CONFERENCE NEWS Coverage of the 45th annual meeting of the American Society of Clinical Oncology
VIEWPOINT Government health plans always ration care
fo gi r Y st ou er ww r F To w. re day co e CE ex m .co m
M u Sec lti ond p le a My nnu elo al m Con a page 12 ne sid ws era le t t i o te n s www.theoncologypharmacist.com rs i er n ie s .
page 21 JULY/AUGUST 2009 • VOL. 2, NO. 5
er d a Le and e h T ews in N eeting e M erag Cov HOPA 5th ANNUAL CONFERENCE
Challenges of Oncology Pharmacy Practice in the Community Setting PART I
By Michele Woods, PharmD, BCOP Illinois Cancer Care, Peoria
hen you first pictured yourself practicing pharmacy, either as a hospital pharmacist or a clinical pharmacist, you probably imagined yourself as part of a staff of pharmacists
guided by a clinical coordinator or a pharmacy director. Many of us who chose the field of oncology pharmacy, however, find ourselves as the lone voice of pharmacy at a cancer center full of oncology
physicians, nurses, and other professionals. Most community practices have only one pharmacist, if they have one at all, and he or she may not always have complete forContinued on page 18
Cindy O’Bryant, outgoing HOPA president, catches up on her reading at the 5th annual conference in Miami, Florida. Turn to page 9 to see more of your friends and colleagues.
COMPLIMENTARY CE CREDIT
Complying with USP <797>: Getting Your Center Up to Speed
Richard Schilsky, MD, ASCO President: “Personalizing Cancer Care” Is Everyone’s Mission
ow that the updated US Pharmacopeia (USP) <797> regulations are official, compliance by compounding pharmacies is not a matter of debate. What should you be doing to bring your system into compliance? USP <797> is a far-reaching regulation that governs a range of pharmacy policies and procedures (www. usp.org/products/797Guidebook/). Its intent is to prevent harm to patients resulting from microbial con-
ORLANDO—The “personalization of cancer care”— delivering the right care to the right patient at the right time—is becoming a universal and realizable goal, said American Society of Clinical Oncology (ASCO) president Richard Schilsky, MD, professor of medicine and associate dean of clinical research, University of Chicago. The challenges of the past year have been many: the
Continued on page 6
Continued on page 13
Follow-up Care in Medicare Beneficiaries with Colorectal Cancer
YOU COULD BE HOLDING YOUR LAST ISSUE! Register online at www.theoncologypharmacist.com to ensure uninterrupted FREE delivery of The Oncology Pharmacist © 2009 Green Hill Healthcare Communications, LLC
M SUSAN GOODIN, PHARMD, FCCP, BCOP
PATRICK MEDINA, PHARMD, BCOP
ore than 700 oncology pharmacists, students, technicians, industry representatives, and others attended the 5th annual conference of the Hematology/Oncology Pharmacy Association in Miami, Florida. The varied program provided ample opportunity not only to learn about the latest advances in oncology treatment and innovations in pharmacy practice but also to reconnect and exchange ideas with friends and colleagues. Leadership was the theme of the keynote lecture by Ernest R. Anderson, Jr. He spoke of the importance of “emotional intelligence” for success in both a pharmacist’s career and personal life and endorsed the concept of “servant leadership.” At another session on the same theme, Judy L. Chase urged new practitioners to seek opportunities for leadership, and she spoke of the importance of developing good communication as well as clinical skills. The studies presented at the trainee poster session showed the depth and breadth of
EDITORIAL CORRESPONDENCE should be addressed to EDITORIAL DIRECTOR, The Oncology Pharmacist®, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. E-mail: email@example.com. 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. ISSN #1944-9607. The Oncology Pharmacist® is published 7 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 ©2009 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.
knowledge of the new generation of oncology pharmacists and the professionalism and enthusiasm they bring to their work. Their studies suggested new approaches to drug dosing and administration, side effect management, and other clinical issues and explored the use of new technologies, such as use of robots to minimize exposure to hazardous drugs. Another session that attracted much interest dealt with reimbursement issues, presented by Timothy Tyler. He discussed the complex reimbursement challenges in the retail, physician’s office, hospital outpatient clinic, and health maintenance organization settings and previewed changes to come in drug coding. Healthcare economics and the potential of how proposed healthcare reforms might affect oncology practices and patients with cancer were also addressed at numerous sessions at the annual meeting of the American Society of Clinical Oncology. In his presidential address, Richard Schilsky, MD, said that
when it comes to making decisions about costly cancer care, “Oncologists need to be part of the conversation and the solution.” Another speaker, Eric Winer, MD, of DanaFarber Cancer Institute, said, “We have to pay more attention to the cost of care…If we don’t police ourselves, then we are going to be told how to do it by external sources.” What all this means for pharmacists is that now, in addition to our clinical responsibilities, we have to think about the cost of cancer treatments, be prepared to talk to our patients about the financial aspects of their care, and participate in the discussion about how shortcomings in the current healthcare system can be remedied without adversely affecting the quality of cancer care. To play an active role in continuing discussions about healthcare reform, oncology pharmacists and our fellow healthcare providers need more than ever to have a thorough understanding of all the issues—clinical, economic, regulatory—involved in cancer treatment.
News Notes News Updates of Relevance to Everyday Oncology Practice ■ Paying for Cancer Care a Top Fear about the Disease In a survey commissioned by the Community Oncology Alliance, Americans cited the inability to pay for cancer care among their fears regarding cancer. Sixtynine percent of Americans fear paying for cancer, the same percent that fears dying of the disease. Only poor quality of life and being in pain are greater fears, with 75% and 72% of Americans, respectively. Other top concerns include being unable to work (61%) and leaving their families in debt (59%). The survey found that to pay for care, 66% of Americans would accept government assistance, 48% would sell their cars, 38% would sell their homes, 44% would borrow the money, 40% would declare bankruptcy, and most disturbing, 33% would discontinue treatment (Community Oncology Alliance. July 8, 2009). Another recent survey found that more than 60% of personal bankruptcies in the United States are related to medical bills (Himmelstein DU, et al. Am J Med. 2009 Jun 4. Epub ahead of print). To address patients’ financial concerns, the Wellness Community has launched a national education program “Frankly Speaking about Cancer: Coping with the Cost of Care” (www.thewellnesscommunity.org). ■ Idiopathic Erythroderma Associated with Undiagnosed Cancer Unexplained erythema may signal possible underlying malignancies, according to a study presented at the International Congress of Dermatology. Thng and colleagues reviewed records of 218 patients evaluated
for erythroderma from 2001 to 2005 in Singapore. They found cancer in more than 20% of cases of idiopathic erythroderma: 18% with visceral malignancies and 4.6% who developed cutaneous T-cell lymphoma later in the course of follow-up. The researchers found that compared with agestandardized cases in the Singapore Cancer Registry, patients with idiopathic erythroderma had more than triple the risk of visceral malignancy, and they therefore recommend that patients be closely followed and reevaluated for malignancy even if the initial investigation is negative (ICD 2009; Abstract 195). ■ NCCN Updates Guidelines for CNS Cancers The National Comprehensive Cancer Network (NCCN) updated guidelines for central nervous system (CNS) cancers highlight two new recommendations for patients with glioblastoma multiforme. Bevacizumab is now recommended to be given as a single agent for recurrent/salvage therapy, whereas previously it was recommended only in combination with irinotecan. The guidelines have also added the integration of a patient’s Karnofsky performance status score into the adjuvant therapy recommendations for patients with gliobastoma multiforme. For patients with specific low-grade gliomas who are 40 years and older, the guidelines now include additional options to observation following maximal safe resection. These patients can now also choose fractionated external beam radiation therapy or chemotherapy as additional options. The complete guidelines can be downloaded at www.nccn.org.
G REEN H ILL H EALTHCARE C OMMUNICATIONS 1
A Letter from the Editors
Vol. 2, No. 5
Feature Articles 7
Conference News: HOPA
Pharmacy-managed anemia clinic increases monitoring of iron studies, guideline adherence Redesigned chemotherapy process improves accuracy and decreases RPNs Rituximab rapid-infusion protocol can save up to 90 minutes Chemotherapy robot reduces cytotoxic drug exposures for pharmacists, technicians
Continuing Education Follow-up care in Medicare beneficiaries with colorectal cancer
Conference News: ASCO Suggested new standard of care for advanced biliary tract cancer Trastuzumab improves survival in gastric cancer Novel agent omacetaxine active in T315I-positive CML PARP inhibitors show promise in various forms of advanced breast cancer Researchers sound warning about chemotherapy solvent
Viewpoint Government health plans always ration care
Departments 1 1 4 8 23 25
Editors’ Letter News Notes
PUBLISHING STAFF Publisher Philip Pawelko firstname.lastname@example.org Editorial Director Karen Rosenberg email@example.com Associate Editor Dawn Lagrosa Production Manager Lynn Hamilton
Directors, Client Services John W. Hennessy firstname.lastname@example.org
Recent FDA Approvals
Russell Hennessy email@example.com
Oncology Drug Codes
Business Manager Blanche Marchitto firstname.lastname@example.org
In the Literature
Executive Administrator Andrea Boylston
YOU COULD BE HOLDING YOUR LAST ISSUE!
Circulation Department Circulation@greenhillhc.com
GH Green Hill Healthcare Communications
,LLC LLC ™
Register online at
www.theoncologypharmacist.com to ensure uninterrupted FREE delivery of The Oncology Pharmacist
Jim Koeller, MS
Johns Hopkins Bayview Medical Center Baltimore, MD
University of Texas at Austin San Antonio, TX
Anjana Elefante, PharmD, BSc, BScPhm, RPh
Helen L. Leather, BPharm
Roswell Park Cancer Institute Buffalo, NY
University of Florida Gainesville, FL
Beth Faiman, RN, MSN, APRN, BC, AOCN
Christopher J. Lowe, PharmD
Susan Goodin, PharmD, FCCP, BCOP
Christopher Fausel, PharmD
Patrick Medina, PharmD, BCOP Oklahoma University College of Pharmacy Tulsa, OK
John F. Aforismo, BSC Pharm, RPh, FASCP RJ Health Systems International, LLC Wethersfield, CT
David Baribeault, RPh, BCOP Boston Medical Center Boston, MA
Indiana University Simon Cancer Center Indianapolis, IN
Rebecca S. Finley, PharmD, MS Jefferson School of Pharmacy Philadelphia, PA
David C. Gammon, BSPharm University of Massachusetts Memorial Hospital Worcester, MA
Heidi D. Gunderson, PharmD, BCOP Mayo Clinic Cancer Center Rochester, MN
Sandra Horowitz, PharmD, RPh The University of Texas MD Anderson Cancer Center Houston, TX
Lew Iacovelli, BS, PharmD, BCOP, CPP
Sylvia Bartel, RPh, MPH
Moses H. Cone Health System Greensboro, NC
Dana-Farber Cancer Institute Boston, MA
Andrea A. Iannucci, PharmD, BCOP
Deborah Blamble, PharmD, BCOP The University of Texas MD Anderson Cancer Center Houston, TX
Marlo Blazer, RPh, PharmD James Cancer Hospital & Solove Research Institute Columbus, OH
Steven L. D’Amato, RPh, BCOP Maine Center for Cancer Medicine Scarborough, ME
Your Innovative Partners in Medical Media
241 Forsgate Drive, Suite 205C Monroe Twp, NJ 08831
Bryna Delman Ewachiw, BS, PharmD
Cleveland Clinic Taussig Cancer Center Cleveland, OH
Cancer Institute of New Jersey New Brunswick, NJ
University of California Davis Medical Center Sacramento, CA
Cindy Ippoliti, PharmD New York Presbyterian Hospital/Weill Cornell Medical School New York, NY
Dwight Kloth, PharmD, FCCP, BCOP Fox Chase Cancer Center Philadelphia, PA
G REEN H ILL H EALTHCARE C OMMUNICATIONS
Novant Health Winston-Salem, NC
Helen McFarland, PharmD, BCOP Union Memorial Hospital Baltimore, MD
Emily Mackler, PharmD, BCOP University of Michigan Health System & College of Pharmacy Ann Arbor, MI
Laura Boehnke Michaud, PharmD, BCOP, FASHP The University of Texas MD Anderson Cancer Center Houston, TX
Deborah Moradi, PharmD The Angeles Clinic and Research Institute Los Angeles, CA
LeAnn Best Norris, PharmD, BCPS, BCOP South Carolina College of Pharmacy Columbia, SC
Debra L. Phillips, PharmD East Carolina University Greenville, NC
Steve Stricker, PharmD, MS Samford University McWhorter School of Pharmacy Birmingham, AL
Timothy G. Tyler, PharmD, FCSHP Desert Regional Medical Center Palm Springs, CA
John M. Valgus, PharmD, BCOP University of North Carolina Hospitals and Clinics Chapel Hill, NC
Gary C. Yee, PharmD, FCCP, BCOP University of Nebraska College of Pharmacy Omaha, NE
A pioneer in cancer innovation — exploring new directions
At Genentech BioOncology, we’re leading the fight against cancer with innovative science and are working to transform cancer treatment. A family of firsts — Our proven therapeutics are standards of care in 5 of the 6 leading causes of cancer mortality in the United States. A robust pipeline — Our molecules in development target the fundamental mechanisms of cancer growth and include a HER dimerization inhibitor, a Hedgehog pathway inhibitor, an antibody–drug conjugate, and antibodies targeting cancer cell-surface antigens. A commitment to patients — We actively pursue ways to ensure patient access to therapeutics through a variety of patient support programs so healthcare providers can remain focused on patient care. Our goal is to fundamentally change the way cancer is treated — not just with incremental advances, but with new standards of care.
© 2009 Genentech USA, Inc. All rights reserved. 9708100 Printed in USA.
Medical Minutes BY JOHN SCHIESZER
John Schieszer is an award-winning national journalist and radio broadcaster of The Medical Minute. He can be reached at email@example.com.
Novel Therapy May Prove Effective in Treatment of 30% of Cancers A groundbreaking Canadian clinical trial suggests that the common antiviral drug ribavirin may be beneficial in the treatment of cancer patients. The study demonstrates that ribavirin suppresses the activities of the eIF4E gene. This gene is dysregulated in 30% of cancers, including breast, prostate, head and neck, colon, and stomach cancer. The Canadian researchers targeted the gene by giving clinical trial participants a mimic of its natural target, ribavirin. “Our results are the first to show that targeting the eIF4E gene in humans is clinically beneficial,” said Katherine Borden, MD, University of Montreal, Quebec. “We also found that ribavirin not only blocks the eIF4E gene, it has no side effects on the patients.” The trial studied patients with M4/M5 acute myeloid leukemia who had undergone several other treatments that had previously failed. “We had striking clinical improvements with even partial and complete remissions,” said lead investigator
Sarit Assouline, MD, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec. The researchers say these findings may have many important clinical implications. Through a special collaboration, the investigators were able to monitor molecular events in trial patients. They now believe this special collaboration has quickly moved research laboratory findings into patient tests, which may have widespread implications in the field of oncology. The next challenge for the researchers is to overcome the resistance that often develops over time to ribavirin. “Combination therapy with chemotherapeutic agents may enhance the efficacy of this treatment,” Borden explained. “Trials in the near future are planned to overcome this [resistance], and we are looking forward to more complete remissions. We also hope to test whether ribavirin is as effective in the treatment of other cancers with dysregulated eIF4E. Our laboratory studies suggest this is likely.”
New Form of Fentanyl May Be Superior to Standard Care for Breakthrough Cancer Pain New data from a phase 3 trial suggest that a highly differentiated fentanyl citrate nasal spray (NasalFent, Archimedes Pharma) may offer superiority over immediate-release morphine sulphate, which is currently the most commonly prescribed medicine for breakthrough cancer pain. The researchers conducted their study of 135 patients at 35 sites throughout western Europe and India. Among the 135 patients, 110 (82%) entered the open-dose titration phase of the study, and 84 (76%) participated in the double-blind, placebo-controlled portion.
Results covering both primary and secondary outcomes showed statistical superiority for the new nasal spray over placebo and provided evidence of both rapid onset of pain relief (within 5 minutes of dosing) and clinically meaningful pain relief within 10 minutes of dosing. The researchers found that use of rescue medication was low, confirming that this medication was consistently effective. Highly significant improvements across a range of pain assessments were seen. Nasal tolerability was excellent; side effects were generally mild to moderate in intensity and were typical of those associated with fentanyl use in this patient population. “Breakthrough cancer pain is a significant clinical issue, and these data illustrate the potential for NasalFent to offer ultrarapid, consistent pain relief to the many patients who suffer from this ing bevacizumab who are at high risk of bevaunpredictable and extremely debilitatcizumab-associated perforation.” ing pain,” said Allen Burton, MD, proWu and colleagues conducted a systematic fessor and chairman of oncology, the review and meta-analysis of 17 randomized University of Texas M.D. Anderson controlled trials involving 12,294 patients Cancer Center, Houston. with various types of solid tumors to assess the NasalFent is the only one of the new role of bevacizumab in GI perforation. The generation of fentanyl products to have overall incidence of GI perforation among demonstrated statistically significant patients receiving bevacizumab was 0.9%. improvements over immediate-release Among patients with a GI perforation, the morphine sulphate. Significantly better mortality rate was 21.7%. improvements in pain scores for the fenInterestingly, the study results revealed tanyl spray versus immediate-release that risk varied with bevacizumab dose and morphine sulphate were seen at all subsetumor type. The researchers found that the quent time points, indicating that superihigher the dose of the agent, the greater the ority of NasalFent was maintained for 60 risk for GI perforation. Patients taking 2.5 minutes after dosing. mg/kg/week of bevacizumab were 61% more NasalFent has low viscosity and is easlikely to have a perforation. Patients receivily delivered in a low volume of 100 µL ing the highest dose (5 mg/kg/week) had a using a conventional nasal spray pump. 167% higher risk for a perforation. The Archimedes Pharma, the manufacturer, highest risks for GI perforation were found says the pump produces a fine mist of simin patients with advanced colorectal cancer ilarly sized spray droplets that are depositand renal cell carcinoma. The lowest risk ed into the front of the nostril. The calciwas in patients with pancreatic cancer. um ions present in nasal mucosal fluid The researchers believe that because cause the pectin to form a thin gel layer, bevacizumab is extensively used in routine resulting in modulated drug absorption. cancer treatment and the risk for GI perfoThis reportedly allows for rapid but conration is significant, it is important to recogtrolled absorption into the systemic circunize symptoms indicating perforation and to lation and an increased duration of action. intervene to reduce morbidity and mortality.
