciplinarysesradiation therapy (IMRT), and of approach HER2-positive mab gene, (Herceptin), which important targets the brachytherapy sions emphasized a multidisciplinary research presentedtumors, at the 7thaccording European to HER2 is the most to care; a number of them combined with IMRT combined with IMRT research presented at the 7th European HER2 gene, is the most important forbrachytherapy approach to cost care;and a number of them brought out the value issues prostate cancer started to take off Continued on page 27 for 2002, prostate cancer started analysis to take off associated broughtwith out the cost for andgenitourivalue issues Continued on page 27 after caring a new database after 2002, a new database analysis associated with caring for genitourinary cancers. has confirmed. hasthe confirmed. nary cancers. At American Society of Clinical At the American Society of Can Clinical Oncologyâ€™s 2010 Genitourinary - and Womenâ€™s Hospital, Harvard Oncologyâ€™s 2010Paul Genitourinary Can- Medical and Womenâ€™s Hospital, Harvard cers Symposium, L. Nguyen, School, Boston, and his cocerspresented Symposium, Nguyen, Medical School, his cofoundBoston, MIRP and jumped MD, the Paul resultsL. of his investigators MD, analysis presentedof the investigators found MIRP jumped teamâ€™s dataresults from of thehis from 1.5% of radical prostatectomies teamâ€™s analysis of dataand from from of 28.7% radicalinprostatectomies Surveillance, Epidemiology Endthe (RPs) in 1.5% 2002 to 2005. They Surveillance, Epidemiology and End also(RPs) in 2002 28.7% in 2005. They Results (SEER)-Medicare database. found that to IMRT soared from also found that IMRT treatments soared from Results (SEER)-Medicare Dr Nguyen, director of database. Prostate 8.7% of external radiation Dr Nguyen, director of Prostate for 8.7% of external radiation treatments prostate cancer to 81.7%. In addiBrachytherapy, Dana-Farber/Brigham Brachytherapy, Dana-Farber/Brigham for prostate cancer to 81.7%. In 24 addiContinued on page
By Colin Gittens By Colin Gittens
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A new publication for your new vocabulary
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LeAnn Norris Wins New Practitioner Award By Karen Rosenberg
he Hematology/Oncology Phar macy Association (HOPA) New Practitioner Award recognizes a HOPA member early in his or her career who has made a significant contribution to developing or supporting clinical hematology/oncology pharmacy services. This year’s recipient, LeAnn Norris, PharmD, BCPS, BCOP, is assistant professor of clinical pharmacy and outcomes sciences at the South Carolina College of Pharmacy in Columbia and a member of The Oncology Pharmacist editorial board.
completed my PGY2 oncology residency in 2006 and debated staying on in Greensboro or taking a faculty position in South Carolina. I knew that I enjoyed working with students and thought that I would enjoy a career in academia, so I decided to move back to South Carolina and take the position in Columbia in 2006.
I currently cover two services at the hospital here, the outpatient chemotherapy clinic and the hospice and palliative care unit. I’m on service 12 months a year, 20 hours a week per month so I have to try to squeeze in everything in 1 day. Every day is different and every day has a new challenge, and I love that.
Why did you choose to specialize in oncology? I have always had an interest in oncology but I also considered specializing in infectious diseases. Once Please tell us about the I met Lew Iacovelli and career that has led up to your saw the role he has with his winning the Outstanding New patients at the cancer cenPractitioner Award. ter, the positive influence I graduated from the College he has in his patients’ of Pharmacy at the University of lives, and his relationship LeAnn Norris, South Carolina in Columbia, with some of the physiPharmD, BCPS, which is now known as the cians he works with, I BCOP South Carolina College of knew immediately that Pharmacy, in 2004 and completed my that was what I wanted to do. He’s PGY1 pharmacy residency at the Moses been an excellent role model and menCone Health Center in Greensboro, tor for me. North Carolina. Then I stayed on for my PGY2 at the regional cancer center In addition to your teaching duties, within the Moses Cone Health System, do you have any direct contact with where I trained under Lew Iacovelli. I patients?
Do you encourage your students to go on for specialty training? I definitely advise all of my students that if they’re even thinking about residency, they need to pursue it. My opinion about specialty residencies is that if you have a very strong interest in an area, I highly encourage you to go on to a second year of residency, with the understanding that your job possibilities may sometimes be more limited. It’s a very rewarding experience, and generally there are no regrets in spending that extra year to pursue additional training. A lot of students on my rotation will go on to work in a community pharmacy or a chain drugstore. Even if they have no interest in pursuing a career in oncology, I encourage them to make the most out of their rotation when they’re on service with me because everyone is
affected by cancer in some way. I always try to make sure that my students can have an educational conversation with patients and that patients can see them as a good resource, even if it’s just a matter of answering questions for a cancer patient who’s coming in to pick up a prescription for nausea medication. You learn how to counsel patients in pharmacy school, but sometimes when patients are very sick there’s a different way of communicating with them. I personally had to learn how to counsel patients all over again when I started in oncology. Another piece of advice that I would give to students who are perhaps in a PGY1 residency and are interested in pursuing a career in oncology is that networking is key to advancing in this field because just by meeting people, you open doors up to potential jobs or potential collaborations in research. I’ve been a member of HOPA since my first year of residency. It offers a great resource not just for specialists or people who have done oncology training, but also for people who have started in a new oncology pharmacy position, whether they have been practicing in another area for some time or are just starting out in their career. ●
Nab-paclitaxel Plus Gemcitabine May Help Patients with Advanced Pancreatic Cancer By Jill Stein
WASHINGTON, DC—Nanoparticle albumin-bound paclitaxel, often referred to as nab-paclitaxel, combined with gemcitabine boosts survival when given as first-line treatment in patients with advanced pancreatic cancer, according to results released at the 101st annual meeting of the American Association for Cancer Research. “Our study found that the combination of nab-paclitaxel at the maximum tolerated dose plus gemcitabine more than doubled the length of survival that has been reported with solo gemcitabine, which is the treatment standard in this population,” said Daniel Von Hoff, MD, FACP, physician-inchief and senior investigator at the Translational Genomics Research Institute in Phoenix, Arizona. Von Hoff presented findings in 67 patients treated with the combination of nanoparticle albumin-bound paclitaxel and gemcitabine as part of a phase
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1/2 open-label study. Nanoparticle albumin-bound paclitaxel is a novel formulation of paclitaxel that allows for the preferential delivery of active drug to the site of the tumor. “Pancreatic cancer has the worst survivorship of any cancer in the world, with a 1-year survival rate in metastatic disease of about 15% and a 2-year survival rate of less than 5%,” Von Hoff said. Presently, the disease affects approximately 259,000 people worldwide and more than 42,000 people in the United States. In the phase 1 dose-escalation portion of the study, nanoparticle albuminbound paclitaxel (100 mg/m2, 125 mg/m2, 150 mg/m2) in combination with gemcitabine 1000 mg/m2 was administered weekly for 3 weeks with 1 week of rest. The 125-mg/m2 dose was identified as the maximum tolerated dose. Of 44 patients who were treated with
nanoparticle albumin-bound paclitaxel at the maximum tolerated dose with gemcitabine 1000 mg/m2, the median overall length of survival was 12.2 months. “To date, the longest survival that has been reported with gemcit abine alone has been 5.65 months,” Von Hoff said. Of patients treated with the combination therapy, the overall response rate was 50% and the disease control rate was 68%. A disease control rate was defined as a complete response, partial response, or stable disease for 16 weeks or longer according to response evaluation criteria in solid tumor criteria. Overall, three patients in the study population of 67 had a complete response. Also, all patients who had nanoparticle albumin-bound paclitaxel at the recommended dose who were screened for the tumor marker carbohydrate antigen (CA) 19-9 had a decrease in tumor
