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ns io at er id ns Co a m lo ye M

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Photo courtesy of American Society of Clinical Oncology.

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CONFERENCE NEWS ASCO President: “Personalizing cancer care” is everyone’s mission

VIEWPOINT Government health plans always ration care

JULY/AUGUST 2009 • VOL. 1, NO. 4

er t d a e n L The burseme or im dates f e R in e Up ity Cod ommun ts C ologis Onc

PRACTICE MANAGEMENT

Multidisciplinary Cancer Care: A New Model for Community Cancer Centers. Part 1

ASCO ANNUAL MEETING 2009

A roundtable discussion with Mark J. Krasna, MD; Nicholas Petrelli, MD; and Andrew Salner, MD Photo courtesy of American Society of Clinical Oncology.

ancer care requires treatment by multiple modalities. In this roundtable discussion, Mark J. Krasna, MD, medical director of the St. Joseph Cancer Institute in Townsend, Maryland, Nicholas Petrelli, MD, medical director of the

Helen F. Graham Cancer Center at Christiana Care in Wilmington, Delaware, and Andrew Salner, MD, director of the Helen and Harry Gray Cancer Center at Hartford Hospital in Connecticut discuss multidisciplinary care as delivered

in various practice models. They highlight the benefits multidisciplinary clinics offer patients and clinicians, as well as some of the hurdles communities face in setting up these clinics. Continued on page 12

GUIDELINE UPDATES

THE PATIENT’S VOICE

AUA Counters Mainstream Recommendations with New Prostate Cancer Guidelines

Ovarian Cancer National Alliance Works to Increase Awareness of Ovarian Cancer Patient’s Needs, Concerns

CHICAGO—The American Urological Association (AUA) has lowered the recommended age for prostatespecific antigen (PSA) testing by 10 years, from age 50 years to age 40 years. The AUA issued new clinical guidance, which directly contrasts with recent recommendations by other major groups, at its 104th Annual Scientific Meeting in April. The new recommendation by the AUA is that PSA testing should be offered to

varian cancer, the deadliest of gynecologic cancers, is the fifth leading cause of cancer-related deaths among American women. The symptoms of ovarian cancer (Table) are subtle and nonspecific and are often not recognized by women or their physicians. When diagnosed early, nine out of 10 women will survive more than 5 years. But there is no

Continued on page 11

More than 4000 studies were reported at the 45th annual meeting of the American Society of Clinical Oncology, held in Orlando, Florida, May 29 to June 2, 2009. Highlights of clinical and health economics presentations relevant to cancer care in the community setting are presented here.

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MULTIDISCIPLINARY TUMOR BOARD CASE STUDY Treating a Patient with Unfavorable-risk Prostate Cancer Marc H. Siegelbaum, MD Jason R. Citron, MD James W. Eagan Jr, MD Rima J. Couzi, MD

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ONCOLOGY DRUG CODES Medications Used for the Treatment of Genitourinary Cancers

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EDITOR’S LETTER

A Clinician’s Viewpoint on Measuring the Value of Cancer Care

MARK J. KRASNA, MD ST. JOSEPH CANCER INSTITUTE EDITOR-IN-CHIEF

his edition of Journal of Multidisciplinary Cancer Care highlights several important topics in modern cancer care. In addition to the excellent clinical pieces centered around genitourologic malignancies, we have included three separate discussions on the costs of cancer care. I will focus my comments on this particular topic. How do we measure the cost, and how do we measure the value of cancer care? There are standard methods that have been “validated” by health economists for cost, and then there are “value tools,” such as qualityadjusted life-years (QALYs), that have been used for many disease states. I will focus on the personal and perhaps more emotional impact of these types of reports, rather than on their scientific value. This is because I am primarily a clinician, not an economist, and because I perceive certain values that cannot be measured by standard techniques. How does one measure the value of a grandfather living long enough to see his first grandchild born? How does one measure the value of surviving through one more round of chemotherapy and supportive care measures for the parent who lives long enough to get to his or her child’s wedding (which the couple has moved up by 6 months to accommodate the dying mother)? How does one value the young father-to-be with sarcoma who agrees to go on his fifth line of chemotherapy in a phase 1 trial because he knows his young wife will be delivering their first baby in 3 months? He knows he will not be there for the graduation or the wedding, but all he really wants is to hold that child. Can QALYs really measure that inherent value? I have met and mentored many young and

inspired cancer physicians who have made their decisions regarding their career choices after they went through life-altering experiences with family members or friends with cancer. Is there a way to measure the impact

for lung cancer, which kills more patients each year than breast, colon, and prostate cancer combined, the only reason that routine spiral computed tomography is not implemented is cost-related; yet no advo-

Although some are now questioning the value of routine prostate-specific antigen screening and even mammography and colonoscopy screening, it is not true that all these early cancers would otherwise have caused no harm. that spending 1, 2, or 3 extra months with a dying friend or relative may have yielded a clinician scientist who may find a cure or critical breakthrough for this disease some day? It is with these thoughts and with this perspective that I read the articles in this issue on the cost of care. This is likely why I read them in a slightly different, perhaps less scientific, light. Although the United States spends more money than any other country on healthcare, studies have not shown that our high cancer mortality is a sign of failure. We need to probe more deeply on actual expenditures on research and treatment by disease, and then again by geographic region, and then finally by race/ethnicity to get the full story. Likewise, although some are now questioning the value of routine prostate-specific antigen screening and even mammography and colonoscopy screening, it is not true that all these early cancers would otherwise have caused no harm. Again, we need to refine these data. In fact,

cates are racing for the cure of this disease or pushing for a screening program. That may be because so few of these patients live long enough to become advocates. Regionalization and specialization are good ideas, but 85% of cancer care in the United States is delivered in the community, so we need local not just regional centers for excellence. Screening programs are probably best done as part of an overall health program. Other simple approaches, such as limiting off-label use of expensive drugs, will make a huge difference as well. And, lastly, denying healthcare for cancer patients older than a “cutoff age” is not just unethical but impractical—these individuals may not be contributing to the workforce, but they are role models guiding our young people to be future caring individuals. So let us fix the whole system, slowly; we still have the best healthcare in the world. We need to make it even better, more affordable for some and more efficient throughout.

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@greenhillhc.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 by Green Hill Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. Telephone: 732.656.7935. Fax: 732.656.7938. Copyright ©2009 by Green Hill Healthcare Communications, LLC. All rights reserved. Journal of Multidisciplinary Cancer Care™ is a 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. July/August 2009

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EDITOR’S LETTER

A Letter from the Editor

No. 4

July/August 2009 Departments

Feature Articles CONTENTS

Conference News Health Economics: Out-of-pocket costs for oral cancer drugs vary by agent, payer type Dissecting the cost of copay assistance Making physician and hospital alignment work Financial and clinical outcomes in an acute palliative care unit Clinical: Treatment based on rising CA125 offers no survival advantage in recurrent ovarian cancer Trastuzumab improves survival in gastric cancer Multidisciplinary care for thoracic surgery patients, delivered daily, improves pain control

EDITORIAL BOARD

Editorial Director Karen Rosenberg karen@greenhillhc.com

Editor’s Letter

Managing Editor Dawn Lagrosa

Viewpoint

Recent FDA Approvals

23 27

Directors, Client Services John W. Hennessy john@greenhillhc.com

Oncology Drug Codes

Russell Hennessy russell@greenhillhc.com Cristopher Pires cris@greenhillhc.com

Ovarian and prostate cancer

Production Manager Marie RS Borrelli

Meetings

Business Manager Blanche Marchitto blanche@greenhillhc.com Executive Administrator Andrea Boylston

YOU COULD BE HOLDING YOUR LAST ISSUE!

