February 2010, Vol 3, No 1 by Green Hill Healthcare Communications, LLC

FEBRUARY 2010

CANCER CENTER PROFILE

West Michigan Cancer Center: A Cancer Center Innovator By Dawn Lagrosa

The main campus in Kalamazoo offers medical oncology, radiation oncology, a neurooncology clinic, a breast cancer clinic, and a thoracic clinic, along with laboratory and support services.

est Michigan Cancer Center (WMCC) has increased the quality of patient care while updating its business model for today’s economic times. In recognition of this achievement, WMCC received a 2009 Cancer Center Innovator Award. The award was presented by Foley & Lardner at the third annual Cancer Center Business Summit in Dallas, Texas. Journal of Multidisciplinary Cancer Care recently spoke with Terry McKay, president and CEO, about how WMCC accomplished these goals as well as its plans for future improvements.

Cost-savings WMCC was chosen, in part, because of its aggressive stance on expense Continued on page 12

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VOL 3, NO 1

CONFERENCE NEWS

Healthcare Cost and Health Reform: Cost Containment Not Likely By Caroline Helwick

hereas some degree of healthcare reform seems likely to be enacted, what is shaping up as “reform” will likely be a failure in terms of “serious cost containment,” according to Paul B. Ginsburg, PhD, president of the Center for Studying Health System Change, Washington, DC, a think tank that analyzes changes in financing and the delivery of healthcare. Based on his broad experience in the field of healthcare economics and policy, Ginsburg delivered an invited lecture on cost and reform. Simply put, there is no single or simple solution, Ginsburg said. “A single approach to containing costs is unlikely to

be sufficiently successful,” he predicted. “We need to pursue many distinct but consistent approaches to offset the risk that some approaches will not succeed.” Need to contain costs On the national level, rising costs are undermining the mechanisms that finance healthcare and are a key factor in the country’s “dire public fiscal outlook,” he noted. On the individual level, private insurance is increasingly unaffordable, and the affordability problem now affects the middle class, Ginsburg said. The cost of Medicare, Medicaid, and tax expenditures for private health insurance are all growing faster than the gross

Paul B. Ginsburg, PhD, lectures on healthcare cost and reform at ASH.

domestic product (GDP), and the result is that other priorities are neglected, taxes are higher, and the deficit is growing. Continued on page 6

PRACTICE MANAGEMENT

BREAST CANCER

The Chemotherapy Infusion Suite: Staffing for Efficiency

Hypofractionated Whole Breast Irradiation Shows Promise

By Caroline Helwick

ursing challenges can affect the efficiency of the chemotherapy infusion suite. By following a staffing model that works best for your institution, you can improve efficiency, save money, and increase satisfaction among nurses and patients, according to Cathy Maxwell, RN, OCN, of Advanced Medical Specialties, Miami, Florida. Maxwell is employed by a 15site private oncology practice, where she is director of clinical operations for three sites and is

responsible for staffing and running their infusion suites. After trying a number of staffing approaches over the past 28 years, she says she ultimately settled on a “triage nurse” model that works best for her large practice. She discussed the pros and cons of various staffing models at the 2009 Community Oncology Conference in Scottsdale, Arizona. “Most infusion centers have schedules that are set up to fail,” she observed. “Treatments are overbooked, and scheduling of Continued on page 4

Inside Conference News

Conference News

For MDS treatment, azacitidine confers economic value over decitabine Based on a presentation by Risha Gidwani, DrPH

Managed care pharmacists can improve chemotherapy reimbursement Based on a presentation by Shetal S. Desai, PharmD

page 7

page 8

Complimentary CE Credit Multidisciplinary approach to a radiation-associated angiosarcoma of the breast

page 10

By John Schieszer

CHICAGO—A shortened, more intensive course of radiation given to the whole breast, along with an extra dose of radiation given to the surgical bed of the tumor (concomitant boost), have been found to result in excellent local control at a median followup of 2 years after completion of treatment with no significant side effects. Researchers said this shorter treatment, called accelerated hypofractionated whole breast irradiation, is an especially attractive option, because women can receive a full course of radiation therapy in half the time (3 weeks of daily treatments vs 5 to 7 weeks). In addition, the cost of this treatment is lower relative to the cost of standard whole breast radiation and also is less expensive than other new approaches, such as partial breast irradiation (breast brachytherapy). “The observations to date suggest that a 3week course of radiation therapy with concomiContinued on page 21

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Editorial Board EDITOR-IN-CHIEF

Mark J. Krasna, MD St. Joseph Cancer Institute Towson, MD Surgical Oncology

Practice Management Steven L. D’Amato, RPh, BCOP Maine Center for Campus Medicine Scarborough, ME Oncology Pharmacy

Scott E. Eggener, MD

Shaji K. Kumar, MD

University of Chicago Chicago, IL Surgical Oncology

Mayo Clinic Rochester, MN Hematology-Oncology

Beth Faiman, RN, MSN, APRN, BC, AOCN

Terry Macarol, RT(R)(M)(QM)

Cleveland Clinic Taussig Cancer Institute Mayfield Heights, OH Oncology Nursing

Advocate Health Care Oak Brook, IL Radiological Technology

Mehra Golshan, MD

Patrick Medina, PharmD, BCOP

Dana-Farber Cancer Institute Boston, MA Surgical Oncology

Oklahoma University College of Pharmacy Tulsa, OK Oncology Pharmacy

Patrick A. Grusenmeyer, ScD, FACHE

Patricia Molinelli, RN, MSN, AOCNS

Christiana Care Health System Newark, DE Oncology Administration

Somerset Medical Center Somerville, NJ Oncology Nursing

Nicole A. Bradshaw, MS, CIC

Marilyn L. Haas, PhD, CNS, ANP-BC

Judy A. Olson, RT(R), RDMS

Mountain States Tumor Institute Nampa, ID Oncology Administration

Mountain Radiation Oncology Asheville, NC Oncology Nursing

St. Luke’s Mountain States Tumor Institute Boise, ID Oncology Administration

Anna M. Butturini, MD

Dawn Holcombe, MBA, FACMPE, ACHE

Nicholas Petrelli, MD

John F. Aforismo, BSc Pharm, RPh, FASCP RJ Health Systems International Wethersfield, CT Oncology Pharmacy

Elizabeth Bilotti, RN, MSN, APNc John Theuer Cancer Center Hackensack University Medical Center Hackensack, NJ Oncology Nursing

Children’s Hospital Los Angeles Los Angeles, CA Medical Oncology

DGH Consulting South Windsor, CT Oncology Administration

Minsig Choi, MD

Arun Kumar, MD

G. V. Montgomery VA Medical Center Jackson, MS Medical Oncology

VA Medical Center Huntington, WV Medical Oncology

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Helen F. Graham Cancer Center Christiana Care Health System Newark, DE Surgical Oncology

Greg Pilat, MBA Advocate Health Care Oak Brook, IL Oncology Administration

Ritu Salani, MD Ohio State University Medical Center Columbus, OH Medical Oncology

Andrew Salner, MD Hartford Radiation Oncologists Association Hartford, CT Radiation Oncology

Timothy G. Tyler, PharmD, FCSHP Comprehensive Cancer Center Desert Regional Medical Center Palm Springs, CA Oncology Pharmacy

Gary C. Yee, PharmD, FCCP, BCOP University of Nebraska Medical Center Omaha, NE Oncology Pharmacy

YOU COULD BE HOLDING YOUR LAST ISSUE! Register online at: www.jomcc.com to ensure uninterrupted FREE delivery of Journal of Multidisciplinary Cancer Care February 2010 I VOL 3, NO 1

FROM THE EDITOR

PUBLISHING STAFF Publisher Philip Pawelko phil@greenhillhc.com Editorial Director Karen Rosenberg karen@greenhillhc.com Managing Editor Dawn Lagrosa dawn@greenhillhc.com Director, Client Services John W. Hennessy john@greenhillhc.com Cristopher Pires cris@greenhillhc.com Production Manager Marie RS Borrelli Business Manager Blanche Marchitto blanche@greenhillhc.com Executive Administrator Andrea Boylston Circulation Department circulation@greenhillhc.com Editorial Contact: Telephone: 732-992-1891 Fax: 732-656-7938

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EDITORIAL CORRESPONDENCE should be addressed to EDITORIAL DIRECTOR, Journal of Multidisciplinary Cancer Care®, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. E-mail: karen@greenhill hc.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 Journal of Multidisciplinary Cancer Care® do not necessarily reflect those of the Editorial Board, the Editorial Director, or the Publisher. Publication of an advertisement or other product mentioned in Journal of Multidisciplinary Cancer Care® 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 # 1949-0321. Journal of Multidisciplinary Cancer Care® is published 8 times a year by Green Hill Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. Telephone: 732.656.7935. Fax: 732.656.7938. Copyright ©2010 by Green Hill Healthcare Communications, LLC. All rights reserved. Journal of Multidisciplinary Cancer Care® 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.

February 2010 I VOL 3, NO 1

ith this issue of Journal of Multidisciplinary Cancer Care, we continue to improve our journal to better serve the needs of the busy practitioner. You likely have noticed our new, sleeker design, but if you look closer, you will also see that we have added a new feature. We have established colMark J. Krasna, MD laboration with Veritas Institute ST. JOSEPH CANCER for Medical Education, Inc. to INSTITUTE provide a seamless way for you Editor-in-Chief to receive continuing medical education (CME) credit online. Our multidisciplinary tumor board case study will now offer complimentary CME credit. After reading the article, you can apply for CME credits by completing a “posttest” and registering to receive a statement of completion online. Veritas Institute for Medical Education provides a variety of CE/CME activities designed to help physicians, nurses, pharmacists, and other healthcare professionals better treat and educate their patients. In 2007, Veritas Institute received 6-year Accreditation with Commendation from the Accreditation Council for Continuing Medical Education, one of an elite group of accredited providers to

CONTENTS

receive this recognition. We look forward to working with Veritas Institute to provide high-quality educational programs that will help enhance your professional development. Our first installment this year highlights how the prospective discussion of one patient was used to weigh the benefits and risks and determine the team’s best recommendation. As this case illustrates, “personalized medicine” takes into account the complexity of each patient’s medical history. Disease-site specific prospective case conferences represent the best venue for determining the correct multidisciplinary approach to a patient’s cancer care. Of course, clinical decision-making is not the only aspect of healthcare that is complex. As Dr Paul Ginsburg told his audience at the recent annual meeting of the American Society of Hematology, healthcare cost containment also is complex, with a single approach not likely to be the solution. In their ongoing work to remain in the business of providing high-quality cancer care, West Michigan Cancer Center, Advanced Medical Specialties, and USC Norris Cancer Hospital have each implemented business and staffing solutions as part of their cost-saving efforts. This issue highlights these business models for those looking for practice solutions. We hope you continue to benefit from reading the Journal of Multidisciplinary Cancer Care. We look forward to your feedback on our content and layout.

February 2010

VOL 3, NO 1

FEATURE ARTICLES 7 Conference News: ASH For MDS treatment, azacitidine confers greater economic value over decitabine Multiple myeloma treatment costs vary widely 8 Conference News: ASHP Managed care pharmacists can improve chemotherapy reimbursement 10 Continuing Education Multidisciplinary approach to a radiation-associated angiosarcoma of the breast 15 Practice Management Strategy and planning: the difference between being a player or a pawn DEPARTMENTS 18 Oncology Drug Codes Cervical cancer 21 Recent FDA Approval

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Practice Management The Chemotherapy Infusion Suite... Continued from cover infusion chairs is not in sync with what actually happens. This leads to inefficiency, uneven assignments, and dissatisfaction among nurses, physicians, and patients.” The need to optimize staffing for the infusion suite is based on the reality that both understaffing and overstaffing occur from time to time; that staff turnover is disruptive and expensive; that not all new nurses will have oncology experience; and that chemotherapy is complex. An example of the increased complexity of chemotherapy is the higher nursing acuity for a patient receiving chemotherapy for colon cancer. “It takes a minimum of 11 nursing events and close monitoring to hang a FOLFOX [leucovorin/fluorouracil/oxaliplatin] regimen, whereas a 5-FU/LCV [5-fluorouracil/leucovorin] intravenous push given for this same patient a few years ago was just one event,” she pointed out. Factors related to patients, physicians, and reimbursement can also be obstacles to efficiency in the infusion center. Patients who arrive late can impact the schedule, creating more waiting time for other patients. “If you measure patient satisfaction,” she said, “you find that what patients dislike the most is the waiting.” Because oncology scheduling is not an exact science, delays should be anticipated; for instance, the schedule should take into account a patient with special needs or one who has difficult venous access. Physicians impact efficiency when they run late, or request same-day and off-label chemotherapy. Delays in laboratory test results can throw the schedule off, as can a problem with insurance authorization and inconsistency in practice patterns that require clarification. Physician “lag time” should be built into the schedule. “If the patient’s visit is at 10 AM, and you know the physician runs an average of 2 hours behind, you should schedule the infusion chair time to start at 12 PM,” she suggested.

Lower reimbursement for chemotherapy administration is also impacting the potential for efficiency. Financial “cushions” have disappeared and practices cannot afford to waste supplies or pay overtime. Safety products are costly, reimbursement amounts are in flux, and documentation must be precise. “When there is a choice between similar procedures,” she said, “we may sometimes do what costs less and that may not be as efficient.” “We must run an efficient suite,” Mawxell emphasized. Efficiency translates into job satisfaction for the nurses, because they prefer a consistent flow of patient care. Patients are happier, as well, because their waiting time is less. And physicians are happy, because they are rarely required to stay “late.” Finally, reductions in overtime, staff turnover, drug waste, and medical errors—all the result of efficiency— translates into cost-savings, which has become more important today. Triage nurse model Staffing models vary, and some work better at one infusion center than another. “You should use the staffing model that is best suited for your situation,” advised Maxwell, who believes the triage nurse model may be the best approach for most centers. Under this model, the triage nurse operates much like an air-traffic controller, knowing which patients will be treated and what their particular needs will be. The triage nurse also handles a number of pretreatment tasks. Staff nurses are simply assigned the next patient by the triage nurse. “This model has been the best fit for us,” she said. “We started this in 2002 when we hired non-oncology nurses to give chemotherapy because of the nursing shortage. The lack of oncology knowledge worried me. I put an experienced oncology nurse in the triage position, and basically her knowledge filtered out to all our patients. It has been very successful.”