Common Cancer Drug May Increase Risk of GI Perforations Cancer patients treated with the widely used drug bevacizumab in combination with chemotherapy appear to be at a greater risk of life-threatening gastrointestinal (GI) perforations, according to researchers at Stony Brook University Medical Center. The angiogenesis inhibitor has been shown to be effective in treating many forms of cancer, including colorectal cancer, renal cell carcinoma, non–small–cell lung cancer, and breast cancer. The US Food and Drug Administration already has issued a black box warning to discontinue bevacizumab in patients with GI perforations. However, a link between the use of bevacizumab in cancer patients and GI perforations had not been established until these new study results. “Our study establishes a significant association between the use of bevacizumab in cancer patients and the risk for GI perforations, one in which the risk of GI perforations was double in those taking the medication compared with those taking a control medication,” said principal investigator Shenhong Wu, MD, PhD, assistant professor of medicine in the Division of Hematology/ Oncology, Stony Brook University Medical Center, New York. “We hope the study results will help to identify a subset of patients receiv4
G REEN H ILL H EALTHCARE C OMMUNICATIONS
Because some work should never be brought home Prevent hazardous drug exposure with the only clinically proven closed-system drug transfer device (CSTD).
PhaSeal® System by Carmel Pharma
Spiros™ and Vial Adapter CH-61 by ICU Medical Inc.
For more information and evidence-based research—or to earn up to 6 free pharmacy contact hours of safe handling CE—visit www.PhaSeal.com or call 866-487-9250.
Know You’re Safe with PhaSeal Carmel Pharma, Inc. 7029 Huntley Road Suite O Columbus, OH 43229 USA Phone: 614-841-0504 Toll Free: 866-487-9250 Fax: 614-841-0525 E-mail: firstname.lastname@example.org
B. Braun OnGuard System by Teva Medical Ltd.
Alaris’ SmartSite® by Cardinal Health
Complying with USP <797> Continued from cover
tamination and large content errors. It is also a means of protecting staff from exposure to hazardous drugs. Companion guidelines as an adjunct to UPS <797> have been suggested by the National Institute for Occupational Safety and Health (NIOSH) (www.cdc.gov/niosh docs/2004-165/#sum). Together, these guidelines should protect the end product compounded, as well as the staff compounding the product.
the definition of the specific categories described in USP <797> (low-, medium-, or high-risk level, or immediate use), including hazardous drugs as CSPs, must meet the regulations. The standards apply to all personnel who prepare CSPs and all places where CSPs are prepared, including small oncology offices, she explained. At the 2009 Community Oncology Conference, Aslo discussed the key
Clean rooms must have a controlled level of contamination. “USP <797> is a buzzword lately in oncology. Does it really apply to community oncology practices?” said Angel K. Aslo, PharmD, pharmacy director, The Mark H. Zangmeister Center, Columbus, Ohio. “The answer is ‘yes,’” she said. “All compounding of hazardous drugs must comply with USP <797>, including environmental controls, work practices, and personnel training. These should be incorporated into the business plan of every oncology practice. If your center is not compliant, it needs to be.” Institutions that prepare compounded sterile preparations (CSPs) meeting
components of USP <797>, why compliance is important, and how to meet the new standards. She noted that in addition to the US Food and Drug Administration, in 17 states, the State Boards of Pharmacy also can enforce USP <797>. “Most boards do not have the manpower for random inspections, but if a patient makes a complaint, you can expect them to walk into any center that has a license,” she cautioned.
NIOSH alert As part of the Centers for Disease Control and Prevention, NIOSH is the main federal agency for conducting
Figure 1. Class II, type A2 BSC >30% exhaust.
100% of the cabinet’s contaminated airflow passes through the exhaust HEPA filter
60% of the cabinet’s total airflow passes through the supply HEPA filter
40% of the total cabinet’s airflow passes through the front access opening, creating an air barrier
Figure 2. Class II, type B2 100% exhaust. 6
G REEN H ILL H EALTHCARE C OMMUNICATIONS
research in occupational safety and health matters. In 2004, NIOSH released the High Risk Drug Alert, which offered a new standard of practice for handling high-risk drugs. These are guidelines only, but they could form the basis for regulatory action by the Occupational Safety and Health Administration, Aslo said. The intent of the alert, much of which emphasized antineoplastic agents, was to educate healthcare providers to the danger of exposure to high-risk drugs; to minimize potential health risks through procedures for handling hazardous drugs, engineering controls, and proper use of protective equipment; and to optimize operator protection and safety. The difference between USP <797> and the NIOSH alert is that USP <797> focuses on protecting the CSP from harm stemming from lack of sterility and inaccuracy, whereas the NIOSH alert focuses on protecting the compounding personnel and others from harm due to the nature of the handled drugs, she said. “These two documents were initially created with little communication, but USP <797> has incorporated elements of the NIOSH alert into its standards,” Aslo noted. The implementation of these two documents focuses on three areas: (1) environmental and engineering controls, (2) personnel work practices, and (3) competency testing and documentation. “These are three criteria for making your facility compliant,” she said.
Requirements Essentially, the requirements are: • Separate CSP storage, preferably in a negative-pressure room with sufficient exhaust (negative pressure 7 room); antiemetics, antibiotics, and other agents are stored separately from the chemotherapy compounds • Personal protective equipment at all times • Preparation in an International Organization for Standardization (ISO) class 5 biological safety cabinet (BSC) located in an ISO class 7 area • Adequate training for all personnel, with documentation. Environmental and engineering controls The key engineering feature is the construction of a controlled environment, which is, in fact, mandated for compounding sterile preparations and sterile hazardous drugs. Clean rooms must have a controlled level of contamination, as specified in the guidelines according to number of particles/meter3 and maximum particle size, and ante-
Engineering Specifics for a Controlled Environment ISO class 5 BSC (“hoods”) equipment is required: Class II, type A2 BSC (Figure 1) •30% exhaust, 70% recirculated air •used for compounding CSPs •must be located in ISO class 7 positive pressure clean room Class II, type B2 total exhaust (Figure 2) • 100% total exhaust (no recirculation) • used for compounding hazardous drugs • must be located in ISO class 7 negative pressure clean room Glove boxes • 100% total exhaust (no recirculation) • provide physical barrier between operator and compounding activity • materials passed into the main working chamber through enclosed chamber and accessed through glove ports to perform aseptic manipulations BSC indicates biological safety cabinet; ISO, International Organization for Standardization.
rooms must separate the general area from the compounding area. Aslo listed specific guidelines for constructing this controlled environment (see sidebar). “Engineering makes these things happen,” she said. “We have all our ventilation to the roof, both for our chemo area (which is negative pressure) and our non-chemo area (positive pressure). We have four type B2 hoods that are vented completely to the outside.” For centers that do not yet have these controlled environments, she suggested, “Start by assessing the situation for what needs to be done and how far you are from this goal. Determine what it would take to build a clean room and anteroom by first examining your floor plan.”
Other steps you can take Meanwhile, there are other steps one can easily take to enhance a controlled environment: restrict traffic to authorized staff only, forbid food and beverages in the compounding area, reduce clutter and remove any garbage, improve cleaning practices, mandate personal protective equipment, use aseptic techniques during compounding and hazardous drug handling, limit microbial and particulate contamination, and obtain a baseline particle count and monitor every 6 months. Continued on page 8
The 5th Annual Conference of the Hematology/Oncology Pharmacy Association was held at the Doral Marriott in Miami, Florida, June 17-20. A total of 728 participants, including pharmacists and industry representatives, participated in workshops, symposia, poster sessions, and other events.
Influencing, Empowering Others Key to Successful Clinical Practice Leadership MIAMI—Although leadership and management are often used interchangeably, good leadership actually focuses on people (inErnest R. Anderson, Jr., fluencing the MS, RPh behavior of others), whereas management focuses on things (the process of working to accomplish goals), according to two presentations given at the 5th annual conference of the Hematology/Oncology Pharmacy Association. “Building strong leadership skills is especially important in a clinical practice because pharmacists are some of the best people to get stuff done—and the ones who doctors and nurses come to,” said Ernest R. Anderson, Jr., MS, RPh, system vice president of pharmacy, Caritas Christi Health Care, Brighton, Massachusetts, during the meeting’s keynote lecture. “They trust us. Relationships are important.”
Anderson said that high-impact leaders innovate, originate, focus on people and feelings, create movement, espouse a long-range view, challenge the status quo, focus on the what and the why, empower others, ask for feedback, and do the right things. “Leaders are judged on what they say and what they do,” explained Anderson. In addition, emotional intelligence (the ability to identify, assess, and manage the emotions of self, others, and groups) and the practice of servant leadership (a philosophy where the leader is a humble servant who ensures that other people’s highest priority needs are being served) are crucial elements to workplace success. “I think incorporating servant leadership is the best way that pharmacists can become good leaders,” said Anderson. “If you serve the people that are working for you and always ask, ‘How can I help you succeed?’ you’ll win their hearts and souls. If you make them feel important, that’s the greatest way to quickly win them over. And it will make you stand out.”
“I think the first step is realizing you can be a good leader,” said Judy L. Chase, PharmD, FASHP, director of clinical pharmacy services at the University of Texas M.D. Anderson Cancer Center in Houston, during her presentation on leadership for those new to practice. “Start small and do a good job, look for opportunities that expand your scope of experience, and seek out mentors to help you identify appropriate opportunities.” In addition, she explained that credibility is the foundation to leadership. This can include developing strong clinical and communication skills; being available and dependable, flexible and adaptable; and knowing how to say “I don’t know” when faced with a question or situation in which the answer Judy L. Chase, PharmD, is not known. FASHP “Good ways to maintain credibility include getting board certified, continuing your educa-
tion, staying in your scope of practice, and getting credentialed.” Chase said that leadership opportunities can include teaching (pharmacy, nursing, and medical staff training, pharmacy and nursing school lectures, preceptorship, and patient and family education); serving on committees within pharmacy or oncology departments, your institution, or professional organizations; getting involved with research projects; writing up presentations, posters, and articles; joining professional organizations; and mentoring or coaching others. “Early opportunities may not be perfect, but they will lead to better opportunities.” “Real leadership is not about big visions or world-changing initiatives,” concluded Chase. “It is about coaching somebody better, listening better, being more positive, and just making little differences. You will all have opportunities every day. It is whether you choose to lead or not that will make the difference.” —Deborah Brauser
Pharmacy-managed Anemia Clinic Increases Monitoring of Iron Studies, Guideline Adherence MIAMI—Oncology patients in a pharmacy-managed anemia clinic experienced more frequent laboratory monitoring of their baseline iron Jamie Poust, PharmD, studies and closer BCOP adherence to treatment guidelines, along with a higher trend in hemoglobin levels, compared with patients in a physician-managed control group, according to a retrospective chart review presented at the 5th annual conference of the Hematology/ Oncology Pharmacy Association. “The incidence of anemia in patients with cancer varies from 10% to 90% and is dependent on their type of cancer and treatment regimen,” reported Jamie Poust, PharmD, BCOP, oncology pharmacy specialist at the University of Colorado Hospital in Aurora, during her poster presentation.
A pharmacist-managed anemia clinic was created at the University of Colorado Cancer Center (UCCC) after the Colorado State Board of Pharmacy approved medication therapy management in 2006. Because little information has been documented about pharmacist-managed anemia clinics, this study was designed to determine their effects on adherence to an institutional anemia treatment algorithm compared with a patient group managed by physicians. “We sought to evaluate if having a pharmacist directly involved in patient care could improve outcomes,” Poust explained. “We know that physicians are very busy and don’t always have the time that they would like to maximize every patient-care issue.” The investigators reviewed electronic medical records and pharmacy records from patients with chemotherapyinduced anemia who received darbepoetin alfa through the UCCC anemia
clinic between March 2006 and March 2007 (n = 51; mean age, 57 years; 51% male) and a matched physician-managed control group (n = 47; mean age, 57 years; 57% male). Outcomes assessed included the number of patients who achieved target hemoglobin, an iron-study assessment, and adherence to treatment guidelines (a laboratory evaluation of hemoglobin, time to follow-up, and appropriate dose modifications based on measured hemoglobin values). Results showed that baseline iron studies were completed in 90% of the pharmacist-managed group, but in 0% of the physician-managed group (P = .0001). In addition, adherence to treatment guidelines in the pharmacist- and physician-managed groups was 87% and 17%, respectively (P = .0001). The average baseline hemoglobin level was 9.2 g/dL in the pharmacymanaged group and 10.6 g/dL in the one managed by physicians. Although more
patients in the pharmacist group achieved target hemoglobin levels (67% vs 55%, respectively), the difference was not statistically significant (P = .226). “Having an oncology pharmacist involved in direct patient care improves patient outcomes,” Poust said. “This service allowed for a designated pharmacist to focus specifically on anemia management and to maximize the clinical outcomes in that area. The physicians were very excited and supported this service.” When asked about future plans, Poust said, “With the new regulations of [erythropoiesis-stimulating agents] ESAs and the decline of their use, we are entertaining the idea of creating a supportive care clinic. This would continue to include anemia management but venture into other supportive care areas in cancer, such as nausea and vomiting management, pain management, and growth factor support.” —DB
G REEN H ILL H EALTHCARE C OMMUNICATIONS 7
Redesigned Chemotherapy Process Improves Accuracy and Decreases RPNs without Increasing Time Burden MIAMI—An academic medical center’s renovated pharmacy chemotherapy process demonstrated an improvement in safety and accuracy, and reduced steps and risk priority numbers (RPNs) without increasing the time burden, according to a study presented at the 5th annual conference of the Hematology/Oncology Pharmacy Association. “We started a failure mode and effects analysis because we realized there were some problems with our current chemotherapy processing and some areas where there might be potential for errors to occur,” said lead investigator Jeremy Whalen, PharmD, oncology pharmacy resident at the University of Minnesota Medical Center (UMMC), Fairview, in Minneapolis. “Although we initially looked at the process with the doctors and the nurses and everybody, we narrowed the focus as we realized it would be easier to make
Jeremy Whalen, PharmD
that occurred at UMMC from when a pharmacist received a chemotherapy order to its delivery to the patient unit. They then identified what errors could occur and determined process changes that could be implemented to fix those particular errors. They did this by gath-
They found a total RPN reduction of 58%. The new process also reduced the overall required steps from 29 to 21. the changes that would make the process safer and more efficient if we started within the pharmacy.” At the beginning of the study, Whalen and his team listed all the steps
ering baseline information on safety, training, and time requirements of the current process and then completing a series of procedure tracers, reviewing current literature, and examining mod-
els from other institutions. “This process renovation was important because we noticed that a lot of the roles were being duplicated between the [intravenous] IV room pharmacists and the decentralized pharmacists,” Whalen explained. “We decided that it was important to define the roles and make the decentralized pharmacist more of a global position, so that these pharmacists were the ones doing the initial check, verifying everything, and then putting it into the computer system. That allowed the IV room pharmacist to be a complete, independent double-check in the process, ensuring safe preparation.” The investigators then developed new reference tools, including a dosage tracking sheet, a calculator for ease of preparing diluted solutions, a comprehensive chemotherapy database for the pharmacists, and chemotherapy preparation procedure cards for the technicians. The new tools were instituted with comprehensive training. Whalen said that at the study’s start, his team determined that a reduction in RPNs of 30% would be considered a success. At study’s end, they found a total RPN reduction of 58%. The new process also reduced the overall required steps from 29 to 21. Although time studies showed an increased time burden for each order review and entry for decentralized pharmacists (due to increased responsibili-
SAFE HANDLING Continued from page 6
Personnel work practices Medical surveillance programs for employees who routinely work with hazardous drugs are recommended by a number of professional organizations. The purpose is to detect changes in health status. This is achieved by monitoring medical history and exposure history, select laboratory values, comprehensive metabolic panel, liver enzymes, and urinalysis. A baseline examination should be done, with follow-up every 2 years, Aslo said. Competency testing and documentation are also important. “You need to set policies and procedures, then train your personnel according to those policies,” she advised. Staff should be trained for assigned tasks, including drug selection, aseptic techniques, calculations, proper labeling, administra-
G REEN H ILL H EALTHCARE C OMMUNICATIONS
Recent FDA Approvals
Complying with USP <797> For thorough and regular cleaning, which is mandatory, Aslo recommended this schedule: • Clean, sanitize, and organize the clean room • Sanitize counters and supply carts at the beginning of each shift and as needed • Clean counters and floors daily • Clean walls, ceilings, and shelving monthly • Clean work surfaces with an appropriate deactivation agent and cleaning agent before and after each activity and at the end of the work day. “Take these steps before you call in engineering,” she suggested. “You can make changes without undergoing major reconstructions. For example, you can use partitions or you can use a glove box. You have to show you are developing a program of compliance.”
ties) and a decreased time requirement for IV room pharmacists, the differences resulted in a slightly faster overall process. The preprocess change mean times were 18.7 minutes for decentralized pharmacists and 36.1 minutes for IV room pharmacists, for a summative mean of 54.8 minutes. Postprocess change times were 32.7, 17.4, and 50.1 minutes, respectively. In addition, although interruptions per order review and entry stayed virtually the same for decentralized pharmacists before and after the process implementation at 2.6 and 2.5, respectively, that number decreased significantly for IV room pharmacists, from 3.7 to 0.2. Because the study has been such a success, Whalen said that, “we’re now rolling out the new standardization process to the other hospitals and outpatient clinics within our healthcare system. So if techs go from site to site or between pharmacists, it will be the same steps.” When asked if he had any advice for those looking to streamline their own chemotherapy process, Whalen said, “I would really look at role definition and making sure everybody knows what they should be doing and that there’s not those duplications or areas for errors to occur. Also, just really look into standardization so that everyone is using the same process.”
tion processes, waste handling, and spill management. A comprehensive training program should incorporate proper use of all equipment, cleaning and decontamination, labeling, and compounding using aseptic techniques. Validated methods should be used to document decontamination twice a year. Staff should maintain a log of cleaning for the clean room and BSC. Staff should also complete an annual competency evaluation. Aslo reminded her listeners that the regulations are meant to enhance the safety of all parties. “The faster you incorporate these changes into your practices,” she said, “the better off your patients will be. And the more aware you make your staff, the better off they will be as well.”
• Pemetrexed for Maintenance Therapy in Advanced Nonsquamous NSCLC The US Food and Drug Administration (FDA) has approved pemetrexed (Alimta, Eli Lilly) for intravenous use, 100-mg and 500-mg vials, in maintenance treatment in patients with advanced or metastatic nonsquamous non–small-cell lung cancer (NSCLC) whose disease has not progressed after four cycles of platinumbased first-line chemotherapy. Pemetrexed is not indicated for treatment of patients with squamous cell NSCLC. • Mylan’s Generic Bicalutamide for Prostate Cancer The FDA has approved Mylan’s version of bicalutamide tablets, 50 mg, a generic version of Casodex (AstraZeneca). Bicalutamide is indicated for use in combination therapy with a leutinizing hormonereleasing hormone analog for the treatment of stage D2 metastatic carcinoma of the prostate. It is not approved for use alone or with other treatments. Mylan has begun to ship this product.