Multidisciplinary Tumor Board Case Study Treating a patient with unfavorable-risk prostate cancer

PUBLISHING STAFF Publisher Philip Pawelko phil@greenhillhc.com

GH Green Hill Healthcare Communications

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Your Innovative Partners in Medical Media

241 Forsgate Drive, Suite 205C Monroe Twp, NJ 08831

Anna M. Butturini, MD Children’s Hospital Los Angeles Hematology-Oncology

Patricia Molinelli, RN, MSN, AOCNS Somerset Medical Center Oncology Nursing

Scott E. Eggener, MD University of Chicago Genitourinary Cancer

Judy A. Olson, RT(R), RDMS St. Luke’s Mountain States Tumor Institute Breast Care

Beth Faiman, RN, MSN, APRN, BC, AOCN Cleveland Clinic Taussig Cancer Institute Oncology Nursing

Nicholas Petrelli, MD Helen F. Graham Cancer Center Christiana Care Health System Surgical Oncology

EDITOR-IN-CHIEF

Mark J. Krasna, MD St. Joseph Cancer Institute Thoracic Surgery

Mehra Golshan, MD Dana-Farber Cancer Institute Breast Cancer

Practice Management Section Editor Steven L. D’Amato, RPh, BCOP Maine Center for Cancer Medicine Oncology Pharmacy

Marilyn L. Haas, PhD, CNS, ANP-BC Mountain Radiation Oncology Oncology Nursing

John F. Aforismo, BSc, Pharm, RPh, FASCP R•J Health Systems International Oncology Pharmacy

Shaji K. Kumar, MD Mayo Clinic Hematologic Malignancies

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

Terry Macarol, RT(R)(M)(QM) Advocate Health Care Breast Imaging

Nicole A. Bradshaw, MS, CIC Mountain States Tumor Institute Performance Improvement

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Patrick Medina, PharmD, BCOP Oklahoma University College of Pharmacy Oncology Pharmacy

Greg Pilat, MBA Advocate Health Care Practice Management Andrew Salner, MD Hartford Radiation Oncologists Association Radiation Oncology Ritu Salani, MD Ohio State University Medical Center Gynecologic Malignancies Timothy G. Tyler, PharmD, FCSHP Comprehensive Cancer Center Desert Regional Medical Center Oncology Pharmacy Gary C. Yee, PharmD, FCCP, BCOP University of Nebraska Medical Center Oncology Pharmacy

July/August 2009

Viewpoint VIEWPOINT

Government Health Plans Always Ration Care Europe offers a glimpse of the future if President Obama and congressional Democrats have their way.

nly by expanding government control of health care can we bring down its cost. That’s the faulty premise of the various proposals for health reform now being batted around Washington. The claimed cost control depends on politically safe ideas such as preventive care or the adoption of electronic health records. And neither—even according to the Congressional Budget Office—will do much to reduce spending. If these proposals are implemented and fail to produce savings, government will turn to a less appealing but more familiar tool to cut costs: the regulation of access to drugs and medical services. Medicare is already going down this path. What will be new about government-run health care is the instrument of regulatory control. There will be an omnipotent federal health board. Buried in current reform proposals, this board deserves closer scrutiny. Our best look at this construct comes from a bill released by the Senate Health, Education, Labor and Pensions (HELP) Committee. The bill calls for a “Medical Advisory Council” to determine what medical products and services are “essential benefits” and those that shouldn’t be covered by a public insurance plan. The Senate Finance Committee turns to a “Federal Health Board” to compare similar medical treatments in order to steer reimbursement to lowercost options. Senate Finance also proposes a “sustainability commission” charged with finding automatic cuts to Medicare spending that would then pass Congress by a simple up or down vote. Meanwhile, a draft health-care reform proposal introduced last week in the House of Representatives by the three committees with jurisdiction over health policy set up an independent “advisory committee” that will “recommend a benefit package based on stan-

dards set in the law.” It also proposes a new “commission” that may, among other things, help develop treatment protocols based on government-directed research. Congress, of course, can authorize the creation of panels and commissions to provide expert advice to the executive branch. But such bodies are typically advisory, and their advice is free to be rejected or modified by the president. Under the HELP committee’s plan, the health board’s recommendations would

selves of responsibility. Some in Congress and the Obama administration recently tipped their hand on this goal by proposing to make recommendations of the current Medicare Payment Advisory Committee (MedPAC) legally binding rather than mere advice to Congress. Any new health board’s mission will also expand over time, just as MedPAC’s mandate grew to encompass medical practice issues not envisioned when it was created. The idea of an omnipotent board

Rationing is inevitable if we simply expand government control without fixing the way health care is reimbursed so that doctors and patients become sensitive to issues of price and quality. be binding unless Congress acts within a brief period to pass a “joint resolution disapproving such report in its entirety.” President Obama objects when people use the word “rationing” in regards to government-run health care. But rationing is inevitable if we simply expand government control without fixing the way health care is reimbursed so that doctors and patients become sensitive to issues of price and quality. Like Medicare’s recent decisions to curtail the use of virtual colonoscopies, certain wound-healing devices, and even a branded asthma drug, the board’s decisions will be one-size-fits-all restrictions. Such restrictions don’t respect variation in preferences and disease, which make costly products suitable for some even if they are wasteful when prescribed to everyone. Moreover, these health boards prove that policy makers know they’ll need to ration care but want to absolve them-

that makes unpopular decisions on access and price isn’t a new construct. It’s a European import. In countries such as France and Germany, layers of bureaucracy like health boards have been specifically engineered to delay the adoption of new medical products and services, thus lowering spending. In France, assessment of medical products is done by the Committee for the Evaluation of Medicines. Reimbursement rates are set by the National Union of Sickness Insurance Funds, a group that also negotiates pay to doctors. In Germany, the Federal Joint Committee regulates reimbursement and restrictions on prescribing, while the Institute for Quality and Efficiency in Healthcare does formal cost-effectiveness analysis. The Social Insurance Organization, technically a part of the Federal Joint Committee, is in charge of setting prices through a defined formula that monitors doctors’ prescribing be-

havior and sets their practice budgets. In the past 12 months, the 15 medical products and services that cleared this process spent an average 35 months under review. (The shortest review was 19 months, the longest 51.) In short, other countries where government plays a large role in health care aren’t shy about rationing. Mr. Obama’s budget director has acknowledged that rationing reduces costs. Peter Orszag told Congress last year when he headed the Congressional Budget Office that spending can be “moderated” if “diffusion of existing costly services were slowed.” Medicare can already be painstakingly slow. Appealing to it takes patients an average 21 months according to a 2003 Government Accountability Office report (17 months involve administrative processing). Layers of commissions and health boards would delay access still further. When asked to judge the constitutionality of the Senate HELP committee proposal, there’s a reason why the nonpartisan Congressional Research Service said that the proposed Medical Advisory Council “raises potentially significant constitutional concerns.” Our Founders thought politicians should be accountable when it comes to citizens’ right to life, liberty and the pursuit of heart surgery. —Scott Gottlieb Dr. Gottlieb, a physician and resident fellow at the American Enterprise Institute, is a former senior official at the Centers for Medicare and Medicaid Services. He is partner to a firm that invests in health-care companies. Reprinted with permission. © Scott Gottlieb. Originally printed in Opinion Journal. The Wall Street Journal. June 25, 2009.