Tips for Scheduling Chemotherapy Infusions • Develop and follow guidelines for scheduling • Consider time needed for intravenous access and premedication • Allow extra time for new patients • Schedule in 15-minute slots (ie, 2-hour treatment = 8 slots) • Stagger the infusion schedules (ie, recliner 1 at 8:15; recliner 2 at 8:30; …) • Assign four to five recliners per nurse, and arrange them close together in pods • Make necessary adjustments to schedule the day before treatment • Have enough chairs and enough time to handle patients

February 2010 I VOL 3, NO 1

Cathy Maxwell (first row, far right) with some of her staff at Advanced Medical Specialties.

The triage nurse assesses charts the day before chemotherapy and determines what tests are needed. She checks laboratory values and multiplegated acquisition (MUGA) results and orders additional tests per standing orders. She verifies the physician’s orders and prior authorizations. She is an expert at the standing orders for antiemetics and growth factors and understands billing and coding. “The nurses consider the assignments to be fair. They are not bombarded. They don’t get two or three patients at one time, which had been a problem,” she said. “Cancellations and add-ons don’t affect the schedule—each nurse gets the same number of assignments.” Even with this model, there can be some difficulties, she acknowledged. The model requires cross-training, careful scheduling, and tracking of numbers of registered nurses needed. Bottlenecks still occur in the triage area during peak times, requiring additional help to keep the system moving. There are also prerequisites for the triage nurse: she must be very detail-oriented, be able to concentrate on her task, and have a quiet area to work. “This is a high-stress job,” she noted. Other models First come/first serve. This model works well for low-volume practices but can create problems in larger offices. It does not take into account nurse experience and complexity of the chemotherapy regimen. It can result in uneven nursing assignments, overtime, and missed lunchtimes. Careful control of the schedule is required. “We used this model until our office grew too large,” she said. “I found that nurses were picking and choosing patients out of the chart bin. The second

shift usually had to stay late to finish up.” Patient/nurse model. This is calculated by the number of patients per day divided by the number of nurses. It distributes the workload among the staff in an attempt at fairness; however, it does not consider nurse experience or complexity of treatment, can result in overtime and missed lunchtimes, and requires careful control of the schedule. Acuity model. This model is probably the best accepted and fair. It measures nursing time rather than chair time and takes into account different practice patterns and special needs. More patients can be treated per nurse, facilitating productivity. Satisfaction is high among nurses and patients. However, the acuity model needs to be strictly managed, that is, someone must assign the acuity points to the treatment. Schedulers do not always consider the number of nurses on hand, which can ruin the schedule. Acuity is altered when patients’ needs change. Overtime is often needed and lunchtimes are frequently missed. In other words, the acuity model is not always modeled on a “real-time” visit. Schedule by nurse model. This model takes acuity into consideration. Patients are assigned to a specific nurse, which facilitates continuity of care, improves the productivity of the individual nurse, and reduces overtime. Nursing satisfaction is high; however, success depends on careful control of the schedule and knowledge of the exact number of nurses to be needed. Furthermore, the schedule easily becomes inaccurate when there are cancellations and add-ons, and patients come to depend on “their” nurse. Other ways to improve efficiency Maxwell suggested that each patient’s Continued on page 8

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Metastatic Colorectal Cancer: Sound Strategies for Selecting First-Line Therapies

LOG ON TODAY TO PARTICIPATE www.coexm.com/ace01.asp FACULTY

Release Date: November 25, 2009 Expiration Date: November 24, 2010

Neal P. Christiansen, MD Assistant Professor of Medicine Medical University of South Carolina Division of Hematology/Oncology Charleston, South Carolina

TARGET AUDIENCE This activity is intended for hematologists, oncologists, oncology nurses, oncology/specialty pharmacists, and others who are involved with the care of patients with metastatic colorectal cancer (mCRC).

STATEMENT OF NEED Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer death in the United States. Approximately 149,000 new cases are diagnosed each year. At the time of presentation, about 20% of patients with CRC will have metastatic disease. Cure at this stage is rarely possible, although some patients whose metastases are limited (especially if to the liver or lung) may be “cured” by surgical means. For most sufferers of mCRC, however, treatment is palliative, offering prolonged survival, improvement in symptoms, and enhanced quality of life.

EDUCATIONAL OBJECTIVES On completion of this activity, participants should be able to: • Evaluate and assess current findings in the management of mCRC • Identify current first-line therapies, both chemotherapeutic and biologic agents, and practices in mCRC • Tailor a therapeutic regimen to meet the needs of the individual patient with mCRC • Employ select strategies to minimize exposure to ineffective therapies and their toxicities

INSTRUCTIONS To receive a statement of credit, you must: • Review the content of the activity • Successfully complete the post-test (70% or higher) • Complete the evaluation at the end of the activity Your statement of credit will be issued immediately upon successful completion of the post-test and submission of the evaluation

ACCREDITATION STATEMENT 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 the University of California, Irvine School of Medicine (UCI) and Center of Excellence Media, LLC. The University of California, Irvine School of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT The University of California, Irvine School of Medicine designates this educational activity for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. This activity is complimentary.

FACULTY INFORMATION AND DISCLOSURES Dr Christiansen has received consultancy fees from sanofi-aventis and Genentech. Off-label use of cetuximab (in patients in whom irinotecan has not failed) and bevacizumab (continuing after first-line therapy) will be discussed in this presentation. Conflict resolution: This presentation has been peer reviewed for evidence base and fair balance.

GENERAL DISCLOSURE STATEMENT It is the policy of the University of California, Irvine School of Medicine and the University of California CME Consortium to ensure balance, independence, objectivity, and scientific rigor in all CME activities. Full disclosure of conflict resolution will be made in writing via handout materials or syllabus. Bonnie Carroll, Director, CME, UC Irvine School of Medicine, has no financial or other relationship to products or devices with commercial interests related to the content of this CME/CE activity. Center of Excellence Media, LLC: The planners and managers have nothing to disclose related to the content of this activity. Erica Johansson, RN, Astute CE, LLC, has nothing to disclose related to the content of this activity. Dr. Randall F. Holcombe, University of California, Irvine School of Medicine, peer-reviewed the content for evidence base and fair balance. Dr Holcombe has no real or apparent conflicts of interest related to this activity. Conflict resolution: This presentation has been peer reviewed for evidence base and fair balance. This activity is in compliance with California Assembly Bill 1195, which requires continuing medical education components to include curriculum in the subjects of cultural and linguistic competency. For specific information regarding Bill 1195 and definitions of cultural and linguistic competency, please visit the CME web site at http://www.cme.uci.edu. This activity is supported by an educational grant from Genentech BioOncology.

In collaboration with

Conference News ASH 2009 The following articles are based on presentations at the 51st Annual Meeting and Exposition of the American Society of Hematology (ASH) held in New Orleans, Louisiana, December 5-9,2009.

Healthcare Cost and Reform... Continued from cover An international comparison provides evidence of undue healthcare costs in the United States. Although healthcare accounts for 16% of the GDP in this country, for a number of other countries it is around 11%. “Adjusting for income, the United States spends an extra $477 billion per year on healthcare,” he noted. Evidence of rising costs comes from a comparison of cost trends with income trends. “There has been a 37% increase in earnings to support a 120% increase in premiums,” he said. “This gap explains three fourths of the long-term decline in the percent of the insured population.” What’s driving up costs? The key drivers of rising costs are higher incomes (more money is available to spend on healthcare), developments in medical technology, less healthy lifestyles, small gains in productivity related to the delivery of health services, new patterns of competition in healthcare, and, to a lesser degree than most assume, the aging of the population. Aging contributes just one half of one percent or less to the spending trend each year, according to Ginsburg. Additional drivers include the poorly functioning medical liability system and state insurance mandates. At least one third of the trend in spending stems from technological “advances.” New treatments are more effective—yielding better outcomes with lower risks—but the tendency is to overuse them to the point of limited or negative gains, he pointed out. Marginally effective, ineffective, or harmful treatments also add to rising costs, and little funding is available for effectiveness research to weed these out. Unhealthy lifestyles create more health problems. Obesity alone is estimated to account for 12% of the spending growth in recent years. Declines in smoking have held down cost trends but still contribute, he said. Although the prosperity of the economy largely derives from gains in productivity, this is true only for certain industries, such as banking and airlines. “There is much less productivity in healthcare,” he noted. One reason is the lack of the proper incentives for healthcare providers. Few incentives exist to produce episodes of treatment or to help improve a patient’s health more efficiently, he noted. And efficiency of the care delivered varies widely.

February 2010 I VOL 3, NO 1

The term new patterns of competition refers to the “more entrepreneurial delivery system” of today, that is, the expansion of profitable services that may not add true value. Medicare and private insurers have failed to set payment rates to appropriately reflect relative cost of services; this has led hospitals to expand services that are profitable, such as cardiac procedures, and to open special facilities, such as “heart hospitals.” It is possible, he continued, that expansions of capacity are actually creating a demand for services. Tied to this is an increase in physician self-referrals, such as more referrals for magnetic resonance imaging when a physician owns an imaging center. “With ownership of facilities, the scope of physician self-referral is wider, and this is worrisome to me,” he told the audience. Why are costs so hard to contain? Cost containment is complex and, for various reasons, is viewed by many sectors as threatening. “All spending pertains to someone’s income, and there is an increasingly effective lobby to protect incomes,” Ginsburg observed. The country’s political leaders are also “falling down on the job” by fostering the notion that costs can be contained without sacrifice, he added. “The concept of ‘cutting waste, fraud, and

pointed out. “More comprehensive insurance leads to higher spending— bringing the uninsured up to insured status will increase healthcare spending.” The public plan option is also faulty, he said. “Only the ‘robust’ version can impact costs through lower provider payment rates,” he noted. “The version in the bill has little potential to reduce costs.” He said increased competition in insurance markets has limited potential. Cost-savings through increased wellness and prevention is another fallacy, he added. “The evidence on the lack of potential for savings is very strong. Many in Congress are unwilling to accept the evidence, but the Congressional Budget Office analysis found that prevention will not reduce federal outlays.” Which approaches may work? A single approach will not be the sole solution to cost containment, and most of the strategies being discussed have advantages and disadvantages. Increased patient cost-sharing (benefits “buy-downs,” consumer-directed health plans, and health savings accounts) is part of a demand-side approach to cost containment, and it is not favored by political liberals. In fact, patient cost-sharing does a fairly poor job of addressing spending trends, Ginsburg added, because most spending

The motivator of health reform is the expansion of insurance coverage; however, coverage expansion will exacerbate, not alleviate, the cost problem. abuse’ goes way back,” he said. “Politicians claim there will be large savings through reducing waste. It’s a terrific idea, but it won’t solve the cost problem.” It is highly uncertain that such “painless solutions” will contain costs, he maintained. The other current proposals include the promotion of quality reporting and payment for quality, the advancement and adoption of health information technology, and application of comparative effectiveness research. The “red herrings” of healthcare reform and cost containment The motivator of health reform is the expansion of insurance coverage; however, coverage expansion will exacerbate, not alleviate, the cost problem, according to Ginsburg. “Uninsured people spend less,” he

is concentrated within a relatively small population of patients. “The burden of healthcare falls more on the sick and the poor,” he observed. However, patient financial incentives “clearly work,” he continued, but will not accomplish much because healthcare use is not particularly sensitive to patient incentives. Certainly, to be effective, the “tools” for patient incentives need refinement, he said. One proposal is a “value-based benefits design,” which will vary cost-sharing by service type and patient condition— with low barriers to the management of chronic disease and higher barriers for elective services. This approach would promote the choice of more efficient providers, because consumers would reap savings when they choose less costly providers and less efficient providers would have incentives to improve.