marker level of a magnitude that has been shown to correlate with improved overall survival. CA 19-9 has been shown to be highly specific and sensitive for pancreatic cancer. Notably, about two thirds of patients had CA 19-9 decreases of greater than 70%, which correlated with a median overall survival of 15.6%. “This is very dramatic,” Von Hoff noted. “In fact, our study team involving doctors, research nurses, data managers, and so on come from very well-respected cancer centers and have ‘deep’ clinical experience, and we have never seen this level of activity before.” The nanoparticle albumin-bound paclitaxel–gemcitabine combination is now being tested in patients with advanced pancreatic cancer in a phase 3 trial. “Although there have been a lot of false starts in the past and we’re acutely aware of that possibility, we’re definitely encouraged by our findings,” he said. ●
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ONCOLOGY DRUG CODES Supplied by: RJ Health Systems
Medications Used for the Treatment of Colorectal Cancer Colon cancer forms in the tissues of the colon (the longest part of the large intestine). Most colon cancers are adenocarcinomas (cancers that begin in cells that make and release mucus and other fluids). Rectal cancer forms in the tissues of the rectum (the last several inches of the large intestine closest to the anus). The following sections will assist healthcare professionals and payers by providing appropriate coding, billing, and reimbursement information associated with the management of colorectal cancer. The following sections include: • Associated ICD-9-CM codes used for the classification of colorectal cancer • Drugs that have been FDA-approved in the treatment of colorectal cancer • Drugs that are Compendia listed for off-label use for colorectal cancer based on clinical studies that suggest beneficial use in some cases. Please note: if a check mark appears in the FDA column it will NOT appear in the compendia off-label use column • Corresponding HCPCS/CPT® codes and code descriptions • Current Code Price (AWP-based pricing) • Most recent ASP plus 6% (Medicare allowable), if applicable • Possible CPT® Administration Codes for each medication
generic (Brand) name
HCPCS code: code description
bacillus Calmette-Guerin (Tice BCG, TheraCys) bevacizumab (Avastin) capecitabine (Xeloda) capecitabine (Xeloda) carmustine (BiCNU) cetuximab (Erbitux) cisplatin (Platinol AQ) cisplatin (Platinol AQ)
J9031: bCG (intravesical), per installation J9035: injection, bevacizumab, 10 mg J8520: capecitabine, oral, 150 mg J8521: capecitabine, oral, 500 mg J9050: injection, carmustine, 100 mg J9055: injection, cetuximab, 10 mg J9060: cisplatin, powder or solution, per 10 mg J9062: cisplatin, 50 mg
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Associated ICD-9-CM Codes Used for Colorectal Cancer 153 Malignant neoplasm of colon Excludes: benign carcinoid tumor of colon (209.50-209.56) malignant carcinoid tumor of colon (209.10-209.16) 153.0 Hepatic flexure 153.1 Transverse colon 153.2 Descending colon Left colon 153.3 Sigmoid colon Sigmoid (flexure) Excludes: rectosigmoid function (154.0) 153.4 Cecum Ileocecal valve 153.5 Appendix 153.6 Ascending colon Right colon 153.7 Splenic flexure 153.8 Other specified sites of large intestine Malignant neoplasm of contiguous or overlapping sites of colon whose point of origin cannot be determined Excludes: ileocecal valve (153.4) rectosigmoid junction (154.0) 153.9 Colon, unspecified Large intestine, not otherwise specified 154 Malignant neoplasm of rectum, rectosigmoid junction, and anus Excludes: benign carcinoid tumor of rectum (209.57) malignant carcinoid tumor of rectum (209.17) 154.0 Rectosigmoid junction Colon with rectum Rectosigmoid (colon) 154.1 Rectum Rectal ampulla 154.8 Other Anorectum Cloacogenic zone Malignant neoplasm of contiguous or overlapping sites of rectum, rectosigmoid junction, and anus whose point of origin cannot be determined
FDAapproved for colorectal cancer
Compendia listed off-label use for colorectal cancera
Current code price (AWP-based pricing), effective 7/1/10
Medicare allowable (ASP + 6%), effective 7/1/10-9/30/10
CPT ® administration codes
96409, 96413, 96415
96409, 96413, 96415
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ONCOLOGY DRUG CODES Supplied by: RJ Health Systems
generic (Brand) name
HCPCS code: code description
doxorubicin (Adriamycin) floxuridine (FUDR) fluorouracil (Adrucil) irinotecan (Camptosar) leucovorin calcium (Wellcovorin)
J9000: injection, doxorubicin hydrochloride, 10 mg J9200: injection, floxuridine, 500 mg J9190: injection fluorouracil, 500 mg J9206: injection, irinotecan, 20 mg J0640: injection, leucovorin calcium, per 50 mg J0641: injection, levoleucovorin calcium, 0.5 mg
levoleucovorin calcium (Fusilev) lomustine (CeeNu) lomustine (CeeNu) methotrexate sodium methotrexate sodium mitomycin (Mutamycin) mitomycin (Mutamycin) mitomycin (Mutamycin) mitoxantrone (Novantrone) oxaliplatin (Eloxatin) panitumumab (Vectibix) pemetrexed (Alimta) teniposide (Vumon) topotecan (Hycamtin) topotecan (Hycamtin) vinCRIStine (Vincasar) vinCRIStine (Vincasar) vinCRIStine (Vincasar)
FDAapproved for colorectal cancer
Compendia listed off-label use for colorectal cancera
Current code price (AWP-based pricing), effective 7/1/10
Medicare allowable (ASP + 6%), effective 7/1/10-9/30/10
CPT ® administration codes
96372, 96374, 96409
J8999b: prescription drug, oral, chemotherapeutic, not otherwise specified S0178: lomustine, oral, 10 mg
NDC level pricing $10.59
J9250: methotrexate sodium, 5 mg J9260: methotrexate sodium, 50 mg J9280: mitomycin, 5 mg
NDC level pricing S0178: not payable by Medicare $0.19
96372, 96374, 96401, 96409, 96450 96372, 96374, 96401, 96409, 96450 96409
J9290: mitomycin, 20 mg
J9291: mitomycin, 40 mg
J9293: injection, mitoxantrone hydrochloride, per 5 mg J9263: injection, oxaliplatin, 0.5 mg J9303: injection, panitumumab, 10 mg J9305: injection, pemetrexed, 10 mg Q2017: injection, teniposide, 50 mg J8705: topotecan, oral, 0.25 mg J9350: injection topotecan, 4 mg J9370: vincristine sulfate, 1 mg J9375: vincristine sulfate, 2 mg J9380: vincristine sulfate, 5 mg
96409 96422, 96423, 96425
96413, 96415 N/A
Continued on page 22
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ONCOLOGY DRUG CODES Supplied by: RJ Health Systems Continued from page 21
Compendia references available upon request. When billing a non-classified medication using a CMS 1500 claim form you must include both the HCPCS code (ie, J8999 for CeeNu) in Column 24D and the drug name, strength, and National Drug Code (NDC) in Box 19 in order to ensure appropriate reimbursement. a
References HCPCS Level II Expert 2010 • Current Procedural Terminology (CPT®) 2010 • ICD-9-CM for Professionals Volumes 1 & 2 2010 • The Drug Reimbursement Coding and Pricing Guide by RJ Health Systems International, LLC, Volume 7, Number 3, 3rd Quarter 2010 • FDA-approved indication (from product’s prescribing information) • National Cancer Institute® • www.ReimbursementCodes.com powered by RJ Health Systems International, LLC, Wethersfield, Connecticut • CMS (Centers for Medicare& Medicaid Services)—Medicare Allowable 3rd Quarter 2010 (effective dates 7/1/10-9/30/10). Prices listed herein are effective as of July 1, 2010. ASP indicates average sales price; AWP, average wholesale price; CMS, Centers for Medicare & Medicaid Services; CPT ®, Current Procedural Terminology; FDA, US Food and Drug Administration; HCPCS, Healthcare Common Procedure Coding System; NDC, National Drug Code.
This information was supplied by:
PO BOX 290616, Wethersfield, CT 06109 T: (860) 563-1223 • F: (860) 563-1650 www.RJHealthSystems.com
Postmenopausal Women with Breast Cancer Receiving an Aromatase Inhibitor May Be at Increased Risk for Bone Loss
See also page 31.
By John Schieszer
SAN DIEGO—Postmenopausal women with breast cancer receiving an aromatase inhibitor (AI) may experience significant bone loss and may need to have their bone health monitored more closely, according to new data presented at the Endocrine Society’s 92nd Annual Meeting and Expo. Researchers at the University of Connecticut have found that women with normal or mild/moderate bone mineral density (BMD) at initiation of AI treatment appear to have significant bone loss at the lumbar spine, femoral neck, and total hip over the first year of therapy. Markers of bone turnover, including serum C-telopeptide collagen crosslinks (sCTx) and serum procollagen type 1 amino-terminal propeptide (P1NP), increased over the first year of treatment. Women with the greatest increase in vitamin D levels had the lowest increase in markers for bone turnover. Currently, AIs are considered firstline therapy for the treatment of hormone-sensitive breast cancer. Large clinical trials have shown, however, that a reduction in serum estrogen levels by these medications leads to substantial bone loss. Antiresorptive medications are available to prevent this type of bone loss, but they are expensive and they also have significant side effects.