Big Health Firms Underpay Claims

ongressional investigators have discovered that large health insurers in every region of the country are relying on faulty databases to underpay millions of valid insurance claims. In a report released Wednesday, the Senate Commerce Committee said insurance companies nationwide have failed to provide consumers with accu6

rate or understandable information about how they calculate “reasonable” or “customary” charges for out-of-network care. Insurers also signed contracts prohibiting them from disclosing information about the databases to consumers or doctors, the report said. The flawed databases are owned by Ingenix Inc., a subsidiary of United-

G REEN H ILL H EALTHCARE C OMMUNICATIONS

Health Group Inc. UnitedHealth recently settled with the New York attorney general’s office to resolve charges that Ingenix drew up billing rates that underpaid hospitals and doctors for out-of-network care. Patients had to make up the difference. It is unclear how much they have overpaid over the years. An Ingenix spokeswoman said the

company stands by the integrity of its databases. The two databases in question by the committee represent less than 2% of Ingenix’s overall business. Ingenix also said it doesn’t set actual rates for health procedures. Other insurers that purchased Ingenix data in New York—Aetna Inc., CIGNA Corp., and Wellpoint Inc. among them—also paid into the settleJuly/August 2009

—Fawn Johnson

Recent FDA Approvals • Pemetrexed for Maintenance Therapy in Advanced Nonsquamous NSCLC

• Mylan’s Generic Bicalutamide for Prostate Cancer

The US Food and Drug Administration (FDA) has approved pemetrexed (Alimta, Eli Lilly) for intravenous use, 100-mg and 500-mg vials, in maintenance treatment in patients with advanced or metastatic nonsquamous non–small-cell lung cancer (NSCLC) whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. Pemetrexed is not indicated for treatment of patients with squamous cell NSCLC.

The FDA has approved Mylan’s version of bicalutamide tablets, 50 mg, a generic version of Casodex (AstraZeneca). Bicalutamide is indicated for use in combination therapy with a leutinizing hormone-releasing hormone analogue for the treatment of stage D2 metastatic carcinoma of the prostate. It is not approved for use alone or with other treatments. Mylan has begun to ship this product.

VIEWPOINT

ment. Under that agreement, the insurers will help pay for and then use a new not-for-profit research entity that will help determine prices for out-of-network care. Commerce Committee Chairman John Rockefeller, D-W.Va., launched the committee investigation in March, in the wake of the UnitedHealth settlement. Committee oversight staffers sought data from 18 large insurers that didn’t participate in the New York settlement, including American International Group Inc., Humana Group Inc., the Kaiser Foundation Group, several Blue Cross Blue Shield units, and UnumProvident Corp. Together with the New York investigation, the committee’s findings represent roughly two-thirds of the healthinsurance market. The Ingenix databases represent “the great black box of the health-care industry,” according to one health-care CEO quoted in the report. Ingenix also is the only commercial source of such data. Providers and patients have suspected for years that insurers were underpaying for out-of-network care, but they haven’t been able to prove it. Committee investigators found that Ingenix developed its payment models based on claims data provided by its customers, the insurance companies. A committee aide said those companies sometimes would “scrub” the data sent to Ingenix—throwing out outlying high costs. Ingenix then would use questionable statistical models to come to its own rate estimates. The committee’s report comes at a critical moment in Congress, as lawmakers are struggling to craft a massive overhaul to the health-care system designed to cover some 45 million uninsured Americans. In addition to chairing the Commerce Committee, Sen. Rockefeller also chairs the health subcommittee of the Finance Committee, one of two key Senate panels negotiating the healthcare bill. He hopes to insert into the health-care bill language creating some type of independent evaluator that can certify that health claims are evaluated properly. In the meantime, Commerce Committee investigators likely will continue to drill down into individual companies’ practices to understand how they arrive at certain claims rates. The committee also could look into smaller regional insurance carriers to see if they, too, are using faulty data. Republicans and other champions of private-sector insurers have long argued that making health care more consumer-friendly would drive down costs because patients could “shop around” for the best care. But Sen. Rockefeller and other health-policy experts argue that the lack of information in the private health-insurance market has made competition and informed consumer choice almost impossible.

CHEMOTHERAPY FOUNDATION SYMPOSIUM XXVII INNOVATIVE CANCER THERAPY FOR TOMORROW November 10-14, 2009 New York City

Practical Applications for the Practicing Oncologist New Agents, Clinical Trials and Emerging Therapies November 10

SESSION SCHEDULE Pediatric Oncology

November 11

Hematology, GI Cancers

November 12

GYN, Breast, Melanoma, Head & Neck, Sarcoma

November 13

Immunotherapy, Glioma, GU, Lung, Prostate, Renal, Neuroendocrine, Unknown Primary, EHRS, Novel Agents

November 14

New Perspectives in Oncology Practice Oncology Nurse, Nurse Practitioners, Physician Assistants, Case Managers

Register on line at chemotherapyfoundationsymposium.org Contact: Jaclyn.silverman@mssm.edu CME Accredited by the Mount Sinai School of Medicine

Reprinted with permission from The Wall Street Journal. June 25, 2009. July/August 2009

G REEN H ILL H EALTHCARE C OMMUNICATIONS

Richard Schilsky, MD, ASCO President: “Personalizing Cancer Care” Is Everyone’s Mission Photo courtesy of American Society of Clinical Oncology.

CONFERENCE NEWS

Conference News ORLANDO—The “personalization of cancer care”—delivering the right care to the right patient at the right time—is becoming a universal and realizable goal, said American Society of Clinical Richard Schilsky, MD Oncology (ASCO) President Richard Schilsky, MD, Professor of Medicine and Associate Dean of Clinical Research, University of Chicago. The challenges of the past year have been many: the global economic recession, high unemployment, declining physician workforce, and lack of universal access to optimal care. “But it has also been a year of great hope, as we have a new administration that is committed to curing cancer,” Schilsky told annual meeting attendees, in his presidential address. “We hear much about personalized medicine. It is the new buzzword in healthcare and health policy. But what does it mean to patients and oncologists?” he asked.

Both patient and tumor are unique Personalized medicine begins with a concept that cancer specialists have long recognized: that each patient is unique in his or her clinical presentation, treatment response, and supportive care needs. But it also includes the growing recognition that tumors are also unique; therefore, personalized

treatment plans should address both the patient and the tumor, he said. Among more than 100 drugs approved for more than 170 cancer indications, a growing number target specific abnormalities of the cancer. Molecular diagnostics are beginning to guide prescribing practice, based on germline variations in the patient and somatic mutations in the tumor. For example, Kirsten rat sarcoma (KRAS) mutations have become established as biomarkers for the lack of efficacy of epidermal growth factor receptor–targeted monoclonal antibodies, and ASCO has issued a provisional clinical opinion calling for KRAS testing in patients with metastatic colorectal carcinoma. “Personalizing cancer care is all about bringing our insights and skills from biology, medicine, engineering, informatics, social sciences, and other disciplines to solving the enormous problem of cancer,” he said. “We will increasingly be able to design optimal treatment strategies that offer the best hope of controlling cancer with the least toxicity. And with sophisticated imaging techniques, such as volumetric computed tomography, we can more quickly assess treatment efficacy. This all has the potential to substantially reduce the cost of care.” Personalized cancer care does not cease at the end of treatment, but extends to end-of-life care and survivorship, he added, encouraging oncologists to personalize survivorship plans for their patients, and to communicate with survivors “as an individual and not a statistic, as a person with an illness

within a social network.” “As oncologists, our focus has been and must remain treating the person, not the disease,” Schilsky reiterated. “We must acquire the skills and devote the time and receive compensation for doing so in an optimal way.”