Faces at HOPA June 17-20, 2009, Doral Marriott, Miami, Florida
Thomas Sobba of ICU Medical explains the latest devices to Eileen Marley of Dallas.
Pamela MacAvoy of Mercy Hospital, Portland, Maine, chooses an Oncology Pharmacist mug.
John Valgus of the University of North Carolina (UNC) highlights the results of his research to Kamakshi Rao, also of UNC.
Dawn Goetz, Melissa Teichman, and Samantha Price of the H. Lee Moffitt Cancer Center, Tampa, Florida, get together with Susan Klenke and Leigh McFarland of the University of Kansas during the poster reception. Ali McBride of the H. Lee Moffit Cancer Center in Tampa, Florida, gives a big grin after presenting his poster on intravenous busulfan.
Nicole Moore of the Arthur G. James Cancer Hospital at Ohio State University shows off her poster on medicationrelated information received by patients.
Timothy Tyler of Palm Springs, California, chats with keynote speaker Ernest Anderson, of Brighton, Massachusetts.
Betty Chan of the University of Southern California checks out the latest issue of The Oncology Pharmacist.
Grazyna Riebandt confers with her colleagues Bonnie Blum and Sally Blackledge from the Roswell Park Cancer Center, Buffalo, New York.
Kathy DeGregory of the University of Virginia stops for a photo-op while visiting the Green Hill Healthcare booth.
Dave Pearsall, Bonnie Bovee, Mark Farmer, and John Parsons of TopoTarget gather for a group photo.
Dwight Kloth of Fox Chase Cancer Center, Philadelphia, discusses a point with Charles Flannery of GlaxoSmithKline Oncology.
Makala Pace of M.D. Anderson Cancer Center, Houston, Texas, listens intently as Jack Watkins of Methodist University Hospital, Memphis, Tennessee, clarifies his research.
FOR MORE PICTURES, VISIT WWW.THEONCOLOGYPHARMACIST.COM AND CLICK FACES AT HOPA ON THE HOMEPAGE FOR A COMPREHENSIVE COLLAGE. July/August 2009
G REEN H ILL H EALTHCARE C OMMUNICATIONS 9
Rituximab Rapid-infusion Protocol Can Save Up to 90 Minutes Compared with Standard-infusion Protocol MIAMI—Administering rituximab under a rapidinfusion protocol saves approximately 90 minutes per infusion compared with the Kelly M. Gregory, PharmD standard protocol, leading to a decrease in nursing overtime and allowing the scheduling of additional patients, according to a retrospective study presented at the 5th annual conference of the Hematology/Oncology Pharmacy Association. Lead investigator Kelly M. Gregory, PharmD, a pharmacy practice resident at the University of North Carolina Hospitals (UNCH) at Chapel Hill, presented the results in a poster session. She explained that the oncology clinics at UNCH regularly administer rituximab on an outpatient basis and have experienced a 16.5% increase in its use over the past 3 years. “As recent studies have shown the safety of a more rapid 90-minute infusion of rituximab in patients with non-Hodgkin’s lympho-
ma, we felt that implementing a rapidinfusion protocol could significantly impact patient visit time, improve resource utilization, and increase patient satisfaction.” So in this study, Gregory and her team sought to compare the total infusion time between the standard and rapid protocols, assess the impact on resources,
(cycles >1) as long as they experienced no infusion reactions in the past. Results showed that during the month of July 2008, a total of 56 standard protocol rituximab infusions were administered, with an average time of 188 minutes for cycles >1. From November 2008 to June 2009, a total of 309 rituximab infusions were
The most rewarding part is hearing that the patients at the clinic get to go home 90 minutes earlier. and quantify the potential cost-savings and revenue opportunity associated with the new implementation. The investigators examined baseline data from UNCH’s electronic pharmacy database on previous and current rituximab use administered under the standard-infusion protocol, and then obtained data retrospectively from November 2008 through May 2009 for each dose administered under the rapidinfusion protocol (the first 20% of the dose given over 30 minutes, the remaining 80% given over 60 minutes). Patients were considered eligible for rapid infusion for any cycle after the first
administered, 199 of which were eligible for the rapid-infusion protocol. Of these, 50 patients were treated with a total of 99 rapid infusions of rituximab. The rapid infusions had an average time of 97 minutes. “We found that we saved about 90 minutes per infusion with the implementation of the rapid protocol,” Gregory explained. Upon completion of data collection, the team also analyzed the protocol’s impact on resource utilization and developed a model to estimate the ability to backfill patients in their clinic. They found that approximately 450
infusions per year are eligible for the rapid protocol. In addition, the time saved by this protocol allows an additional two-and-one-half to three visits per week or 125 to 150 visits per year. Furthermore, no additional resource expenditure is required to make this increase in clinic capacity. “Based on a very conservative model, we can treat an additional 150 patients per year with no additional immediate resources needed in terms of extra chairs, extra nurses, etc,” said Gregory. “So that was great in terms of our economic outlook, and in money-saving and seeing more patients. However, I think the most rewarding part is hearing that the patients at the clinic get to go home 90 minutes earlier. The pharmacists at the outpatient infusion center have said that the overall responses of the patients have been incredibly positive.” She concluded, “I think the rapidinfusion protocol will become standard practice across the nation. At least it has at UNCH. We went from 14% of patients eligible in November to 85% in May. So it really has become widely accepted.” —DB
Chemotherapy Robot Reduces Cytotoxic Drug Exposures for Pharmacists, Technicians MIAMI—The CytoCare chemotherapy robot (Devon Robotics) improves safety by decreasing the amount of cytotoxic drug exposures for pharmacists and pharmacy technicians preparing chemotherapy orders, without reducing process efficiency, according to results from a pilot study presented at the 5th annual conference of the Hematology/Oncology Pharmacy Association. Jennifer Tobin, PharmD, oncology specialty resident in the Department of Pharmacy at the University of Colorado Hospital (UCH) in Aurora, said that UCH began piloting the chemotherapy robot in the fall of 2007, making it one of the first hospitals in the United States to use this new technology. According to the presentation, “occupational exposure to cytotoxic medications causes 1.4 to 10 cases of cancer per million workers each year.” It has also been linked to “sore throat, chronic cough, infections, eye irritation, headaches, and reproductive abnormalities.” The chemotherapy robot’s overall purpose at UCH has been to improve safety by minimizing the exposure to these hazardous drugs and to make chemotherapy preparation and dispensing more efficient and accurate, while
incurring cost-savings for its pharmacy department. Over a 3-week period, the investigators measured the efficiency of the robot process by comparing the time it took to fully complete a chemotherapy order (times from technician entering data into computer for the robot to begin preparation, for the robot to complete the preparation, and for final pharmacist verification and bagging for dispensing) versus the time it took for their standard manual process (including times for: technician to begin chemotherapy preparation, pharmacist to initiate and then complete double-check, and pharmacist to complete final verification and bagging for dispensing). The results showed that both processes had almost equal efficiency. The median total time to prepare chemotherapy for dispensing was 33 minutes for the chemotherapy robot process and 34 minutes for the standard pharmacist/technician process. However, Tobin said that the robot’s biggest overall advantage is that it does more than just reduce the risk of cytotoxic exposure, it totally eliminates it. “There’s absolutely no risk of exposure to pharmacists or pharmacy technicians
G REEN H ILL H EALTHCARE C OMMUNICATIONS
Jennifer Tobin, PharmD
during the entire process,” explained Tobin. “Everything is entered into a computer system, and then the chemotherapy is made entirely closed within the robot’s system.” She added that, as this is a pilot project, there are still a few problems with the new technology. “When it works, it works great,” said Tobin. “But just like every other big gadget, it’s not without its limitations, and there are instances where it doesn’t exactly make the medication correctly. So the robot fails, and then we have to revert back to our man-
ual process.” That is why at UCH the majority of cytotoxic medications are still currently made via standard processes. “The robotic process is still something we just do on the side,” Tobin said. Nonetheless, she is extremely optimistic about the chemotherapy robot. “In the long run, I think this is actually the way of the future—to have a process in place where we can make chemotherapy with no risk of exposure.” Tobin concluded, “When big new gadgets come out, the first ones always have some limitations. But once you’re able to work out the kinks, everything is great. I think this is the future for not only how we’re going to make cytotoxic medications but noncytotoxics as well.” —DB
Coverage of the HOPA 5th Annual Conference continues in the September/October issue of The Oncology Pharmacist.
STRONG. FROM THE START.
FOR A SUCCESSFUL CINV PREVENTION STRATEGY FROM THE FIRST CYCLE When patients experience acute chemotherapy-induced nausea and vomiting (CINV) during their first cycle of chemotherapy, they may have an increased risk of CINV on subsequent days and in subsequent cycles.1-3 ALOXI®: A single IV dose lasts up to 5 days after MEC4,5* The only IV 5-HT3 antiemetic specifically approved for prevention of both acute and delayed CINV associated with MEC6* Can be used with multiple-day chemotherapy regimens6† * Moderately emetogenic chemotherapy. † Based on sNDA approval in August 2007, the restriction on repeated dosing of ALOXI (palonosetron HCl) injection within a 7-day interval was removed.
ALOXI® (palonosetron HCl) injection 0.25 mg is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy, and acute nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy. Important Safety Information ALOXI is contraindicated in patients known to have hypersensitivity to the drug or any of its components. Most commonly reported adverse reactions include headache (9%) and constipation (5%). Please see the following brief summary of prescribing information. REFERENCES: 1. The Italian Group for Antiemetic Research. Dexamethasone alone or in combination with ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy. N Engl J Med. 2000;342:1554-1559. 2. Hickok JT, Roscoe JA, Morrow GR, et al. 5-Hydroxytryptamine-receptor antagonists versus prochlorperazine for control of delayed nausea caused by doxorubicin: a URCC CCOP randomised controlled trial. Lancet Oncol. 2005;6:765-772. Epub September 13, 2005. 3. Cohen L, de Moor CA, Eisenburg P, Ming EE, Hu H. Chemotherapyinduced nausea and vomiting: incidence and impact on patient quality of life at community oncology settings. Support Care Cancer. 2007;15:497503. Epub November 14, 2006. 4. Gralla R, Lichinitser M, Van der Vegt S, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol. 2003;14:1570-1577. 5. Eisenberg P, Figueroa-Vadillo J, Zamora R, et al. Improved Prevention of Moderately Emetogenic Chemotherapy-induced Nausea and Vomiting with Palonosetron, a Pharmacologically Novel 5-HT3 Receptor Antagonist: Results of a Phase III, Single-Dose Trial Versus Dolasetron. Cancer. 2003;98:2473-2482. 6. ALOXI® (palonosetron HCl) injection full prescribing information.
ALOXI® is a registered trademark of Helsinn Healthcare SA, Switzerland, used under license. Distributed and marketed by Eisai Inc. © 2008 Eisai Inc. All rights reserved. Printed in USA. AL349 A 10/08
New Study Suggests New Standard of Care for Patients with Advanced Biliary Tract Cancer ORLANDO—Two agents may be better than one when it comes to advanced biliary tract cancer. In the largest study of its kind, researchers have found that a combination of gemcitabine and cisALOXI® (palonosetron HCl) injection BRIEF SUMMARY OF PRESCRIBING INFORMATION INDICATIONS AND USAGE Chemotherapy-Induced Nausea and Vomiting ALOXI is indicated for: • Moderately emetogenic cancer chemotherapy – prevention of acute and delayed nausea and vomiting associated with initial and repeat courses • Highly emetogenic cancer chemotherapy – prevention of acute nausea and vomiting associated with initial and repeat courses DOSAGE AND ADMINISTRATION Recommended Dosing Chemotherapy-Induced Nausea and Vomiting Dosage for Adults - a single 0.25 mg I.V. dose administered over 30 seconds. Dosing should occur approximately 30 minutes before the start of chemotherapy. Instructions for I.V. Administration ALOXI is supplied ready for intravenous injection. ALOXI should not be mixed with other drugs. Flush the infusion line with normal saline before and after administration of ALOXI. Parenteral drug products should be inspected visually for particulate matter and discoloration before administration, whenever solution and container permit. CONTRAINDICATIONS ALOXI is contraindicated in patients known to have hypersensitivity to the drug or any of its components. [see Adverse Reactions (6) in full prescribing information ] WARNINGS AND PRECAUTIONS Hypersensitivity Hypersensitivity reactions may occur in patients who have exhibited hypersensitivity to other 5-HT3 receptor antagonists. ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates reported in practice. In clinical trials for the prevention of nausea and vomiting induced by moderately or highly emetogenic chemotherapy, 1374 adult patients received palonosetron. Adverse reactions were similar in frequency and severity with ALOXI and ondansetron or dolasetron. Following is a listing of all adverse reactions reported by ≥ 2% of patients in these trials (Table 1). Table 1: Adverse Reactions from ChemotherapyInduced Nausea and Vomiting Studies ≥ 2% in any Treatment Group ALOXI Ondansetron Dolasetron Event 0.25 mg 32 mg I.V. 100 mg I.V. (N=410) (N=633) (N=194) Headache 60 (9%) 34 (8%) 32 (16%) Constipation 29 (5%) 8 (2%) 12 (6%) Diarrhea 8 (1%) 7 (2%) 4 (2%) Dizziness 8 (1%) 9 (2%) 4 (2%) Fatigue 3 (< 1%) 4 (1%) 4 (2%) Abdominal Pain 1 (< 1%) 2 (< 1%) 3 (2%) Insomnia 1 (< 1%) 3 (1%) 3 (2%) In other studies, 2 subjects experienced severe constipation following a single palonosetron dose of approximately 0.75 mg, three times the recommended dose. One patient received a 10 mcg/kg oral dose in a postoperative nausea and vomiting study and one healthy subject received a 0.75 mg I.V. dose in a pharmacokinetic study. In clinical trials, the following infrequently reported adverse reactions, assessed by investigators as treatment-related or causality unknown, occurred following administration of ALOXI to adult patients receiving concomitant cancer chemotherapy: Cardiovascular: 1%: non-sustained tachycardia, bradycardia, hypotension, < 1%: hypertension, myocardial ischemia, extrasystoles, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles and QT prolongation. In many cases, the relationship to ALOXI was unclear. Dermatological: < 1%: allergic dermatitis, rash. Hearing and Vision: < 1%: motion sickness, tinnitus, eye irritation and amblyopia. Gastrointestinal System: 1%: diarrhea, < 1%: dyspepsia, abdominal pain, dry mouth, hiccups and flatulence.
platin may reduce the risk of death by 32% and the risk of cancer progression by 30% in patients with inoperable advanced gallbladder and bile duct cancer compared with gemcitabine treat-
ment alone. Until now, advanced biliary tract cancer had no scientifically proven effective treatment. “Based on these findings, we can now establish the first-ever standard of care for
General: 1%: weakness, < 1%: fatigue, fever, hot flash, flu-like syndrome. Liver: < 1%: transient, asymptomatic increases in AST and/or ALT and bilirubin. These changes occurred predominantly in patients receiving highly emetogenic chemotherapy. Metabolic: 1%: hyperkalemia, < 1%: electrolyte fluctuations, hyperglycemia, metabolic acidosis, glycosuria, appetite decrease, anorexia. Musculoskeletal: < 1%: arthralgia. Nervous System: 1%: dizziness, < 1%: somnolence, insomnia, hypersomnia, paresthesia. Psychiatric: 1%: anxiety, < 1%: euphoric mood. Urinary System: < 1%: urinary retention. Vascular: < 1%: vein discoloration, vein distention. Postmarketing Experience The following adverse reactions have been identified during postapproval use of ALOXI. 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. Very rare cases (<1/10,000) of hypersensitivity reactions and injection site reactions (burning, induration, discomfort and pain) were reported from postmarketing experience of ALOXI 0.25 mg in the prevention of chemotherapy-induced nausea and vomiting. DRUG INTERACTIONS Palonosetron is eliminated from the body through both renal excretion and metabolic pathways with the latter mediated via multiple CYP enzymes. Further in vitro studies indicated that palonosetron is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4/5 (CYP2C19 was not investigated) nor does it induce the activity of CYP1A2, CYP2D6, or CYP3A4/5. Therefore, the potential for clinically significant drug interactions with palonosetron appears to be low. Coadministration of 0.25 mg I.V. palonosetron and 20 mg I.V. dexamethasone in healthy subjects revealed no pharmacokinetic drug-interactions between palonosetron and dexamethasone. In an interaction study in healthy subjects where palonosetron 0.25 mg (I.V. bolus) was administered on day 1 and oral aprepitant for 3 days (125 mg/80 mg/80 mg), the pharmacokinetics of palonosetron were not significantly altered (AUC: no change, Cmax: 15% increase). A study in healthy volunteers involving single-dose I.V. palonosetron (0.75 mg) and steady state oral metoclopramide (10 mg four times daily) demonstrated no significant pharmacokinetic interaction. In controlled clinical trials, ALOXI injection has been safely administered with corticosteroids, analgesics, antiemetics/antinauseants, antispasmodics and anticholinergic agents. Palonosetron did not inhibit the antitumor activity of the five chemotherapeutic agents tested (cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C) in murine tumor models. USE IN SPECIFIC POPULATIONS Pregnancy Teratogenic Effects: Category B Teratology studies have been performed in rats at oral doses up to 60 mg/kg/day (1894 times the recommended human intravenous dose based on body surface area) and rabbits at oral doses up to 60 mg/ kg/day (3789 times the recommended human intravenous dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to palonosetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, palonosetron should be used during pregnancy only if clearly needed. Labor and Delivery Palonosetron has not been administered to patients undergoing labor and delivery, so its effects on the mother or child are unknown. Nursing Mothers It is not known whether palonosetron is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants and the potential for tumorigenicity shown for palonosetron in the rat carcinogenicity study, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use Safety and effectiveness in patients below the age of 18 years have not been established. Geriatric Use Population pharmacokinetics analysis did not reveal any differences in palonosetron pharmacokinetics between cancer patients ≥ 65 years of age and younger patients (18 to 64 years). Of the 1374 adult cancer patients in clinical studies of palonosetron, 316 (23%) were ≥ 65 years old, while 71 (5%) were ≥ 75 years old. No overall differences in safety or effectiveness were observed between these subjects and the younger subjects, but greater sensitivity in some older individuals cannot be ruled out. No dose adjustment or special monitoring are required for geriatric patients. Of the 1520 adult patients in ALOXI PONV clinical studies, 73 (5%) were ≥65 years old. No overall differences in safety were observed between older and younger subjects in these studies, though the possibility of heightened sensitivity in some older individuals cannot be excluded. No differences in efficacy were observed in geriatric patients for the CINV indication and none are expected for geriatric PONV patients. However, ALOXI efficacy in geriatric patients has not been adequately evaluated. Renal Impairment Mild to moderate renal impairment does not significantly affect palonosetron pharmacokinetic parameters. Total systemic exposure increased by approximately 28% in severe renal impairment relative to healthy subjects. Dosage adjustment is not necessary in patients with any degree of renal impairment. Hepatic Impairment Hepatic impairment does not significantly affect total body clearance of palonosetron compared to the healthy subjects. Dosage adjustment is not necessary in patients with any degree of hepatic impairment. Race Intravenous palonosetron pharmacokinetics was characterized in twenty-four healthy Japanese subjects over the dose range of 3 – 90 mcg/kg. Total body clearance was 25% higher in Japanese subjects compared to Whites, however, no dose adjustment is required. The pharmacokinetics of palonosetron in Blacks has not been adequately characterized. OVERDOSAGE There is no known antidote to ALOXI. Overdose should be managed with supportive care. Fifty adult cancer patients were administered palonosetron at a dose of 90 mcg/kg (equivalent to 6 mg fixed dose) as part of a dose ranging study. This is approximately 25 times the recommended dose of 0.25 mg. This dose group had a similar incidence of adverse events compared to the other dose groups and no dose response effects were observed. Dialysis studies have not been performed, however, due to the large volume of distribution, dialysis is unlikely to be an effective treatment for palonosetron overdose. A single intravenous dose of palonosetron at 30 mg/kg (947 and 474 times the human dose for rats and mice, respectively, based on body surface area) was lethal to rats and mice. The major signs of toxicity were convulsions, gasping, pallor, cyanosis and collapse. PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling (17.2) in full prescribing information Instructions for Patients • Patients should be advised to report to their physician all of their medical conditions, any pain, redness, or swelling in and around the infusion site [see Adverse Reactions (6) in full prescribing information]. • Patients should be instructed to read the patient insert.