August 2010 I VOL 3, NO 5
Treating all women with breast cancer with an antiresorptive agent while they are receiving letrozole or anastrozole may not be the most cost-effective and appropriate approach. Researchers at the University of Connecticut hypothesized that women who demonstrate high bone turnover,
after treatment with aromatase inhibitors. The interesting thing we found is that women who had the greatest increase in vitamin D levels from baseline to 6 months had the least increase in uNTx, which is a bone resorption marker,” said study coinvestigator Faryal Mirza, MD, an assistant professor
“This would suggest that replacement with vitamin D may be a good way to decrease bone loss as a result of aromatase inhibitor therapy.” —Faryal Mirza, MD
as reflected by bone turnover markers in the first 3 to 6 months on treatment, will have greater bone loss. The current study evaluated women during their first year of treatment with anastrozole or letrozole, receiving adequate calcium and vitamin D. All the subjects had normal or moderately low bone mass at the start of the study. The investigators looked at whether early changes in bone turnover markers correlated with bone loss at 1 year. “We found there were declines in bone density at 3 months and 6 months
of medicine at the University of Connecticut Health Center, Farmington. “This would suggest that replacement with vitamin D may be a good way to decrease bone loss as a result of aromatase inhibitor therapy.” Mirza and her colleagues reported at this meeting on the first 13 women who have completed the study. They hope to soon have more data on the remaining subjects in the trial. The investigators measured hormones and bone turnover markers at baseline, 1, 3, 6, and 12 months. The hormones
included estradiol (E2) and sex hormone– binding globulin. BMD was measured at baseline and then again at 6 and 12 months at the lumbar spine, femoral neck, and total hip using dualenergy x-ray absorptiometry. The researchers found that lumbar spine BMD declined by 2% and total hip BMD decreased by 1.4% at 6 months and by 3.4% and 2.0%, respectively, at 12 months. The patients with the highest E2 levels had the lowest sCTx, and the patients with the largest increase in serum vitamin D levels were found to have the least increase at 3 months in uNTx from baseline. “This is a small study and it needs to be validated in a larger subset of patients,” said Mirza in an interview with The Oncology Pharmacist. “To our knowledge, this is the first study to show this. A lot of women are receiving aromatase inhibitors and so this is a very important issue, and the risk of fracture has to be addressed.” She said this study is an important first step for identifying which women on AIs should or should not be put on a bisphosphonate. Mirza said that it is hoped that this study can point to ways of treating bone loss while delaying the need for bisphosphonates in this patient population. ●
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Pharmacy Education and Training Time Out for Teaching... Continued from cover • Does the learner leave my rotation valuing the contributions made to patient care? Although imparting clinical knowledge is an invaluable contribution of any preceptor, the answers to these questions are what often turn a basic experience into one learners will remember for the rest of their careers.
related complications in patients with cancer. The major difference in these two objectives is the replacement of the vague term “appropriateness” with better defined activities the learner is expected to apply and practice. If treating a patient with pain, for instance, a plan should be ready in case the implemented plan fails
All goals and expectations must be clearly laid out for learners at the beginning of the experience. Each of these must be measurable and realistic.
Setting baseline expectations to control the pain. If a patient started Have you ever limited the feedback chemotherapy, a plan should be in place that you wanted to give a learner? If you to treat common toxicities. If switching a have ever delivered feedback by begin- patient to oral medications for discharge, ning with “I should have emphasized this the patient’s ability to obtain that medat the beginning of the rotation” or “I ication as an outpatient should be conknow I wasn’t able to spend as much time firmed. If an antibiotic is initiated, an with you as I would have liked,” then you alternative plan should be in place in case have. You know exactly the things you the patient develops a rash or his or her would like to have said to a learner, but condition worsens. Although this objecfor a variety of reasons you didn’t. Or if tive is not perfect by any means, it you did, you portrayed the feedback in a emphasizes systematic, directed applicaway where you, the preceptor, take partial tion of preestablished expectations. responsibility for failure to meet expectations. This is one of the biggest dis- Individualizing the learning plan Consider the background of the learner. A services you can do to a learner. Although it may be difficult to deliver preceptor should not expect the same feedback, it is our responsibility to give from a pharmacy student as from a speour learners honest, constructive feed- cialty resident. One must also consider back. Setting up well-defined baseline each learner’s timeframe in the educaexpectations is the best way to lay this tional year and his or her previous experiences. For example, any learner’s first foundation. All goals and expectations must be experience in a new environment, regardless of how “good” the clearly laid out for learners learner is, will need to include at the beginning of the time to focus on issues that have experience. Each of these nothing to do with oncology. must be measurable and Navigating the medical records realistic. In this way, when system, locating key locations you give feedback, you will throughout the practice, and be able to relate it directly identifying and communicating to one of the goals or expecwith appropriate healthcare protations clearly stated at the fessionals are all important onset of the experience. John M. Valgus, aspects that need to be addressed Consider this example of PharmD, BCOP for learners to be effective in two variations of a similar their role. One must also considlearning objective for an er the learner’s previous experience in oncology rotation: 1. Following completion of the rota- any particular setting. For example, a tion, the learner should be able to learner who has performed excellently in prospectively monitor drug thera- early rotations in pharmacy distribution py for appropriateness in the man- or ambulatory care may struggle with the agement of disease- and treat- first experience in an acute-care setting. ment-related complications in Finally, one must consider the learner’s previous experience in a specialty. A prepatients with cancer. 2. Following the completion of the ceptor should not have the same expecexperience, the learner should be tations for a learner who has completed able to prospectively monitor drug several previous oncology experiences as therapy for resolution/failure, toxici- for one who has not had exposure to ties, complications, and possible oncology since the third year in pharmatherapeutic alternatives in the man- cy school. Consider the needs of the learner. Needs agement of disease- and treatment-
August 2010 I VOL 3, NO 5
based on previous and future experiences should always be considered when setting objectives for any learner. One must identify any educational gaps that the particular experience or preceptor can fill. It is often beneficial to identify these needs early in the experience so the preceptor can set this up in advance. Having access to past evaluations as well as knowledge of future plans can greatly aid in this process but is often a barrier to implementing this strategy. It is also important to identify self-perceived areas of improvement. One can ask learners to identify things they would like to develop, not only over the course of the current experience, but also throughout the year. Learners often may not know that opportunities exist within a given experience but, if given the chance to identify areas of development, may discover that such opportunities exist. Consider the goals of the learner. Regardless of a learner’s desired career path, it is the responsibility of the preceptor to respect each learner’s professional development. One can ask learners what tools are going to be needed to be successful in their chosen career. I am always struck by the number of learners who, when asked what they want to do with their career, state that they are too late in the course of their training to pursue a given career path. Preceptors should consider it their responsibility to set up learners not only to succeed over the course of their current experience, but also to lead them toward success in their desired career path. It was not until late in my third year of pharmacy school that I made the decision to pursue residency training. At the time, I had decent grades but no significant involvement in professional organizations and no student leadership experience. When compared with others in my class, I felt there was no way I could compete for a residency. I was fortunate to have several preceptors who were interested in my career aspirations and were willing to mentor me in achieving residency training. Before applications were due, I was able to add several projects and two publications to my experience with subsequent letters of recommendation. In the end, I was granted interviews at some of the top programs in the country and ended up matching with a great program. When I look back, I know this would not have been the case without the help of my very dedicated preceptors who made sure I was set up to succeed not only during their rotation but also in my chosen career path. This is just my example of how influential, dedicated preceptors can be in helping learners achieve their career goals and establish lasting relationships.
Delivering proper feedback Almost 30 years ago, Dr Jack Ende provided suggestions for giving feedback in clinical medical education.1 Although the terms “feedback” and “evaluation” are often used interchangeably, he made key distinctions between the two that continue to mold the way I function as a preceptor. Some of these distinctions include that feedback presents facts, not judgment, and that feedback allows learners to remain on course toward their goals. In contrast, evaluations often include judgment of performance, are often summative, and describe how well or poorly a learner is meeting goals. The delivery of feedback is also extremely important. Feedback must be well timed. Although, giving feedback on rounds in front of the medical team may not be appropriate, neither is waiting until the end of the rotation when learners do not have the ability to do anything to correct their actions. Whenever possible, feedback should be based on firsthand knowledge and should focus on specific performance, not generalizations. Relying on information passed from others clouds the facts of a given situation. Specific examples of a learner’s actions emphasize how these actions are related to the given expectations. Finally, feedback should be regulated in quantity. Although inexperienced learners may have plenty of room for improvement, feedback overload or destructive delivery can lead to hopelessness and desensitization. There are many possible consequences to allowing learners to pass through an experience without proper feedback. Not only can mistakes go uncorrected, but good performance may not be reinforced. If proper feedback is not given, less forceful learners can get lost and overindependence gains unwarranted approval. Serving as a role model Like it or not, we are role models for our young learners. Many of us have been molded by the people who have surrounded us. Although you may not have had the perfect role model, you can pick and choose the characteristics of individuals that are appreciated the most and use them to create the professional you would like to be. Are you pushing yourself as much as you push your learners? Do you have a steep learning curve? Are you getting the most out of your role? If not, your learners will know, and they may not get the most of their experience. How is your attitude? I have residents and new preceptors who have the same attitude about the department or Continued on page 27
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The Essential Role of Immunotherapy in Follicular Lymphoma Management LOG ON TODAY TO PARTICIPATE www.coexm.com/ace03.asp Release Date: March 19, 2010 Expiration Date: March 18, 2011
TARGET AUDIENCE This activity is intended for hematologists, oncologists and other healthcare professionals who are involved with the care of patients with follicular lymphoma.