Another “tool” is the excise tax on the so-called “Cadillac plans.” Also part of the demand-side approach is greater research on price and quality, which in theory is favored by all except providers, but in practice may be less useful because its impact will not be felt for years. The government’s role would be in data gathering rather than price setting, which would fall to insurers to customize and simplify. In addition, some believe that programs aimed at wellness and health promotion will help contain costs, but the effect of prevention is unproven, he reiterated. More accurate payment structure proposed As a supply-side approach, the crafting of a more accurate payment structure is widely proposed, based on the unintended wide variation in profitability by service. Medicare is well positioned to make structures more accurate (and private insurers and Medicaid programs will follow), but Medicare needs to apply more political and financial resources to this, which is problematic because many hold a negative view of Medicare governance, he added. The supply-side approach also includes broader payment units (BPUs) as a means of reducing the role of fee-forservice, which is faulted by having incentives for service volume and lacking motivations or rewards for coordinated services. BPUs introduce elements of capitation in the form of accountable care organizations. The strategy can incorporate episode-based payments, in which actual per-episode payments can be made to a joint entity or by fee-for-service with incentives for all involved. But Ginsburg questioned whether BPUs will be developed and implemented and whether the idea will succeed. “BPUs have opportunities for physicians—rewards for reducing spending on hospital care, pharmaceuticals, and devices. They can save money by reducing hospitalizations, choice of drugs, and so forth and not just by reducing the physician’s own services. They can capture rewards from this,” he said. Finally, he concluded, the search for a solution is geared toward “pragmatism that recognizes the need to build on present institutions.” Although debate once focused on “competition versus regulation,” he pointed out that the country proved unwilling to embrace either of these approaches. l

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Conference News

For MDS Treatment, Azacitidine Confers Greater Economic Value Over Decitabine

n a cost-effectiveness analysis for the treatment of myelodysplastic syndrome (MDS), azacitidine was shown to be cost-saving or cost-effective, compared with decitabine. The analysis, funded by Celgene, was performed by Abt Bio-Pharma Solutions, Inc (Lexington, MA) and presented by Risha Gidwani, DrPH, lead health economist for the research company. The National Comprehensive Cancer Network 2010 clinical practice guidelines recommend azacitidine and decitabine for the treatment of MDS, with azacitidine being the preferred category 1 treatment for inter-mediate-2 or high-risk patients ineligible for transplant. “While the clinical benefits of azaci-

tidine have been shown, this is the first study to evaluate its cost-effectiveness relative to decitabine,” Gidwani said. Investigators developed a decisionanalytic Markov model with 1-month cycles, which was run alternatively for 12-month and 36-month periods. Patients in the model replicated the demographics of subjects enrolled in phase 3 trials for the drugs, and based on these data, the patients modeled in the decitabine arm had lower MDS severity than those in the azacitidine arm. During each cycle of the Markov model, patients could either remain in or transition among four health states, including MDS and transfusion independence, MDS and transfusion dependence, progression to acute myeloid

Table. Comparisons for Azacitidine and Decitabine Parameter Total cost per patient at 12 months Total cost per patient at 36 months QALYs gained at 12 months QALYs gained at 36 months

Azacitidine $53,518 $154,112 0.579 1.446

Decitabine $62,760 $142,578 0.526 1.175

QALYs indicates quality-adjusted life-years.

leukemia (AML), or death. Therefore, in any given model cycle a patient could be stable or become healthier, sicker, or die. The analysis used model parameters derived from published literature, product labels, clinical trial data, and drug pricing and medical services cost databases. “Despite a higher-risk profile in the underlying data for azacitidine, treatment of MDS with azacitidine was either cost- Risha Gidwani, DrPH saving—meaning that it cost less and conferred greater clinical bene- (QALYs), attained a greater number of fit—or was cost-effective, compared with transfusion-independent months, and decitabine,” Gidwani reported. were more likely to avoid progression to “Azacitidine changed from dominat- AML (Table). ing decitabine in the 12-month scenario In the 12-month scenario, the use of to being cost-effective in the 36-month azacitidine resulted in $9242 saved per scenario due to the survival advantage patient. In the 36-month scenario, azacifor azacitidine-treated patients. Patients tidine treatment cost $11,534 more than treated with azacitidine live longer, and treatment with decitabine, but conferred a therefore have more opportunity to incur clinical benefit of 0.2707 additional treatment costs,” she explained. QALYs gained. The incremental costIn both the 12-month and 36-month effectiveness ratio of $42,615 per QALY is scenarios, azacitidine-treated patients considered cost-effective, she noted. l experienced a greater number of life—CH years and quality-adjusted life-years

Multiple Myeloma Treatment Costs Vary Widely

cost analysis that compared treatments for multiple myeloma found that bortezomib, which is an injectable drug, was associated with less out-of-pocket expense than the oral medications lenalidomide and thalidomide, according to a study presented. Bortezomib is a proteasome inhibitor, and lenalidomide and thalidomide are immunomodulatory drugs. These agents are sometimes combined in regimens. “Multiple myeloma is a complex disease. Improved outcomes have been achieved with these novel agents; however, few studies have reported the economic burden on patients,” said Brett W. Pinsky, MPH, a senior researcher at i3 Innovus, Eden Prairie, Minnesota. The study was sponsored by Millennium: The Takeda Oncology Company. The investigators drew from a claims database of a large national commercial health plan with 14 million members. Treatment episodes (defined as each course of therapy) were identified from claims records for each patient. Patient out-of-pocket costs and patient visit

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data were examined for 1 year from the beginning of each treatment episode. Descriptive analyses were supplemented with multivariate regression analyses to control for patient characteristics, comorbidities, and line of treatment. A total of 2642 treatment

comorbidities by multivariate analysis. Patients were also burdened with a significant number of outpatient hospital visits, which occurred most frequently with thalidomide. Pinsky said that patients must visit doctors more often to receive bortez-

“For the Medicare Advantage group, there is the doughnut-hole effect that is causing a huge spike in the cost of the oral drugs.” episodes were identified for the 1900 patients. The majority of episodes were classified as “other chemotherapy or radiation therapy” (66.6%), followed by thalidomide (20.8%), bortezomib (9.2%), and lenalidomide (3.4%). Ambulatory visits accounted for much of the patient visit burden. As expected, patients treated with bortezomib for injection had more visits than those treated with oral lenalidomide, but the difference was not significant after adjustment for patient characteristics, line of treatment, and

omib injections; therefore, it is assumed this is a more expensive treatment. The data did not support that assumption, he pointed out. Patient out-of-pocket costs “Direct out-of-pocket costs were significantly higher for patients treated with the oral drugs thalidomide and lenalidomide compared with bortezomib for injection,” Pinsky reported. The total adjusted patient out-ofpocket costs for the year after treatment initiation were $3504 for bortezomib,

$4443 for thalidomide, and $4766 for lenalidomide. The differences were greatest for Medicare patients, with the adjusted costs being $4395, $8824, and $12,568, respectively. This means treatment with bortezomib amounted to less than half the cost of oral drug therapy, he said. “The out-of-pocket cost discrepancy was magnified in the Medicare population likely due to the coverage gap, commonly known as the ‘doughnut hole,’ in Medicare Part D,” added Henry Henk, PhD, also of i3 Innovus. “For the Medicare Advantage group, there is the doughnut-hole effect that is causing a huge spike in the cost of the oral drugs,” he pointed out. The investigators concluded that because patients with myeloma require a great deal of care and resources, most patients will not see a major difference in the number of healthcare visits regardless of type of treatment, but they may feel the pinch of higher out-ofpocket costs with the oral drugs. l —CH

February 2010 I VOL 3, NO 1

Conference News ASHP Midyear Clinical Meeting The following article is based on a presentation at the 44th American Society of Health-System Pharmacists (ASHP) Midyear Clinical Meeting held in Las Vegas, Nevada, December 6-10, 2009.

Managed Care Pharmacists Can Improve Chemotherapy Reimbursement By Jill Stein

anaged care pharWhen Desai was brought macists, through onboard, the facility was havimplementation of ing problems with payer a clinical authorization reimbursement of chemoprocess, can play a pivotal therapy agents. “In fact, role in securing payer reimmonthly total disputed bursement of chemotherapy claims dollars averaged beagents at a cancer hospital, tween $600,000 and $1 milaccording to recent data. lion,” she said. What’s more, by developThe hospital administraing a clinically staffed chemo- Shetal S. Desai, PharmD tion was unclear about the therapy authorization departreasons for unpaid or disputment, managed care pharmacists can also ed claims, she added. help increase the procurement of reDesai, who is also an assistant professor placement chemotherapy drugs. at the USC School of Pharmacy, found: Those conclusions were reported by • The main reasons for disputed or Shetal S. Desai, PharmD, who was unpaid claims were a lack of authorhired 2 years ago as the director of the ization before treatment was adminClinical Authorization Center at the istered and the use of an agent for University of Southern California (USC) unapproved indications Norris Cancer Hospital in Los Angeles. • Bevacizumab was the most common“My study is actually my job,” said ly used chemotherapy agent and the Desai, who has worked extensively in one most frequently disputed; the managed care. Her job required that she main reason why the claims were examine the issues surrounding finandisputed was that payment was cial reimbursement of chemotherapy being requested for off-label use of drugs. Afterward, she was responsible bevacizumab (eg, treating metastatfor implementing procedures that were ic breast cancer before it had been intended to decrease disputed claims approved for that indication) and improve drug replacement through • Roughly 40% of all visits for chemoenrollment in pharmaceutical manufactherapy administration were not turer–driven programs. scheduled in advance The USC Norris Cancer Hospital is a • Physician chemotherapy orders were private, 60-bed research and teaching not routinely sent to the authorizahospital with an onsite outpatient tion department prior to a scheduled chemotherapy infusion center that servappointment ices between 20 and 45 patients daily. • Third-party payers requested from 3 The payer mix includes commercial to 5 days to respond to an authorizainsurers and Medicare. tion request

• Authorizations were requested by nonclinical hospital personnel, who did not have the clinical knowledge to be able to respond to clinical questions prospective payers needed answered before authorizing payment • It was difficult to request payment from payers when authorizations for chemotherapy were not accurately obtained or appropriately documented • Clinical criteria for authorization varied by payer and coverage plan. After reporting her results to the hospital administration, Desai recommended that a new clinically staffed chemotherapy authorization department be developed. “A staff that is clinical is crucial, because they can actually speak the language of the insurance companies and they can obtain the proper authorization before treatment,” she said. “In addition, they can supply the insurance companies with any peerreviewed journal articles that might provide enough evidence for treatment in unapproved indications.” Ideally, a managed care pharmacist should serve as the director of the authorization department, and nurses with a case-management background should be hired as clinical authorization specialists, Desai observed. Medical staff, she said, should submit orders 3 to 5 days before treatment to allow sufficient time to obtain authorization. The authorization department should also determine whether patients being considered for off-label treatments are eligible for pharmaceutical manufactur-

er–sponsored patient-assistance programs. If an insurance company denies reimbursement because a drug is to be used off-label, the authorization department will contact the company that manufactures the drug to determine whether the patient is eligible for drug replacement through the pharmaceutical manufacturer–sponsored patientassistance programs, she added. One year after the implementation of a clinical-based authorization center, more than $1.1 million in total drug replacement has been recovered, Desai reported. Also, claims were processed more rapidly and in some cases on the same day the request was made. There was also a reduction in the number of claims denied due to lack of authorization. An additional benefit of the new clinically staffed authorization department is improved communication between the authorization department and medical and nursing staff. Desai was unable to determine the extent of improvement in reimbursement to the hospital for chemotherapy with the new authorization process, because her hospital changed ownership earlier this year and retrospective data thus became unavailable. “If hospitals want to improve their reimbursement, they need to have a managed care pharmacist in charge of this area,” Desai said. “Otherwise you’ll have someone who will not know how to get around some of the obstacles the insurance companies put up.” l

PRACTICE MANAGEMENT

The Chemotherapy Infusion Suite... Continued from page 4 office visit and pretreatment assessment occur the day before the treatment visit. Under this approach, the patient will have been assessed for toxicities and the need for dose reductions prior to entering the infusion suite. Patients like this approach, as it shortens their waiting time. It also avoids the nurse’s wait for the patient to complete the office visit. Scheduling of chair time and staffing is more accurate when these visits are separate, and more patients can be treated in a given day. There is tighter inventory control and less drug waste.

February 2010 I VOL 3, NO 1

Efficiency is also increased when noninfusion needs are managed in a separate area staffed by one or two nurses and one or two medical assistants, depending on the number of patients. Procedures handled in this area will include injections, pump disconnects, complete blood counts, monitoring, nursing assessment, and port flushes. “This allows infusion nurses to concentrate on giving chemotherapy, making assessments, educating patients, and performing nursing interventions,” she noted. Maxwell also recommends having a

per diem pool of registered nurses who can be brought onboard as needed, without restrictions, such as mandatory number of working hours. Float nurses can be used to enhance patient flow by covering for nurses who are at lunch or out sick. Start times should be staggered and extra staff hired for peak times. If oncology nurses are not available, non-oncology nurses can be used in the infusion area for non-chemotherapy infusions. Nurses should rotate to satellite sites as needed, which allows flexibility with staffing based on the patient census.

They should also be rewarded for mentoring new nurses and sharing knowledge with each other. Finally, because nursing salaries are a large part of the budget, making efficient use of nurses translates into cost-savings. When possible, ancillary staff should perform tasks for which a registered nurse is not necessary. These might include tasks related to authorizations, telephoning, drug assistance, coding, scheduling, injections, vital signs, escorting patients, laboratory work, and stocking and ordering of supplies. l

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CONTINUING EDUCATION CREDITS Current activities at www.COEXM.com include:

CONTINUING EDUCATION EDITORIAL BOARD

PROGRAM MCC1 • RELEASE DATE: FEBRUARY 15, 2010 • EXPIRATION DATE: FEBRUARY 15, 2011

Emily J. Penman, MD

ESTIMATED TIME TO COMPLETE: 1.0 HOUR

Medical Director Breast Center at the Helen F. Graham Cancer Center Associate Vice Chair Department of Surgery Christiana Care Health System 4701 Ogletown-Stanton Road Newark, DE 19713

Jon F. Strasser, MD Assistant Professor of Radiation Oncology Thomas Jefferson University 111 South 11th Street Philadelphia, PA 19107 Attending Physician in Radiation Oncology Helen F. Graham Cancer Center Christiana Care Health System 4701 Ogletown-Stanton Road Newark, DE 19713

David D. Biggs, MD Assistant Professor of Medicine Thomas Jefferson University 1025 Walnut Street Philadelphia, PA 19107 Chief of Oncology Section Helen F. Graham Cancer Center Christiana Care Health System 4701 Ogletown-Stanton Road Newark, DE 19713

PLANNING COMMITTEE Gloria Mui Medical Director Veritas Institute for Medical Education, Inc. 611 Route 46 West Hasbrouck Heights, NJ 07604

Multidisciplinary Approach to a Radiation-associated Angiosarcoma of the Breast By Emily J. Penman, MD; Jon F. Strasser, MD; David D. Biggs, MD Helen F. Graham Cancer Center, Christiana Care Health System, Newark, Delaware STATEMENT OF NEED

LEARNING OBJECTIVES

This program will enhance comprehension of the thought processes involved in applying personalized medicine by elucidating one team’s prospective discussion in their treatment decisions for a woman with an angiosarcoma of the breast.

After completing this activity, the reader should be better able to: • Identify risk factors and characteristics for radiation-associated angiosarcoma of the breast

TARGET AUDIENCE

• Discuss appropriate diagnostic testing and preoperative evaluation techniques

Medical, surgical, and radiation oncologists, and other interested healthcare professionals, especially those caring for cancer patients.

• Review the benefits and limitations of postsurgical radiation and/or chemotherapy

The Breast Cancer Multidisciplinary Clinic at the Helen F. Graham Cancer Center offers its patients the latest and most comprehensive breast care, diagnosis, and treatment. The following case illuminates the thought processes behind the treatment decisions for a woman with an angiosarcoma of the breast. Commentaries by the surgical, radiation, and medical oncologists discuss the evidence and show how the multidisciplinary approach benefited the patient.