Meeting the growing needs By 2030 the global cancer burden will triple and cancer will be the leading cause of death. Because this will be coupled with a 30% shortfall in oncologists, new approaches are greatly needed to meet these needs, he said. One part of the solution is the use of multidisciplinary care teams, the aim being to “extend the reach of oncology services” through mid-level providers. Primary care providers, if oncologists “better engage” them, can also help lighten the workload, he said. With regard to the increasing cost of care, “oncologists need to be part of the conversation and the solution,” he maintained. A new ASCO task force is developing a plan of action on cost of care. Among the recommendations will be greater emphasis on discussions with patients, uniform definitions of “value,” examination of factors that underlie cost, and advancement of steps related to comparative effectiveness. Finally, clinical trial obstacles must be overcome, he said. The US research infrastructure is “the best in the world” but is underfunded and “mired in a regulatory matrix that slows our progress and saps our energy,” Schilsky noted. In 2009, more than 700 drugs are in development for cancer, but fewer than

10% of these will probably be approved, he predicted. “There are not enough patients, dollars, and time,” he said, “to test all these within our conventional clinical trial paradigm.” ASCO has convened an expert group to tackle some of the key aspects of the clinical trials problem and to produce a white paper for the US Food and Drug Administration. Meanwhile, Schilsky advocated for the use of biomarkers to streamline patient selection, preliminary marketing approval based on randomized phase 2 (rather than phase 3) trials, removal of barriers to the completion of confirmatory trials, and streamlining of the processes that support the filing of supplemental new drug applications for new indications. Such changes would require the willingness of pharmaceutical companies to trade the rewards they reap from shortterm widespread use of a drug in large populations to long-term use of a drug in more limited populations, and will necessitate much greater participation in trials on the part of oncologists and patients alike. Most important, the clinical trials process must be revamped for greater efficiency. Currently, a phase 3 cooperative group trial requires close to 400 steps and 2 years to launch because of a bureaucratic process that involves a multitude of review loops, regulatory requirements, and contract negotiations. “We must fix this problem now,” Schilsky concluded, “because our patients cannot wait.” —Caroline Helwick

Out-of-pocket Costs for Oral Cancer Drugs Vary by Agent, Payer Type ORLANDO—Most out-of-pocket payments for oral cancer drugs are less than $50, although about one in five patients has out-of-pocket expenses greater than $500, according to a study of pharmaceutical claims from 98 managed care plans in the United States. The pharmacy benefit design trend toward higher tiered copayments for specialty drugs, such as oral oncologic agents, has the potential to increase the out-of-pocket cost burden to patients, said the study’s lead investigator, Elise M. Pelletier, MS, director, Health Economics and Outcomes Research, IMS Consulting, Watertown, Massachusetts. 8

As the costs of these therapies increasingly become part of treatment decisions, a better understanding of patient out-of-pocket costs is important to inform these decisions. Pelletier and her colleagues identified 10,400 patients from 98 health plans with evidence of receiving at least one of 13 oral oncologic agents in 2007. The oral cancer drugs of interest were bexarotene, erlotinib, lapatinib, sunitinib, vorinostat, capecitabine, gefitinib, lenalidomide, temozolomide, dasatinib, imatinib, sorafenib, and thalidomide. Out- of-pocket payments were calculated as the allowed amount

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minus the paid amount. Two thirds of the patients were in a health maintenance organization or preferred provider organization (PPO) plan; 83% were insured by a commercial payer. The most common cancer was lung cancer, with one fourth of the patients having this diagnosis. The median out-of-pocket costs ranged from $14 to $39. Sixty-nine percent of patients were paying less than $50 per claim, but 22% had out-ofpocket costs of $250 or more. Seventeen percent of out-of-pocket payments were more than $500. Among the 13 therapies, capecitabine

had the lowest out-of-pocket payment, averaging $117, and lenalidomide had the highest, with an average of $1014. Out-of-pocket expenses ranged from 4.9% of the cost of vorinostat to 16.4% of the cost of lenalidomide. PPO plans and indemnity plans had the largest out-of-pocket payments for almost all of the therapies. When analyzed by payer type, out-ofpocket payments were significantly higher with Medicaid and Medicare Advantage plans compared with commercial payers ($586 vs $309; P <.001). —Wayne Kuznar July/August 2009

ORLANDO—Wilshire Oncology, an 11-person community oncology practice in the Los Angeles area, is committed to helping needy patients pay for the out-of-pocket costs of cancer care. Its method is a structured program that targets foundations, and its success rate is 91%. But it has to fund one half-time administrative position to make this happen. Twenty percent of cancer patients spend their entire life savings on cancer care, and deaths are increasingly being blamed on inadequate insurance. Foundations have been established to help defray these costs, but there is no model for coordinating foundation support with patients, and the costs of such coordination are unknown. Wilshire Oncology, therefore, documented its approach, and concluded that to get money for patients a practice has to spend some of its own. “We have to figure out how to pay for this. Practices cannot afford this,” said Carey Presant, MD, a senior member of the group. “It costs us $75 per patient, and you may say that’s trivial, but it’s not, because we are operating at a miniscule margin.” He noted that 85% of cancer care is given in the community oncology setting where funding cutbacks have led to staff reductions—and at a time when patients need help navigating the increasingly complex reimbursement system. The group’s aim was to develop a patient support program that would coordinate patient applications to copay-assistance and cancer-specific support foundations. It also wanted to determine the efficiency, the costs, and the cost-effectiveness of their system.

One half-time employee was hired as a patient support coordinator. Between September 2008 and March 2009 (7 months), 500 patients were prescribed chemotherapy with 555 treatment plans. Of these, 487 had insurance and 13 did not. Of the insured patients, 52% had no copay/coshare, 29% had a copay/coshare less than $500, and 17% had a copay/coshare more than $500. For the 13 uninsured patients, efforts to get assistance resulted in seven (54%) receiving free drugs through a manufacturer drug replacement program, and six (46%) not receiving free drugs, for a variety of reasons. An additional 46 “underinsured” patients (9%) expressed a need for financial assistance as they were unable to pay the copay/coshare. For these patients, 161 total applications were submitted to foundations (Table), averaging 23 per month. The approval rate per application was 52%, while 47% were denied. Ultimately, however, 42 patients (91%) were approved for grants and four (9%) were denied, reported Swapni P. Rajurkar, MD, lead author of the paper presented at the annual meeting of the American Society of Clinical Oncology (ASCO). Denials were based on patient factors (income too high), foundation factors (out of funds), and treatment factors (specific medication or diagnosis not covered). The impact of being denied funds from all foundations, for the four patients in this study, was that one patient relied on his children for the recommended treatment, one chose and paid for an alternative treatment, one declined any treatment, and one was referred to a county facility for care.