G REEN H ILL H EALTHCARE C OMMUNICATIONS
Rx Only Mfd by OSO Biopharmaceuticals, LLC, Albuquerque, NM, USA or Pierre Fabre, Médicament Production, Idron, Aquitaine, France and Helsinn Birex Pharmaceuticals, Dublin, Ireland.
ALOXI® is a registered trademark of Helsinn Healthcare SA, Switzerland, used under license. Distributed and marketed by Eisai Inc., Woodcliff Lake, NJ 07677. © 2008 Eisai Inc. All rights reserved. Printed in USA. AL350 10/08
advanced biliary tract cancers. We found that adding cisplatin to gemcitabine therapy significantly slowed cancer progression and extended survival for these rare but hard-to-treat cancers,” said lead study author Juan Valle, MD, senior lecturer and medical oncologist at the University of Manchester, England. “Previous smaller studies supported these findings, but our study is the largest and most reliable study of patients with this cancer to ever be reported.” In this phase 3 National Cancer Research Network study, investigators randomized 410 patients in the United Kingdom with inoperable metastatic biliary tract cancers to receive either a combination of gemcitabine and cisplatin (n = 206) or gemcitabine alone (n = 204). Valle, who presented the study findings at the annual meeting of the American Society of Clinical Oncology, said the median age of the patients was 64 years (range, 23-85 years) and 47% were men. Patients had a variety of tumor types: gallbladder (36%), bile duct (59%), and ampulla (5%). Disease stage was either metastatic (75%) or locally advanced (25%). The researchers found that progression-free survival was longer among patients who received gemcitabine plus cisplatin (8.5 months) compared with those who received gemcitabine alone (6.5 months). The patients who received both drugs also lived significantly longer (11.7 vs 8.2 months) than patients on gemcitabine alone. “One of the problems with biliary tract cancers is that the numbers are small and there are a lot of small series and lots of small studies with just four or five patients,” Valle said. “So until now, there had been no consensus. One of the biggest advantages is that this puts to bed some of the questions about whether chemotherapy has any benefit at all. We know it is now an option. In the past that was in question.” He said gemcitabine plus cisplatin was generally well tolerated. The most common side effect was moderate neutropenia, occurring in 22.6% of patients receiving both drugs and 17.9% of those receiving gemcitabine alone. He noted, however, that most of the patients who suffered from neutropenia were asymptomatic. “The most important message is that chemotherapy should be considered as an option with patients with biliary tract cancer, and combination therapy appears to offer an advantage over monotherapy and it appears to be well tolerated,” Valle said. —John Schieszer
Continued from cover (KRAS) mutations have become established as biomarkers for the lack of efficacy of epidermal growth factor receptor–targeted monoclonal antibodies, and ASCO has issued a provisional clinical opinion calling for KRAS testing in patients with metastatic colorectal carcinoma. “Personalizing cancer care is all about bringing our insights and skills from biology, medicine, engineering, informatics, social sciences, and other disciplines to solving the enormous problem of can-
We will increasingly be able to design optimal treatment strategies that offer the best hope of controlling cancer with the least toxicity. Both patient and tumor are unique Personalized medicine begins with a concept that cancer specialists have long recognized: that each patient is unique in his or her clinical presentation, treatment response, and supportive care needs. But it also includes the growing recognition that tumors are also unique; therefore, personalized treatment plans should address both the patient and the tumor, he said. Among more than 100 drugs approved for more than 170 cancer indications, a growing number target specific abnormalities of the cancer. Molecular diagnostics are beginning to guide prescribing practice, based on germline variations in the patient and somatic mutations in the tumor. For example, Kirsten rat sarcoma
cer,” he said. “We will increasingly be able to design optimal treatment strategies that offer the best hope of controlling cancer with the least toxicity. And with sophisticated imaging techniques, such as volumetric computed tomography, we can more quickly assess treatment efficacy. This all has the potential to substantially reduce the cost of care.” Personalized cancer care does not cease at the end of treatment, but extends to end-of-life care and survivorship, he added, encouraging oncologists to personalize survivorship plans for their patients, and to communicate with survivors “as an individual and not a statistic, as a person with an illness within a social network.” “As oncologists, our focus has been and must remain treating the person, not the disease,” Schilsky reiterated.
10% of these will probably be approved, he predicted. “There are not enough patients, dollars, and time,” he said, “to test all these within our conMeeting the growing needs ventional clinical trial paradigm.” By 2030 the global cancer burden ASCO has convened an expert will triple and cancer will be the lead- group to tackle some of the key aspects ing cause of death. Because this will be of the clinical trials problem and to coupled with a 30% shortfall in oncol- produce a white paper for the US Food ogists, new approaches are greatly and Drug Administration. needed to meet these needs, he said. Meanwhile, Schilsky advocated for One part of the solution is the use of the use of biomarkers to streamline multidisciplinary care teams, the aim patient selection, preliminary marketing being to “extend the reach of oncology approval based on randomized phase 2 services” through mid-level providers. (rather than phase 3) trials, removal of Primary care providers, barriers to the completion of confirif oncologists “better matory trials, and streamlining of engage” them, can also the processes that support the filing help lighten the workof supplemental new drug applicaload, he said. tions for new indications. With regard to the Such changes would require the increasing cost of care, willingness of pharmaceutical “oncologists need to companies to trade the rewards be part of the converthey reap from short-term widesation and the soluspread use of a drug in large popution,” he maintained. Richard Schilsky, MD lations to long-term use of a drug A new ASCO task in more limited populations, and force is developing a plan of action will necessitate much greater participaon cost of care. Among the recom- tion in trials on the part of oncologists mendations will be greater emphasis and patients alike. on discussions with patients, uniform Most important, the clinical trials definitions of “value,” examination of process must be revamped for greater factors that underlie cost, and ad- efficiency. Currently, a phase 3 cooperavancement of steps related to compar- tive group trial requires close to 400 steps ative effectiveness. and 2 years to launch because of a Finally, clinical trial obstacles must bureaucratic process that involves a mulbe overcome, he said. The US research titude of review loops, regulatory requireinfrastructure is “the best in the world” ments, and contract negotiations. but is underfunded and “mired in a reg“We must fix this problem now,” ulatory matrix that slows our progress Schilsky concluded, “because our and saps our energy,” Schilsky noted. patients cannot wait.” In 2009, more than 700 drugs are in development for cancer, but fewer than —CH “We must acquire the skills and devote the time and receive compensation for doing so in an optimal way.”
Photo courtesy of American Society of Clinical Oncology.
global economic recession, high unemployment, declining physician workforce, and lack of universal access to optimal care. “But it has also been a year of great hope, as we have a new administration that is committed to curing cancer,” Schilsky told annual meeting attendees, in his presidential address. “We hear much about personalized medicine. It is the new buzzword in healthcare and health policy. But what does it mean to patients and oncologists?” he asked.
Trastuzumab Improves Survival in Gastric Cancer
improved overall survival with a personalized, targeted treatment for gastric cancer,” Van Cutsem said, adding that it is the first time trastuzumab has been shown to improve survival in a tumor other than breast cancer. David Cunningham, MD, consultant, Royal Marsden Hospital, United Kingdom, who discussed the study at the oral session, commented, “This is an absolutely excellent study. It was a major undertaking to screen nearly 4000 patients for the presence of HER2 expression, and to recruit them for treatment in a timely fashion. All the end points were positive.”
HER2 overexpression found in 22% of patients Similar to what is seen in breast cancer, HER2 overexpression is often found in gastric cancers. Investigators from the
ToGA study, which involved sites in with the combination. The overall Europe, Latin America, and Asia, test- response rate with the combination ed 3807 patients with advanced gastric was 47.3% versus 34.5% with chemocancer for overexpression of HER2, therapy alone, again a highly signifiwhich they found in 810 cant difference (P = .0017). patients (22%). In a preplanned subgroup The study then randomanalysis, patients with the highest ized 594 HER2-positive degree of HER2 overexpression patients to standard chemo(fluorescence in situ hybridizatherapy or chemotherapy tion–positive/3+ by immunohisplus trastuzumab, given tochemistry) had even greater every 3 weeks for six cycles, benefit from trastuzumab, overall with trastuzumab continued survival being 17.8 months versus until disease progression. 12.3 months for chemotherapy Eric Van Cutsem, Median overall survival MD, PhD alone. This represented a 42% was significantly greater reduction in the risk of death. with the addition of trastuzumab, 13.8 The combination was well tolerated, versus 11.1 months with standard with no significant increase in the chemotherapy (P = .0048), Van Cutsem occurrence of symptomatic congestive reported. heart failure; as expected, however, After a median of 17 months of folContinued on page 18 low-up, mortality was reduced by 26% Photo courtesy of American Society of Clinical Oncology.
ORLANDO—Although trastuzumab is thought of as a breast cancer drug, when it is added to chemotherapy for gastric cancer, it outperformed the standard treatment for this tumor in patients overexpressing human epidermal growth factor receptor 2 (HER2), according to the results of an international, randomized, phase 3 trial reported at the annual meeting of the American Society of Clinical Oncology (ASCO). In the first large phase 3 study of trastuzumab in patients with gastric cancer, patients receiving trastuzumab had a 26% reduction in the risk of death, compared with chemotherapy with cisplatin and capecitabine or 5fluorouracil (5-FU), reported Eric Van Cutsem, MD, PhD, University Hospital Gasthuisberg, Leuven, Belgium. “This is the first phase 3 study to report
G REEN H ILL H EALTHCARE C OMMUNICATIONS 13
Personalizing Cancer Care
AT WWW.THEONCOLOGYPHARMACIST.COM Program #CIK10188 • RELEASE DATE: August 15, 2009 • EXPIRATION DATE: August 14, 2010
EDITORIAL BOARD Betty M. Chan, PharmD, BCOP Assistant Professor of Clinical Pharmacy University of Southern California Clinical Pharmacist USC/Norris Comprehensive Cancer Center 1441 Eastlake Avenue Los Angeles, CA 90033
Gregory S. Cooper, MD Division of Gastroenterology University Hospitals Case Medical Center 11100 Euclid Avenue Cleveland, OH 44106-5066 Tzuyung Doug Kou, MPH, MA Comprehensive Cancer Center Case Western Reserve University 11100 Euclid Avenue Cleveland, OH 44106-5066 Harry L. Reynolds, Jr., MD Division of Colorectal Surgery University Hospitals Case Medical Center 11100 Euclid Avenue Cleveland, OH 44106-5066 Pamela Hallquist Viale, RN, MS, CS, ANP, AOCNP Oncology Nurse Practitioner Saratoga, CA 95970 Assistant Clinical Professor Dept of Physiological Nursing University of California San Francisco Box 0610 San Francisco, CA 94143-0610
PLANNING COMMITTEE Lois Colburn Executive Director Center for Continuing Education University of Nebraska Medical Center 986800 Nebraska Medical Center Omaha, NE 68198-6800 Brenda Ram, CMP Coordinator Center for Continuing Education University of Nebraska Medical Center 986800 Nebraska Medical Center Omaha, NE 68198-6800 Dawn Lagrosa Associate Editor Green Hill Healthcare Communications, LLC 241 Forsgate Drive Monroe Twp, NJ 08831 Karen Rosenberg Editorial Director Green Hill Healthcare Communications, LLC 241 Forsgate Drive Monroe Twp, NJ 08831
Follow-up Care in Medicare Beneficiaries with Colorectal Cancer BY GREGORY S. COOPER, MD1,2; TZUYUNG DOUG KOU, MPH, MA2; HARRY L. REYNOLDS, JR., MD3 1Division of Gastroenterology, University Hospitals Case Medical Center; 2Comprehensive Cancer Center, Case Western Reserve University; 3Division of Colorectal Surgery, University Hospitals Case Medical Center, Cleveland, Ohio
HOW TO RECEIVE CREDIT To receive continuing education credit, learners must: • Read the article in its entirety • Take the CE self-assessment test and complete the evaluation test: 1. Log on to www.theoncologypharmacist.com. 2. Click on “CE Credits.” 3. Click on “Click Here To complete the post-test and obtain a CE certificate online.” 4. Click on “CE Credits.” 5. Enter program # CIKI0188 • The learner must answer at least 70% of the questions on the post-test correctly. • The estimated time to complete this activity is 1 hour. Your continuing education certificate can be printed by following the directions online after successful completion of the post-test. DISCLAIMERS The opinions or views expressed in this continuing education activity are those of the faculty and do not necessarily reflect the opinions or recommendations of the University of Nebraska Medical Center (UNMC), Center for Continuing Education.
outine postoperative surveillance is recommended for patients with colorectal cancer who undergo potentially curative resection.1-8 The goals of surveillance are to detect recurrent cancer in the colon or metastatic sites before the onset of other symptoms or signs, as well as to screen for cancers and polyps. Most guidelines recommend a combination of regularly scheduled office visits, colonoscopy, and carcinoembryonic antigen (CEA) testing, and two metaanalyses have reported improved long-term survival compared with minimal follow-up.9,10 However, there are no national, populationbased studies on the actual adherence to published comprehensive guidelines, as well as on the potential use of excessive testing. We therefore conducted the present study to determine compliance with guideline-based surveillance recommendations as well as to describe the potential overuse of follow-up testing in colorectal cancer survivors.
Methods The cohort was identified from a database that included tumor reg-
LEARNING OBJECTIVES After completing this activity, the reader should be better able to: • Describe current guidelines for follow-up care of colorectal cancer survivors • Discuss how these guidelines are applied in clinical management of elderly patients • Explain reasons for disparities between recommended care and that received by elderly patients TARGET AUDIENCE Registered pharmacists and other interested healthcare professionals, especially those caring for cancer patients. COST This program is complimentary for all learners.
istry data from the Surveillance, Epidemiology and End Results (SEER) Program and Medicare claims data.11,12 SEER consists of a series of population-based registries that capture approximately 25% of the US population, and for patients who are age-eligible (65 years and older) Medicare beneficiaries, inpatient, outpatient, and physician-supplier Medicare claims are linked. Patients were included if they were diagnosed with adenocarcinoma of colon or rectum during years in which oncology society guidelines were continuously available, 2000 through June 2001. The follow-up period of interest was from 6 months after diagnosis through 42 months after diagnosis. Procedures within 6 months were excluded to avoid including tests to evaluate possible postoperative complications and routine postoperative visits. Procedures were identified through billing codes and included office visits, CEA testing, colonoscopy, computed tomography (CT) scan, and positron emission tomography (PET) scan. Continued on page 16
FACULTY/PLANNER DISCLOSURES It is the policy of the University of Nebraska Medical Center, Center for Continuing Education that all planners and faculty participating in continuing education activities provided by the University of Nebraska Medical Center, Center for Continuing Education are to disclose to the audience any real or apparent conflicts of interest with providers of commercial products and/or devices relating to the topics of this educational activity and also disclose discussion of labeled/unapproved uses of drugs or devices discussed in their presentation. The planners and faculty have been advised that this activity must be free from commercial bias and based upon all the available scientifically rigorous data from research that conforms to accepted standards of experimental design, data collection, and analysis. The authors, reviewers, and planning committee members list-
While the University of Nebraska Medical Center, Center for Continuing Education is an ACPE-accredited organization, this does not imply endorsement by the UNMC or ACPE of any commercial products affiliated with this activity.
G REEN H ILL H EALTHCARE C OMMUNICATIONS
ed below have stated they have no significant or substantial relationship with providers of commercial products and/or devices discussed in this activity and/or with any commercial supporter of this activity. • Lois Colburn • Gregory S. Cooper, MD • Tzuyung Doug Kou, MPH, MA • Dawn Lagrosa • Brenda Ram, CMP • Karen Rosenberg The following authors have stated that he/she has the following financial relationships: • Betty M. Chan, PharmD, BCOP, has received research/ grant support from Merck & Co. • Pamela Hallquist Viale, RN, MS, CS, ANP, AOCNP, is a speaker for Amgen, Bristol-Myers Squibb, Merck & Co, and Novartis. She also is on the advisory board for Bristol-Myers Squibb.
• Harry L. Reynolds, Jr., MD, is a course instructor for Covidien. ACCREDITATION AND CONTACT HOURS STATEMENT The University of Nebraska Medical Center, Center for Continuing Education is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. The ACPE provider number is 447-000-09-068-H04-P. To receive the 1 contact hour of continuing education credit, pharmacists should complete the activity requirements and evaluation at the conclusion of the activity. Approval is valid from the initial release date of August 15, 2009. The expiration date is August 14, 2010. A statement of credit will be available for printing online upon completion of the post-test with a score of 70% or better and the evaluation instrument.