Case Presentation Chief complaint: Pain in the right breast nipple and a skin lesion. History of present illness: A 58-year-old white woman presented with acute changes in her right breast, including pain, eversion of a previously inverted nipple, and a “blood blister” on the nipple that she thought was traumatic. Eight years ago, she was treated for a right-breast, stage IIB, grade 3 invasive ductal carcinoma that was 3.8 cm with 1/18 nodes positive for metastatic disease; she underwent a lumpectomy, axillary node dissection, doxorubicin/cyclophosphamide/paclitaxel chemotherapy, and standard breast radiation. Other medical history: None.

Julie Ann Tagliareni CME Director Veritas Institute for Medical Education, Inc. 611 Route 46 West Hasbrouck Heights, NJ 07604

Anne L. Finger President Veritas Institute for Medical Education, Inc. 611 Route 46 West Hasbrouck Heights, NJ 07604

Dawn Lagrosa Managing Editor Green Hill Healthcare Communications, LLC 241 Forsgate Drvie Monroe Twp, NJ 08831

Karen Rosenberg Editorial Director Green Hill Healthcare Communications, LLC 241 Forsgate Drvie Monroe Twp, NJ 08831

Other surgical history: Cholecystectomy. Family history: Leukemia, lung, and brain

cancers. No family history of breast cancer. Social history: Unemployed, smoked in the past, no alcohol use, divorced with three children. Medications: None. Allergies: None. Physical examination: General: Obese, in no acute distress. Head, eyes, ears, nose, and throat: No pallor, no icterus. Neck: No lymphadenopathy, no thyroid mass. Respiratory: Clear to auscultation. Cardiovascular: Regular rate and rhythm, no murmurs. Breasts: Right nipple enlarged with a deep bluish purple hue and nonspecific subareolar fullness, periareolar skin thickened and edematous. Left breast had no masses or

skin changes. No axillary adenopathy noted. Abdomen: Soft, nontender, no hepatosplenomegaly, normal bowel sounds. Extremities: Full range of motion. Imaging studies: Mammography/breast ultrasound: Skin thickening and ill-defined hypoechoic retroareolar 3.7-cm mass. Computed tomography: Chest, abdomen, and pelvis negative for metastatic disease. Pathology: Ultrasound-guided core biopsy revealed an angiosarcoma. Laboratory values: White blood cell count: 6.9 x 103/µL; hemoglobin/hematocrit: 13.1 g/dL/40%; platelets: 314 x 103/µL; segmented neutrophils: 51%; lymphocytes: 30%; eosinophils%: 1; monocytes: 7%; alkaline phosphatase: 82 U/L; aspartate aminotransferase: 54(H) U/L; alanine aminotransferase U/L: 26; bilirubin: 0.4 mg/dL.

CONTINUING MEDICAL EDUCATION ACCREDITATION AND DESIGNATION OF CREDIT STATEMENT

This activity is provided free of charge to participants.

Veritas Institute for Medical Education, Inc. is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Veritas Institute for Medical Education, Inc. designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

FINANCIAL DISCLOSURES

METHOD OF PARTICIPATION

1. Read the article in its entirety 2. Log on to www.jomcc.com 3. Click on “CME Credits” 4. Click on “Click here to complete the posttest and obtain a CME certificate online” 5. Register to participate 6. Enter program number MCC1 7. Complete and submit the CME posttest and CME Activity Evaluation and Request for Credit Form online 8. Print your Certificate of Credit

February 2010 I VOL 3, NO 1

Veritas Institute for Medical Education, Inc. is required to disclose to the activity audience the relevant financial relationships of the planners and faculty involved in the development of CME/CE content. An individual has a relevant financial relationship if he or she has a financial relationship in any amount occurring in the last 12 months with a commercial interest whose products or services are discussed in the CME/CE activity content over which the individual has control. In addition, all faculty are expected to openly disclose any unlabeled/unapproved/investigational uses of drugs or devices discussed in this activity. Disclosures are as follows: • Emily J. Penman, MD, has nothing to disclose. • Jon F. Strasser, MD, has nothing to disclose. • David D. Biggs, MD, has nothing to disclose. The staffs of Veritas Institute for Medical Education, Inc. and Green Hill Healthcare Communications, LLC have nothing to disclose. DISCLAIMER

The opinions expressed in this activity are those of the presenters and do not necessarily reflect the opinions or recommendation of Veritas Institute for Medical Education, Inc. Copyright © 2010 Veritas Institute for Medical Education, Inc. All rights reserved.

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www.JOMCC.com Surgical oncologist’s commentary radiation-naïve angiosarcoma patients.1 A 58-year-old white woman presented The median interval is 7 to 8 years from to the Helen F. Graham completion of their radiation Breast Cancer Multidistherapy to diagnosis of their ciplinary Clinic. Her chief angiosarcoma.1 A patient with angiosarcomplaints were pain, evercoma can present with redsion of a previously inverted dish purple papules on the nipple, and a “blood blister” skin. The patient may also on the nipple of her right have a breast lesion, which breast. Although she bemay or may not be palpable. lieved the papule was from Diagnostic imaging is nontrauma, her history suggested specific, with skin thickenit should be investigated. ing and occasionally spicuEight years previously, the Emily J. Penman, MD patient had a right-breast, stage IIB, grade lated masses seen on mammography 3 invasive ductal carcinoma that was 3.8 and nonspecific hypo- or hyperechoic cm with 1/18 nodes positive for meta- masses detected on ultrasound. Breast static disease. At that time, she had a magnetic resonance imaging can indilumpectomy, axillary node dissection, cate malignancy, with rapid enhancedoxorubicin/cyclophosphamide/paclitax- ment of the angiosarcoma.5 Diagnosis should be established by an el chemotherapy, and standard breast image-guided core biopsy, not an exciradiation.

Diagnostic imaging is nonspecific, with skin thickening and occasionally spiculated masses seen on mammography and nonspecific hypoor hyperechoic masses detected on ultrasound. We investigated the current symptoms with a mammogram and breast ultrasound, which revealed skin thickening and an ill-defined hypoechoic retroareolar 3.7-cm mass. Ultrasound-guided core biopsy revealed an angiosarcoma. She then underwent computed tomography (CT) of the chest, abdomen, and pelvis, which indicated that she was negative for metastatic disease. Angiosarcoma of the breast is a very rare clinical entity. The estimated incidence of postradiation soft-tissue sarcomas of the breast ranges from 0.01% to 0.02% per year.1 Very few series have been published because of its rarity. In a retrospective analysis of patients treated at The University of Texas M. D. Anderson Cancer Center between 1990 to 2003, Vorburger and colleagues identified only 55 patients treated for angiosarcoma of the breast, of whom only 23 had radiation-associated disease.1 Working with the Rare Cancer Network, Bosquet and associates performed a retrospective multicenter analysis of 103 patients treated from 1976 to 2002.2 They reported only 42 radiation-associated angiosarcomas of the breast. Posttreatment lymphedema has been thought to be associated with the development of postradiation sarcoma, possibly by affecting local growth factors.3 There are reports of an increased incidence of postradiation angiosarcoma in BRCA1- and BRCA2positive patients.4 Radiation-associated angiosarcoma patients are older (>60 years), and they tend to have a higher grade sarcoma than

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sional biopsy. Fine-needle aspiration should be avoided, because it is often not diagnostic.5 Immunohistochemistry may be necessary to establish the diagnosis in higher grade tumors. Stains for vimentin, CD31, CD34, and factor VIII support the diagnosis of angiosarcoma. Poor prognostic indicators are size greater than 5 cm, positive surgical margins, a high pathologic grade, premenopausal age at diagnosis, and metastatic disease at diagnosis.2 Angiosarcomas have particularly infiltrative margins. Preoperative evaluation should include CT scans to detect metastatic disease, which usually occurs in the lung and bone. A higher percentage of patients with radiation-associated angiosarcoma present with distant metastatic disease than of those who are radiation-naïve (38% vs 13%, respectively).1 Treatment of breast angiosarcoma is surgical. Because these tumors present in an irradiated breast, a mastectomy is

Vorburger and associates,1 the 2- and 5year overall survival rates were 64% and 38%, respectively. Survival rates improved if patients presented with localized disease. Within 3.6 years of diagnosis, 28% experienced recurrences. This was seen in the higher risk groups—especially if the angiosarcoma was >5 cm at diagnosis. Positive surgical margins also were associated with very high risk for local recurrence. Luini and colleagues,3 in a retrospective review of 16 patients treated from January 1996 to January 2006, found that the median time to first recurrence was 5 months, and locoregional recurrence developed in 25% of their patients. We recommended this patient undergo a mastectomy. The patient accepted the treatment. After removal of the mass, pathologic examination revealed a 4.5-cm high-grade angiosarcoma. All margins were pathologically negative. Radiation oncologist’s commentary This patient had a stage IIB breast cancer diagnosed in 2001 that was treated with breastconserving therapy, adjuvant systemic chemotherapy, and adjuvant breast radiation therapy. Jon F. Strasser, MD She received a total dose of 60 Gy to the right breast delivered in two courses. The first course of radiotherapy was targeted to the whole breast and delivered a total dose of 45 Gy in 25 fractions of 1.8 Gy/day using standard tangential-based treatment techniques. Given her breast size and chest wall separation, this treatment was delivered with a combination of 6 MV and 23 MV photons to improve dose homogeneity. She then received a boost to the lumpectomy site of an additional 15 Gy in 8 fractions of 1.88 Gy/day using a 12-MeV en face electron beam prescribed to the 90% isodose line. Although angiosarcomas have been

Given the patient’s relatively recent radiotherapy in 2001 along with a complete surgical resection, we believed the risks of re-irradiation outweighed the limited benefit that radiation would provide. the procedure of choice.2 Axillary nodes need not be sampled, because angiosarcomas do not spread to lymph nodes.2 Immediate reconstruction is somewhat controversial at this time because of the reported high local recurrence rate. In the retrospective analysis by

seen after breast radiotherapy, they are rare events, often developing in patients who have Stewart-Treves syndrome after comprehensive chest wall radiation.6 However, radiation therapy is a risk factor in the development of soft-tissue sarcomas, which are seen as a

late event in many other disease sites where radiation therapy is used with a curative intent (ie, radiation therapy for Hodgkin’s disease). Mery and associates evaluated the Surveillance, Epidemiology and End Results (SEER) database for second sarcomas after breast cancer radiotherapy and noted that patients who had radiation had a higher incidence of soft-tissue sarcoma versus those who had no breast radiotherapy (31 vs 22 per 100,000 person-years; hazard ratio [HR], 1.5), with angiosarcomas having an HR of 7.7.7 Also based on analysis of the SEER database, Huang and Mackillop found that this risk peaked at 10 years, but extended 23 years after radiation.8 In general, overall survival was poor for soft-tissue sarcomas after radiation (32% at 5 years). DeSmet and colleagues reported similar poor overall survival (27% at 5 years) in sarcomas that developed within a previously radiated bed.9 Cahan and colleagues found that a few angiosarcomas occur with doses less than 30 Gy, and that virtually all who get this disease have had doses over 40 Gy.10 In this patient, given her prior history of whole breast radiotherapy, there is, unfortunately, a limited role for additional radiotherapy after mastectomy. Although some have advocated using hyperfractionated radiotherapy after surgery to combat the high growth rate of this tumor type, the data are retrospective and the risks of long-term complications or recurrence are high.11 Some have advocated hyperthermia in combination with radiotherapy, but again the data are limited. In this case, given the patient’s relatively recent radiotherapy in 2001 along with a complete surgical resection, we believed the risks of reirradiation outweighed the limited benefit that radiation would provide. Medical oncologist’s commentary Improvements in early detection and adjuvant therapy have resulted in increasing numbers of long-term survivors from breast cancer. As breast conservation is the acknowledged standard of care for most breast cancer patients and the indications for postmastectomy radiation therapy have become broader, more longterm survivors have received David D. Biggs, MD radiation therapy. Ionizing radiation is a well-recognized risk factor for sarcomas in general and angiosarcomas in particular. The absolute incidence of angiosarcoma postradiation is difficult to assess, Continued on page 12

February 2010 I VOL 3, NO 1

CONTINUING EDUCATION Continued from page 11

because it is an uncommon event. In a review of the SEER database, the cumulative 15-year risk of angiosarcoma in breast cancer patients was 0.9 per 1000 for patients who received radiation and 0.1 per 1000 for those who did not.12 Angiosarcomas have a latency of 5 to

nificant activity in angiosarcomas.15 Overall prognosis of radiation-associated angiosarcoma is poor. Median survival is 2.3 years; 5-year survival is in the 30% range.12 Because angiosarcomas are composed of vascular tissue, the use of agents with antiangiogenic prop-

Urgent mastectomy is the treatment of choice if the breast is intact. Large chest wall resection may be required if the patient already had a mastectomy. 7 years after treatment.13 They tend to involve a larger field than initially apparent clinically. Urgent mastectomy is the treatment of choice if the breast is intact. Large chest wall resection may be required if the patient already had a mastectomy. Local recurrences are common (up to 73%11) and repeated chest wall resections may be indicated. The benefit of adjuvant therapy is undefined. For the treatment of unresectable or metastatic disease, pegylated-liposomal doxorubicin has activity.14 In contrast to other sarcomas, the taxanes have also been shown to have sig-

erties is under study.16 It is hoped that clinical trials using bevacizumab, sorafenib, and thalidomide, as well as other agents, will result in improved treatment options. No data are available on adjuvant or neoadjuvant chemotherapy for a radiation-associated angiosarcoma of the breast. As there is no role for breast conservation, standard indications for neoadjuvant chemotherapy would not apply. If there was disease extending outside the breast onto the chest wall, one could consider using chemotherapy to try to reduce the tumor size to allow

for mastectomy and chest wall resection. In this setting, I would consider a taxane, as they have been shown to have the most activity in this disease. Again, there is no data to support this approach. Conclusion Early diagnosis improves overall survival as the tumor size is important as a prognostic indicator. For this patient, our discussion guided us to a recommendation of mastectomy because we believed the risks of re-irradiation outweighed the limited benefit that radiation would provide and the benefit of adjuvant chemotherapy is not yet determined. With many agents under study, multimodal treatment recommendations may change the future for these patients. This patient continues to do well after 1 year. l References 1. Vorburger SA, Xing Y, Hunt KK, et al. Angiosarcoma of the breast. Cancer. 2005;104:2682 -2688. 2. Bosquet G, Confavreux C, Magné N, et al. Outcome and prognostic factors in breast sarcoma: a multicenter study from the rare cancer network. Radiother Oncol. 2007;85:355-361. 3. Luini A, Gatti G, Diaz J, et al. Angiosarcoma of the breast: the experience of the European Institute of Oncology and a review of the literature. Breast