Medicare, to ensure that practices can Average grant exceeded the need A total of 85 grants were approved, hire specialized personnel to assist totaling $252,747. Although the aver- patients with their financial needs. “The way Medicare could do this,” age patient needed $1600 to $2500 to pay out-of-pocket costs, the average Presant suggested, “is to have a separate grant came in at $6018, Rajurkar treatment planning code. We could also tell the manufacturers we want to bill reported. “We had to give back the difference,” them for the cost, but I think that he said. “Some patients got more than would be illegal [under the self-referral, they needed and others didn’t get any. fraud, and abuse regulations].” He would like to see state societies or That’s a problem.” The larger-than-needed awards tie up ASCO facilitate coordinated foundafunds for 120 to 150 days. Although tion financial support programs and these unused grant funds are reallocated implement a universal application form. to patients who qualified a numTable. Foundations Identified for Potential Support ber of months earlier, most patients will have “moved HealthWell Foundation on” by that time, Patient Advocate Foundation Co-Pay Relief Program he said. They make alternative Cancer Care Co-Payment Assistance Foundation choices or even Patient Access Network Foundation forego therapy, and Chronic Disease Fund then it is too late to help them. Beckstrand Cancer Foundation The cost of a National Brain Tumor Society half-time patient The Leukemia & Lymphoma Society support coordinator, based on $16 National Organization for Rare Disorders per hour and benefits, was $1733 “The foundations would receive supper month; for a total 7-month cost to the practice of $12,131. In addition, the plemental grant money from all the manufacturers to cover our administrapractice spends $75 per application. Such a program is necessary for time- tion costs and keep our practices ly and sustainable cancer care for all whole,” he explained, “while at the patients, the group believes, but the cost same time [these funds] would assure is a substantial burden on an oncology our patients that we can do as many applications as needed to get assistance practice. The oncologists would like to see for them.” “reimbursement support” come from the foundations, drug manufacturers, or —CH

Making Physician and Hospital Alignment Work ORLANDO—Under growing economic threats and stresses, oncology practices are considering new ways to stay afloat. To some, aligning with the local hospital makes sense. Patrick A. Grusenmeyer, ScD, vice president of cancer services, Christiana Care Health System and the Helen F. Graham Cancer Center, Wilmington, Delaware, discussed how physician and hospital interests can successfully merge at a session convened during the annual meet-

helping hand to defray the cost of malpractice insurance. These benefits are most attractive when physicians can also retain control of their practices (financial, decision-making) as well as maintain their own income and autonomy. The hospital’s interest in such partnerships is generally to engage physicians more fully and to attract and retain quality physicians on staff. They like to assure that physicians’ interests

Although physicians remain in control of their daily practice, the hospital is given strategic involvement in several areas and is granted “reserved powers.” ing of the American Society of Clinical Oncology. Such partnerships offer a number of benefits to physicians, including obtaining access to the financial resources of the hospital, being a part of a larger system to deal with payers, and having a July/August 2009

are aligned with their own organizational strategy, and that they minimize any risks that could come from owning a physician practice.

Subsidiary physician corporations These aims can often be satisfied

within the “subsidiary physician corporation” alignment model. Typically, this is a separate legal entity solely owned by the hospital, and it can be attractive to both parties. “You develop the subsidiary physician corporation to fit a level of comfort within your own environment,” Grusenmeyer said, although there are certain immutable requirements that must be met. Although physicians remain in control of their daily practice, the hospital is given strategic involvement in several areas and is granted “reserved powers.” Under these reserved powers, the hospital is allowed to: • Approve the strategic plan of the corporation, amendments to bylaws, and annual capital and operating budgets • Approve the merger, consolidation, division, sale of assets, creation of a subsidiary or any other fundamental corporate transaction by the corporation • Nominate and terminate the president of the corporation. There are two classes of membership

on the subsidiary physician corporation board: hospital representatives and physician representatives. “Supermajorities” of each (eg, two-thirds majority) are required for major decisions, including approval of the nominee for president, termination of the employment of a physician, approval of physician employment agreements entered into by the corporation and any amendments, and approval of the physician compensation plan.

What does each partner get? “The physicians run their practice within the limits of hospital-reserved powers and supermajority requirements,” he said. The practice keeps its own pay scale and benefits and is not required to use any hospital services, although it can. The practice retains its net revenue, minus expenses, and there are no corporate overhead charges. Fringe benefits, 401(k) plans, and the like remain in place. “We have found that aligning with the hospital through a subsidiary corpoContinued on page 11

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CONFERENCE NEWS

Dissecting the Cost of Copay Assistance

Conference News CONFERENCE NEWS

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ORLANDO—Treatment for recurrent ovarian cancer based solely on rising blood levels of cancer antigen (CA) 125 does not improve survival compared with delaying treatment until clinically indicated, said Gordon Rustin, MD, at the 2009 annual meeting of the American Society of Clinical Oncology. This new study showed “for the first time, women can be reassured that there’s no benefit to early detection of recurrence by CA125 measurements, and they can be told even if CA125 rises, chemotherapy can be safely delayed until they have signs or symptoms of recurrence,” he said. “We now have informed choices to be able to decide. Most of my patients now, when I give them this information, say ‘we do not want routine CA125 measurements.’” CA125 measurements in women who have undergone treatment for ovarian cancer tend to be a source of confusion to physicians, who have no

Photo courtesy of American Society of Clinical Oncology.

Treatment Based on Rising CA125 Offers No Survival Advantage in Recurrent Ovarian Cancer other biomarkers to guide them in determining recurrence, and a source of anxiety to patients, who often opt for frequent blood tests in the hopes of catching a recurrence early, said Rustin, Gordon Rustin, MD professor of oncology at Mount Vernon Cancer Center, Hertfordshire, United Kingdom. His study assessed survival in a group of women who achieved complete clinical remission of ovarian cancer with a normal CA125 after platinum-based chemotherapy. The women had their CA125 levels measured every 3 months, but the patients and the clinical trial investigators were blinded to the results. From this group, 529 women whose CA125 blood levels had risen to twice the upper limit of normal were entered into the study. They were ran-

domized to immediate treatment or further blinding of CA125 measurements and initiation of treatment at the appearance of clinical or symptomatic recurrence.

effects,” said Rustin. “Ninety-nine out of 100 women would say that life off chemotherapy is nicer than life on chemotherapy. Therefore, if you can delay that chemotherapy, and there’s no

For the first time, women can be reassured that there’s no benefit to early detection of recurrence by CA125 measurements. The women assigned to early treatment started second-line chemotherapy an average of 4.8 months earlier and third-line chemotherapy an average of 4.6 months sooner than those in the group that waited until signs or symptoms appeared. Overall survival was not affected by early treatment, with a hazard ratio of 1.0 after a median follow-up of 49 months. “We can treat this relapsed disease, but chemotherapy has considerable side

disadvantage to delaying it, you’ve actually done that woman a huge service, because she can enjoy life longer without having the side effects of chemotherapy.” CA125 measurements remain useful as a screening tool for early diagnosis (stage Ia) to offer the best chance for cure of ovarian cancer and to monitor the progress of cancer, he said. —WK

Photo courtesy of American Society of Clinical Oncology.

Trastuzumab Improves Survival in Gastric Cancer ORLANDO— Although trastuzumab is thought of as a breast cancer drug, when it is added to chemotherapy for gastric cancer, it outperformed the standard treatment for this tumor in paEric Van Cutsem, tients overexpressMD, PhD ing human epidermal growth factor receptor 2 (HER2), according to the results of an international, randomized, phase 3 trial reported at the annual meeting of the American Society of Clinical Oncology (ASCO). In the first large phase 3 study of trastuzumab in patients with gastric cancer, patients receiving trastuzumab had a 26% reduction in the risk of death, compared with chemotherapy with cisplatin and capecitabine or 5-fluorouracil (5-FU), reported Eric Van Cutsem, MD, PhD, University Hospital Gasthuisberg, Leuven, Belgium. “This is the first phase 3 study to report improved overall survival with a personalized, targeted treatment for gastric cancer,” Van Cutsem said, adding that it is the first time trastuzumab has been shown to improve survival in a tumor other than breast cancer. David Cunningham, MD, consult10

ant, Royal Marsden Hospital, United Kingdom, who discussed the study at the oral session, commented, “This is an absolutely excellent study. It was a major undertaking to screen nearly

until disease progression. Median overall survival was significantly greater with the addition of trastuzumab, 13.8 versus 11.1 months with standard chemotherapy (P = .0048),

“This is the first phase 3 study to report improved overall survival with a personalized, targeted treatment for gastric cancer.” 4000 patients for the presence of HER2 expression, and to recruit them for treatment in a timely fashion. All the end points were positive.”