STATEMENT OF NEED Non-Hodgkin's lymphoma (NHL), the most common hematologic malignancy, represents a large proportion of the case load for the typical oncology practitioner. That load is likely to grow, since NHL is increasing in prevalence. The introduction of rituximab, the monoclonal antibody against CD20, changed the treatment landscape of lymphoma and it has been advanced further by immunotherapies that combine CD20-directed targeting with radiotherapy. The recent rapid advances in therapeutics and impressive research across this broad, heterogeneous group of malignancies represent an educational challenge for the clinician trying to stay current and provide the most appropriate, up-to-date therapy tailored for the individual patient. Immunotherapy plays a key role at all stages of the disease in reaching the goal of the highest quality response.
EDUCATIONAL OBJECTIVES On completion of this activity, participants should be able to: • Define the goals of therapy for follicular lymphoma (FL) • Describe strategies for patient selection for immunotherapy (including radioimmunotherapy [RIT]), in both the up-front and relapsed/refractory setting • Define different immunotherapy approaches in terms of efficacy, safety, and tolerability • Propose strategies to overcome adverse events and access issues that create barriers to the provision of optimal immunotherapy in FL
FACULTY Stephanie A. Gregory, MD Professor of Medicine Director, Section of Hematology Rush University Medical Center Chicago, Illinois
David Maloney, MD, PhD Associate Professor of Medicine Division of Oncology University of Washington Member Fred Hutchinson Cancer Research Center Seattle, Washington
With commentary by: Peter S. Conti, MD, PhD Professor Nuclear Medicine Keck School of Medicine University of Southern California Los Angeles, California
This activity is supported by an educational grant from Spectrum Pharmaceuticals.
This activity has been approved for 1.0 AMA PRA Category 1 Credits™. For further information and to participate, please go to: www.coexm.com/ace03.asp
In collaboration with
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Cancer Center Profile Albert Einstein Cancer Center Joins the NCCCP Continued from cover
Dr William Tester, a medical oncologist, and Tiffany Raroha, an oncology social worker, counsel a patient.
groups, some of whom are uninsured or underinsured. But the staff believes they can do better. For example, radiation oncology “has advanced radiation treatment equipment for patient care,” Lawrence J. Solin, MD, FACR, FASTRO, chair, Department of Radiation Oncology, told The Oncology Pharmacist. “It is extremely important to make sure that our patients not only have access to treatment, but that we provide them with the support services to complete their prescribed therapy.” To help patients do
diagnosed patients as well as being able to do continuous follow-up of their psychosocial needs,” said Raroha. Einstein also plans to add patient navigators to help patients get through the system more easily. Enhancing quality For more than 20 years, Einstein has employed site-specific multidisciplinary cancer programs. For most disease sites, physicians and support staff meet and discuss all new cases as well as cases where a problem has arisen or a patient
“For those patients that are starting chemotherapy for the first time, we have developed what we call a patient teaching appointment. The patient comes in and has one-on-one time with a social worker, a treatment nurse, and a dietician.” —Tiffany Raroha, MSW
that, Einstein plans to expand its nutrition, dietary, and social services for patients undergoing radiation oncology. These expansions will go well beyond radiation oncology. “For those patients that are starting chemotherapy for the first time, we have developed what we call a patient teaching appointment. The patient comes in and has one-on-one time with a social worker, a treatment nurse, and a dietician,” explained Tiffany Raroha, MSW, who is one of two oncology social workers at Einstein. The center’s plan is to reach every patient starting a new cancer treatment, expanding social services not only to radiation oncology patients but also to surgical oncology patients. “We plan to be more proactive with doing psychosocial assessments up front with newly
August 2010 I VOL 3, NO 5
has a recurrence. These groups include more than just the medical, surgical, and radiation oncologists. In addition to these oncologists, for example, the lung cancer program has regular attendance by its thoracic surgeon, its pulmonologist, a research nurse, social services, and a pathologist, according to Tester. In the breast health program, 15 to 20 people meet every Wednesday, including representatives from breast surgery, medical oncology, radiation oncology, radiology, pathology, plastic surgery, genetics, and rehabilitation. “This is a great way to involve all the experts, so when a patient returns for her 1-week checkup after completing her surgery, and I tell her that she needs to see the medical oncologist, that physician has already fully reviewed her case. I can tell the
patient what the medical oncologist plans on giving her and which trials will be available to her,” said Lisa Jablon, MD, FACS, a breast surgeon who is director of the Breast Health Program. At present, Einstein has multidisciplinary programs in breast cancer, lung cancer, gastrointestinal cancer, and hematologic malignancies, and hopes to develop an active urologic program with the NCCCP funding. To integrate care further, Tester has one initiative he has been thinking about and is excited about the possibility of implementing now that Einstein is an NCCCP cancer center. “What we could do with NCCCP support is bring the patient into the multidisciplinary conferences. We have always discussed cases, reviewed pathology, radiologic imaging, and clinical trials that would be appropriate, but we have never actually brought the patient into the discussion room. Multidisciplinary care is an initiative that is important to the NCCCP, and we are planning and want to make that work. At the very least, we want to have a multidisciplinary clinic that meets after the tumor board meeting where the patient could actually meet three or four of the clinicians involved in his or her care. The presence of the patient will show him or her that our approach is truly multidisciplinary, and that his or her personal issues and input is considered in making final treatment decisions.” In addition, Einstein plans to incorporate more survivorship services. “Our plan is to offer survivorship strategies to all patients at the time of diagnosis and continue that through and beyond treatment,” said Tester. The NCCCP grant allows Einstein to hire a coordinator to run survivorship services. Jablon provided an illustration of how this would work in breast health: “We do have an active cancer program and social workers. Plus, different organizations like the American Cancer Society offer a lot of programs that are integrated with our local hospital, such as Reach to Recovery and Look Good…Feel Better. We would like to make survivorship even more of a focus for our patients after they have passed through their primary treatment. For example, I just got back from a conference where they talked a lot about how we don’t integrate improvements in exercise or weight control into our cancer population. Even though we tell our patients that they need to lose weight, we offer no specific, active programs for them to go out and do that. One of my thoughts is to go out into the community and organize walking groups of cancer survivors and people interested in cancer prevention to integrate exercise into the community practice.”
Clinical trials and biospecimen research Einstein has been active in clinical trials since it was originally funded by the NCI in 1972. “We have always had a strong commitment to offering patients state-of-the-art clinical trials, and I think that is exemplified by the array of clinical trials we offer through the Eastern Cooperative Oncology Group (ECOG), the Radiation Therapy Oncology Group (RTOG), and the National Surgical Adjuvant Breast and Bowel Project (NSABP),” Solin said. “One of the things we would like to do is enhance access to clinical trials for our population through the NCCCP grant.” Biospecimen collection, however, will be something new. “We have done a lot of clinical work at Einstein but not as much in the basic science arena,” said Tester in an interview with The Oncology Pharmacist. “But with the NCCCP to support our collection of biospecimens, we are going to be creating our own tissue bank and we are going to be able to be involved in more translational research activities.” For example, Einstein currently works in collaboration with Thomas Jefferson University, which has a strong basic science program and translational research. Tester believes that Einstein’s involvement in those types of research “could increase as we put aside tumor specimens and ship them for special molecular studies, and then tie that into clinical trials where we are going to evaluate the effect of certain new targeted therapies on patients according to which molecules are expressed by their tumors. With the assistance of Corrado Minimo, MD, and our pathology department, we plan to develop a strong biomarker program this summer.” To the future “Cancer affects not just the patient but the entire family as a unit. So our hope is to expand our program to meet the needs of not just the patient but the family unit. We are hoping we can provide a bereavement program for families of those unfortunate patients who lose the battle to cancer and, possibly, some programs that will meet the needs of children whose parents have cancer,” Raroha told The Oncology Pharmacist. ●
Did You Know? In 2005, only 0.08% of US women aged 40 to 79 years without a personal history of breast cancer took tamoxifen for prevention of breast cancer, according to National Health Interview Survey data.
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Investment Advisor or Financial Planner for Your Investments: Who Is Right for You? By Eileen Koutnik-Fotopoulos
he current economic recession may have you pondering whether you have enough money saved for retirement. If you are just starting out in your profession, you may wonder if you should postpone planning for your retirement until the economy bounces back. It is never too early to plan for the future, even if you can only put a small amount into your retirement plan at this juncture. When it comes to starting or continuing to invest in your retirement plan, you may want to consider the expertise of an investment advisor (often referred to as a broker) or financial planner. This may be a hard decision because there are so many of them. Let’s take a look at the difference between these professionals. Investment advisors are required to have licenses with the Financial Industry Regulatory Authority and register with the Securities and Exchange Commission. This distinction allows them to charge for advice or access to advice. Keep in mind that often these advisors work as an employee for large financial services or brokerage companies.