Cancer Res Treat. 2007;105:81-85. 4. West JG, Weitzel JN, Tao ML, et al. BRCA mutations and the risk of angiosarcoma after breast cancer treatment. Clin Breast Cancer. 2008;8:533-537. 5. Pencavel TD, Hayes A. Breast sarcoma—a review of diagnosis and management. Int J Surg. 2009;7: 20-23. 6. Abbott R, Palmieri C. Angiosarcoma of the breast following surgery and radiotherapy for breast cancer. Nat Clin Pract Oncol. 2008;12:727-736. 7. Mery C, George S, Bertagnolli MM, Raut CP. Secondary sarcomas after radiotherapy for breast cancer: sustained risk and poor survival. Cancer. 2009;115:4055-4063. 8. Huang J, Mackillop W. Increased risk of soft tissue sarcoma after radiotherapy in women with breast carcinoma. Cancer. 2001;92:172-180. 9. DeSmet S, Vandermeeren L, Christiaens MR, et al. Radiation induced sarcoma: analysis of 46 cases. Acta Chir Belg. 2008;108:574-579. 10. Cahan WG, Woodard HQ, Higinbothavn, NL, et al. Sarcoma arising in irradiated bone: report of 11 cases. Cancer. 1948; 1:3-29. 11. Monroe A, Feigenberg SJ, Mendenhall NP. Angiosarcoma after breast-conserving therapy. Cancer. 2003;97:1832-1840. 12. Yap J, Chuba PJ, Thomas R, et al. Sarcoma as a second malignancy after treatment for breast cancer. Int J Radiat Ondol Biol Phys. 2002;52:1231-1237. 13. Sher T, Hennessy BT, Valero V, et al. Primary angiosarcomas of the breast. Cancer. 2007;110:173-178. 14. Skubitz KM, Haddad PA. Paclitaxel and pegylatedliposomal doxorubicin are both active in angiosarcoma. Cancer. 2005;104:361-366. 15. Fury MG, Antonescu CR, Van Zee KJ, et al. A 14year retrospective review of angiosarcoma: clinical characteristics, prognostic factors, and treatment outcomes with surgery and chemotherapy. Cancer J. 2005;11:241-247. 16. Vogt T, Hafner C, Bross K, et al. Antiangiogenetic therapy with pioglitazone, rofecoxib and metronomic trofosfamide in patients with advanced malignant vascular tumors. Cancer. 2003;98:2251-2256.

CANCER CENTER PROFILE

West Michigan Cancer Center... Continued from cover reduction and revenue enhancement, which is evident by its consolidation and affiliation efforts, according to Foley & Lardner. McKay explained how technology cut overall spending: “The single most important endeavor we pursued for efficiency and cost-effectiveness was to implement an electronic medical record [EMR]. We have had an EMR since 2004, and it has taken half a million dollars out of operating expenses each year. We saved in medical records, the charts themselves, the paper, the copying of the paper, and the filing of the paper. We saved in goods and services and personnel.” Benchmarks were also used to ensure that staff need and staff numbers aligned. Since 2000, WMCC has placed all of its employees, both clinical and nonclinical, on productivity benchmarks. “We use those benchmarks to monitor the employees’ productivity, but also to determine if an additional employee is needed,” McKay explained. “Managers no longer request additional staff unless they can substantiate the need through additional benchmarks, which is a pretty concrete number.” WMCC also tracks the American Society of Clinical Oncology’s Quality Oncology Practice Initiative (QOPI) indicators for clinical quality. Each year,

February 2010 I VOL 3, NO 1

one or two indicators are tracked. To date, WMCC has tracked the QOPI guidelines in chemotherapy, clinical staging, and appropriate conversation and referral to hospice, according to McKay. In 2010, WMCC is tracking chemotherapy treatments in the last 14

2009, the center’s goal was to see patients within 15 minutes, 65% of the time. This year, that goal has been increased to 70% of the time, according to McKay. “We track [satisfaction] very carefully. If any other issues are brought up in our satisfaction survey, we address

“The single most important endeavor we pursued for efficiency and costeffectiveness was to implement an electronic medical record.” —Terry McKay President and CEO

days of life. “I think when you start to examine your processes and you can measure them and you compare them, you can always see room to improve,” said McKay. “What we did was general awareness with physicians. Just by them knowing that we are tracking a guideline, it becomes more top of mind.” WMCC also tracks patient satisfaction through satisfaction surveys. Twice a year, staff meet to determine what they can change to make the patient experience better. As an example, in

those very quickly and head-on to make sure that we continuously strive for high patient satisfaction,” McKay explained. Patient-focused WMCC, a joint venture of Borgess Medical Center and Bronson Metho dist Hospital, is its region’s only truly comprehensive cancer treatment facility. In its main campus in Kalamazoo, WMCC offers medical oncology, radiation oncology, a neurooncology clinic, a breast cancer clinic, a thoracic clinic, laboratories,

x-ray technology, positron-emission tomography/computed tomography, pharmaceutical services, social and psychological counseling, nutrition counseling, and key allied support services for patients and their families. WMCC also has six satellite locations where its medical oncologists treat patients. The center employs a multidisciplinary approach with thoracic, breast, and neurooncology. Although not as large as the breast clinic, the thoracic and neurooncology teams are “aggressive and progressive.” WMCC has recently expanded the multidisciplinary approach to gynecologic cancers, with a new team onboard. The center’s current goals include adding additional clinics for palliative care and survivorship. This year, “we are going to start laying the groundwork for them,” said McKay. WMCC has always had the philosophy of treating the entire person, not just the disease. To this end, the center offers many services: social workers, psychologists, onsite pharmacy, dietitians/nutritionists, and personal coaches. It also offers Tai Chi, meditation, Pilates, yoga, and massage therapy. In addition, the center provides financial counseling, transportation assistance, and lodging. Continued on page 16

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Totect® – Brief prescribing information Please refer to the package insert for full prescribing information. Each Totect carton contains 10 vials of Totect® (dexrazoxane for injection) 500 mg and 10 vials of 50 mL diluent. Indication: Treatment of extravasation resulting from IV anthracycline chemotherapy. Dosage and administration: Administration of Totect should begin as soon as possible and within 6 hours following the anthracycline extravasation. Totect should be given as an intravenous (IV) infusion once daily for 3 consecutive days. The dose of Totect is based on the patient’s body surface area: day one, 1000 mg/m2; day two, 1000 mg/m2; day three, 500 mg/m2. For patients with a body surface area of > 2 m2, a dose of 2000 mg should be given on days 1 and 2, and a dose of 1000 mg should be given on day 3. The Totect dose should be reduced 50% for patients with creatinine clearance values of <40 mL/minute. Cooling procedures such as ice packs should be removed from the affected area at least 15 minutes prior to Totect administration. Totect (dexrazoxane for injection) must be reconstituted with diluent, supplied in the carton. The patient’s Totect dose is diluted in 0.9% 1000 mL NaCl prior to administration. Contraindications: None known. Warnings: Pregnancy Category D. Dexrazoxane was toxic to pregnant rats at doses of 2 mg/kg (1/80 the human dose on a mg/ m2 basis) and embryotoxic and teratogenic at 8 mg/kg when given daily during the period of organogenesis. Teratogenic effects in the rat included imperforate anus, microphthalmia, and anophthalmia. In offspring allowed to develop to maturity, fertility was impaired in the male and female rats treated in utero during organogenesis at 8 mg/kg. In rabbits, doses of 5 mg/kg daily during the period of organogenesis caused maternal toxicity and doses of 20 mg/kg were embryotoxic and teratogenic. Terato-

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genic effects in the rabbit included several skeletal malformations such as short tail, rib and thoracic malformations, and soft tissue variations including subcutaneous, eye and cardiac hemorrhagic areas, as well as agenesis of the gallbladder and of the intermediate lobe of the lung. There is no adequate information about the use of Totect in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Precautions: Totect is a cytotoxic drug. When administered to patients receiving anthracycline-containing cytotoxic therapy, additive cytotoxicity may occur. Treatment with Totect is associated with leukopenia, neutropenia, and thrombocytopenia. Reversible elevations of liver enzymes may occur. Blood counts and liver enzymes should be monitored. Greater exposure to dexrazoxane may occur in patients with compromised renal function. The Totect dose should be reduced by 50% in patients with creatinine clearance values <40 mL/min. Dimethyl sulfoxide (DMSO) should not be used in patients who are receiving dexrazoxane to treat anthracycline-induced extravasation. Women who have the potential to become pregnant should be advised that Totect might cause fetal harm. There are no known drug interactions. No carcinogenicity studies have been done with Totect in animals. The carcinogenic potential of dexrazoxane has not been investigated. Long term dosing with razoxane (the racemic mixture of dexrazoxane, ICRF-187, and its enantiomer ICRF-186) is associated with the development of malignancies in rats and possibly in mice. Dexrazoxane was not mutagenic to bacteria in vitro (Ames assay), but caused significant chromosomal aberrations in mammalian cells in vitro. It also increased the formation of micronucleated polychromatic erythrocytes in mice. Dexrazoxane is mu-

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tagenic and clastogenic. The possible adverse effects of Totect on the fertility of humans and experimental animals, male or female, have not been adequately studied. Testicular atrophy was seen with dexrazoxane administration at doses as low as 30 mg/kg weekly for 6 weeks in rats (about 1/5 the human dose on a mg/m2 basis) and as low as 20 mg/kg weekly for 13 weeks in dogs. The effect of dexrazoxane on labor and delivery in humans has not been studied. It is not known whether dexrazoxane or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from dexrazoxane, 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. The safety and effectiveness of Totect in pediatric patients have not been established. No differences in safety or efficacy were observed between older and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older patients has been observed. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Adverse reactions: Adverse reactions of nausea/ vomiting, diarrhea, stomatitis, bone marrow suppression (neutropenia, thrombocytopenia), altered liver function (increased AST/ALT), and infusion site burning have been observed. These adverse reactions have been reversible.

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Practice Management

Strategy and Planning: The Difference between Being a Player or a Pawn By Dawn Holcombe, FACMPE, MBA, ACHE DGH Consulting, South Windsor, Connecticut

he world is changing all around regular monthly operational reviews and benchmarking where possible. Those oncology practices today. Money meetings? On a monthly basis, a well- data become a platform for more strateis tight, staff and run oncology practice is gic questions and issues, found in what physicians are stressed, pareviewing both financial is commonly called a SWOT analysis tients have more choices and operational dashboards, (Strengths, Weaknesses, Opportunities, than they can understand, watching the flow of rev- and Threats) (Table 1). and those who pay for care enues and expenses, staffing are worried about waste, levels, chair utilization, and Oncology issues are in the eye of quality, and value. Taking patient satisfaction. The the beholder One of the best values to be derived time away from your pracpractice is also trending pattice and family to suspend terns in referrals, new through a strategic planning process, the daily routine and focus patients, disease-specific vol- especially when using the correct conon strategic planning and umes, and patient care and sulting facilitator, is to be able to look at both oncology and your practice/cancer the future for yourselves Dawn Holcombe, retention. FACMPE, MBA, ACHE center from the perspectives of potenand your partners may seem tial competition or key payers. It is easy impossible, but it may be the most Know your market/environment Strategic planning means stepping to fall into the trap of myopic vision, important step you take this year to regain control of where you are headed. away from the daily routine to look at especially when the daily routine is conStrategic planning is a staple of busi- the practice from an internal and exter- sumed with caring for patients, seeking ness management. It affords those respon- nal perspective and allows the time to reimbursement, and addressing billing sible for the business an opportunity for consider options and goals and to set and authorization issues. To patients, in addition to the diagnoreflection, introspection, and vision. action plans and timelines. Practices When done with the guidance and sup- will collect certain statistics relating to sis of cancer and all that entails in terms port of a strong facilitator who not only patient volume, staffing, financials, and of the battle ahead, changes by employunderstands strategy but also the unique physician expectations, as well as ers and insurers are forcing new attention chaos that is unfolding in the public and private sectors for oncology, it can Table 1. Key Elements of a SWOT Analysis increase the understanding and awareness of practice physicians and leaders of Strengths—identification of the practice’s new opportunities and threats. • Unique characteristics • Value/assets, both quantifiable and perceived Who’s managing oncology? How to manage the costs and quality • Positive or supportive key relationships/collaborations choices involved in oncology practice is • Positive differentiating factors in local, regional, or other markets one of the most common topics of con• Solid knowledge/understanding of financial and market position versations in the public and private • Leadership and business skill sets that reveal strengths payer markets. Numerous external organizations are knocking on the doors of medical and pharmacy directors presenting programs intended to reduce oncology spending. Hospitals and other organizations are exploring the creation of cancer and infusion centers, mostly through affiliations with or employment of physicians and physician extenders. Where will you go from here? What are the immediate and pending issues for your practice in your market? Who are the players, and what role are you going to play in that market? What market do you expect to serve? What is happening or might happen to your referral base? What external trends or national discussions might affect your practice while you are looking in another direction? These are the questions that a practice/cancer center will address in the course of strategic planning. Know yourself What are the basics of strategic planning, and how does it differ from your

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to choices of providers, choices of drugs or treatment options, sources for drugs and treatments, and even preferential benefit design that may drive patient choices via copayment or coinsurance discounts. This means that patients may consider the source and cost of care more carefully both before and after selecting a provider, perhaps in addition to consideration of “one-stop shopping,” as well as the provider’s position on their insur-

“Planning is bringing the future into the present so that you can do something about it now.” —Alan Lakein

Opportunities—identification of the practice’s • Expected and unexpected market changes that could open up new possibilities • New potential or possible improvements/enhancements of existing key relationships/collaborations • Potential reconfigurations/expansion/enhancement of services and assets • Physician plans and expectations for personal and professional goals and opportunities

ance’s preferred network. Understanding those issues, in addition to the service and care that would normally be expected, is critical to developing your strategy for future direction. Payers see oncology care as a very expensive cost. Sometimes, payers need to focus on the short term when considering financial costs. This may make choices such as more costly drugs that will lower long-term costs and the chance of recurrence less appealing to them and their stakeholders than treatment choices that are less costly compared with alternatives during a 1-year window. The message they want to hear is how oncology costs are going to be reduced in the next year. As oncology practices/cancer centers prepare to more deeply engage their key payers in discussions on oncology management, the payers will not be receptive to those who are unprepared to address the message of costs. “Quality of care,” “best care,” and “most appropriate care” actually can have different meanings whether you are a patient, physician, center administrator, hospital administrator, payer, or employer. Good strategic planning and an experienced facilitator should recognize these differences so that the practice/cancer center can clarify its intended messages and approaches for each of these constituent markets.