HER2 overexpression found in 22% of patients Similar to what is seen in breast cancer, HER2 overexpression is often found in gastric cancers. Investigators from the ToGA study, which involved sites in Europe, Latin America, and Asia, tested 3807 patients with advanced gastric cancer for overexpression of HER2, which they found in 810 patients (22%). The study then randomized 594 HER2-positive patients to standard chemotherapy or chemotherapy plus trastuzumab, given every 3 weeks for six cycles, with trastuzumab continued

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Van Cutsem reported. After a median of 17 months of follow-up, mortality was reduced by 26% with the combination. The overall response rate with the combination was 47.3% versus 34.5% with chemotherapy alone, again a highly significant difference (P = .0017). In a preplanned subgroup analysis, patients with the highest degree of HER2 overexpression (fluorescence in situ hybridization-positive/3+ by immunohistochemistry) had even greater benefit from trastuzumab, overall survival being 17.8 months versus 12.3 months for chemotherapy alone. This represented a 42% reduction in the risk of death. The combination was well tolerated, with no significant increase in the occurrence of symptomatic congestive

heart failure; as expected, however, asymptomatic left ventricular ejection fraction decreases were reported more frequently with the combination (4.6%5.9%, depending on the criteria) than with chemotherapy alone (1.1%), he reported. In his discussion of the study, Cunningham maintained, “Trastuzumab produced a modest but clinically meaningful improvement in outcome for patients who have a relatively poor prognosis with conventional therapies. It is a safe and effective option and should be considered for all patients with advanced gastric cancer who test HER2positive.” “The magnitude of benefit may be even greater than observed in ToGA,” he predicted, “if we apply the definition of overexpression that is used in selecting breast cancer patients for trastuzumab treatment, that is, if patients are more highly selected.” ASCO President Richard Schilsky, MD, University of Chicago Medical Center, called the study “a great example of the concept of personalized medicine.” He said that for the first time, there is an indication that “we need to think about two different molecular subtypes of stomach cancer—HER2positive and HER2-negative.” —CH July/August 2009

AUA Counters Mainstream well-informed men aged 40 years or older who have a life expectancy of at least 10 years. The PSA test, as well as how it is used to guide patient care (ie, at what age men should begin regular testing, intervals at Peter Carroll, MD which the test should be repeated, and at what point a biopsy is necessary), are highly controversial. The AUA believes, however, that when offered and interpreted appropriately, the PSA test may provide essential information for the diagnosis, pretreatment staging or risk assessment, and posttreatment monitoring of prostate cancer. The new Best Practice Statement updates the AUA’s previous guidance, which was issued 9 years ago. Major changes to the AUA statement include new recommendations about who should be considered for PSA testing, as well as when a biopsy is indicated following an abnormal PSA reading. According to the AUA, early detection and risk assessment of prostate cancer should be offered to well-informed men 40 years of age or older who have a life expectancy of at least 10 years. A baseline PSA level above the median for age 40 is a strong predictor of prostate cancer. Such testing may not only allow for earlier detection of more curable cancers, but may also allow for more efficient, less frequent testing, according to the AUA. Men who wish to be screened for prostate cancer should have both a PSA test and a digital rectal examination. The statement by the AUA also notes that other factors, such as family history, age, overall health, and ethnicity, should be combined with the results of PSA testing and physical examination to better determine the risk of prostate cancer. The statement recommends that the benefits and risks of screening for prostate cancer should be discussed, including the risk of overdetection (detecting some cancers which may not need immediate treatment). “The single most important message of this statement is that prostate cancer testing is an individual decision that patients of any age should make in conjunction with their physicians and urologists. There is no single standard that applies to all men, nor should there be at this time,” said Peter Carroll, MD, chair of the panel that developed the statement. “[The] panel carefully reviewed the most recently reported trials of PSA testing in both the United States and Europe before finalizing its guidelines. The strengths and limitations of these trials are reviewed in the guidelines.” In regard to biopsy, a continuum of risk exists at all values, and major studies have demonstrated that there is no safe PSA value below which a man may July/August 2009

be reassured that he does not have biopsy-detectable prostate cancer. Therefore, the AUA does not recommend a single PSA threshold at which a biopsy should be obtained. Rather, the decision to perform a biopsy should take into account additional factors, including free and total PSA levels, PSA velocity and density, patient age, family history, race/ethnicity, previous biopsy history, and comorbidities. In addition, the AUA statement emphasizes that not all prostate cancers require active treatment and that not all prostate cancers are life-threatening. The decision to proceed to active treatment is one that men

• Serum PSA should fall to a low level following radiation therapy, high-intensity focused ultrasound, and cryotherapy and should not rise on successive occasions. • PSA nadir after androgen-suppression therapy predicts mortality. • Bone scans are indicated for the detection of metastases following initial treatment for localized disease, but the PSA level that should prompt a bone scan is uncertain. Additional important prognostic information can be obtained by evaluation of PSA kinetics (velocity). • The kinetics of PSA rise after

Early detection and risk assessment of prostate cancer should be offered to well-informed men 40 years of age or older who have a life expectancy of at least 10 years. should discuss in detail with their physician to determine whether active treatment is necessary, or whether surveillance may be an option for their prostate cancer. “Prostate cancer comes in many forms, some aggressive and some not,” said Carroll, who is professor and chair of urology at the University of California, San Francisco. “The AUA is committed to timely, expert, and appropriate care for men either with or at risk of getting prostate cancer and is prepared to revise these guidelines continuously as new information becomes available.”

Key points The Best Practice Statement by the AUA also clarifies a number of key points about the use of PSA in treatment selection and posttreatment follow-up of prostate cancer patients: • Serum PSA predicts the response of prostate cancer to local therapy. • Routine use of a bone scan is not required for staging asymptomatic men with clinically localized prostate cancer when their PSA level is ≤20.0 ng/mL. • Computed tomography or magnetic resonance imaging scans may be considered for the staging of men with high-risk clinically localized prostate cancer when the PSA is >20.0 ng/mL or when locally advanced or when the Gleason score is ≥8. • Pelvic lymph node dissection for clinically localized prostate cancer may not be necessary if the PSA level is <10.0 ng/mL and the Gleason score is ≤6. • Periodic PSA determinations should be offered to detect recurrence. • Serum PSA should decrease and remain at undetectable levels after radical prostatectomy.

local therapy for prostate cancer can help distinguish between local and distant recurrence. “What is also important in this document is that we clearly acknowledge

the risks of overdetection and overtreatment. I think that brings us in line with other groups,” Carroll said in an interview. “We are no longer recommending a single PSA cut point but to use PSA in conjunction with age, digital rectal examination, ethnicity, family history, and other PSA parameters. This is a more sensitive and specific way of diagnosing prostate cancer.” William Catalona, MD, who is a professor of urology at Northwestern University, Chicago, said dropping the age for a baseline PSA to age 40 may be an important new approach because it can better guide clinicians by potentially providing significantly more information. “I think it is important. Not so much for diagnosing prostate cancer at age 40, but for establishing a baseline so that you can get data for PSA velocity. So, if you start at age 40, the PSA should be less than 1.0 ng/mL. After that, you can track it,” said Catalona in an interview. “I think early PSA velocity is a promising new marker for identifying men destined to die of prostate cancer. It can help detect cancer earlier than we can now detect it using any other method. Perhaps we can now treat them and save their lives. This adds to our ability to identify the worse cancers early.” —John Schieszer