Financial planners usually help individuals with a range of money matters. When it comes to investments in the United States, you should look for a financial planner who has a Certified Financial Planner (CFP) certification. These professionals have passed an exam administered by the Certified Financial Planner Board of Standards that focuses on more than 100 topics of concern to the financial planning field. The CFP certification demonstrates a proven expertise within the financial planning profession. How do you go about finding the right financial professional? You will need to start by reviewing your personal financial situation, including income, debts, insurance, and cash reserve. This checklist should help you determine if an investment advisor or financial planner is better suited to meet your investment needs. • Determine what you want to accomplish. If your goal is long term, you want an individual with a strong background in financial plan-
ning. If you want to make a little money quickly, you want an individual with experience trading stocks. • Ask family, friends, and colleagues for referrals. For example, if a specific type of professional has been successful managing their finances. • Ask for professional recommendations from a certified accountant or lawyer. Professional associations such as the Financial Planning Association (www.fpanet.org) and National Association of Personal Financial Advisors (www.napfa.org) may offer guidance. • Prepare a list of questions and interview potential investment advisors and financial planners. Ask beforehand if there is a charge for this meeting. • Find out the fee structure. Some investment advisors charge a straight commission for every transaction. Other investment advisors may charge a fee based on the amount of money they are managing. A financial planner may charge an hourly rate.
Selecting a financial advisor or financial planner is a personal decision. Make sure you feel comfortable with the financial professional you have chosen to manage your investments. ●
Guidelines on Adjuvant Endocrine Therapy from the American Society of Clinical Oncology (ASCO). Optimal duration of use and specific incorporation strategies remain unresolved. The analyzed data suggest that including an AI as primary
monotherapy or as sequential treatment after 2 to 3 years of tamoxifen yields similar outcomes. Side effect profiles and patient preferences should be considered in deciding duration and timing of an AI (ASCO. July 12, 2010). ●
News Notes Thirdhand Smoke Identified as Health Hazard Residual nicotine from tobacco smoke sorbed to indoor surfaces was found to react with ambient nitrous acid to form carcinogenic tobacco-specific nitrosamines (TSNAs). This recently identified chemical reaction poses an unappreciated health hazard. This tobacco residue, termed “thirdhand smoke,” can enter the human body through dermal exposure, dust inhalation, and ingestion. Performing both laboratory and field testing, researchers developed a process to measure the presence of TSNAs on common indoor surfaces, including hair, skin, and cotton and in homes and on furniture. In laboratory testing using cellulose as a model indoor material, they found a >10-fold increase of surface bound TSNAs when sorbed secondhand smoke was exposed to 60 ppbv ambient nitrous acid for 3 hours (Sleiman M, et al. Proc Natl Acad Sci U S A. 2010;107:6576-6581).
Statin Use May Slow Prostate Cancer Progression after Radical Prostatectomy In men undergoing radical prostatectomy (RP), statin use was found to
be associated with a dose-dependent reduction in the risk of biochemical recurrence. Researchers evaluated the records of 1319 treated with RP, of whom 236 were taking statins at time of surgery. They found that statin use was associated with a 30% lower risk of prostate-specific antigen biochemical recurrence (HR, 0.70; 95% CI, 0.50-0.97; P = .03). The benefit of statin use was dose dependent relative to no statin use (dose equivalent <20 mg of simvastatin: HR, 1.08; 95% CI, 0.66-1.73; P = .78; dose equivalent = 20 mg simvastatin: HR, 0.57; 95% CI, 0.32-1.00; P = .05; dose equivalent >20 mg simvastatin: HR, 0.50; 95% CI, 0.27-0.93; P = .03). These finding will need to be confirmed (Hamilton RJ, et al. Cancer. 2010;116:3389-3398).
ASCO Guideline Update: AI Therapy for HR-positive Breast Cancer Postmenopausal women with hormone receptor (HR)-positive breast cancer should consider an aromatase inhibitor (AI) at some point during adjuvant treatment, according to the recently updated Clinical Practice
PHARMACY EDUCATION AND TRAINING
Time Out for Teaching... Continued from page 24 our practice model as our preceptors who have been here for 20 years. How does that happen in 3 months? Most likely, it is not from their personal experience. My guess is that it is from picking up on the office conversations that are commonplace in every institution. It is good to expose our learners to the reality of our professions, but we need to put on our professional filters so that healthy, constructive information reaches our learners and they are not prematurely jaded before they are able to develop their own opinions. Conclusion This short article can barely brush the surface of what it takes to become a great preceptor. We will continue to
pass our knowledge to learners we work with, but it is my hope that after reading this article that we will rethink how we are passing on this knowledge. Clear baseline expectations are the foundation of a learning experience. Consistent constructive feedback is necessary to ensure our learners are on the path to success. Finally, preceptors who demonstrate a high level of professionalism and embody the characteristics of a role model will provide learners with a road map for what it means to be a great pharmacist and mentor for tomorrow’s future practitioners. ● Reference 1. Ende J. Feedback in clinical medical education. JAMA. 1983;250:777-781.
AugusT 2010 I VOL 3, NO 5
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Reports from the 25th Anniversary EAU Annual Congress and the 15th Congress of the EHA By Jill Stein
Once-yearly Histrelin Implant Provides Sustained Improvement in Prostate Cancer Patients BARCELONA—Investigators have documented the long-term efficacy and tolerability of a once-yearly histrelin subdermal implant in men with advanced prostate cancer. Histrelin acetate, a synthetic luteinizing hormone-releasing hormone (LHRH) agonist, is available as an implant and is inserted subcutaneously under local anesthesia during an officebased procedure. After 12 months, the implant is removed, and another implant may then be inserted, if indicated. Neal D. Shore, MD, FACS, with Carolina Urologic Research Center/ Atlantic Urology Clinics in Myrtle Beach, South Carolina, reported the findings of an extension trial that included 138 patients assigned to the histrelin arm in the original 52-week, phase 3 registration study. All men enrolled in the extension trial had achieved the primary end point of testosterone suppression at 4 weeks in the phase 3 trial. The histrelin subdermal implants,
which were replaced every 12 months, maintained the testosterone suppression initially documented at 1 year for a full 4 years without evidence of surge in serum testosterone. The most common side effects were mild-tomoderate hot flashes. Because histrelin only needs to be replaced every 12 months, the implant may be preferable to other LHRH agonists, which are usually given by injection and need to be repeated at 1-, 3-, 4-, or 6-month intervals, he said. Shore presented the data at the 25th Anniversary European Association of Urology (EAU) Annual Congress.
Zoledronic Acid Boosts Survival in Multiple Myeloma Patients BARCELONA—Zoledronic acid im proves survival in newly diagnosed multiple myeloma (MM) patients compared with clodronate, investigators announced at the 15th Congress of the European Hematology Associa tion (EHA). Their study also found that zoledronic
“Side effects.” 28
August 2010 I VOL 3, NO 5
acid was associated with a larger decrease in skeletal-related events (SREs). Zoledronic acid’s survival advantage was independent of the SRE reduction. The results are from the phase 3 Medical Research Council Myeloma IX study, which was conducted by a UK group. Principal investigator Gareth J. Morgan, MD, with the Institute of Cancer Research in London, said that the findings bolster earlier preclinical studies suggesting anticancer activity for zoledronic acid. In the study, newly diagnosed MM patients were randomized to intravenous zoledronic acid (4 mg, dose-adjusted based on renal function) every 3 to 4 weeks plus first-line chemotherapy or to daily oral clodronate (1600 mg) plus first-line chemotherapy. Bone disease is common in MM patients, and bisphosphonates are widely used to prevent or treat bone disease in this population, Morgan pointed out. About 70% of patients in each treatment group had bone disease. Patients continued treatment with their assigned bisphosphonate at least until disease progression. A total of 1960 patients were evaluable, with a median follow-up of 3.7 years. Zoledronic acid plus first-line chemotherapy significantly improved overall survival by 16%, with a 5.5month difference in the median overall survival. The percent of patients who experienced an SRE was decreased by 24% in patients receiving zoledronic acid versus clodronate. SREs included bone fractures, radiation to bone, surgery to bone, and spinal cord compression. Zoledronic acid’s survival benefit was maintained after controlling for the potential effect of SREs on survival. Both bisphosphonates were generally well tolerated. “Our findings provide evidence that zoledronic acid should be considered for early integration into treatment regimens in patients with newly diagnosed MM,” Morgan said.
diac siderosis and is also well tolerated, according to data released at the 15th Congress of the European Hematology Association (EHA). Dudley J. Pennell, MD, FRCP, FACC, with the Royal Brompton Hospital in London, United Kingdom, presented results in 82 heavily transfused betathalassemia patients with myocardial siderosis who had completed a 1-year trial of deferasirox and then continued treatment for an additional year. “Iron chelation therapy has markedly improved survival for many regularly transfused patients with beta-thalassemia; however, heart failure due to cardiac iron deposition has been a leading cause of death,” Pennell said. “While the efficacy of chelation in reducing cardiac iron has been demonstrated using myocardial T2* in several prospective clinical trials of up to 1 year, longer term data are needed since T2* normalization may take several years.” Deferasirox was started at 30 mg/ kg/day and increased to 40 mg/kg/day by the time patients entered the trial’s extension phase. Dose decreases were allowed for safety reasons. The data showed that continued treatment with monotherapy deferasirox at greater than 30 mg/kg/day for up to 2 years significantly improved cardiac T2* and allowed 57% of patients with moderate-to-mild baseline cardiac siderosis to normalize and 43% of patients with severe baseline cardiac siderosis to achieve moderateto-mild cardiac T2* values. The investigators also found that significant improvements in cardiac T2* over 2 years were associated with the maintenance of normal cardiac function. Deferasirox treatment was well tolerated. The findings are especially noteworthy considering that all patients had received chelation therapy with other agents for a median of 12.2 years before enrolling in the study, Pennell said. The study is the first to report 2year data on cardiac iron removal for any iron-chelating agent, he added. ●
Deferasirox Treatment Provides Ongoing Benefit in Beta-thalassemia and Myocardial Siderosis
Did You Know?