AT WWW.THEONCOLOGYPHARMACIST.COM Program #CIK10188 • RELEASE DATE: August 15, 2009 • EXPIRATION DATE: August 14, 2010
Table. Recommended Colorectal Cancer Surveillance Guidelines Guideline (year)
American Gastroenterological Association (1989)a
Every 3-6 months for 2 years, then 6-12 months for 2 years
Every 2 months for 2 years, then every 4 months for 2 years
1 year, then every 3 years
American Society of Clinical Oncology (1999, 2000)
Every 6 months for 3 years
Every 2-3 months for at least 2 years in stages II and III
Every 3-5 years
American Society of Clinical Oncology (2005)b
Every 3-6 months for 3 years
Every 3 months for at least 3 years in stages II and III
3 years; if normal, every 5 years
American Society of Colon and Rectal Surgeons (2004)c
At least three times yearly for 2 years
At least three times yearly for 2 years
Every 3 years
National Comprehensive Cancer Network (updated yearly)
Every 3-6 months for 2 years, then every 6 months
Every 3-6 months for 2 years, then every 6 months
1 year, 3 years later, 5 years later
CEA indicates carcinoembryonic antigen; CT, computed tomography; FOBT, fecal occult blood test. aAlso recommend FOBT and liver enzymes every 3-6 months for 2 years then every 6-12 months for 2 years, chest x-ray every 6-12 months for 2 years then yearly. bAlso recommend annual CT scans for patients at higher risk of recurrence. cAlso recommend considering annual CT scans for patients at high risk for recurrence (ie, lymphatic or venous invasion or poorly differentiated tumors). Reprinted with permission from Cooper GS, Kou T, Reynolds HL. Receipt of guideline-recommended follow-up in older colorectal cancer survivors. Cancer. 2008;113:2029-2037. ©2008. Wiley-Liss, Inc.
COMMENTARY Follow-up Care in Medicare Beneficiaries with Colorectal Cancer: A Pharmacist’s Perspective BY BETTY M. CHAN, PHARMD, BCOP University of Southern California/Norris Comprehensive Cancer Center, Los Angeles
n the article by Cooper and colleagues on followup care in Medicare beneficiaries with colorectal cancer, the authors report that the majority of patients (92.3%) fulfilled the surveillance guidelines for physician follow-up office visits, but overall guideline-based recommendations were met in only 17.1% of patients, with 60.2% of patients receiving testing below the minimum frequency. Being aged 70 to 74 years, African-American race, having local-stage, nonpoorly differentiated colorectal cancers, and increased comorbidity scores were factors identified by the authors as most strongly associated with lack of guideline adherence. Since 1998, incidence rates of colorectal cancer have been rapidly declining among both men and women.1 Between 1996 and 2004, only 40% of patients with colorectal cancer were diagnosed with local-stage disease, for which the 5-year relative survival rate is 90%; for patients diagnosed with regionalstage disease, the 5-year relative survival rate decreases to 68%, and for patients diagnosed with distant-stage disease, the 5-year relative survival rate decreases further to 11%.2 With the introduction of 5fluorouracil–based adjuvant chemotherapy for stage III resectable colon cancer in the late 1980s, mortality from colon cancer was further reduced by 30%.3 These statistics, along with the case study included by Cooper and colleagues, further illustrate the impor-
tance of follow-up and surveillance for cancer survivors with early stages of disease. Posttreatment surveillance of colorectal cancer patients is performed to evaluate for possible therapeutic complications and to discover early recurrence of disease at its early resectable stages, which allows for curative treatment, as well as at its preinvasive stage, which affords for better treatment outcomes. Several meta-analyses of randomized controlled trials have demonstrated the advantages of intensive follow-up surveillance for colorectal cancer patients.4-7 The National Comprehensive Cancer Network clinical practice guidelines regarding colon cancer patients recommend outlining a prescription plan for survivorship upon transfer of care to a primary care physician, which should include8: • Overall summary of treatment received, including all surgeries, radiation, and chemotherapy • Description of clinical course, including expected time to resolution of acute toxicities, long-term effects of treatment, and possible late sequelae from treatment • Recommendations for follow-up surveillance. Although surveillance guidelines are available for clinicians, adherence to the guidelines can be a challenge and often requires a multidisciplinary approach that involves the patients and their family members or caregivers to ensure patient compliance with follow-
up appointments. Oncology nurses and pharmacists can also assist by developing follow-up care plans and a patient-care database to help track and document methods of follow-up and surveillance.
References 1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71-96. 2. Ries L, Melbert D, Krapcho M, et al. SEER Cancer Statistics Review 1975-2005. http://seer.cancer.gov/csr/1975_2005/. Based on November 2007 SEER data submission, posted to the SEER website 2008. Accessed July 8, 2009. 3. Moertel CG, Fleming TR, Macdonald JS, et al. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990;322:352-358. 4. Figueredo A, Charette ML, Maroun J, et al. Adjuvant therapy for stage II colon cancer: a systematic review from the Cancer Care Ontario Program in evidence-based care’s gastrointestinal cancer disease site group. J Clin Oncol. 2004;22:3395-3407. 5. Jeffery M, Hickey BE, Hider PN. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database Syst Rev. 2007:CD002200. 6. Renehan AG, Egger M, Saunders MP, O’Dwyer ST. Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials. BMJ. 2002;324:813. 7. Hewitt M, Greenfield S, Stovall E; for the Committee on Cancer Survivorship: Improving Care and Quality of Life, Institute of Medicine and National Research Council. From Cancer Patient to Cancer Survivor: Lost in Transition. Washington, DC: The National Academies Press; 2006. 8. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. V.2.2009. www.nccn.org/professionals/physician_gls/PDF/colon.pdf. Accessed July 8, 2009.
G REEN H ILL H EALTHCARE C OMMUNICATIONS 15
AT WWW.THEONCOLOGYPHARMACIST.COM Program #CIK10188 • RELEASE DATE: August 15, 2009 • EXPIRATION DATE: August 14, 2010 The primary outcome of interest was adherence to professional society guidelines for routine surveillance, such as those of the American Society of Clinical Oncology (ASCO)2,3 and the National Comprehensive Care Network (NCCN)6 (Table). Because we could not ascertain which individual set of guidelines was most likely referenced in practice, we selected a composite minimum frequency of service and procedure receipt to measure guideline adherence: • Guidelines met: two or more office visits per year, two or more CEA tests per year in years 1 and 2, one or more colonoscopies within 3 years • Excess of guidelines: patient met guidelines and received one or more CT scans for cancers not poorly differentiated and/or one or more PET scans. All others were considered to have failed to have
met guidelines. Differences in the proportion of eligible patients who met guidelines for individual procedures (office visits, CEA testing, colonoscopy) as well as overall guidelines were compared according to patient and clinical characteristics, and a multivariable logistic regression model was used to determine the independent association of factors with receipt of meeting or exceeding guidelines (vs not meeting guidelines). The study was approved by the Institutional Review Board at University Hospitals Case Medical Center.
Results A total of 9426 patients (mean age, 76.9 years; 54.5% women) who met the study eligibility criteria were identified. We found that 92.3% of patients fulfilled surveillance guidelines for office visits, with at least two
visits in each year of follow-up. Although statistically significant differences were found across certain patient subgroups, with the exception of age ≥80 years, the differences in general were not of large magnitude. We found that only 46.7% of patients in the study cohort met the guideline-based recommendations for CEA testing, lower rates being associated with age ≥80 years, African-American race, and increased comorbidity scores. Certain cancer-specific characteristics were associated with greater use of CEA testing (ie, regionalvs local-stage, poorly differentiated vs others), but no more than 63.5% of a specific subgroup fulfilled the testing criteria. Only 73.6% of patients met guideline-specified criteria for colonoscopy (at least one examination within 3 years of diagnosis). Advancing age, especially age 70 to 74 years, African-American race, and increased
COMMENTARY Follow-up Care in Medicare Beneficiaries with Colorectal Cancer: A Nurse’s Perspective BY PAMELA HALLQUIST VIALE, RN, MS, CS, ANP, AOCNP Oncology Nurse Practitioner, Saratoga, California; Department of Physiological Nursing, University of California San Francisco
lthough reductions have occurred in the death rate from colorectal cancer, this tumor type remains the third most commonly occurring cancer for both men and women, and the third leading cause of cancer death for both sexes.1 The majority of these cancers occur in the elderly, with a median age at diagnosis of 71 years. Despite this fact, the elderly do not participate in many clinical trials and may also receive less than standard therapy or guideline-based care compared with their younger counterparts.2,3 Recently, a national, retrospective chart review of 520 elderly patients treated in community practices noted that these patients were less likely to receive first-line doublet chemotherapy than younger patients and that the use of targeted therapy agents, such as bevacizumab, was much lower in the elderly population as well.2 The reasons for the treatment disparity included the presence of comorbidities, which could have prevented elderly patients from being able to receive doublet chemotherapy, and the fact that many of these older patients required hospitalization for their increased adverse side effects, such as gastrointestinal complaints.2 The literature indicates that the elderly should not be considered for treatment by their chronological age alone, and comprehensive evaluation, including assessment of the preferences of the elderly patients themselves, is essential in determining the appropriate treatment.4 The treatment disparities described above are primarily related to concerns regarding the increased adverse events and higher hospitalization rates associated with chemotherapy and targeted therapy agents in the elderly. Cooper and colleagues, however, also noted disparities in the surveillance care
of elderly patients after their initial treatment. Surveillance guidelines included recommendations for biomarker testing, visits to clinicians, and radiographic tests or procedures. In their study, elderly patients received carcinoembryonic antigen (CEA) testing below the reommended guidelines and did not undergo the recommended colonoscopy examinations as frequently as recommended either. Cooper and colleagues note that these results reflect a large population of colorectal cancer survivors who should be receiving adequate surveillance to determine recurrence of disease. In addition, differences in frequency of surveillance testing were noted in certain racial groups, such as African Americans, which could affect overall survival. The authors point out limitations to their data, such as accuracy of procedure coding for Medicare patients and lack of information for the reason procedures were performed. Nonetheless, the observed disparities between the recommended frequency of testing and the actual frequency of testing are disturbing, and the authors recommend further study of the reasons for poor adherence to guidelines in this population as well as its potential effect on patient outcome. Because colorectal cancer remains a common cancer in the elderly, clinicians, including oncology nurses, should have increased awareness of the specific needs of this population of patients. The National Comprehensive Cancer Network (NCCN) provides specific clinical practice guidelines for the care of the senior adult oncology patient, which call for careful assessment and an individual approach.5 Assessment tools for geriatric functional assessment are included, and clinicians are cautioned to remain aware of the specific physical needs of the older
G REEN H ILL H EALTHCARE C OMMUNICATIONS
patient. After active treatment has concluded, surveillance should be conducted to determine whether there are posttreatment complications and to detect recurrence of disease as early as possible, rendering metastatic disease potentially curable.6 The 2009 NCCN clinical practice guidelines for colon cancer survivors call for history and physical examination every 3 to 6 months for 2 years, then every 6 months for 3 years, with CEA testing every 3 to 6 months for 2 years, then every 6 months for 3 years.6 A computed tomography scan of the abdomen and pelvis should be conducted annually for 3 years, with a colonoscopy at 1 year, repeated as clinically indicated.6 These recommendations apply to all patients, with no differences noted in frequency of surveillance testing for elderly patients. Oncology nurses and clinicians should advocate for compliance with guideline-based treatment and surveillance for elderly patients. Future studies should gather additional information regarding compliance and recommended surveillance for this population.
1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71-96. 2. McKibbin T, Frei CR, Greene RE, et al. Disparities in the use of chemotherapy and monoclonal antibody therapy for elderly advanced colorectal cancer patients in the community oncology setting. Oncologist. 2008;13:876-885. 3. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106-130. 4. Sanoff HK, Bleiberg H, Goldberg RM. Managing older patients with colorectal cancer. J Clin Oncol. 2007;25:1891-1897. 5. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Senior Adult Oncology. V.2.2007. www.nccn.org/professionals/physician_gls/PDF/senior.pdf. Accessed January 24, 2009. 6. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. V.1.2009. www.nccn.org/professionals/physician_gls/PDF/colon.pdf. Accessed January 24, 2009.
AT WWW.THEONCOLOGYPHARMACIST.COM Program #CIK10188 • RELEASE DATE: August 15, 2009 • EXPIRATION DATE: August 14, 2010
Case Study An otherwise healthy 70-year-old AfricanAmerican man presented for first-time screening colonoscopy and was found to have a nonobstructing mass lesion in the cecum with pathology showing well-differentiated adenocarcinoma. In addition, two polyps were removed from the sigmoid colon, each of which was a tubular adenoma. He underwent right hemicolectomy, with the surgical margins free of residual cancer and 14 lymph nodes negative for malignancy. Postresection, his carcinoembryonic antigen level was 1 ng/mL. He was considered to be TNM Stage II, and a medical oncology consultant did not recommend adjuvant chemotherapy. He was seen by the surgeon 2 weeks, 1 month, and 3 months postoperatively and, because he had made a complete recovery, no further surgical follow-up was recommended. Approximately 1 year after surgery, he presented to his primary care physician for routine evaluation. The primary care physician assumed that any recommended cancer-related follow-up would be coordinated by other specialists and recommended that he return for an annual physical examination in 1 year. When the patient returned at that time, he reported a 3-month history of intermittent rectal bleeding and was referred for an urgent colonoscopy. He was found to have an ulcerated mass in the sigmoid colon, with pathology showing moderately well-differentiated adenocarcinoma, requiring a subtotal colectomy.
comorbidity scores were associated with decreased use of colonoscopy. Across the SEER registries, the vast majority of patients in all sites received the requisite number of office visits (range, 86.0%-95.6%), but there was wider variation in adherence with colonoscopy (67.6%-78.8%) and CEA testing (37.2%-49.8%). When we examined the use of two procedures that are not routinely recommended for cancer surveillance, abdominal/pelvic CT scans and PET scans, we found that 47.7% of patients received at least one CT scan. Although guidelines recommend that CT scanning be considered for poorly differentiated tumors, we found that 51.4% of patients with poorly differentiated cancer compared with 47.1% of others underwent CT scans. Overall, the findings showed that guideline-based recommendations were met in 17.1% of patients and exceeded in 22.7%, 60.2% receiving testing below the minimum frequency. Among the factors that were most strongly associated with lack of adherence to guidelines were local stage and nonpoorly differentiated cancers. Age 70 to 74 years, African-American race, and increased comorbidity scores were also associated with less than recommended surveillance included. In a multivariate logistic regression model, the variables that were most strongly associated with meeting or exceeding guidelines for surveillance care were younger age group and regional-stage cancers. Patients who were non–African-American and who had lower inpatient comorbidity scores and poorly differentiated
cancers were more likely to undergo testing. Differences were also observed across geographic location, with odds ratios ranging from 0.60 (New Mexico) to 1.57 (Michigan).
Discussion Approximately three of four patients diagnosed with colorectal cancer have local- or regional-stage tumors and, assuming that these patients receive treatment with curative intent, the population of survivors in whom routine surveillance testing would be recommended is extremely large. The goals of surveillance testing are to discover a recurrence that is potentially resectable, identify metachronous neoplasms at an early stage, and provide reassurance to the patient. Professional society practice guidelines include recommendations for routine colorectal cancer surveillance testing (Table).1-8 The present study of a large cohort of patients treated in routine clinical practice showed that the majority of patients did not receive testing according to practice guidelines for cancer surveillance. Despite including the lowest extreme of the recommended range for testing from these guidelines (two office visits per year, two CEA tests per year in years 1 and 2, one colonoscopy in 3 years), we found that fewer than half the patients achieved compliance. Conversely, a subset of patients received procedures not routinely recommended by guidelines, such as CT and PET scans. Although some of these nonrecommended tests were likely performed because of signs or symptoms and/or abnormal results of routine testing, we suspect that many were obtained for routine follow-up. Some of the differences in surveillance testing may be explained by clinical factors, such as stage of disease or perceived longevity as measured by age or comorbidity, but we also found important differences across racial groups and geographic sites. The generally lower use of testing in African Americans is likely a contributing factor to their poorer stage-specific survival compared with whites.13 The results, especially the geographic differences across SEER sites, also suggest that patient and physician preferences may influence choice of testing. The data used for this study had several inherent limitations. First, the accuracy of procedure coding in the Medicare population has not been formally studied, although we have evaluated its accuracy in a similar population from a large health plan.14 Second, the study did not measure the indication for procedures, which could have been performed for diagnostic purposes as well as routine surveillance, particularly for procedures such as CEA testing and CT and PET scans, which are used to detect metastatic disease. Third, the database was limited to older patients (≥66 years) with colorectal cancer, and thus adherence in younger individuals could not be assessed. Fourth, because physician identifiers or specialty were not available in this database, we could not measure potential differences in practice according to provider type. Finally, we did not measure other factors that could have an impact on procedure use, such as access to care and socioeconomic status, which could not be ascertained from this database.
Summary Our study of this population-based cohort of older colorectal cancer survivors showed that most patients underwent colorectal surveillance testing below a minimum frequency specified by clinical practice guidelines. We also found that a significant number of patients underwent procedures not recommended by clinical practice guidelines, suggesting potential overuse of surveillance tests. Further studies should ascertain the reasons for poor compliance with clinical practice guidelines and the effect this may have on patient outcome. Acknowledgments This study used the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, National Cancer Institute; the Office of Research, Development and Information, Centers for Medicare & Medicaid Services; Information Management Services, Inc; and SEER Program tumor registries in the creation of the SEER-Medicare database. This study was supported by a research project grant (RSGT-01-072-03-CPHPC) from the American Cancer Society. References 1. Fleischer DE, Goldberg SB, Browning TH, et al. Detection and surveillance of colorectal cancer. JAMA. 1989;261:580-585. 2. Desch CE, Benson AB 3rd, Smith TJ, et al. Recommended colorectal cancer surveillance guidelines by the American Society of Clinical Oncology. J Clin Oncol. 1999;17:1312-1321. 3. Benson AB 3rd, Desch CE, Flynn PJ, et al; for the American Society of Clinical Oncology. 2000 update of American Society of Clinical Oncology colorectal cancer surveillance guidelines. J Clin Oncol. 2000;18:3586-3588. 4. Desch CE, Benson AB 3rd, Somerfield MR, et al; for the American Society of Clinical Oncology. Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol. 2005;23:8512-8519. 5. Anthony T, Simmang C, Hyman N, et al; for the Standards Practice Task Force, The American Society of Colon and Rectal Surgeons. Practice parameters for the surveillance and follow-up of patients with colon and rectal cancer. Dis Colon Rectum. 2004;47:807-817. 6. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. V.2.2009. www.nccn.org/pro fessionals/physician_gls/PDF/colon.pdf. Accessed July 8, 2009. 7. Rex DK, Kahi CJ, Levin B, et al. Guidelines for colonoscopy surveillance after cancer resection: a consensus update by the American Cancer Society and US Multi-Society Task Force on Colorectal Cancer. CA Cancer J Clin. 2006;56:160-167. 8. Davila RE, Rajan E, Baron T; for the Standards of Practice Committee, American Society for Gastrointestinal Endoscopy. ASGE guideline: colorectal cancer screening and surveillance. Gastrointest Endosc. 2006;63:546-557. 9. Renehan AG, Egger M, Saunders MP, O’Dwyer ST. Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials. BMJ. 2002;324:813. 10. Tjandra JJ, Chan MK. Follow-up after curative resection of colorectal cancer: a meta-analysis. Dis Colon Rectum. 2007;50:1783-1799. 11. Potosky AL, Riley GF, Lubitz JD, et al. Potential for cancer related health services research using a linked Medicare-tumor registry database. Med Care. 1993;31:732-748. 12. Warren JL, Klabunde CN, Schrag D, et al. Overview of the SEERMedicare data. Med Care. 2002;40(8 suppl):IV-3–IV-18. 13. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71-96. 14. Cooper GS, Schultz L, Simpkins J, Lafata JE. The utility of administrative data for measuring adherence to cancer surveillance care guidelines. Med Care. 2007;45:66-72.