Threats—identification of the practice’s • Market changes that might close doors or create barriers • Relationships/expectations changing due to influence or activity of external players in the oncology space • Internal expectations or decisions that might derail opportunities or progress

Becoming a player or a pawn No matter where you deliver cancer care, someone is talking about the costs of care in that area. Someone else is talking about creating databases on

Weaknesses—identification of the practice’s • Internal or external distractions from daily business, discord, problems, or behaviors • Lack of knowledge/understanding of financial and market position • Weak or troublesome key relationships/collaborations • Lack of or negative distinguishing factors in local, regional, or other markets • No recognition/identification of value/assets (either quantifiable or perceived) • Leadership or skill set issues that expose weaknesses

Continued on page 16

February 2010 I VOL 3, NO 1

Practice Management Strategy and Planning... Continued from page 15 oncology treatments, drugs, or care. Someone else is offering to help payers evaluate their cancer spending and reduce their costs through a variety of methods. Yet someone else is offering to deliver drugs to offices at a lower cost or a better revenue or control process to drive reductions in care variation and compliance. Careful strategic planning and action is the most effective weapon you hold to recognize these issues and develop your approach. Planning in and of itself will not solve the issue of getting you a seat at the table (player) or getting blindsided by changes out of your control (pawn). It is essential to set aside time to decide where you want to go, and what will need to happen to get you there. Table 2 details some strategies and action plans created out of the planning process. Where to go from here? There is an old axiom about when is the best time to plan and strategize: When business is good, or when business is bad? The answer: All the time. When business is good, strategic planning is essential to maintain and improve mar-

“To be prepared is half the victory.” —Miguel de Cervantes Saavedra ket position and business successes in the future. When business is bad, strategic planning can help to understand what is going wrong and determine what, if any, corrections are possible to achieve successes in the future. The selection of a facilitator for the strategic planning process is also essential. You want a guide with specific strengths, especially in oncology trends

Table 2. Strategies and Action Plans Created Out of the Planning Process Defining/Implementing Market Position • What steps need to be taken in the next months and years to solidify, establish, or reinforce the role and market position you will achieve to meet your goals? Operational/Facility Position • What changes/modifications need to be taken to position you to meet the market demands and your expectations for services? Affiliations/Collaborations • What are the critical factors and drivers of the referral market in your area? • Where can you enhance/improve relations with other key institutions and payers, and when do you bring them closer and when do you watch or compete? • Where do you prioritize affiliations or collaborations? • Are mergers or consolidations an option? Infrastructure/Leadership • What infrastructure will achieve the goals of the group? • What skill sets are strong or weak, and how will necessary adjustments be made? • Are changes in leadership needed, and how will that be accomplished? • What will public ramifications of leadership changes be? • What are the personal and professional goals of the physicians in the group? • Does the practice have the financial and operational or leadership and business skills to navigate through the next few years and change needed? Marketing/Referral Relations • What are referral trends? • What are implications of key hospital market strategies on your group? • What does your internal and external marketing plan cover, what is missing, and what needs to change? Payer Relations/Negotiations • How will you interact with payers? • What messages/programs will you offer that recognize competing organizations’ messages? • Who else is talking to payers about oncology in this market (or at a national level), and what programs will be needed to maintain a key position in the management of oncology in the market?

and payer relationships. Many facilitators are well equipped for general business strategy, but oncology practices and cancer centers in the current market need facilitators who are also experienced in public and private oncology policy issues and who understand not only oncology but also the payer and other third-party

“It pays to plan ahead. It wasn’t raining when Noah built the ark.” —Unknown players who are seeking to enter and manage the oncology market. A window of opportunity still exists for oncology practices and cancer centers to make the strategic adjustments necessary to survive in their markets. It is critical to understand the keen interest in managing oncology by other third-party organizations and the needs/ expectations of payers and employers regarding the costs and variation of the oncology spend. When oncology practices/cancer centers are proactive and bring that message to their regional markets and payers, they preserve the ability to sit at the table and be a player in the management of oncology for their patients. On the other hand, when they are not proactive and don’t make an effort to understand and get involved in their markets, they open the door for someone to fill that void and offer to manage the oncology market for their payers (also taking dollars out of the healthcare system in fees), making the physician a pawn to be moved around or managed according to someone else’s goals. Stepping out of the daily routine and engaging in strategic planning can be the first step in moving from “pawn” to “player” status. l

CANCER CENTER PROFILE

West Michigan Cancer Center... Continued from page 12 WMCC’s focus on its patients and their families has afforded it high standing in its community. “Our programs— the psychological counseling, the nutrition, the Tai Chi, the meditation, the Pilates, the yoga, everything we have— extend to the caregiver as well. We are very encompassing of what the family member is going through caring for the patient,” said McKay. The old medical records room did not go to waste. WMCC has converted it into a fitness center. “The fitness center is open all day for patients and their

February 2010 I VOL 3, NO 1

caregivers, as well as our staff during specific hours. Patients are actively

“We have a very robust clinical trial program funded by the NCI, and we put on about 112 to 115 patients a year.” involved in living a healthier lifestyle even if it is for the first time in their life that they decided to exercise, because of

the cancer diagnosis,” explained McKay. Many decide to continue after cancer. “We have a lot of patients who still use our facilities after cancer; we don’t put a time limit on it,” McKay said. Nationally affiliated WMCC receives timely results of National Cancer Institute (NCI) clinical trials of advanced cancer treatment drugs and techniques. For the right patient, participation in a trial of a new medication or procedure is available at the center or in his or her home. “We

have a very robust clinical trial program funded by the NCI, and we put on about 112 to 115 patients a year,” said McKay. “That is a double-digit percentage of new patients who go on clinical trials, which is rather impressive.” WMCC also works closely with regional physicians and healthcare professionals, and with cancer specialists throughout the United States. In addition, WMCC is professionally affiliated with the NCI, Susan G. Komen Race for the Cure, and the American Cancer Society. l

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ONCOLOGY DRUG CODES Supplied by: RJ Health Systems

Medications Used for the Treatment of Cervical Cancer Cervical cancer forms in tissues of the cervix (the organ connecting the uterus and vagina). It is usually a slow-growing cancer that may not have symptoms but can be found with regular Pap tests. Cervical cancer is almost always caused by human papillomavirus (HPV) infection. The following sections will assist healthcare professionals and payers by providing appropriate coding, billing, and reimbursement information associated with the management of cervical cancer.

Associated ICD-9-CM Codes Used for Cervical Cancer

The following sections include: • Associated ICD-9-CM codes used for the classification of cervical cancer • Drugs that have been FDA-approved in the treatment of cervical 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 cervical cancer. NCCN is recognized by CMS (Centers for Medicare & Medicaid Services) 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

generic (Brand) name

HCPCS code: code description

bevacizumab (Avastin) bleomycin (Blenoxane) carboplatin (Paraplatin) cisplatin (Platinol AQ) cisplatin (Platinol AQ) docetaxel (Taxotere) doxorubicin HCl liposome (Doxil) epirubicin (Ellence)

J9035: injection, bevacizumab, 10 mg J9040: injection, bleomycin sulfate, 15 units J9045: injection, carboplatin, 50 mg J9060: cisplatin, powder or solution, per 10 mg J9062: cisplatin, 50 mg J9171: injection, docetaxel, 1 mg J9001: injection, doxorubicin hydrochloride, all lipid formulations, 10 mg J9178: injection, epirubicin HCl, 2 mg

180 Malignant neoplasm of cervix uteri Includes: invasive malignancy [carcinoma] Excludes: carcinoma in situ (233.1) 180.0 Endocervix Cervical canal, not otherwise specified Endocervical canal Endocervical gland 180.1 Exocervix 180.8 Other specified sites of cervix Cervical stump Squamocolumnar junction of cervix Malignant neoplasm of contiguous or overlapping sites of cervix uteri whose point of origin cannot be determined 180.9 Cervix uteri, unspecified 233 Carcinoma in situ of breast and genitourinary system 233.1 Cervix uteri Adenocarcinoma in situ of cervix Cervical intraepithelial glandular neoplasia, > grade III < Cervical intraepithelial neoplasia III [CIN III] Severe dysplasia of cervix Excludes: cervical intraepithelial neoplasia II [CIN II] (622.12) cytologic evidence of malignancy without histologic confirmation (795.06) high-grade squamous intraepithelial lesion (HGSIL) (795.04) moderate dysplasia of cervix (622.12)

FDAapproved for cervical cancer

NCCN Drugs & Biologics Compendium off-label use for cervical cancer

Medicare allowable (ASP + 6%), effective 1/10/10-3/31/10

CPT administration codes

$66.99

$57.46

96413, 96415

$45.30

$28.47

96401, 96409

✓

$85.10

$4.84

96409, 96413, 96415

✓

$4.33

$2.08

96409, 96413, 96415

✓

$21.66

$10.41

96409, 96413, 96415

✓

$23.23

$17.62

96413

✓

$559.32

$471.38

96413

✓

$8.16

$2.65

✓

Current code price (AWP-based pricing), effective 1/10/10

96409, 96413 Continued on page 20

February 2010 I VOL 3, NO 1

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Presents the Third Annual Curriculum for

CONSIDERATIONS IN MULTIPLE MYELOMA A Newsletter Series for Cancer Care Professionals Center of Excellence Media, along with Editor-in-Chief Sagar Lonial, MD, of Emory University, are pleased to offer your multidisciplinary cancer team this series of newsletters focusing on the challenges of treating patients with multiple myeloma.

SAGAR LONIAL, MD Associate Professor of Hematology and Oncology Emory University School of Medicine

# Earn Continuing Education Credits # 8-part newsletter series

CASE STUDY DISCUSSIONS: • Front-line therapy

• Non-Transplant Patients

• Maintenance Settings

• Cytogenetics

• Transplant Settings

• Side Effect Management

• Retreatment Settings

• Bone Health

Each newsletter will feature: • Contributions from thought-leading physicians, nurses, and pharmacists

• Continuing Education credits available to physicians, nurses, and pharmacists

PARTICIPATE TODAY at www.COEXM.com For complete learning objectives and accreditation information, please refer to each activity.

Target Audience These activities were developed for physicians, nurses, and pharmacists.

These activities are jointly sponsored by

These activities are supported by an educational grant from Millennium Pharmaceuticals, Inc.

ONCOLOGY DRUG CODES Supplied by: RJ Health Systems Continued from page 18

generic (Brand) name

HCPCS code: code description

fluorouracil (Adrucil) gemcitabine (Gemzar) ifosfamide (Ifex) irinotecan (Camptosar) mesna (Mesnex) mitomycin (Mutamycin) mitomycin (Mutamycin) mitomycin (Mutamycin) paclitaxel (Taxol, Onxol) pemetrexed (Alimta) topotecan (Hycamtin) vinorelbine (Navelbine)

J9190: injection, fluorouracil, 500 mg J9201: injection, gemcitabine hydrochloride, 200 mg J9208: injection, ifosfamide, 1 gram J9206: injection, irinotecan, 20 mg J9209: injection, mesna, 200 mg J9280: mitomycin, 5 mg J9290: mitomycin, 20 mg J9291: mitomycin, 40 mg J9265: injection, paclitaxel, 30 mg J9305: injection, pemetrexed, 10 mg J9350: injection, topotecan, 4 mg J9390: injection, vinorelbine tartrate, per 10 mg

FDAapproved for cervical cancer

NCCN Drugs & Biologics Compendium off-label use for cervical cancer

Current code price (AWP-based pricing), effective 1/10/10

Medicare allowable (ASP + 6%), effective 1/10/10-3/31/10

CPT administration codes

✓

$3.30

$1.60

96409

✓

$169.46

$144.93

96413

✓

$56.40

$30.08

96413, 96415

✓

$84.71

$6.94

96413, 96415

✓

$10.44

$4.64

96409

✓

$67.20

$17.15

96409

✓

$218.40

$68.60

96409

✓

$300.00

$137.19

96409

✓

$17.70

$9.44

✓

$59.25

$50.59

96409

$1264.99

$1031.91

96413

$42.60

$11.59

96409

✓

96413, 96415

References • HCPCS Level II Expert 2010 • CPT 2010 • ICD-9-CM for Professionals Volumes 1 & 2; 2010 • The Drug Reimbursement Coding and Pricing Guide, Vol 7, No 1; RJ Health Systems International LLC; 1st Quarter 2010 • FDA-approved indication (from products’ prescribing information) • The NCCN Drugs & Biologics Compendium™ © 2010 National Comprehensive Cancer Network, Inc. Available at: http://www.ncc.org. Accessed [January 1, 2010]. To view the most recent and complete version of The NCCN Compendium, go online to www.nccn.org • National Cancer Institute • www.ReimbursementCodes.com powered by RJ Health Systems International, LLC, Wethersfield, Connecticut • CMS-Medicare allowable 1st Quarter 2010 (effective dates 1/1/10-3/31/10). Prices listed herein are effective as of January 1, 2010. ASP indicates average sales price; AWP, average wholesale price; CMS, Centers for Medicare & Medicaid Services; CPT, Current Procedural Terminology; FDA, US Food and Drug Administration; HCPCS, Healthcare Common Procedure Coding System; NCCN, National Comprehensive Cancer Network.