BARCELONA—Continued therapy with deferasirox over 2 years is effective in removing cardiac iron in beta-thalassemia patients with car-
New statistics from the American Cancer Society show that cancer incidence rates fell by 1.3% per year from 2000 to 2006 in men and 0.5% per year from 1998 to 2006 in women.
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NEW YORK, NY Chemotherapy Foundation Symposium chemotherapyfoundationsymposium. org
Sept 29-Oct 2 ST. LOUIS, MO Association of Community Cancer Centers 27th Annual Oncology Economics Conference www.accc-cancer.org
WASHINGTON, DC Breast Cancer Symposium www.asco.org
MONTREAL, QUEBEC 18th International Congress on Palliative Care www.pal2010.com
8-9 NEW YORK, NY NCCN 5th Annual Congress: Hematologic Malignancies www.nccn.org
14 BETHESDA, MD
NCCN Patient Safety Summit www.nccn.org
21-24 BOSTON, MA Annual Congress of the International Society of Paediatric Oncology www.siopboston2010.com
ORLANDO, FL American Society of Hematology Annual Meeting www.hematology.org
RITUXAN® (Rituximab) Brief summary—Please consult full prescribing information. counts prior to each Rituxan course. During treatment with Rituxan and chemotherapy, obtain CBC and platelet counts at weekly to monthly intervals and more frequently in WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), patients who develop cytopenias. [See Adverse Reactions]. s The duration of cytopenias SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL caused by Rituxan can extend months beyond the treatment period. ADVERSE LEUKOENCEPHALOPATHY (PML) REACTIONS The most common adverse reactions of Rituxan (incidence ≥25%) Infusion Reactions: Rituxan administration can result in serious, including observed in clinical trials of patients with NHL were infusion reactions, fever, fatal infusion reactions. Deaths within 24 hours of Rituxan infusion have lymphopenia, chills, infection, and asthenia. The most common adverse reactions of occurred. Approximately 80% of fatal infusion reactions occurred in Rituxan (incidence ≥25%) observed in clinical trials of patients with CLL were: infusion association with the first infusion. Carefully monitor patients during reactions and neutropenia. Clinical Trials Experience in Lymphoid Malignancies infusions. Discontinue Rituxan infusion and provide medical treatment for Because clinical trials are conducted under widely varying conditions, adverse reaction Grade 3 or 4 infusion reactions [see Warnings and Precautions, Adverse rates observed in the clinical trials of a drug cannot be directly compared to rates in the Reactions]. s Tumor Lysis Syndrome (TLS): Acute renal failure requiring clinical trials of another drug and may not reflect the rates observed in practice. The data dialysis with instances of fatal outcome can occur in the setting of TLS described below reflect exposure to Rituxan in 2282 patients, with exposures ranging from a single infusion up to 6–8 months. Rituxan was studied in both single-agent and following treatment of non-Hodgkin’s lymphoma (NHL) patients with Rituxan active-controlled trials (n = 356 and n = 1926). The population included 679 patients [see Warnings and Precautions, Adverse Reactions]. s Severe Mucocutaneous with low-grade follicular lymphoma, 927 patients with DLBCL, and 676 patients with Reactions: Severe, including fatal, mucocutaneous reactions can occur in CLL. Most NHL patients received Rituxan as infusion of 375 mg/m2 per infusion, given as patients receiving Rituxan [see Warnings and Precautions, Adverse a single agent weekly for up to 8 doses, in combination with chemotherapy for up to 8 Reactions]. s Progressive Multifocal Leukoencephalopathy (PML): JC virus doses, or following chemotherapy for up to 16 doses. CLL patients received Rituxan 375 infection resulting in PML and death can occur in patients receiving Rituxan mg/m2 as an initial infusion followed by 500 mg/m2 for up to 5 doses, in combination with [see Warnings and Precautions, Adverse Reactions]. s fludarabine and cyclophosphamide. Seventy-one percent of CLL patients received 6 cycles and 90% received at least 3 cycles of Rituxan-based therapy. Infusion INDICATIONS AND USAGE Non-Hodgkin’s Lymphoma (NHL) Rituxan® (rituximab) is Reactionss In the majority of patients with NHL, infusion reactions consisting of fever, indicated for the treatment of patients with: Relapsed or refractory, low-grade or chills/rigors, nausea, pruritus, angioedema, hypotension, headache, bronchospasm, follicular, CD20-positive, B-cell NHL as a single agent; Previously untreated follicular, urticaria, rash, vomiting, myalgia, dizziness, or hypertension occurred during the first CD20-positive, B-cell NHL in combination with CVP chemotherapy; Non-progressing Rituxan infusion. Infusion reactions typically occurred within 30 to 120 minutes of (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after beginning the first infusion and resolved with slowing or interruption of the Rituxan first-line CVP chemotherapy; Previously untreated diffuse large B-cell, CD20-positive infusion and with supportive care (diphenhydramine, acetaminophen, and intravenous NHL in combination with CHOP or other anthracycline-based chemotherapy regimens. saline). The incidence of infusion reactions was highest during the first infusion (77%) Chronic Lymphocytic Leukemia (CLL) Rituxan® (rituximab) is indicated, in and decreased with each subsequent infusion. [See Boxed Warning, Warnings and combination with fludarabine and cyclophosphamide (FC), for the treatment of patients Precautions.] Infections Serious infections (NCI CTCAE Grade 3 or 4), including sepsis, with previously untreated and previously treated CD20-positive CLL. Limitations of use occurred in less than 5% of patients with NHL in the single-arm studies. The overall Rituxan is not recommended for use in patients with severe, active infections. incidence of infections was 31% (bacterial 19%, viral 10%, unknown 6%, and fungal WARNINGS AND PRECAUTIONS Infusion Reactions Rituxan can cause severe, 1%). [See Warnings and Precautions.] In randomized, controlled studies where Rituxan including fatal, infusion reactions. Severe reactions typically occurred during the first was administered following chemotherapy for the treatment of follicular or low-grade infusion with time to onset of 30–120 minutes. Rituxan-induced infusion reactions and NHL, the rate of infection was higher among patients who received Rituxan. In diffuse sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, large B-cell lymphoma patients, viral infections occurred more frequently in those who pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, received Rituxan. Cytopenias and hypogammaglobulinemiaa In patients with NHL ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death. Premedicate receiving rituximab monotherapy, NCI-CTC Grade 3 and 4 cytopenias were reported in patients with an antihistamine and acetaminophen prior to dosing. Institute medical 48% of patients. These included lymphopenia (40%), neutropenia (6%), leukopenia management (e.g. glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion (4%), anemia (3%), and thrombocytopenia (2%). The median duration of lymphopenia reactions as needed. Depending on the severity of the infusion reaction and the required was 14 days (range, 1–588 days) and of neutropenia was 13 days (range, 2–116 days). interventions, temporarily or permanently discontinue Rituxan. Resume infusion at a A single occurrence of transient aplastic anemia (pure red cell aplasia) and two minimum 50% reduction in rate after symptoms have resolved. Closely monitor the occurrences of hemolytic anemia following Rituxan therapy occurred during the singlefollowing patients: those with pre-existing cardiac or pulmonary conditions, those who arm studies. In studies of monotherapy, Rituxan-induced B-cell depletion occurred in experienced prior cardiopulmonary adverse reactions, and those with high numbers of 70% to 80% of patients with NHL. Decreased IgM and IgG serum levels occurred in 14% circulating malignant cells (≥25,000/mm3). [See Boxed Warning, Warnings and of these patients. Relapsed or Refractory, Low-Grade NHL Adverse reactions in Table 1 Precautions, Adverse Reactions.] Tumor Lysis Syndrome (TLS) Acute renal failure, occurred in 356 patients with relapsed or refractory, low-grade or follicular, CD20-positive, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, B-cell NHL treated in single-arm studies of Rituxan administered as a single agent. [See some fatal, can occur within 12–24 hours after the first infusion of Rituxan in patients Clinical Studies.] Most patients received Rituxan 375 mg/m2 weekly for 4 doses. with NHL. A high number of circulating malignant cells (≥25,000/mm3) or high tumor burden Table 1 confers a greater risk of TLS. Administer aggressive intravenous hydration and anti- Incidence of Adverse Reactions in ≥5% of Patients with Relapsed or Refractory, Lowhyperuricemic therapy in patients at high risk for TLS. Correct electrolyte abnormalities, Grade or Follicular NHL, Receiving Single-agent Rituxan (N = 356)a,b monitor renal function and fluid balance, and administer supportive care, including dialysis as All Grades (%) Grade 3 and 4 (%) All Grades (%) Grade 3 and 4 (%) indicated. [See