G REEN H ILL H EALTHCARE C OMMUNICATIONS
Challenges of Oncology Pharmacy Practice PHARMACY PRACTICE
Continued from cover
mal training or the resources common to oncology pharmacists in large teaching institutions. Oncology pharmacy practitioners working in the community setting face challenges unknown to our peers at major medical facilities. For instance, instead of having the ability to recruit a specialty residency–trained oncology pharmacist, community practices are often limited to a selection of local hospital pharmacists who are willing to
years. I never expected the amount of responsibility I would have over the entire clinic area in addition to the intravenous (IV) preparation process. I did not know that my opinion might be sought for everything from what kind of material can be used to vent out a hood to what parts of an inoperable biological safety cabinet require hazardous material handling for disposal. Suddenly, I had to be an expert in every area of pharmacy operations. In fact, now I often wish that
I never expected the amount of responsibility I would have over the entire clinic area in addition to the intravenous preparation process. learn on the job. We often do not have a more experienced pharmacist director to mentor us or colleagues with whom to discuss new information. We do not receive memos about new information. Instead, we have to find creative ways to make sure we receive the new information first, and then we are the ones to send the memos. We seldom have access to hospital resources, such as a medical library. Many of us are expected to learn oncology on our own, while we work, by studying, attending tumor boards, asking questions, etc. I worked in a hospital-based outpatient cancer center for about 6 years before I relocated to work in a large 14physician private practice in central Illinois, where I have been for about 4
I had taken college minors in engineering and business. The most important discovery in my community oncology education was that the project managers of clinic remodel and design are often not pharmacists, and they do not always know when a pharmacist needs to be involved in a project. On every project with a new team, I educate them about a pharmacist’s needs and make sure that I am aware of decisions that are being made that affect the IV preparation area. I have developed a system that helps me be part of the process from the beginning.
The multidisciplinary team First, it is imperative that you be a
Trastuzumab Improves Survival Continued from page 13 asymptomatic left ventricular ejection fraction decreases were reported more frequently with the combination (4.6%-5.9%, depending on the criteria) than with chemotherapy alone (1.1%), he reported. In his discussion of the study, Cunningham maintained, “Trastuzumab produced a modest but clinically meaningful improvement in outcome for patients who have a relatively poor prognosis with conventional therapies. It is a safe and effective option and should be considered for all patients with advanced gastric cancer who test HER2-positive.” “The magnitude of benefit may be
even greater than observed in ToGA,” he predicted, “if we apply the definition of overexpression that is used in selecting breast cancer patients for trastuzumab treatment, that is, if patients are more highly selected.” ASCO President Richard Schilsky, MD, University of Chicago Medical Center, called the study “a great example of the concept of personalized medicine.” He said that for the first time, there is an indication that “we need to think about two different molecular subtypes of stomach cancer—HER2positive and HER2-negative.” —CH
G REEN H ILL H EALTHCARE C OMMUNICATIONS
part of the multidisciplinary team for the project. This may well be your biggest challenge, especially if you are new to the practice or are being hired specifically for the clinic that is to be opened. At first, just getting the right people to make you aware that a project is being planned may take all your people skills. The best multidisciplinary team will consist of members from within your own group or hospital (the internal team) as well as members representing the owners and/or other users of your new space (the external team). The internal team should include the oncology pharmacist and/or staff pharmacists who will be covering the area, a representative pharmacy technician, the project manager or another administrator with decision-making power, a representative from building maintenance, and if possible, representatives from nursing. Some practices may include a physician in the multidisciplinary team for clinic design, while others will only designate a physician to handle problems or approve important decisions. The external team will usually be made up of administration, maintenance, and information services personnel from the facility you are planning to
area must be carefully evaluated. Consider patient flow throughout the clinic, as well as the roles of nurses, pharmacists, and pharmacy technicians as they relate to the IV preparation area. Discussion of all this information by the multidisciplinary team will help ensure efficient placement of the IV area within the clinic. Ideally, meetings of the multidisciplinary team should be actual live meetings between your group and the hospital/site personnel. Face-to-face communication allows everyone to work together toward the same goal: a functioning clinic for good patient care. Some communication will still likely be via conference calls, and the vast majority will be exchanged by email. Use this to your advantage. I make a practice of confirming every major conversation with e-mail followup. The e-mail only needs to contain a casual greeting and a summary of any commitments that were made in the verbal conversation. You can then keep a file of these e-mails. This helps prevent the person you were talking with from forgetting the commitment and helps protect you from taking the blame if a problem occurs. At first, this
Many of us are expected to learn oncology on our own, while we work. develop. If the space is inside a hospital, that hospital’s director may participate, either directly or indirectly. If members of all of those services are not represented, you should feel very comfortable requesting that they be included so that they can be involved in the planning process from the beginning. It is far too late to ask for a compatible data line for your computer while your first patients are in chairs waiting for their treatments. If new space is to be built, contractors and architects will make up part of your team as well.
Dividing labor At this point, the division of labor, or workflow, can be determined. Some of the questions that need to be answered before you can proceed include how chemotherapy drugs will be mixed at your clinic and who will be checking them. If a pharmacist is doing the mixing, will there be a second pharmacist checking it, or will a double-check be possible? If you will use nurses or pharmacy technicians for mixing chemotherapy, where will the pharmacist be located? Both orders and chemotherapy preparations will need to be checked, and pharmacist supervision will be needed nearby; therefore, the distance between the IV preparation area and the treatment
may seem unnecessary, but you should do it routinely. You will find that most savvy hospital administrators already practice this. Over the course of the next several articles, I will share with you some of the challenges I have encountered in the setup and remodeling of multiple IV preparation areas under various conditions in community pharmacy, including availability of resources, space limitations, and state regulations, and provide suggestions on overcoming these challenges. I will discuss how you can build and work as part of a multidisciplinary team with nurses, administrators, and/or physicians while trying to align different priorities. And I will present some creative solutions that I find improve quality in community oncology, with a focus on private clinics. In the next installment, I will discuss some of the “hardware” requirements necessary for a new or remodeled clinic area, including selection of hoods, automated dispensing systems, and refrigeration and refrigerator monitoring. In a future installment, I will explore some “software” options, including computer and data needs, reference materials, the benefits of having a written and posted formulary, and how to start a Pharmacy and Therapeutics Committee in a community oncology practice.
ORLANDOâ€”In patients with a challenging form of chronic myeloid leukemia (CML), a first-in-class agent may prove to be an effective treatment option. Tyrosine kinase inhibitors (TKIs) have significantly improved the outcomes of patients with CML; currently available TKIs, however, have no activity against the type of CML associated with the T315I-mutant form of BCR-ABL. This mutation renders patients insensitive to TKIs, and is responsible for up to 20% of the point mutations that develop with imatinib resistance.
Omacetaxine is a semisynthetic formulation of the natural alkaloid homoharringtonine. Results from a phase 2/3 study presented at the annual meeting of the American Society of Clinical Oncology indicate that the novel agent omacetaxine, the first agent in the cetaxine class, has clinical activity in this subtype. â€œOmacetaxine may offer a new therapy for patients with T315I-positive CML, where we have no other options except allogeneic transplantation,â€? said lead author Jorge Cortes, MD, University of Texas, M.D. Anderson Cancer Center, Houston, in his oral presentation. Omacetaxine is a semisynthetic formulation of the natural alkaloid homoharringtonine, a compound that was used to treat CML until the advent of imatinib. The mechanism of action of omacetaxine is independent of tyrosine kinase inhibition. Instead, it inhibits protein synthesis and induces apoptosis, Cortes explained. The open-label study included 66 patients with imatinib-resistant T315Ipositive CML who were in chronic, accelerated, or blast phase of disease. Eighty percent of the patients had received two or more prior treatments. Induction therapy was with 1.25 mg/m2 of omacetaxine, self-administered daily for 14 days on a 28-day cycle. After one or more induction cycles, and on achievement of hematologic response, patients received maintenance therapy with the same dose for 7 days of every cycle. Treatment with omacetaxine led to a complete hematologic response in 85% of the 40 patients with chronicphase CML, in 50% of the 16 patients with accelerated-phase CML, and in 50% of the 10 patients with blastphase CML, Cortes reported. The median duration of complete hematologic response was 8.9 months (range, 1.7-23.9 months) for patients
in chronic phase, and 4.1 months and 3.3 months for accelerated and blast phases, respectively. A cytogenetic response was achieved in 28% of patients in chronic phase and 6% of those in accelerated phase. For six (15%) of the 40 chronic-phase patients, this was a major cytogenetic response lasting a median of 6.1 months. For the chronic-phase patients, overall survival was nearly 90% after
more than 2 years, and the median survival time had not been reached. Median survival was almost 19 months for accelerated-phase patients but less than 2 months for accelerated-phase patients. â€œIn many patients there was a disappearance of the T315I clone,â€? Cortes added. Omacetaxine was generally well tolerated, the primary toxicity being myelosuppression that was usually
transient and manageable with dose reductions. â€œWe can adjust the dose to minimize myelosuppression over time,â€? Cortes noted. Thrombocytopenia occurred in 58%, anemia in 41%, neutropenia in 36%, and febrile neutropenia in 15% of patients. Diarrhea and fatigue affected <3% of patients. â€”CH
NNew ew PPerspectives erspectives iinn Oncology Practice Saturda Saturday, d y, November Novemb ber 14 New York York ork Marriott Marquis Mar M quis New Chemotherapy C Chemotherap y Foundation Symposium ymposium XXV XXVII II An Accredited Pr Program P ogram for for Oncology logy Nur Nurses ses and Provider v s Other Cancer Care Providers P by the Mount M Schoo ol of Medicine and d Presented by Sinai School Ch hemotherapy Foundation Foun ndation The Chemotherapy s %XPANDING %XPAN NDING 2OLE OF 4 4ARGETED ARGETED A 4HERAPIES 4H ERAPIES ,EU UKEMIA AND ,YMPHOMA ,YMPHOMA IN ,EUKEMIA s 3E XUA ALITY AND #ANCER %GG "AN NKING 3EXUALITY "ANKING ITIIONAL -ANAGEMENT OF #HE EMOTHERAPY s .UTR .UTRITIONAL #HEMOTHERAPY % ECTS %FF 3IDE %FFECTS O #ANCER -EDICATIONS IN A s #OST OF 3LUMP PING %CONOMY %CONOMY 3LUMPING s 3ARCO OMAS 3ARCOMAS s /NCOL LOGIC %MERGENCIES /NCOLOGIC s -ULTID DISCIPLINAR Y )SSUES IN (EAD D AND -ULTIDISCIPLINARY . K #ANCERS .EC # .ECK
s s s s s s s s s
!LTER NATIVE #OPING -ECHANISMS !LTERNATIVE 'ASTR IC %SOPHAGEAL #ANCERS 'ASTRIC %SOPHAGEAL #LINICAL 4 RIALS IN /NCOLOGY #ARE 4RIALS 3URVIVAL FROM THE 0ATIENTS 0ATIENTS #ANCER 3URVIVAL 0ERSPEC CTIVE 0ERSPECTIVE ' )SS SUES ,ATEST 'UIDELINES AND #ONTROL )SSUES FOR %RYTHROPOETINS %RYTH HROPOETINS FOR #A ANCER IN 7OMEN 7OMEN ,UNG #ANCER "IOLOGICCS IN #ANCER 4REATMENT 4RREATMENT "IOLOGICS .EW 4ECHNOLOGY 4E ECHNOLOGY IN /NCOLOGYY 0RACTICE 0RACTICE 4HE .EW !DH NCE TO !DHEREN T /RAL / /RALL -EDICATIONS - DI TI !DHERENCE
We Wednesday-Friday, ednesd day-Friday, November Novemb ber 11-13 INNO VATIVE CA CANCER NCER THERAPY FOR OR T OMMOROW INNOVATIVE TOMMOROW Practical Applic cations ffor or the Medical Med dical Oncologist Applications Ne w Ag ents, Clin nical T rials and Eme erging Therapies New Agents, Clinical Trials Emerging Tuesda u y, November November 10 1 Tuesday, PEDIA ATRIC ONCOLOGY ONCOLOG GY PEDIATRIC Saturday only Saturday only $50 T uesday-Satturday (inclusive) (inclusive) Tuesday-Saturday $150 Compliment tarry Breakfasts, Lunches, Lunches s, Dinner rs Complimentary Dinners
For co conference onference program details visit www.reedmeded.com/Chemo www.rreedmeded.com/Chhemo Register Regisster on line at www.chemotherapyfoundationsymposium.org www w.chemotherapyfounndationsymposium..org #ONTACTS #ONTAC CTS GAMATR GAMATRUDA UDA REEDMEDEDCOM REEDMEDEDCOM JACLYNSILVER JACLYNSILVERMAN E MAN MSSMEDU 0RESENTED 0 RESENTED IN CONJUNCTION WITH
G REEN H ILL H EALTHCARE C OMMUNICATIONS 19
Novel Agent Omacetaxine Active in T315I-Positive CML
ORLANDO—Inhibitors of poly (ADPribose) polymerase (PARP) show significant activity in triple-negative and BRCA-deficient advanced breast cancer, said researchers at the 2009 annual meeting of the American Society of Clinical Oncology. In the treatment of triple-negative breast cancer, the PARP-1 inhibitor BSI-201 on top of standard chemotherapy significantly improved progressionfree and overall survival compared with chemotherapy alone, reported Joyce O’Shaughnessy, MD. Triple-negative breast cancer is a highly aggressive cancer (30% of patients develop metastatic disease) for which no targeted therapies exist. PARP is a nuclear enzyme that is involved in DNA base excision repair and is upregulated in most triple-negative breast cancers, said O’Shaughnessy, co-director of the Breast Cancer Research Program at the Baylor Cancer Center, Dallas, Texas. Similar to BRCA1-associated cancers, triple-neg-
ative breast cancers “block the ability days 1 and 8) alone or in combination to repair double-stranded DNA breaks. with BSI-201 (given on days 1, 4, 8, When they block that ability, they’re and 11). Patients were allowed to cross reliant on single-strand DNA repair, over to the BSI-201 arm at disease proand that’s where PARP comes in. Most gression, and 40% did so. triple-negative breast Progression-free survival more cancers have a lot of than doubled, from a median of this PARP enzyme be3.3 months to 6.9 months (P cause they block the <.0001), with the addition of ability to repair douBSI-201. Overall survival inble-stranded breaks,” creased from a median of 5.7 she said. months with gemcitabine and BSI-201 is an intracarboplatin alone to 9.2 months venous PARP-1 inwith the addition of BSI-201 (P hibitor that potenti= .0005). The objective overall ates the effects of Joyce O’Shaughnessy, MD tumor response rate increased platinum-based chefrom 16% to 48% (P = .002) by motherapy. “Interestingly, and kind of adding the PARP inhibitor. different from what we’re used to in the There were no additional toxicities cancer world, BSI-201 does not add any by adding BSI-201 to the gemcitabine toxicity to chemotherapy,” O’Shaugh- and carboplatin regimen. A large phase nessy noted. It was tested in a phase 2 3 trial is currently recruiting patients. trial of 120 women with metastatic An oral PARP inhibitor, olaparib, triple-negative breast cancer, who were also showed significant activity as a randomized to 21-day cycles of gem- single agent in a phase 2 trial of citabine and carboplatin (given on women with BRCA-deficient adPhoto courtesy of American Society of Clinical Oncology.