2010 UPDATES OF THE HEALTHCARE COMMON PROCEDURE CODING SYSTEM (HCPCS)

This information was supplied by:

Effective: January 1, 2010 New C9257: injection, bevacizumab, 0.25 mg (Avastin) J9155: injection, degarelix, 1 mg (Firmagon) J9171: injection, docetaxel, 1 mg (Taxotere) J9328: injection, temozolomide, 1 mg (Temodar) Deleted Q2024: injection, bevacizumab, 0.25 mg (code deleted effective 1/1/10; see C9257 and J9035) J9170: injection, docetaxel, 20 mg (code deleted effective 1/1/10; see J9171) C9253: injection, temozolomide, 1 mg (code deleted effective 1/1/10; see J9328)

February 2010 I VOL 3, NO 1

PO BOX 290616, Wethersfield, CT 06109 T: (860) 563-1223 F: (860) 563-1650 www.RJHealthSystems.com

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Breast Cancer Hypofractionated Irradiation... Continued from cover

tant boost results in outcomes comparable with that of a 5- to 7-week course for early-stage breast cancers. Additional studies with a larger body of data and a longer follow-up period will help establish whether this type of radiation treatment should be routinely used,” said lead author of the study Manjeet Chadha, MD, who is the associate chairman of radiation oncology at Albert Einstein College of Medicine and a radiation oncologist at Beth Israel Medical Center, New York, New York. “Studies from Europe and Canada have used accelerated schedules for breast radiation therapy with favorable results reported on longer follow-up. In the United States, however, there are limited data on this topic.” Chadha, who presented the study findings at the American Society of Radiation Oncology’s 51st annual meeting, said the radiation therapy technique used in this study is different from previously published experiences. For each patient, the clinicians developed a conformal, personalized plan using three-dimensional dosimetry data derived from the patient’s unique computed tomography scan images. The researchers analyzed data on 112 women who were treated from June 2004 to the present for early-stage breast cancer. All patients had breastconserving surgery and received accelerated hypofractionated whole breast irradiation plus concomitant boost. The results were reported on 105 patients who had completed therapy and had a minimum of 6 months of follow-up. The median age of the women was 66 years. The concomitant boost was delivered using photons in 88 patients, and electron boost was used in 18 patients. The researchers found this approach was highly effective as well as safe. The cancer did not return to the original site or to the surrounding region in any of the patients. The mean follow-up was 24 months (range, 6-57 months). Survival was greater than 95% for patients with 5 years of follow-up. The researchers also found no significant physical or cosmetic side effects from the radiation treatment. The investigators concluded that the 3-week accelerated hypofractionated whole breast radiation therapy with concomitant boost appears to be a welltolerated schedule and worthy of further evaluation. Their findings suggest excellent local control and results that are comparable with what other investigators have found. However, they caution that more research is needed. l

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Recent FDA Approval Abraxane for Pancreatic Cancer and Stage IIB to IV Melanoma The US Food and Drug Administration (FDA) has granted orphan drug status to nanoparticle albumin-bound paclitaxel for injectable suspension (Abraxane, Abraxis BioScience) for the treatment of pancreatic cancer as well

as stage IIB to IV melanoma. The drug is currently entering two phase 3 trials. One will compare paclitaxel plus gemcitabine against gemcitabine alone as a first-line therapy for advanced metastatic pancreatic cancer. The other will compare paclitaxel against dacarbazine in chemo-naïve melanoma patients. l

GEMZAR姞 (GEMCITABINE HCl) FOR INJECTION

Drug Interactions—No specific drug interaction studies have been conducted. For information on the pharmacokinetics of Gemzar and cisplatin in combination, see Drug Interactions under CLINICAL PHARMACOLOGY. Radiation Therapy—A pattern of tissue injury typically associated with radiation toxicity has been reported in association with concurrent and non-concurrent use of Gemzar. Non-concurrent (given >7 days apart)—Analysis of the data does not indicate enhanced toxicity when Gemzar is administered more than 7 days before or after radiation, other than radiation recall. Data suggest that Gemzar can be started after the acute effects of radiation have resolved or at least one week after radiation. Concurrent (given together or ≤7 days apart)—Preclinical and clinical studies have shown that Gemzar has radiosensitizing activity. Toxicity associated with this multimodality therapy is dependent on many different factors, including dose of Gemzar, frequency of Gemzar administration, dose of radiation, radiotherapy planning technique, the target tissue, and target volume. In a single trial, where Gemzar at a dose of 1000 mg/m2 was administered concurrently for up to 6 consecutive weeks with therapeutic thoracic radiation to patients with non-small cell lung cancer, significant toxicity in the form of severe, and potentially life-threatening mucositis, especially esophagitis and pneumonitis was observed, particularly in patients receiving large volumes of radiotherapy [median treatment volumes 4795 cm3]. Subsequent studies have been reported and suggest that Gemzar administered at lower doses with concurrent radiotherapy has predictable and less severe toxicity. However, the optimum regimen for safe administration of Gemzar with therapeutic doses of radiation has not yet been determined in all tumor types.

BRIEF SUMMARY (OVARIAN). For complete safety please consult the package insert for complete prescribing information. INDICATION AND USAGE: THERAPEUTIC INDICATION—Ovarian Cancer—Gemzar in combination with carboplatin is indicated for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy. CLINICAL STUDIES: Ovarian Cancer—Gemzar was studied in a randomized Phase 3 study of 356 patients with advanced ovarian cancer that had relapsed at least 6 months after first-line platinum-based therapy. Patients were randomized to receive either Gemzar 1000 mg/m2 on Days 1 and 8 of a 21-day cycle and carboplatin AUC 4 administered after Gemzar on Day 1 of each cycle or single-agent carboplatin AUC 5 administered on Day 1 of each 21-day cycle as the control arm. The primary endpoint of this study was progression free survival (PFS). The addition of Gemzar to carboplatin resulted in statistically significant improvement in PFS and overall response rate. Approximately 75% of patients in each arm received poststudy chemotherapy. Only 13 of 120 patients with documented poststudy chemotherapy regimen in the carboplatin arm received Gemzar after progression. There was not a significant difference in overall survival between arms. CONTRAINDICATION: Gemzar is contraindicated in those patients with a known hypersensitivity to the drug (see Allergic under ADVERSE REACTIONS). WARNINGS: Caution—Prolongation of the infusion time beyond 60 minutes and more frequent than weekly dosing have been shown to increase toxicity (see CLINICAL STUDIES in the full Prescribing Information). Hematology—Gemzar can suppress bone marrow function as manifested by leukopenia, thrombocytopenia, and anemia (see ADVERSE REACTIONS), and myelosuppression is usually the dose-limiting toxicity. Patients should be monitored for myelosuppression during therapy. See DOSAGE AND ADMINISTRATION in the full Prescribing Information for recommended dose adjustments. Pulmonary—Pulmonary toxicity has been reported with the use of Gemzar. In cases of severe lung toxicity, Gemzar therapy should be discontinued immediately and appropriate supportive care measures instituted (see Pulmonary under Single-Agent Use and under Post-marketing experience in ADVERSE REACTIONS in the full Prescribing Information). Renal—Hemolytic Uremic Syndrome (HUS) and/or renal failure have been reported following one or more doses of Gemzar. Renal failure leading to death or requiring dialysis, despite discontinuation of therapy, has been rarely reported. The majority of the cases of renal failure leading to death were due to HUS (see Renal under Single-Agent Use and under Post-marketing experience in ADVERSE REACTIONS in the full Prescribing Information). Hepatic—Serious hepatotoxicity, including liver failure and death, has been reported very rarely in patients receiving Gemzar alone or in combination with other potentially hepatotoxic drugs (see Hepatic under Single-Agent Use and under Post-marketing experience in ADVERSE REACTIONS in the full Prescribing Information). Pregnancy—Pregnancy Category D. Gemzar can cause fetal harm when administered to a pregnant woman. Gemcitabine is embryotoxic causing fetal malformations (cleft palate, incomplete ossification) at doses of 1.5 mg/kg/day in mice (about 1/200 the recommended human dose on a mg/m2 basis). Gemcitabine is fetotoxic causing fetal malformations (fused pulmonary artery, absence of gall bladder) at doses of 0.1 mg/kg/day in rabbits (about 1/600 the recommended human dose on a mg/m2 basis). Embryotoxicity was characterized by decreased fetal viability, reduced live litter sizes, and developmental delays. There are no studies of Gemzar in pregnant women. If Gemzar is used during pregnancy, or if the patient becomes pregnant while taking Gemzar, the patient should be apprised of the potential hazard to the fetus. PRECAUTIONS: General—Patients receiving therapy with Gemzar should be monitored closely by a physician experienced in the use of cancer chemotherapeutic agents. Most adverse events are reversible and do not need to result in discontinuation, although doses may need to be withheld or reduced. There was a greater tendency in women, especially older women, not to proceed to the next cycle. Laboratory Tests—Patients receiving Gemzar should be monitored prior to each dose with a complete blood count (CBC), including differential and platelet count. Suspension or modification of therapy should be considered when marrow suppression is detected (see DOSAGE AND ADMINISTRATION in the full Prescribing Information). Laboratory evaluation of renal and hepatic function should be performed prior to initiation of therapy and periodically thereafter (see WARNINGS). Carcinogenesis, Mutagenesis, Impairment of Fertility—Long-term animal studies to evaluate the carcinogenic potential of Gemzar have not been conducted. Gemcitabine induced forward mutations in vitro in a mouse lymphoma (L5178Y) assay and was clastogenic in an in vivo mouse micronucleus assay. Gemcitabine was negative when tested using the Ames, in vivo sister chromatid exchange, and in vitro chromosomal aberration assays, and did not cause unscheduled DNA synthesis in vitro. Gemcitabine IP doses of 0.5 mg/kg/day (about 1/700 the human dose on a mg/m2 basis) in male mice had an effect on fertility with moderate to severe hypospermatogenesis, decreased fertility, and decreased implantations. In female mice, fertility was not affected but maternal toxicities were observed at 1.5 mg/kg/day IV (about 1/200 the human dose on a mg/m2 basis) and fetotoxicity or embryolethality was observed at 0.25 mg/kg/day IV (about 1/1300 the human dose on a mg/m2 basis). Pregnancy—Category D. See WARNINGS. Nursing Mothers—It is not known whether Gemzar or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from Gemzar in nursing infants, the mother should be warned and 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 and the potential risk to the infant. Elderly Patients—Gemzar clearance is affected by age (see CLINICAL PHARMACOLOGY in the full Prescribing Information). There is no evidence, however, that unusual dose adjustments (i.e., other than those already recommended in DOSAGE AND ADMINISTRATION section in the full Prescribing Information) are necessary in patients over 65, and in general, adverse reaction rates in the single-agent safety database of 979 patients were similar in patients above and below 65. Grade 3/4 thrombocytopenia was more common in the elderly. Gender—Gemzar clearance is affected by gender (see CLINICAL PHARMACOLOGY in the full Prescribing Information). In the single-agent safety database (N=979 patients), however, there is no evidence that unusual dose adjustments (i.e., other than those already recommended in DOSAGE AND ADMINISTRATION section in the full Prescribing Information) are necessary in women. In general, in single-agent studies of Gemzar, adverse reaction rates were similar in men and women, but women, especially older women, were more likely not to proceed to a subsequent cycle and to experience Grade 3/4 neutropenia and thrombocytopenia. Pediatric Patients—The effectiveness of Gemzar in pediatric patients has not been demonstrated. Gemzar was evaluated in a Phase 1 trial in pediatric patients with refractory leukemia and determined that the maximum tolerated dose was 10 mg/m2/min for 360 minutes three times weekly followed by a one-week rest period. Gemzar was also evaluated in a Phase 2 trial in patients with relapsed acute lymphoblastic leukemia (22 patients) and acute myelogenous leukemia (10 patients) using 10 mg/m2/min for 360 minutes three times weekly followed by a one week rest period. Toxicities observed included bone marrow suppression, febrile neutropenia, elevation of serum transaminases, nausea, and rash/desquamation, which were similar to those reported in adults. No meaningful clinical activity was observed in this Phase 2 trial. Patients with Renal or Hepatic Impairment—Gemzar should be used with caution in patients with preexisting renal impairment or hepatic insufficiency as there is insufficient information from clinical studies to allow clear dose recommendation for these patient populations. Administration of Gemzar in patients with concurrent liver metastases or a preexisting medical history of hepatitis, alcoholism, or liver cirrhosis may lead to exacerbation of the underlying hepatic insufficiency. GEMZAR姞 (GEMCITABINE HCl) FOR INJECTION