CONFERENCE NEWS Physician and Hospital Alignment Continued from page 9 ration can help with malpractice expenses,” he said. “In fact, these can be significantly reduced, and with other negotiations, we can often piggyback on other hospital contracts. If these are favorable, this can also increase revenue to the practice.” The hospital obtains strategic control and is also more able to attract and retain physicians on staff. The hospital’s financial responsibility for the physician practice, meanwhile, is minimal. “There can be some ‘complexity of

management,’ with multiple boards, bylaws, and so forth,” he acknowledged, “but this model works well for many, especially when physicians understand that good management practices are still required. The challenge, when 10 or 20 physicians all see themselves as legal partners, is to have leadership in the practice—an individual that is empowered to make decisions that will move the practice forward.” —CH

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Community Cancer Centers Roundtable PRACTICE MANAGEMENT

Continued from cover There are several different definitions of multidisciplinary cancer care. How do you define multidisciplinary care? Mark J. Krasna (MK): I am going to confine myself to the key clinical aspect of the definition, which involves the physicians engaged in cancer care. To me, multidisciplinary care means Mark J. Krasna, MD an integrated prospective approach by all of the medical specialties that are involved in the patient’s care from the beginning: the medical oncologist, the radiation oncologist, surgeons, and any of the other medical subspecialists needed for a specific patient. All the specialists that will be involved in the care are involved from the beginning so that they all know about the patient before any one of them begins treatment. Nicholas Petrelli (NP): I would add only one other thing. We all know that cancer care is very complex and when patients get the diagnosis of cancer, their anxiety level is very high, Nicholas Petrelli, MD not only about the diagnosis, but also about what to do next and how to get treated. If patients and their families can see the major disciplines along with support service personnel in a single visit, their anxiety level decreases dramatically. And providers believe that their care is more efficient and of higher quality. I would emphasize that the multidisciplinary approach includes not only the three major disciplines of surgical oncology, medical oncology, and radiation oncology, but also the support services such as genetic counseling, dentistry and nutrition for head and neck cancer patients, gastroenterology for hepatobiliary and pancreatic cancer patients, and pulmonologists for thoracic cancer patients. Andrew Salner (AS): As a radiation oncologist, I look at multidisciplinary care from just a slightly different vantage point but would agree that it provides great advantage to patients Andrew Salner, MD and their families. For the whole care team to have involvement from as early a point in time as possible allows decision-making to be made prospectively in terms of diagnostic and treatment steps. It also amplifies the notion that the care team includes not only the physicians who need to be involved in the treatment but also the support team—nurses, 12

social workers, pastoral care people, physical therapists, and those who are going to support the patient during all aspects of care and restore and return the patient to some sense of normalcy after the treatment is completed. Depending on the system of care, it is not always feasible for all patients to be seen in one visit. Although it is convenient for the patient and the team to have a one-visit scenario, at Hartford one of our issues is geography and space. In addition, patients like to see their physicians in satellite offices that are closer to their homes, so at times multiple visits or visits on the same day in a couple of places are necessary. The

ly are required to help. Others’ functions are more logistic, and we use care coordinators who have a master’s of public health. These individuals are comfortable and familiar with the workings of the healthcare system so they make great coordinators in those situations. Although it is an individual situation as to how the coordination is done, the coordination itself is quite important. MK: I will just illustrate. At the St. Joseph Cancer Institute, we started with a single navigator who was in charge of everything, from when the patient started treatment through survivorship. Then we added a coordinator in each of our disease sites.

The multidisciplinary approach includes not only the three major disciplines of surgical oncology, medical oncology, and radiation oncology, but also the support services. notion is not necessarily that everybody has to be under one roof. The notion is that the care team has to see the patient and has to communicate and coordinate the care.

Are nurses, pharmacists, and other personnel involved in these discussions? MK: Absolutely. One of the key components to any successful multidisciplinary cancer care program is the central nurse, usually called the nurse navigator or nurse coordinator. Any successful program that we have launched has always had a nurse navigator. NP: The care coordinator or nurse navigator is the critical individual in making the multidisciplinary clinic run efficiently. He/she guides the patient through the maze of cancer care and, in my mind, that individual is the most important component out of all the disciplines we mentioned. After a patient and the physicians leave the multidisciplinary clinic, somebody has to make sure that the coordination of care continues through treatment and survivorship programs. That person is the nurse navigator or care coordinator. AS: I agree and would add that we have several people in our system who fulfill some of those roles. We have nurse and patient coordinators who work for the hospital. We also have staff employed by some of the physicians’ private offices, either surgeons or medical oncologists, who work together to provide and coordinate some of the care for a patient, particularly if the patient is in a corresponding phase of care. It is a network of individuals who ensure that the patient’s care is coordinated, that there is seamlessness between treatments, and that the patient is not lost between the cracks. Certain functions are best accomplished by nurses. So I agree with Dr Petrelli. In select scenarios, nurses real-

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Now we have five coordinators/navigators, two in the thoracic program because of the high volume of lung and esophageal cancer patients. We have one who solely handles breast cancer and one who handles gastrointestinal/ genitourinary/gynecologic cancers. Because she has gotten so busy in the gastrointestinal program, we will probably recruit another full-time coordinator to handle gastrointestinal cancers, leaving our current coordinator free to handle genitourinary and gynecologic cancers. We also recruited a navigator whose focus is survivorship. Survivorship is an area where community cancer centers and academic practice centers historically have not done a good job taking care of cancer patients. We need to take care of the whole patient after he or she has completed the last treatment and maintain follow-up, as well as overall health and other issues such as mental health.

Are there various levels or different practice models for multidisciplinary care? MK: The three of us are involved in the National Cancer Institute’s Community Cancer Center Program (NCCCP), a 3-year pilot program to test the concept of a national network of community cancer centers to expand cancer research and deliver the latest, most advanced cancer care to a greater number of Americans in the communities in which they live. The NCCCP developed a multidisciplinary care matrix tool that shows the spectrum of multidisciplinary care. At one end of the spectrum, the least common denominator is for all the physicians, wherever they may practice, to come together and discuss the patient as a team, preferably before any treatment, but at least at some point. The other end of the spectrum is

where all the physicians are in the same place, see the patient at the same time, and then discuss the patient at one conference. I do not want to say that a single-visit model is better than the model Dr Salner discussed, but rather if it is feasible some data support that the more toward a single-visit model you go, the greater the impact on the patient’s overall cancer care. Our goal in NCCCP is sharing best practices among ourselves and implementing changes in real time. NP: The multidisciplinary clinics at Christiana Care have the three major disciplines, or at least part of that team, see the patient together and discuss what would be the next step. But I agree that it does not have to be done that way. For us, it works better because our medical oncologists’ and radiation oncologists’ offices are in one building. Also important is that we have a separate space for our multidisciplinary clinic, which requires resources as well. AS: I would agree with the notion that being able to see a patient all at once allows a dynamic discussion to occur face-to-face, and we all know that faceto-face discussions sometimes are better than discussions by phone and e-mail. Every patient’s cancer situation is different. Even though a patient is assigned a particular stage to his or her cancer and we can use the protocols and guidelines to deliver a treatment recommendation that is evidenced-based, each patient requires some level of individualized care, tailored specifically to his or her situation, which might involve not only the tumor status but also other medical history or comorbidities, such as heart disease or lung disease. It also might involve the patient’s social situation, whether he or she lives alone or has other social situations which would dictate a portion of the care. These are other reasons why getting to know the patient as a team and collaborating on the care ahead of time is so important. NP: Cancer today is a chronic disease. In the past, perhaps a patient’s hypertension or adult-onset diabetes was not a major issue, but now because cancer is a chronic disease, treating the other chronic diseases becomes extremely important, because patients are going to live with both. So the primary care physician also needs to be involved in the care of the cancer patient.