PARP Inhibitors Show Promise in Various Forms of Advanced Breast Cancer vanced breast cancer, reported Andrew Tutt, MD, PhD, director of the Breakthrough Cancer Research Unit, Kings College, London. Olaparib targets the DNA repair weakness in BRCA1/BRCA2 tumors, he said. In an open-label study, olaparib was given either at 100 mg twice daily or 400 mg twice daily to 54 women with advanced breast cancer that was refractory to chemotherapy. The women had been exposed to a median of three prior lines of chemotherapy. The overall response rate was 22% in the 100-mg twice-daily arm and 41% in the 400-mg twice-daily arm. One patient (400-mg arm) had complete tumor disappearance. The median progressionfree survival was 5.7 months. The most common side effects were low-grade nausea (26%), fatigue (33%), and vomiting (15%); grade 3 or 4 fatigue occurred in five patients and grade 3 or 4 nausea occurred in two patients. —Wayne Kuznar
Researchers Sound Warning About Chemotherapy Solvent ORLANDO—Researchers at Northwestern University Feinberg School of Medicine are now warning that Cremophor EL (polyethoxylated castor oil)-containing paclitaxel-associated anaphylaxis may be a greater concern than oncology nurses and pharmacists may have previously thought. A review of case reports for Cremophor EL–containing paclitaxelinduced hypersensitivity has found that 109 patients have experienced fatal reactions. In addition, 22% of the fatalities occurred despite prophylaxis before paclitaxel therapy, and 15% experienced life-threatening respiratory arrest. “It can happen when patients are appropriately treated in advance. I think it is an issue that people need to know about, and it is important to know that even with prophylaxis there is some risk,” lead study investigator Charles Bennett, MD, told The Oncology Pharmacist. “So patients should be considered for an alternative formulation of paclitaxel, which does not have hypersensitivity associated with it.” The new study from the Research on Adverse Drug Events and Reports (RADAR) pharmacovigilance program at Northwestern University identified 287 unique cases of hypersensitivity reactions submitted to the US Food and Drug Administration (FDA) Adverse Event Reporting System between 1997 and 2007. The researchers 20
found 109 (38%) deaths in patients who received Cremophor EL–containing paclitaxel, a solvent-administered taxane chemotherapy. The findings from the study were presented at the annual meeting of the American Society of Clinical Oncology. Adverse event reports generally only represent from 1% to 10% of actual incidence, so the number of hypersensitivity reactions and deaths is likely
ly had 40 years of life ahead of them,” Bennett said. Cremophor EL–containing paclitaxel has been associated with hypersensitivity reactions, with responses ranging from mild skin conditions to more severe effects, including anaphylaxis and cardiac collapse. Current US product labeling for Cremophor EL–containing paclitaxel includes a black-box warning, alerting clinicians and patients
It is important to know that even with prophylaxis there is some risk. significantly higher, according to Bennett. The severe allergic reactions are believed to be caused by Cremophor EL, the chemical solvent, which is a derivative of castor oil. This chemical is used to dissolve some insoluble drugs before they can be injected into the bloodstream. Two patients who died from an allergic reaction had early-stage breast cancer, which had been surgically removed, and were being treated with Cremophor EL–containing paclitaxel to prevent recurrence. Both of these patients had received medications before chemotherapy administration to reduce the risk of hypersensitivity reactions. “The deaths of women with early-stage breast cancer are particularly disturbing because without the adverse reaction, they could have like-
G REEN H ILL H EALTHCARE C OMMUNICATIONS
of potential toxicity and recommending the use of corticosteroids and other medications before chemotherapy administration to reduce the risk of hypersensitivity reactions. In addition to the two women with early-stage breast cancer who died after treatment with the Cremophor EL–based paclitaxel, four other women with early-stage breast cancer experienced life-threatening anaphylaxis reactions. Each of them had received prophylactic medications to prevent the reactions. Bennett and his colleagues reviewed adverse event reports submitted to regulatory agencies in the United States, Europe, and Japan. The most common cancer diagnosis for these patients with allergic reactions was lung cancer followed by breast cancer
and ovarian cancer. “We were surprised by the number of deaths and number of adverse events. It was very clear in many of these cases that the hypersensitivity started within minutes of when the intravenous drip was started. It was surprising that some had received prophylaxis,” explained Bennett, RADAR program coordinator and professor of hematology/oncology at Northwestern’s Feinberg School of Medicine, Chicago. “Despite how serious it is, the reporting on this has been poor and there is probably more out there that we have not heard about. We reviewed the quality of the reporting and the reporting was rather poor. So it is disturbing.” He said clinicians should be aware of the availability of a potential alternative therapy for these patients, a recently FDA-approved Cremophor EL–free nanoparticle paclitaxel formulation (paclitaxel protein-bound particles for injectable suspension/ albumin-bound). —JS
Coverage of the 2009 Annual Meeting of ASCO continues in the September/October issue of The Oncology Pharmacist. July/August 2009
Government Health Plans Always Ration Care Europe offers a glimpse of the future if President Obama and congressional Democrats have their way.
nly by expanding government control of health care can we bring down its cost. That’s the faulty premise of the various proposals for health reform now being batted around Washington. The claimed cost control depends on politically safe ideas such as preventive care or the adoption of electronic health records. And neither—even according to the Congressional Budget Office—will do much to reduce spending. If these proposals are implemented and fail to produce savings, government will turn to a less appealing but more familiar tool to cut costs: the regulation of access to drugs and medical services. Medicare is already going down this path. What will be new about government-run health care is the instrument of regulatory control. There will be an omnipotent federal health board. Buried in current reform proposals, this board deserves closer scrutiny. Our best look at this construct comes from a bill released by the Senate Health, Education, Labor and Pensions (HELP) Committee. The bill calls for a “Medical Advisory Council” to determine what medical products and services are “essential benefits” and those that shouldn’t be covered by a public insurance plan. The Senate Finance Committee turns to a “Federal Health Board” to compare similar medical treatments in order to steer reimbursement to lowercost options. Senate Finance also proposes a “sustainability commission” charged with finding automatic cuts to Medicare spending that would then pass Congress by a simple up or down vote. Meanwhile, a draft health-care reform proposal introduced last week in the House of Representatives by the three committees with jurisdiction over health policy set up an independent “advisory committee” that will “recommend a benefit package based on standards set in the law.” It also proposes a new “commission” that may, among other things, help develop treatment protocols based on government-directed research. Congress, of course, can authorize the creation of panels and commissions to provide expert advice to the executive branch. But such bodies are typically advisory, and their advice is free to be rejected or modified by the president. Under the HELP committee’s plan, the health board’s recommendations would be binding unless Congress acts within a July/August 2009
brief period to pass a “joint resolution disapproving such report in its entirety.” President Obama objects when peo-
ple use the word “rationing” in regards to government-run health care. But rationing is inevitable if we simply
expand government control without fixing the way health care is reimbursed Continued on page 22
Presents The Second Annual 2009 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 with this series of newsletters focusing on the challenges in treating patients with multiple myeloma.
SAGAR LONIAL, MD Associate Professor of Hematology and Oncology Emory University
Earn Continuing Education Credits Eight part newsletter series
CLINICAL TOPICS: • Retreatment Settings • Maintenance Therapy • Do CRs Correlate with Clinical Benefit?
• Perspectives on Relevant Endpoints of Clinical Trials • Stem Cell Mobilization • Cytogenic Testing in the MM Patient
• To Transplant or Not to Transplant…That is the Question • Sequencing Strategies in MM: Treatment with Case Studies
Each newsletter will feature: • Contributions from thought-leading physicians, pharmacists, and nurses
• Continuing Education credits available to physicians, pharmacists, and nurses
TO REQUEST FREE COPIES
Call 732-992-1040 or visit www.coexm.com
Do Complete Responses Correlate with Clinical Benefit? Statement of Need The purpose of this activity is to enhance knowledge concerning the treatment of patients with multiple myeloma (MM). Target Audience This activity was developed for physicians, nurses, and pharmacists. Learning Objectives At the completion of this activity participants should be able to: • Define the clinical significance of achieving complete response (CR) on novel therapy for treatment of newly diagnosed multiple myeloma (MM) • Describe various methods for assessing CR in patients with MM • Report new data from clinical trials in newly diagnosed MM as reported at the 2008 ASH meeting • Interpret new data from clinical trials of novel therapies for relapsed/refractory MM as reported at the 2008 ASH meeting Physician Accreditation This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Global Education Group (Global) and Medical Learning Institute, Inc. (MLI). Global is accredited by the ACCME to provide continuing medical education for physicians.
Physician Credit Designation Global Education Group designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity. Registered Nurse Designation Medical Learning Institute, Inc. Provider approved by the California Board of Registered Nursing, Provider 15106, for 1.0 contact hour. Registered Pharmacy Designation MLI 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 program number for this activity is 468-999-09-016-H01-P. Estimated time to complete this activity: 1 hour Date of original release:: June 10, 2009 Valid for CME credit through: June 10, 2010
This activity is jointly sponsored by
This activity is supported by an educational grant from Millennium Pharmaceuticals, Inc.
G REEN H ILL H EALTHCARE C OMMUNICATIONS 21
Government Health Plans Continued from page 21
so that doctors and patients become sensitive to issues of price and quality. Like Medicare’s recent decisions to curtail the use of virtual colonoscopies, certain wound-healing devices, and even a branded asthma drug, the board’s decisions will be one-size-fits-all restrictions. Such restrictions don’t respect variation in preferences and disease, which make costly products suitable for some even if they are wasteful when prescribed to everyone.
Moreover, these health boards prove that policy makers know they’ll need to ration care but want to absolve themselves of responsibility. Some in Congress and the Obama administration recently tipped their hand on this goal by proposing to make recommendations of the current Medicare Payment Advisory Committee (MedPAC) legally binding rather than mere advice to Congress. Any new health board’s mission will also expand over time, just as MedPAC’s
mandate grew to encompass medical practice issues not envisioned when it was created. The idea of an omnipotent board that makes unpopular decisions on access and price isn’t a new construct. It’s a European import. In countries such as France and Germany, layers of bureaucracy like health boards have been specifically engineered to delay the adoption of new medical products and services, thus lowering spending.
THANK YOU YOU for making The T Oncology Oncology Pharmacist Pharm macist the most widely w read n onncologgy pharmacy pharmaccy community and requested newspaper of the oncology
Join o over ver e 10,000 off y your our collea colleagues agues To T o ensure ensure uninterrupted uninterrupted F FREE REE d delivery elivery o off The The O Oncology ncology PPharmacist, harmacist, rregister egister o nline a www.theoncologypharmacist.com online att www.theoncologypharmacist.com Written W ritten b byy aand nd for for ooncology ncology p pharmacists harmacists ooffering ffering yyou ou tthe he ffollowing: ollowing: Concise rreviews Concise eviews of of hot hot topics topics in in the the peer-reviewed peer-reviewed literature literature by clinical clinical specialists specialists with with k ey p oint ‘‘takeaways’ takeaways’ by key point C overage o ey rresearch esearch sstudies tudies and and on-the-scene on-the-scene rreports eports Coverage off k key ffrom rom oncology oncology medical medical meetings meetings C ontinuing education education a rticles a nd p ost-tests a o ccharge, harge, Continuing articles and post-tests att n no o ffering you you a convenient convenient way way to to obtain obtain contact contact hours hours offering IInterviews nterviews with with renowned renowned thought thought lleaders eaders iin n the the oncology oncology p harmacy community community pharmacy C overage of of legislation legislation and and p olicy cchanges hanges that that affect affect cancer cancer care care Coverage policy iin n your your areas areas of of practice practice IICD-9-CM CD-9-CM and and J-code J-code updates, updates, with with F DA- and and Compendia-approved Compendia-approved uses uses FDA-
GH GGreen rreeen H Hill iilllll H Healthcare eaalltthhcarree C Communications ommunications
,,LLC LL LLC L LC™
YYour our Innovative Innovative Partners Partners in in Medical Medical Media Media
G REEN H ILL H EALTHCARE C OMMUNICATIONS
In France, assessment of medical products is done by the Committee for the Evaluation of Medicines. Reimbursement rates are set by the National Union of Sickness Insurance Funds, a group that also negotiates pay to doctors. In Germany, the Federal Joint Committee regulates reimbursement and restrictions on prescribing, while the Institute for Quality and Efficiency in Healthcare does formal cost-effectiveness analysis. The Social Insurance Organization, technically a part of the Federal Joint Committee, is in charge of setting prices through a defined formula that monitors doctors’ prescribing behavior and sets their practice budgets. In the past 12 months, the 15 medical products and services that cleared this process spent an average 35 months under review. (The shortest review was 19 months, the longest 51.) In short, other countries where government plays a large role in health care aren’t shy about rationing. Mr. Obama’s budget director has acknowledged that rationing reduces costs. Peter Orszag told Congress last year when he headed the Congressional Budget Office that spending can be “moderated” if “diffusion of existing costly services were slowed.” Medicare can already be painstakingly slow. Appealing to it takes patients an average 21 months according to a 2003 Government Accountability Office report (17 months involve administrative processing). Layers of commissions and health boards would delay access still further. When asked to judge the constitutionality of the Senate HELP committee proposal, there’s a reason why the nonpartisan Congressional Research Service said that the proposed Medical Advisory Council “raises potentially significant constitutional concerns.” Our Founders thought politicians should be accountable when it comes to citizens’ right to life, liberty and the pursuit of heart surgery. —Scott Gottlieb
Dr. Gottlieb, a physician and resident fellow at the American Enterprise Institute, is a former senior official at the Centers for Medicare & Medicaid Services. He is partner to a firm that invests in healthcare companies. Reprinted with permission. © Scott Gottlieb. Originally printed in Opinion Journal. The Wall Street Journal. June 25, 2009.
Medications Used for the Treatment of Prostate Cancer The following sections include: • Associated ICD-9-CM codes used for the classification of prostate cancer • Drugs that have been FDA-approved in the treatment of prostate cancer. Please note: if a check mark appears in the FDA column it will NOT appear in the compendia section even if a drug is included in the NCCN (National Comprehensive Cancer Network) Drugs & Biologics Compendium • Drugs included in the NCCN Drugs & Biologics Compendium for off-label use in genitourinary cancers. NCCN is recognized by the Centers for Medicare & Medicaid Services (CMS) as a referencing source • Corresponding HCPCS/CPT codes and code descriptions • Current Code Price (AWP-based pricing) • Most recent ASP plus 6% (Medicare allowable) • Possible CPT Administration Codes for each medication.
FDAapproved for prostate cancer
The following sections will assist healthcare professionals and payers by providing appropriate coding, billing, and reimbursement information associated with the management of prostate cancer.
Associated ICD-9-CM Code Used for Prostate Cancer 185 Malignant neoplasm of prostate Excludes: seminal vesicles (187.8)
NCCN Drugs & Biologics Compendium off-label use for prostate cancer
Current code price (AWPbased pricing)
Medicare allowable (ASP + 6%), effective 7/1/09-9/30/09
CPT administration codes
Generic (brand) name
HCPCS code: code description
J8999*: prescription drug, oral, chemotherapeutic, not otherwise specified
J9045: injection, carboplatin, 50 mg
96409, 96413, 96415
cisplatin (Platinol AQ)
J9060: cisplatin, powder or solution, per 10 mg
96409, 96413, 96415
cisplatin (Platinol AQ)
J9062: cisplatin, 50 mg
96409, 96413, 96415
J9999*: not otherwise classified, antineoplastic drugs OR C9399: unclassified drugs or biological
J9170: injection, docetaxel, 20 mg
J8499*: prescription drug, oral, nonchemotherapeutic, not otherwise specified
NDC level pricing
NDC level pricing
J8999*: prescription drug, oral, chemotherapeutic, not otherwise specified
NDC level pricing
NDC level pricing
J9181: injection, etoposide, 10 mg
J8560: etoposide, oral, 50 mg
J8999*: prescription drug, oral, chemotherapeutic, not otherwise specified
NDC level pricing
NDC level pricing
NDC level pricing
NDC level pricing
NDC level pricing
NDC level pricing
G REEN H ILL H EALTHCARE C OMMUNICATIONS 23
ONCOLGY DRUG CODES
Oncology Drug Codes
ONCOLGY DRUG CODES
FDAapproved for prostate cancer
NCCN Drugs & Biologics Compendium off-label use for prostate cancer
Current code price (AWPbased pricing)
Medicare allowable (ASP + 6%), effective 7/1/09-9/30/09
Generic (brand) name
HCPCS code: code description
J9202: goserelin acetate implant, per 3.6 mg
J9225: histrelin implant (Vantas), 50 mg
J8499*: prescription drug, oral, nonchemotherapeutic, not otherwise specified
leuprolide (Lupron Depot, Eligard)
J9217: leuprolide acetate (for depot suspension), 7.5 mg
J9293: injection, mitoxantrone hydrochloride, per 5 mg
J8999*: prescription drug, oral, chemotherapeutic, not otherwise specified
NDC level pricing
J7506: prednisone, oral, per 5 mg
triptorelin (Trelstar LA, Trelstar Depot)
J3315: injection, triptorelin pamoate, 3.75 mg
zoledronic acid (Zometa)
J3487: injection (Zometa), zoledronic acid, 1 mg
NDC level pricing
NDC level pricing
NDC level pricing
CPT administration codes 96372, 96402 11981, 11982, 11983 N/A
96409, 96413 N/A
*When billing a nonclassified medication using a CMS 1500 claim form you must include both the HCPCS code (ie, J8999 for Degarelix) in column 24D and the drug name, strength, and National Drug Code (NDC) in box 19 to ensure appropriate reimbursement. References • HCPCS Level II Expert, 2009 • CPT 2009; 2008 • ICD-9-CM for Professionals Volumes 1 & 2; 2009 • The Drug Reimbursement Coding and Pricing Guide, Vol 6, No 3; RJ Health Systems International LLC; 3rd Quarter 2009 • FDA-approved indication (from products’ prescribing information) • NCCN • National Cancer Institute • www.ReimbursementCodes.com powered by RJ Health Systems International, LLC, Wethersfield, Connecticut • CMS-Medicare allowable 3rd Quarter 2009 (effective dates 7/1/09-9/30/09). Prices listed herein are effective as of July 1, 2009. 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; NCCN, National Comprehensive Cancer Network.
This information was supplied by:
The Most Comprehensive HCPCS/CPT Drug and Product Reimbursement Coding and Pricing Service Available! ReimbursementCodes.com is an online HCPCS/CPT reimbursement coding and pricing service that provides up-to-date reimbursement information. You have the ability to accurately match reimbursement to the corresponding date of service for every claim! • Drugs which are injected subcutaneously, intramuscularly, or intravenously • Selected orally administered chemotherapeutic and antiemetic agents • Nutritional agents and ostomy care products • Drugs administered via nebulizers or other DME equipment • Radiopharmaceuticals Plus a fast and efficient avenue to HCPCS/CPT coding and reimbursement information! • In billable units matching the CMS- and AMA-established reimbursement code description • A validated pricing methodology • Includes all price changes that have occurred for each code, along with the effective date of the change(s) Does your revenue stream run as productively as possible? Contact RJ Health Systems, and mention The Oncology Pharmacist. PO BOX 290616, Wethersfield, CT 06109 • T: (860) 563-1223 • F: (860) 563-1650 • www.RJHealthSystems.com
G REEN H ILL H EALTHCARE C OMMUNICATIONS
MORE ONCOLOGY DRUG CODES ONLINE Bladder Cancer Kidney Cancer Ovarian Cancer Testicular Cancer Uterine Cancer
www.theoncologypharmacist.com July/August 2009
Concise Reviews of Studies Relevant to Cancer Care ■ Weekly Topotecan and Docetaxel in Heavily Pretreated Patients with Recurrent Uterine and Ovarian Cancers Background: Recurrent gynecologic cancers tend to be difficult to treat, and although topotecan and docetaxel are commonly used agents, they are not always used in combination. Design: Patients with epidermal growth factor receptor–positive colorectal cancer with unresectable metastases were randomized to receive FOLFIRI either alone or in combination with cetuximab. Design: In a phase 2 trial without a comparison group, researchers evaluated the efficacy and safety of weekly topotecan (3.5 mg/m2) and docetaxel (30 mg/m2) for 3 consecutive weeks in heavily pretreated patients with recurrent uterine or epithelial ovarian cancers. Cycles were repeated every 4 weeks for six cycles. Response was assessed as per RECIST. Time to best response and overall survival were calculated using Kaplan-Meier statistical methods. Summary: Of the 24 patients evaluable for response, the majority had received two prior chemotherapy regimens. Patients experienced three grade 4 neutropenias and 10 grade 3 toxicities, six of which were not related to treatment. Overall response rate was 25% (95% CI, 7.7%-42.3%; 8% CR; 17% PR). Thirty-eight percent had clinical benefit (95% CI, 18.1%-56.9%; CR+ PR+13% SD). Median duration of response was 8.5 months; median overall survival was 18.5 months. Takeaway: Weekly combination therapy with topotecan plus docetaxel has clinical benefit for and is well tolerated by heavily pretreated patients with recurrent uterine or epithelial ovarian cancers. Gupta D, et al. Gynecol Oncol. 2009;113:327-330. ■ Insulin Resistance and Risk Factors for Cardiovascular Disease in Young Adult ALL Survivors Background: Long-term survivors of childhood acute lymphoblastic leukemia (ALL) have been found to have a significantly elevated risk of premature mortality and serious morbidity. With the number of survivors increasing and entering middle-age, further study is needed to determine whether the risk of cardiovascular disease (CVD) is increased. Design: The researchers estimated insulin resistance in 118 survivors of childhood ALL (median age, 23 years; range, 18-37 years) using the homeostasis model for assessment of insulin resistance (HOMA-IR). Sex-specific comparisons were made with a cohort of 30- to July/August 2009
37-year-old patients from the Dallas Heart Study (DHS, N = 782). Survivors were stratified by treatment with/without cranial radiotherapy (CRT). Summary: Using the DHS participants as controls (female: mean, 2.4; 95% CI, 2.2-2.7; male: mean, 2.3; 95% CI, 2.1-2.6), female survivors had a significantly higher HOMA-IR (CRT: mean, 4.6; 95% CI, 3.6-5.7; no CRT: RITUXAN® (Rituximab) Brief summary—Please consult full prescribing information. WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) Infusion Reactions: Rituxan administration can result in serious, including fatal infusion reactions. Deaths within 24 hours of Rituxan infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Carefully monitor patients during infusions. Discontinue Rituxan infusion and provide medical treatment for Grade 3 or 4 infusion reactions [see Warnings and Precautions, Adverse Reactions]. Tumor Lysis Syndrome (TLS): Acute renal failure requiring dialysis with instances of fatal outcome can occur in the setting of TLS following treatment of non-Hodgkin’s lymphoma (NHL) patients with Rituxan [see Warnings and Precautions, Adverse Reactions]. Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan [see Warnings and Precautions, Adverse Reactions]. Progressive Multifocal Leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving Rituxan [see Warnings and Precautions, Adverse Reactions].