Boxed Warning.] Severe Mucocutaneous Reactions Mucocutaneous Any Adverse Events 99 57 Respiratory p y System y 38 4 reactions, some with fatal outcome, can occur in patients treated with Rituxan. These Bodyy as a Whole 86 10 Increased Cough 13 1 Fever 53 1 Rhinitis 12 1 reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid Chills 33 3 Bronchospasm 8 1 dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of these Infection 31 4 Dyspnea 7 1 Asthenia 26 1 Sinusitis 6 0 reactions has varied from 1–13 weeks following Rituxan exposure. Discontinue Rituxan Headache 19 1 Metabolic and Nutritional in patients who experience a severe mucocutaneous reaction. The safety of Abdominal Pain 14 1 Disorders 38 3 Pain 12 1 Angioedema 11 1 readministration of Rituxan to patients with severe mucocutaneous reactions has not Back Pain 10 1 Hyperglycemia 9 1 been determined. [See Boxed Warning, Adverse Reactions.] Progressive Multifocal Throat Irritation 9 0 Peripheral Edema 8 0 5 0 LDH Increase 7 0 Leukoencephalopathy (PML) JC virus infection resulting in PML and death can occur HemeFlushing and Lymphatic y p System y 67 48 Digestive g System y 37 2 in Rituxan-treated patients with hematologic malignancies or with autoimmune diseases. Lymphopenia 48 40 Nausea 23 1 Leukopenia 14 4 Diarrhea 10 1 The majority of patients with hematologic malignancies diagnosed with PML received Neutropenia 14 6 Vomiting 10 1 Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell Thrombocytopenia 12 2 Nervous System y 32 1 8 3 Dizziness 10 1 transplant. The patients with autoimmune diseases had prior or concurrent Skin Anemia Anxiety 5 1 and Appendages pp g 44 2 immunosuppressive therapy. Most cases of PML were diagnosed within 12 months of Night Sweats 15 1 Musculoskeletal System y 26 3 Rash 15 1 Myalgia 10 1 their last infusion of Rituxan. Consider the diagnosis of PML in any patient presenting Arthralgia Pruritus 14 1 10 1 with new-onset neurologic manifestations. Evaluation of PML includes, but is not limited Urticaria 8 1 Cardiovascular System y 25 3 Hypotension 10 1 to, consultation with a neurologist, brain MRI, and lumbar puncture. Discontinue Rituxan Hypertension 6 1 and consider discontinuation or reduction of any concomitant chemotherapy or a b immunosuppressive therapy in patients who develop PML. [See Boxed Warning, Adverse Adverse reactions observed up to 12 months following Rituxan. Adverse reactions graded for severity Reactions.] Hepatitis B Virus (HBV) Reactivation Hepatitis B virus (HBV) reactivation by NCI-CTC criteria. with fulminant hepatitis, hepatic failure, and death can occur in patients with hematologic In these single-arm Rituxan studies, bronchiolitis obliterans occurred during and up to malignancies treated with Rituxan. The median time to the diagnosis of hepatitis was 6 months after Rituxan infusion. Previously Untreated Low-Grade NHLL In Study 4, approximately 4 months after the initiation of Rituxan and approximately one month after patients in the R-CVP arm experienced a higher incidence of infusional toxicity and the last dose. Screen patients at high risk of HBV infection before initiation of Rituxan. neutropenia compared to patients in the CVP arm. The following adverse reactions Closely monitor carriers of hepatitis B for clinical and laboratory signs of active HBV occurred more frequently (≥5%) in patients receiving R-CVP compared to CVP alone: infection for several months following Rituxan therapy. Discontinue Rituxan and any rash (17% vs. 5%), cough (15% vs. 6%), flushing (14% vs. 3%), rigors (10% vs. 2%), concomitant chemotherapy in patients who develop viral hepatitis, and institute pruritus (10% vs. 1%), neutropenia (8% vs. 3%), and chest tightness (7% vs. 1%). In appropriate treatment including antiviral therapy. Insufficient data exist regarding the Study 5, the following adverse reactions were reported more frequently (≥5%) in safety of resuming Rituxan in patients who develop hepatitis subsequent to HBV patients receiving Rituxan following CVP compared to patients who received no further reactivation. [See Adverse Reactions.] Infections Serious, including fatal, bacterial, therapy: fatigue (39% vs. 14%), anemia (35% vs. 20%), peripheral sensory fungal, and new or reactivated viral infections can occur during and up to one year neuropathy (30% vs. 18%), infections (19% vs. 9%), pulmonary toxicity (18% vs. following the completion of Rituxan-based therapy. New or reactivated viral infections 10%), hepato-biliary toxicity (17% vs. 7%), rash and/or pruritus (17% vs. 5%), included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, arthralgia (12% vs. 3%), and weight gain (11% vs. 4%). Neutropenia was the only West Nile virus, and hepatitis B and C. Discontinue Rituxan for serious infections and Grade 3 or 4 adverse reaction that occurred more frequently (≥2%) in the Rituxan arm institute appropriate anti-infective therapy. [See Adverse Reactions.] Cardiovascular Discontinue infusions for serious or life-threatening cardiac arrhythmias. Perform compared with those who received no further therapy (4% vs. 1%). [See Clinical s the following adverse reactions, cardiac monitoring during and after all infusions of Rituxan for patients who develop Studies.] DLBCLL In Studies 6 and 7, [see Clinical Studies] clinically significant arrhythmias, or who have a history of arrhythmia or angina. [See regardless of severity, were reported more frequently (≥5%) in patients age ≥60 years receiving R-CHOP as compared to CHOP alone: pyrexia (56% vs. 46%), lung disorder Adverse Reactions.] Renal Severe, including fatal, renal toxicity can occur after Rituxan administration in patients with NHL. Renal toxicity has occurred in patients who (31% vs. 24%), cardiac disorder (29% vs. 21%), and chills (13% vs. 4%). Detailed safety data collection in these studies was primarily limited to Grade 3 and 4 adverse experience tumor lysis syndrome and in patients with NHL administered concomitant cisplatin therapy during clinical trials. The combination of cisplatin and Rituxan is not an reactions and serious adverse reactions. In Study 7, a review of cardiac toxicity approved treatment regimen. Monitor closely for signs of renal failure and discontinue determined that supraventricular arrhythmias or tachycardia accounted for most of Rituxan in patients with a rising serum creatinine or oliguria. Bowel Obstruction and the difference in cardiac disorders (4.5% for R-CHOP vs. 1.0% for CHOP). The Perforation Abdominal pain, bowel obstruction and perforation, in some cases leading following Grade 3 or 4 adverse reactions occurred more frequently among patients in to death, can occur in patients receiving Rituxan in combination with chemotherapy. In the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs. postmarketing reports, the mean time to documented gastrointestinal perforation was 6 7%) and lung disorder (6% vs. 3%). Other Grade 3 or 4 adverse reactions occurring (range 1–77) days in patients with NHL. Perform a thorough diagnostic evaluation and more frequently among patients receiving R-CHOP were viral infection (Study 7), institute appropriate treatment for complaints of abdominal pain. [See Adverse neutropenia (Studies 7 and 8), and anemia (Study 8). CLL The data below reflect Reactions.] Immunization The safety of immunization with live viral vaccines following exposure to Rituxan in combination with fludarabine and cyclophosphamide in 676 s The age range was Rituxan therapy has not been studied and vaccination with live virus vaccines is not patients with CLL in Study 9 or Study 10 [see Clinical Studies]. recommended. Laboratory Monitoring In patients with lymphoid malignancies, during 30–83 years and 71% were men. Detailed safety data collection in Study 9 was limited treatment with Rituxan monotherapy, obtain complete blood counts (CBC) and platelet to Grade 3 and 4 adverse reactions and serious adverse reactions. Infusion-related
ANAHEIM, CA American Society of Health-System Pharmacists Midyear Clinical Meeting www.ahsp.org