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ADVERSE REACTIONS: Combination Use in Ovarian Cancer—In the Gemzar plus carboplatin versus carboplatin study, dose reductions occurred with 10.4% of Gemzar injections and 1.8% of carboplatin injections on the combination arm, versus 3.8% on the carboplatin alone arm. On the combination arm, 13.7% of Gemzar doses were omitted and 0.2% of carboplatin doses were omitted, compared to 0% of carboplatin doses on the carboplatin alone arm. There were no differences in discontinuations due to adverse events between arms (10.9% versus 9.8%, respectively). Table 1 presents the adverse events (all grades) occurring in ≥10% of patients in the ovarian cancer study. Table 1: Adverse Events From Comparative Trial of Gemzar Plus Carboplatin Versus Single-Agent Carboplatin in Ovarian Cancera CTC Grades (% incidence) Gemzar plus Carboplatin (N=175) Carboplatin (N=174) All Grades Grade 3 Grade 4 All Grades Grade 3 Grade 4 Laboratory b Hematologic Neutropenia 90 42 29 58 11 1 Anemia 86 22 6 75 9 2 Leukopenia 86 48 5 70 6 <1 Thrombocytopenia 78 30 5 57 10 1 38 15 RBC Transfusions c 9 3 Platelet Transfusions c Non-laboratory b Nausea 69 6 0 61 3 0 Alopecia 49 0 0 17 0 0 Vomiting 46 6 0 36 2 <1 Constipation 42 6 1 37 3 0 Fatigue 40 3 <1 32 5 0 Neuropathy-sensory 29 1 0 27 2 0 Diarrhea 25 3 0 14 <1 0 Stomatitis/pharyngitis 22 <1 0 13 0 0 Anorexia 16 1 0 13 0 0 a Grade based on Common Toxicity Criteria (CTC) Version 2.0 (all grades ≥10%). b Regardless of causality. c Percent of patients receiving transfusions. Transfusions are not CTC-graded events. Blood transfusions included both packed red blood cells and whole blood. In addition to blood product transfusions as listed in Table 1, myelosuppression was also managed with hematopoetic agents. These agents were administered more frequently with combination therapy than with monotherapy (granulocyte growth factors: 23.6% and 10.1%, respectively; erythropoetic agents: 7.3% and 3.9%, respectively). The following are the clinically relevant adverse events, regardless of causality, that occurred in >1% and <10% (all grades) of patients on either arm. In parentheses are the incidences of Grade 3 and 4 adverse events (Gemzar plus carboplatin versus carboplatin): AST or ALT elevation (0 versus 1.2%), dyspnea (3.4% versus 2.9%), febrile neutropenia (1.1% versus 0), hemorrhagic event (2.3% versus 1.1%), hypersensitivity reaction (2.3% versus 2.9%), motor neuropathy (1.1% versus 0.6%), and rash/desquamation (0.6% versus 0). No differences in the incidence of laboratory and non-laboratory events were observed in patients 65 years or older, as compared to patients younger than 65. Post-marketing experience—The following adverse events have been identified during post-approval use of Gemzar. These events have occurred after Gemzar single-agent use and Gemzar in combination with other cytotoxic agents. Decisions to include these events are based on the seriousness of the event, frequency of reporting, or potential causal connection to Gemzar. Cardiovascular—Congestive heart failure and myocardial infarction have been reported very rarely with the use of Gemzar. Arrhythmias, predominantly supraventricular in nature, have been reported very rarely. Vascular Disorders—Clinical signs of peripheral vasculitis and gangrene have been reported very rarely. Skin—Cellulitis and non-serious injection site reactions in the absence of extravasation have been rarely reported. Severe skin reactions, including desquamation and bullous skin eruptions, have been reported very rarely. Hepatic—Increased liver function tests including elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, and bilirubin levels have been reported rarely. Serious hepatotoxicity including liver failure and death has been reported very rarely in patients receiving Gemzar alone or in combination with other potentially hepatotoxic drugs. Pulmonary—Parenchymal toxicity, including interstitial pneumonitis, pulmonary fibrosis, pulmonary edema, and adult respiratory distress syndrome (ARDS), has been reported rarely following one or more doses of Gemzar administered to patients with various malignancies. Some patients experienced the onset of pulmonary symptoms up to 2 weeks after the last Gemzar dose. Respiratory failure and death occurred very rarely in some patients despite discontinuation of therapy. Renal—Hemolytic-Uremic Syndrome (HUS) and/or renal failure have been reported following one or more doses of Gemzar. Renal failure leading to death or requiring dialysis, despite discontinuation of therapy, has been rarely reported. The majority of the cases of renal failure leading to death were due to HUS. Injury, Poisoning, and Procedural Complications — Radiation recall reactions have been reported (see Radiation Therapy under PRECAUTIONS). Dosage and administration: Gemzar is for intravenous use only. Please consult full prescribing information for complete dosage and administration guidelines.

Literature revised May 7, 2007 PV 4067 AMP

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February 2010 I VOL 3, NO 1

GEMZAR/carboplatin is one option for 2nd-line treatment of your patients with platinum-sensitive* advanced ovarian cancer. Myelosuppression is usually the dose-limiting toxicity with GEMZAR therapy.

G MZ GE ZAR AR iin n cco om mb bin nat atio ion wi with t car th arbo bo b opl p attin n is in ndi d ca c te ed fo for or th t e tr t eaatm t en e t of o pattie ient nsw nt wiith th adv d an a ced ce ed o ovvar aria ian n caanc n er e tha h t has haas rre elaapsed psed ps d aatt le easst 6 mo m ntth hss aft fter er er comp co m le mp eti t on o of p pllat atin inum in u -b um -bas baasse ed d the eraapyy. My M ye ellossu up p ppr p essssiion pr on is us usua ua allly th he do ose se-l -lim -l im mittin ng to oxi x ciitty y wit ith h GEMZ GEMZ GE M AR A th he era rapy py py. y.

Overall response rate (%)†

Median progression-free survival (months) GEMZAR plus Carboplatin

95% Cl (8.0-9.7) (N=178)

Carboplatin 95% Cl (5.2-7.1) (N=178)

(p=0.0038)

GEMZAR plus Carboplatin (N=178)

8.6

Carboplatin (N=178)

5.8 6

(p=0.0016)

10%

47.2%

30.9% 20%

30%

40%

50%

* Pl Plat a in at num m-s -sen en nsiti siitive tivee ti †

pat a ie ient nts ar nt aree de defi fine ine ned d as pat a ie i ntts wh w o deve deveelo de lop di lop dise sease se asse pr prog oggre ress s ioon ≥6 m ss moont n hs h aft f er er rec ecei eivi ei viingg firrst st-l -lin -l inee p in pllat a in inum um-b um -bas asseed d che h mo m th ther erap er ap apy. py. Inve In veest stig iggat ator or-rrev or evie vie iewe wd we d..

The Th eo ovverralll su surv r iv rv ival a dif al iffe f rre fe enc n e be b tw wee een G GE EM EMZ MZ ZAR A /c /car a bo ar opl p attin ((18 18 8.0 mon nths) th hs) vs ca carb bop oplaattiin (1 opla ( 7. 7 3 mo mont nths nt nths hs)) wa was no ot si s gn g if i iccan nt (p=0 0.8 897 977) 7. 7) Se S ele ecctt IImp mp m por ortta an ntt Saffet ety y In nfo orm matio attio on GEMZ GE M AR MZ R ssho houl ho u d no ul not be b adm dmin inis in isste tere re red ed tto o pat a iie en ntts wi with th h kno nown wn nh hyp yper yp per e se s ns n itiv ittiv ivit itty tto o thi hs drrug. ug g. Infu In nfu usiion n times im mes es of GE GEMZ MZ ZAR A lon onge ge er th than an n 60 mi m nu nute t s an te nd mo more e fre requ qu q ue en n ntt th han week we e lyy dos ek osin ing in g ha ave e bee een n sh s ow wn to o in nccre reas asse to oxi xici c tyy. P ci Pu ulm lmon on nar aryy to oxxiiciityy has a be ee en en re epo port rted rt e . In casses ed e of se eve ere e lun u g to t xi xici c ty ci ty,, GE EMZ M AR AR the h ra apyy ssho houl ho uld ul d be b dis i co cont cont n in nu ue ed im mme medi d attel eya an nd ap ppr p op opri riiatte ssu upp por orti t ve ti e ccar arre m me eas asur u ess iins ur nssti n t tu ute ed. d Hem e ol o yytticc U em Ur micc Syndr yn ndrrom ome e (H HUS US)) an a d d//or o re en nal ffai aiilu l rre e havve be een n rrep epo epor ep orrte ted d ffo olllow o in ng on one e or mo ore ed dos o es os es of GEMZ GEMZ GE MZAR AR A R. Re R na n l fa f ililur ure ur e le ead din i g to o dea dea eath th h or re equ quir uir i in ng di d al a ys y is is,, de desp spit ie it d sccon di nti t nu nuat a iio at on of o tthe he h era apyy, ha h s be been e rarrel en e y re epo p rt rted e . Th ed he ma m jo jori r ty of th ri the e ca ase es of o r nal re na al fa f illur u e le lead ad ding in ng to o dea eath t wer ere e du due e to t HUS US.. Se eri r ou o s he h pa atto oto oxi x ci city ityy, in incllud udin din ing g lilive v r fa ve faililiurre a an nd de eat ah h,, has bee e n re r po p rt rted d vver eryy ra er are elyy in p pa ati te en nts ts rrec e eiivi ec ving ng g GEM MZA AR allon one or o in co c mb mbin in na attio on wi with tth h oth ther ther e potten nti t al a lyy h hep e at ep atot otoxxicc drru ug gss. GE EMZ M AR R is Prreg P e n na anc ncyy C Ca ate t go g ryy D. GE G MZ ZAR A can n cau usse e fet e al a ha arrm rm wh when n admin dmin dm nisste ere red d to to a pr p eg gna nant nt wom oman a . Use an Usse ca c ut u io ion n in pat pat atie ie ient entts wi with h pre re-e - xist -e xiissttin ing g re en na al impa im mpa air irme m n me ntt or hep e atticc iins n uffffiici ns c en ncyy. Ad A mi mini nisttra ni attiion n of GE EMZ MZAR AR A R may a exa acerb ce erb bat ate e un u d de erl r yi ying ng g he epa pati ticc in nsu uff f ic icie ienc ie n y. y T The h opt he p im i um u reg egim men n for saf afe e ad dmi m ni nist s ra st ati to on n of of GE EMZ MZAR A AR wiith the w the era r pe p ut utic iicc doses osess of ra os radi diat attio on ha as no nott ye et be been e det en ee errmine miin ne ed in n all tum u or ttyp yp pes e . G MZ GE ZAR R hass rrad adio ad io ose ens nsit itiz it izzin ng a accti t vi v ty ty a and nd d ra ad dia iati tion ti on n re eccal all re reac acti ac t on ti ns ha ave v bee een n repo re po p ort rted ed d. It iiss not no ot kn know ow o wn wh whet e he et h r GE GEMZ MZA AR R or itts meta me eta abo b liite es ar are e exxcrret e ed e in GEMZ G E AR AR®

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human hu ma an mi m lk lk.. Th T e ef effe fect fe cttiivven e esss off G GEM EMZA EM ZA AR in in ped dia atrric ic pat a ie ent ntss h ha as n no ot be been e en de d emo on nsstrat trrat a ed ed.. Th T e to toxi xici xi citi ci t es ti e of GE G MZ MZAR A obsser erve v d in ve n ped e ia iatr ttrric pattie entts we were re e sim millar a to tho osse e rep epor orte or t d in te i adu d ltts. GEM MZA ZAR cl c eara ea ara ranc ncce is i aff ffec e te ec ed by b age g as we elll as gend ge end nder err. Pa ati t en nts reccei e viing g tthe he era r py py wit ith GE GEM MZ ZAR AR sho houl oul uld d be be mo on nit i or o ed clo lose osse elyy b byy a ph hys ysic icia ia an exp ex pe erriien ence ce ed in the eu use sse e of ca c nc ncer e cche er he emo moth her erap ap peu e ttiic ag agen ents en nts ts.. Ab bb brrev e ia ate ed Ad Adve Adve vers rsse Ev ven e ts t (% in ncciide enc nce e)) The most Th mo ostt sev e er e e ad adve vve ers rse e evve en nts t (Gr G ad des 3//4 4) wi w th h GEM MZA AR pl p us u car a bo op pllat atin in n ver ersu suss su cca arbop rb bopla opla op atin tin a ti allon one, e rres e, esspe ecttiv ivel e y, ffor el or the he tre eattm me ent n of pa pati tiien e ts wit ith ha ad dvva anc n ed d ovari va ari r an a c nc ca ncer er werre ne er euttro op pe eniia (7 71 vs v 12) 2));; th hro romb mb m boc o yt ytop open op e ia ia (35 3 vs 11 1); leu uko ope p ni n a (5 53 vss 7); a em an e ia a ((28 28 vs 11 28 1);; nau use ea (6 vs 3 3)); vo vomi m ti mi t ng g ((6 6 vs v 3 3); );; and nd const onst on stip ip ipat pat a io i n (7 7 vs 3) 3).. Th The e mo most stt comm co mm m mon na adv d er dv erse se e eve v nt ntss (a (alll Gra ade es) we erre ne neut u ro ut ope peni n a (9 90 vs v 5 58) 8);; leuk 8) leuk le u op open pen enia ia ((86 8 vs 7 86 70 0); ) an nem mia a (86 6 vs 75 7 ); thr h om mbo ocy cyto yto tope peniia (7 peni pe 78 vs v 57)); R RB BC trran nsf sfus u io us on (3 38 vs vs 15) 5 ; al a op o eccia a (4 49 vs vs 1 17) 7)); ne neur urrop opat atth a hyy/s /sen e sory en soryy (2 so 29 9 vs 27 7));; nau ause se ea (6 (69 9 vs 61) 1);; fa fati t gue ti gu ue (4 40 vs v 32)); vo omi m ting tiing (4 46 vs v 36)); di d ar a rhea rh hea a ((25 25 5 vs 14 4); ); and n con onst s ip st i a attio on (4 42 vss 37) 7).. Fo F or ad a di diti tion ti on nal a saf a etty in info ffo ormat rmat rm atio ion, n, pleas le ea asse se see e Br B iie ef Su S mm mmar a y of ar of Pre esc s ri r biing g IIn nfo form rm ma attion io on on o adj d ac a e en nt p pa age ge.. Fo or mo ore r iinf nffor n orma m ti ma to on n abo b utt can ance cerr tr ce trea ea e atm me en nt wi witth h GEM E ZA AR, vis isit itt GE G MZ ZAR AR.c .cco om m.