INDICATIONS AND USAGE Non-Hodgkin’s Lymphoma (NHL) Rituxan® (rituximab) is indicated for the treatment of patients with: Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent; Previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy; Non-progressing (including stable disease), low-grade, CD20positive B-cell NHL, as a single agent, after first-line CVP chemotherapy; Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens. WARNINGS AND PRECAUTIONS Infusion Reactions Rituxan can cause severe, including fatal, infusion reactions. Severe reactions typically occurred during the first infusion with time to onset of 30–120 minutes. Rituxan-induced infusion reactions and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, or anaphylactoid events. Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medical management (e.g., glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion reactions as needed. Depending on the severity of the infusion reaction and the required interventions, consider resumption of the infusion at a minimum 50% reduction in rate after symptoms have resolved. Closely monitor the following patients: those with preexisting cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells (≥25,000/mm3). [See Boxed Warning, Warnings and Precautions, Adverse Reactions.] Tumor Lysis Syndrome (TLS) Rapid reduction in tumor volume followed by acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia, can occur within 12–24 hours after the first infusion. Fatal TLS cases have occurred after administration of Rituxan. A high number of circulating malignant cells (≥25,000/mm3) or high tumor burden confers a greater risk of TLS after rituximab. Consider prophylaxis for TLS in patients at high risk. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated. [See Boxed Warning.] Severe Mucocutaneous Reactions Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with Rituxan. These reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of these reactions has varied from 1–13 weeks following Rituxan exposure. Discontinue Rituxan in patients who experience a severe mucocutaneous reaction. The safety of readministration of Rituxan to patients with severe mucocutaneous reactions has not been determined. [See Boxed Warning, Adverse Reactions.] Progressive Multifocal Leukoencephalopathy (PML) JC virus infection resulting in PML and death can occur in Rituxan-treated patients with hematologic malignancies or with autoimmune diseases. The majority of patients with hematologic malignancies diagnosed with PML received Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell transplant. The patients with autoimmune diseases had prior or concurrent immunosuppressive therapy. Most cases of PML were diagnosed within 12 months of their last infusion of Rituxan. Consider the diagnosis of PML in any patient presenting with new-onset neurologic manifestations. Discontinue Rituxan and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML. [See Boxed Warning, Adverse Reactions.] Hepatitis B Virus (HBV) Reactivation Hepatitis B Virus (HBV) reactivation with fulminant hepatitis, hepatic failure, and death can occur in patients with hematologic malignancies treated with Rituxan. The median time to the diagnosis of hepatitis was approximately 4 months after the initiation of Rituxan and approximately one month after the last dose. Screen patients at high risk of HBV infection before initiation of Rituxan. Closely monitor carriers of hepatitis B for clinical and laboratory signs of active HBV infection for several months following Rituxan therapy. Discontinue Rituxan and any concomitant chemotherapy in patients who develop viral hepatitis, and institute appropriate treatment including antiviral therapy. Insufficient data exist regarding the safety of resuming Rituxan in patients who develop hepatitis subsequent to HBV reactivation. [See Adverse Reactions.] Other Viral Infections The following additional serious viral infections, either new, reactivated, or exacerbated, have been identified in clinical studies or postmarketing reports. The majority of patients received Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell transplant. These viral infections included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis C. In some cases, the viral infections occurred as late as one year following discontinuation of Rituxan and have resulted in death. [See Adverse Reactions.] Cardiovascular Discontinue infusions for serious or life-threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of Rituxan for patients who develop clinically significant arrhythmias or who have a history of arrhythmia or angina. [See Adverse Reactions.] Renal Severe, including fatal, renal toxicity can occur after Rituxan administration in patients with hematologic malignancies. Renal toxicity has occurred in patients with high numbers of circulating malignant cells (≥25,000/mm3) or high tumor burden who 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 approved treatment regimen. Use extreme caution if this non-approved combination is used in clinical trials and monitor closely for signs of renal failure. Consider discontinuation of Rituxan for patients with a rising serum creatinine or oliguria. Bowel Obstruction and Perforation Abdominal pain, bowel obstruction and perforation, in some
mean, 3.3; 95% CI, 2.8-3.8) as did male survivors (CRT: mean, 4.0; 95% CI, 2.8-5.6; no CRT: mean, 3.4; 95% CI, 2.9-3.9). Of women treated with CRT, 80% had at least three of six CVD risk factors and were significantly more likely to have these risk factors than controls (OR = 5.96; 95% CI, 2.15-16.47). Male survivors were no more likely to have multiple CVD risk
factors than the controls. Takeaway: ALL survivors, regardless of sex and therapy, have an increased prevalence of insulin resistance. Women treated with CRT have a substantially increased prevalence of various CVD risk factors, and thus close monitoring and risk-reduction strategies are warranted. Oeffinger KC, et al. J Clin Oncol. June 29, 2009. Epub ahead of print.
cases leading to death, can occur in patients receiving Rituxan in combination with chemotherapy. In postmarketing reports, the mean time to documented gastrointestinal perforation was 6 (range 1–77) days in patients with NHL. Perform a thorough diagnostic evaluation and institute appropriate treatment for complaints of abdominal pain, especially early in the course of Rituxan therapy. [See Adverse Reactions.] Immunization The safety of immunization with live viral vaccines following Rituxan therapy has not been studied and vaccination with live virus vaccines is not recommended. For NHL patients, the benefits of primary or booster vaccinations should be weighted against the risks of delay in initiation of Rituxan therapy. Laboratory Monitoring Because Rituxan binds to all CD20positive B lymphocytes (malignant and non-malignant), obtain complete blood counts (CBC) and platelet counts at regular intervals during Rituxan therapy and more frequently in patients who develop cytopenias [see Adverse Reactions]. The duration of cytopenias caused by Rituxan can extend months beyond the treatment period. ADVERSE REACTIONS The most common adverse reactions of Rituxan (incidence ≥25%) observed in patients with NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia. The most important serious adverse reactions of Rituxan are infusion reactions, tumor lysis syndrome, mucocutaneous toxicities, hepatitis B reactivation with fulminant hepatitis, PML, other viral infections, cardiac arrhythmias, renal toxicity, and bowel obstruction and perforation. Clinical Trials Experience Non-Hodgkin’s Lymphoma Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to Rituxan in 1606 patients, with exposures ranging from a single infusion up to 6–8 months. Rituxan was studied in both single-agent and active-controlled trials (n = 356 and n = 1250). These data were obtained in adults with low-grade, follicular, or DLBCL NHL. Most patients received Rituxan as an infusion of 375 mg/m2 per infusion, given as a single agent weekly for up to 8 doses, in combination with chemotherapy for up to 8 doses, or following chemotherapy for up to 16 doses. Infusion Reactions In the majority of patients with NHL, infusion reactions consisting of fever, chills/rigors, nausea, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, dizziness, or hypertension occurred during the first Rituxan infusion. Infusion reactions typically occurred within 30 to 120 minutes of beginning the first infusion and resolved with slowing or interruption of the Rituxan infusion and with supportive care (diphenhydramine, acetaminophen, and intravenous saline). The incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion. [See Boxed Warning, Warnings and Precautions.] Infections Serious infections (NCI CTCAE Grade 3 or 4), including sepsis, occurred in less than 5% of patients with NHL in the single-arm studies. The overall incidence of infections was 31% (bacterial 19%, viral 10%, unknown 6%, and fungal 1%). [See Warnings and Precautions.] In randomized, controlled studies where Rituxan was administered following chemotherapy for the treatment of follicular or low-grade NHL, the rate of infection was higher among patients who received Rituxan. In diffuse large B-cell lymphoma patients, viral infections occurred more frequently in those who received Rituxan. Cytopenias and hypogammaglobulinemia In patients with NHL receiving rituximab monotherapy, NCI-CTC Grade 3 and 4 cytopenias were reported in 48% of patients. These included lymphopenia (40%), neutropenia (6%), leukopenia (4%), anemia (3%), and thrombocytopenia (2%). The median duration of lymphopenia was 14 days (range, 1–588 days) and of neutropenia was 13 days (range, 2–116 days). A single occurrence of transient aplastic anemia (pure red cell aplasia) and two occurrences of hemolytic anemia following Rituxan therapy occurred during the single-arm studies. In studies of monotherapy, Rituxan-induced B-cell depletion occurred in 70% to 80% of patients with NHL. Decreased IgM and IgG serum levels occurred in 14% of these patients. Single-Agent Rituxan Adverse reactions in Table 1 occurred in 356 patients with relapsed or refractory, lowgrade or follicular, CD20-positive, B-cell NHL treated in single-arm studies of Rituxan administered as a single agent. Most patients received Rituxan 375 mg/m2 weekly for 4 doses. Table 1 Incidence of Adverse Events in ≥5% of Patients with Relapsed or Refractory, LowGrade or Follicular NHL, Receiving Single-agent Rituxan (N = 356)a,b
Chemotherapy for DLBCL In Studies 6 and 7, the following adverse reactions, 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 (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 reactions and serious adverse reactions. In Study 7, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R-CHOP vs. 1.0% for CHOP). The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs. 7%) and lung disorder (6% vs. 3%). Other Grade 3 or 4 adverse reactions occurring more frequently among patients receiving R-CHOP were viral infection (Study 7), neutropenia (Studies 7 and 8), and anemia (Study 8). 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, antihuman anti-chimeric 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 rituximab treated patients is unclear. Postmarketing Experience The following adverse reactions have been identified during postapproval 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. 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 breastfeeding. 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, activecontrolled 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 All Grades (%) Grade 3 and 4 (%) All Grades (%) Grade 3 and 4 (%) greater. No overall differences in effectiveness were observed between these Respiratory System 38 4 Any Adverse Events 99 57 patients and younger patients. Cardiac adverse reactions, mostly supraventricular 86 10 Increased Cough 13 1 Body as a Whole arrhythmias, occurred more frequently among elderly patients. Serious pulmonary Fever 53 1 Rhinitis 12 1 Chills 33 3 Bronchospasm 8 1 adverse reactions were also more common among the elderly, including Infection 31 4 Dyspnea 7 1 Asthenia 26 1 Sinusitis 6 0 pneumonia and pneumonitis. Low-Grade or Follicular Non-Hodgkin’s Headache 19 1 Metabolic and Nutritional Lymphoma Clinical studies of Rituxan in low-grade or follicular, CD20-positive, Abdominal Pain 14 1 Disorders 38 3 Pain 12 1 Angioedema 11 1 B-cell NHL did not include sufficient numbers of patients aged 65 and over to Back Pain 10 1 Hyperglycemia 9 1 Throat Irritation 9 0 Peripheral Edema 8 0 determine whether they respond differently from younger subjects. Flushing 5 0 LDH Increase 7 0 OVERDOSAGE There has been no experience with overdosage in human clinical Heme and Lymphatic System 67 48 Digestive System 37 2 Lymphopenia 48 40 Nausea 23 1 trials. Single doses of up to 500 mg/m2 have been given in dose-escalation Leukopenia 14 4 Diarrhea 10 1 Neutropenia 14 6 Vomiting 10 1 clinical trials. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Thrombocytopenia 12 2 Nervous System 32 1 Impairment of Fertility No long term animal studies have been performed to Anemia 8 3 Dizziness 10 1 Skin and Appendages 44 2 Anxiety 5 1 establish the carcinogenic or mutagenic potential of Rituxan or to determine Night Sweats 15 1 Musculoskeletal System 26 3 Rash 15 1 Myalgia 10 1 potential effects on fertility in males or females. PATIENT COUNSELING Pruritus 14 1 Arthralgia 10 1 INFORMATION Patients should be provided the Rituxan Medication Guide and Urticaria 8 1 Cardiovascular System 25 3 Hypotension 10 1 provided an opportunity to read prior to each treatment session. Because caution Hypertension 6 1 should be exercised in administering Rituxan to patients with active infections, it is a b Adverse reactions observed up to 12 months following Rituxan. Adverse reactions graded for severity by important that the patient’s overall health be assessed at each visit and any NCI-CTC criteria. questions resulting from the patient’s reading of the Medication Guide be In these single-arm Rituxan studies, bronchiolitis obliterans occurred during and discussed. Rituxan is detectable in serum for up to six months following up to 6 months after Rituxan infusion. Rituxan in Combination With completion of therapy. Individuals of childbearing potential should use effective Chemotherapy Adverse reactions information below is based on 1250 patients contraception during treatment and for 12 months after Rituxan therapy. who received Rituxan in combination with chemotherapy or following chemotherapy. Rituxan in Combination With Chemotherapy for Low-Grade NHL In Study 4, patients in the R-CVP arm experienced a higher incidence of infusional toxicity and neutropenia compared to patients in the CVP arm. The following adverse reactions occurred more frequently (≥5%) in patients receiving R-CVP compared to CVP alone: rash (17% vs. 5%), cough (15% vs. 6%), flushing (14% vs. 3%), rigors (10% vs. 2%), pruritus (10% vs. 1%), neutropenia (8% vs. 3%), and chest tightness (7% vs. 1%). In Study 5, the following adverse reactions Revised 9/2008 (4835505) were reported more frequently (≥5%) in patients receiving Rituxan following CVP Jointly Marketed by: compared to patients who received no further therapy: fatigue (39% vs. 14%), Biogen Idec Inc. 5200 Research Place San Diego, CA 92122 anemia (35% vs. 20%), peripheral sensory neuropathy (30% vs. 18%), infections Genentech USA, Inc. 1 DNA Way South San Francisco, CA 94080-4990 (19% vs. 9%), pulmonary toxicity (18% vs. 10%), hepato-biliary toxicity (17% vs. 7%), rash and/or pruritus (17% vs. 5%), arthralgia (12% vs. 3%), and weight gain (11% vs. 4%). Neutropenia was the only Grade 3 or 4 adverse reaction that occurred more frequently (≥2%) in the Rituxan arm compared with those who received no further therapy (4% vs. 1%). Rituxan in Combination With ©2008 Biogen Idec Inc. and Genentech, Inc. 7140917 October 2008
G REEN H ILL H EALTHCARE C OMMUNICATIONS 25
IN THE LITERATURE
In the Literature
For previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens
When planning a treatment course for DLBCL
Take the essential path toward improved survival
Cumulative Cumulative Proportion Proportion Surviving Surviving
RITUXAN+CHOP is proven to prolong survival in DLBCL
in 7-year OS in GELA* trial 1,2
0.8 0.6 0.4 R-CHOP (n=202) CHOP† (n=197) p =0.0004
0.2 0 0 Years
• At 7 years, 8 cycles of RITUXAN+ CHOP increased overall survival (OS) from 36% to 53% compared with CHOP alone1 • At 5 years, 8 cycles of RITUXAN+ CHOP increased OS from 46% to 58% compared with CHOP alone5
BOXED WARNINGS and Additional Important Safety Information The most important serious adverse reactions of RITUXAN are fatal infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, progressive multifocal leukoencephalopathy (PML), hepatitis B reactivation with fulminant hepatitis, other viral infections, cardiovascular events, renal toxicity, and bowel obstruction and perforation. The most common adverse reactions of RITUXAN (incidence ≥25%) observed in patients with NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia.5 RITUXAN in Combination with CHOP Chemotherapy for DLBCL: The following adverse reactions, 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 (31% vs 24%), cardiac disorder (29% vs 21%), and chills (13% vs 4%). In the GELA LNH 98-5 study, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R-CHOP vs 1.0% for CHOP).5 The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs 7%) and lung disorder (6% vs 3%). Other Grade 3 or 4 adverse reactions reported more frequently among patients receiving R-CHOP were viral infection (GELA LNH 98-5 study), neutropenia (GELA LNH 98-5 and MInT studies), and anemia (MInT study).5
Please see brief summary of prescribing information on adjacent page. Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion. *GELA (Groupe d’Etude des Lymphomes de l’Adulte) LNH 98-5 trial: A Phase III trial of 399 previously untreated elderly (age ≥60 years) DLBCL patients.3,4 †CHOP: Cyclophosphamide, doxorubicin, vincristine, and prednisone. References: 1. Coiffier B, Feugier P, Mounier N, et al. Long-term results of the GELA study comparing R-CHOP and CHOP chemotherapy in older patients with diffuse large B-cell lymphoma show good survival in poor-risk patients. J Clin Oncol. 2007;25(suppl 18S):443s. Abstract 8009. 2. Coiffier B, Feugier P, Mounier N, et al. Long-term results of the GELA study comparing R-CHOP and CHOP chemotherapy in older patients with diffuse large B-cell lymphoma show good survival in poor-risk patients. Paper presented at: 43rd American Society of Clinical Oncology Annual Meeting; June 1-5, 2007; Chicago, Ill. Abstract 8009. 3. Coiffier B, Lepage E, Brière J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235-242. 4. Data on file, Genentech, Inc. 5. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2008.
PROVE N. POWE R FU L.
©2008 Genentech, Inc., and Biogen Idec Inc. All rights reserved. 3 Printed in USA on Recycled Paper 8974801 April 2008