adverse reactions were defined by any of the following adverse events occurring during or within 24 hours of the start of infusion: nausea, pyrexia, chills, hypotension, vomiting, and dyspnea. In Study 9, the following Grade 3 and 4 adverse reactions occurred more frequently in R-FC–treated patients compared to FC-treated patients: infusion reactions (9% in R-FC arm), neutropenia (30% vs. 19%), febrile neutropenia (9% vs. 6%), leukopenia (23% vs. 12%), and pancytopenia (3% vs. 1%). In Study 10, the following Grade 3 or 4 adverse reactions occurred more frequently in R-FC–treated patients compared to FC-treated patients: infusion reactions (7% in R-FC arm), neutropenia (49% vs. 44%), febrile neutropenia (15% vs. 12%), thrombocytopenia (11% vs. 9%), hypotension (2% vs. 0%), and hepatitis B (2% vs. <1%). Fifty-nine percent of R-FC–treated patients experienced an infusion reaction of any severity. Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Rituxan with the incidence of antibodies to other products may be misleading. Using an ELISA assay, anti-human antichimeric antibody (HACA) was detected in 4 of 356 (1.1%) patients with low-grade or follicular NHL receiving single-agent Rituxan. Three of the four patients had an objective clinical response. The clinical relevance of HACA formation in Rituxan-treated patients is unclear. Postmarketing Experience The following adverse reactions have been identified during post-approval use of Rituxan in hematologic malignancies. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to Rituxan. Hematologic: prolonged pancytopenia, marrow hypoplasia, and late-onset neutropenia, hyperviscosity syndrome in Waldenstrom’s macroglobulinemia. Cardiac:: fatal cardiac failure. Immune/ Autoimmune Events: uveitis, optic neuritis, systemic vasculitis, pleuritis, lupus-like syndrome, serum sickness, polyarticular arthritis, and vasculitis with rash. Infection: viral infections, including progressive multifocal leukoencephalopathy (PML), increase in fatal infections in HIV-associated lymphoma, and a reported increased incidence of Grade 3 and 4 infections in patients with previously treated lymphoma without known HIV infection. Neoplasia:: disease progression of Kaposi’s sarcoma. Skin: severe mucocutaneous reactions. Gastrointestinal: bowel obstruction and perforation. Pulmonary: fatal bronchiolitis obliterans and pneumonitis (including interstitial pneumonitis). DRUG INTERACTIONS Formal drug interaction studies have not been performed with Rituxan. In patients with CLL, Rituxan did not alter systemic exposure to fludarabine or cyclophosphamide. USE IN SPECIFIC POPULATIONS Pregnancy Category C: There are no adequate and well-controlled studies of rituximab in pregnant women. Postmarketing data indicate that B-cell lymphocytopenia generally lasting less than six months can occur in infants exposed to rituximab in-utero. Rituximab was detected postnatally in the serum of infants exposed in-utero. Non-Hodgkin’s lymphoma is a serious condition that requires treatment. Rituximab should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Reproduction studies in cynomolgus monkeys at maternal exposures similar to human therapeutic exposures showed no evidence of teratogenic effects. However, B-cell lymphoid tissue was reduced in the offspring of treated dams. The B-cell counts returned to normal levels, and immunologic function was restored within 6 months of birth. Nursing Mothers It is not known whether Rituxan is secreted into human milk. However, Rituxan is secreted in the milk of lactating cynomolgus monkeys, and IgG is excreted in human milk. Published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts. The unknown risks to the infant from oral ingestion of Rituxan should be weighed against the known benefits of breast-feeding. Pediatric Use The safety and effectiveness of Rituxan in pediatric patients have not been established. Geriatric Use Diffuse Large B-Cell NHL Among patients with DLBCL evaluated in three randomized, active-controlled trials, 927 patients received Rituxan in combination with chemotherapy. Of these, 396 (43%) were age 65 or greater and 123 (13%) were age 75 or greater. No overall differences in effectiveness were observed between these patients and younger patients. Cardiac adverse reactions, mostly supraventricular arrhythmias, occurred more frequently among elderly patients. Serious pulmonary adverse reactions were also more common among the elderly, including pneumonia and pneumonitis. Low-Grade or Follicular Non-Hodgkin’s Lymphoma Clinical studies of Rituxan in low-grade or follicular, CD20-positive, B-cell NHL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. Chronic Lymphocytic Leukemia Among patients with CLL evaluated in two randomized active-controlled trials, 243 of 676 Rituxan-treated patients (36%) were 65 years of age or older; of these, 100 Rituxan-treated patients (15%) were 70 years of age or older. In exploratory analyses defined by age, there was no observed benefit from the addition of Rituxan to fludarabine and cyclophosphamide among patients 70 years of age or older in Study 9 or in Study 10; there was also no observed benefit from the addition of Rituxan to fludarabine and cyclophosphamide among patients 65 years of age or older in Study 10 [see Clinical Studies]. s Patients 70 years or older received lower dose intensity of fludarabine and cyclophosphamide compared to younger patients, regardless of the addition of Rituxan. In Study 9, the dose intensity of Rituxan was similar in older and younger patients, however in Study 10 older patients received a lower dose intensity of Rituxan. The incidence of Grade 3 and 4 adverse reactions was higher among patients receiving R-FC who were 70 years or older compared to younger patients for neutropenia [44% vs. 31% (Study 9); 56% vs. 39% (Study 10)], febrile neutropenia [16% vs. 6% (Study 9)], anemia [5% vs. 2% (Study 9); 21% vs. 10% (Study 10)], thrombocytopenia [19% vs. 8% (Study 10)], pancytopenia [7% vs. 2% (Study 9); 7% vs. 2% (Study 10)] and infections [30% vs. 14% (Study 10)]. OVERDOSAGE There has been no experience with overdosage in human clinical trials. Single doses of up to 500 mg/m2 have been administered in clinical trials. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term animal studies have been performed to establish the carcinogenic or mutagenic potential of Rituxan or to determine potential effects on fertility in males or females. PATIENT COUNSELING INFORMATION Patients should be provided the Rituxan Medication Guide and provided an opportunity to read prior to each treatment session. It is important that the patient’s overall health be assessed at each visit and the risks of Rituxan therapy and any questions resulting from the patient’s reading of the Medication Guide be discussed. Rituxan is detectable in serum for up to six months following completion of therapy. Individuals of childbearing potential should use effective contraception during treatment and for 12 months after Rituxan therapy. Revised 02/2010 (4851501) Jointly Marketed by: Biogen Idec Inc. 5200 Research Place San Diego, CA 92122 Genentech USA, Inc. 1 DNA Way South San Francisco, CA 94080-4990 ©2010 Biogen Idec Inc. and Genentech, Inc. 7140919 February 2010
AugusT 2010 I VOL 3, NO 5
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NOW IN THE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
DRIVING BETTER OUTCOMES RITUXAN+FC improved median PFS in first-line and previously treated CLL1,2 In relapsed/refractory* CLL 2.1-year follow-up
In first-line CLL 1.7-year follow-up
39.8 months R-FC
21.7 months FC
improvement in median
improvement in median
CLL8 TRIAL (N=817)
REACH TRIAL (N=552) RITUXAN-NAIVE PATIENTS
In the CLL8 trial2 RITUXAN+FC more than doubled CR in first-line CLL compared with FC alone (36% vs 17%; p<0.0001)
In the REACH trial 2 Patients who responded to RITUXAN+FC (n=167) maintained their responses for nearly 2 years longer (48 months vs 27 months; p=0.0294) than those treated with FC alone (n=134)
Treatment considerations These trials were not designed or powered to detect a significant difference in PFS by age category. However, exploratory analyses defined by age suggest no observed benefit with the addition of RITUXAN to FC chemotherapy in previously untreated CLL patients 70 years of age or older and in previously treated CLL patients 65 years of age or older.1 *In the REACH trial, patients had received 1 prior therapy. Patients who had previously received RITUXAN or both fludarabine and cyclophosphamide, either sequentially or in combination, were excluded from the trial, as were fludarabine-refractory patients; alkylator-refractory patients were permitted.2 R=RITUXAN; FC=fludarabine and cyclophosphamide; PFS=progression-free survival; CR=complete response.
Indication RITUXAN® (Rituximab) is indicated, in combination with fludarabine and cyclophosphamide (FC), for the treatment of patients with previously untreated and previously treated CD20-positive CLL. RITUXAN is not recommended for use in patients with severe, active infections.
BOXED WARNINGS RITUXAN administration can result in serious, including fatal, adverse reactions. These include infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (PML)
Warnings and Precautions RITUXAN can also result in serious, including fatal, adverse reactions. These include hepatitis B reactivation with fulminant hepatitis and hepatic failure resulting in death; other infections, including bacterial, fungal, new or reactivated viral infections; cardiovascular events; severe, including fatal, renal toxicity; and abdominal pain, bowel obstruction and perforation, in some cases leading to death
Additional Important Safety Information The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with CLL were infusion reactions and neutropenia. Most patients treated with R-FC experienced at least one Grade 3 or 4 adverse reaction. The most frequently reported Grade 3 or 4 adverse reaction was neutropenia In clinical trials, CLL patients 70 years of age or older who received R-FC had more Grade 3 and 4 adverse reactions compared with younger CLL patients who received the same treatment
For additional safety information, please see following page for brief summary of full prescribing information, including BOXED WARNINGS. Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion. References: 1. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2010. 2. Data on file, Genentech, Inc. ©2010 Genentech USA, Inc., and Biogen Idec Inc. All rights reserved.