What are the advantages for the patient as well as for the overall program of having a multidisciplinary approach at whatever level of the spectrum? MK: Communication between members of the team, and communication between the team members and patient is the chief advantage. In addition, patients feel a sense of understanding and consensus because of the team approach. They know that the team is speaking with one voice. If you can add another aspect, which is possible for some teams, July/August 2009

great minds together. MK: Let’s take that a step further. I am going to challenge both of you: You have to convince doctors in private practice or community cancer centers who are not doing multidisciplinary care that multidisciplinary care is important or that they should be doing it. How do you actually prove that to them? NP: When we started the genitourinary multidisciplinary clinic, I was told that it was never going to work because

Team involvement gives patients a sense of confidence that their holistic needs are being addressed. aspect of treatment or views treatment from one level of expertise. Having a team involved helps to give them a sense of comfort and confidence that a group of experts have gotten together, have thought about all the possible scenarios and alternative treatments, and have come up with a recommendation based on the evidence in terms of guidelines, protocols, or clinical research. MK: Dr Petrelli, what other improvements might patients experience by having a multidisciplinary approach versus an approach where patients see multiple specialists at different times and different places, according to the outcome measures compiled at Christiana Care? NP: The patient’s treatment plan is done in a shorter period of time. Part of that reduction is the time between the diagnosis and radiologic imaging, whether it is a positron-emission tomography/computed tomography (CT) scan, a CT scan alone, or a bone scan. We also have shown that multidisciplinary care reduces the average length of hospital stay, which is very important, especially in today’s economic climate. This approach meets the emotional, social, and spiritual needs of patients and their families. Most patients will bring a family member with them to the multidisciplinary clinic, which we encourage because it can be overwhelming when a patient gets so much information at one time. MK: I will just add, the term “patient satisfaction” is often used in surveys, and those surveys have shown improvements in patient satisfaction with multidisciplinary clinics. AS: In terms of patient satisfaction, one of the methodologies at Hartford Hospital for making sure the multiple modalities communicate is a series of multidisciplinary tumor boards. All the tumor boards meet weekly—gastrointestinal, pulmonary, breast, thoracic, pediatric, and lymphoma. At those tumor boards, discussion occurs not only among the care team (those who take care of the patient), but also among a much larger number (50 or 70) of people, many of whom are experts in a specific area. We discuss the patient’s situation and develop a consensus based on that discussion. Patients greatly appreciate that there has been prospective discussion of their case among experts and that the ultimate decision or recommendation to the patients and their families is a result of putting a lot of July/August 2009

you have to be able to get a urologic surgeon to talk to a radiation oncologist about a patient who has prostate cancer and have them agree that the patient has to either get radiation or surgery. In actuality, it works great, because when they are talking about a specific patient, they will decide what is best for that patient. I think it comes down to what we have been talking about. Cancer care is complex, and two or three highquality providers are better than one. MK: Ultimately, the reason it works is because when other providers hear that your team is doing what is best for patients, they want to refer more patients to you. AS: I would add two things. One is the synergies in the care we deliver. We frequently use radiation and chemotherapy together before and after surgery to get the best of all three modalities. Synergy can be gained by having the caregivers get together before treatment is given. You get a one plus one equals four by having the right people in the room, because the quality of the discussion and the impact on patient care can be much better. The other is that providers love to come to the multidisciplinary conferences, because it is a venue in which they can discuss their challenging and difficult cases, talk to their colleagues and develop a game plan for a situation. In our experience, this solved the problem of how we were going to get already busy people to find the time to attend the multidisciplinary conferences and tumor boards. We have found huge satisfaction with this approach among both patients and physicians. Physicians feel their time is well spent in terms of the collaboration they have with their colleagues to develop individualized care recommendations. MK: We tell all new physicians joining our multidisciplinary conferences to leave their egos at the door, as our only focus is what is best for each patient. After a session or two, they see the transparent, patient-first approach and are not threatened. They value the prospective approach and start thinking of it as routine.

Have there been any studies published on outcomes of the multidisciplinary care approach? AS: There are very limited published data on the benefit of multidisciplinary care. This is interesting, because we have evolved into this approach after

recognizing that patients benefit from multiple modalities in the treatment of their breast cancer. We have learned over time that overall treatment outcomes improve if multiple modalities of treatment are administered. And, when you have multiple modalities of treatment given, all the providers need to talk with one another and work together in a prospective fashion, because in some scenarios treatment before surgery is better and in others treatment after surgery is better. You need the providers in the room together to help make those decisions for each patient. We have data that care is better and outcomes are better when multiple modalities are used in selected situations, but we have very little evidence on whether multidisciplinary care as an entity is better for patients. That is one of the things the NCCCP hopes to accomplish—to develop pilot data on how we can study this approach to demonstrate if indeed it is better. We believe it is, at least from our experiences, but we also are driven to try and prove that point scientifically.

Is there any need to do so to ensure reimbursement for care for different providers? AS: We have to demonstrate to the payers that multidisciplinary care is not only better but, because it is provided in

ciplinary clinic, only one provider charged at level 5, the other two charged at a lower level. Doctors need to be reimbursed because the one thing we have not mentioned is that a doctor can see a lot more patients working alone in a private office than in the multidisciplinary clinic where that doctor has to discuss each patient with two colleagues, which is time-consuming. MK: Delaware was the first state to pass a statewide act that guarantees cancer care for 2 years in patients who are uninsured. In addition, throughout the state, patients are referred to specific points of contact for their cancer care as part of the statewide screening program for colorectal cancer. We are trying to copy this model in the state of Maryland. At present, two systems have adopted the Delaware payment model. These payers chose to reimburse as Dr Petrelli described. The main reason is, if you look at lung cancer, colon cancer, and breast cancer (right now I’ll leave prostate out), more than 90% of patients will require at least two modalities of care if not all three modalities. UnitedHealthcare conducted an experiment, in which it paid X amount of money per patient to receive the best possible care. The only condition was that the team adhere to specific out-

We clarified for the third-party carriers that this is cost-effective for them. a coordinated fashion, may actually be more cost-effective. In Connecticut, we do not get reimbursement if multiple specialists see a patient on the same day. We only get reimbursed for one specialist by certain payers. In other states, clinicians have been able to negotiate payment so that each specialist can get recognized for the service provided, even if it is on the same day as other clinicians. We have to keep working on that issue in the states where it is not permitted. NP: In Delaware, we have a unique situation. We met with the medical directors and the third-party carriers before starting the multidisciplinary clinics at Christiana Care. We convinced the payers to give global precertification rather than precertifying each of the disciplines, because that would have been time-consuming and impractical. They agreed with that. The way we set it up, using the esophageal clinic as an example, if a patient with esophageal cancer comes into the multidisciplinary clinic and the three major disciplines see that patient and the team decides that surgery up front is going to be done on that patient, then the surgeon charges the higher level and the medical oncologist and the radiation oncologist, who will be giving chemotherapy and radiation postoperatively, charge as consultants. We clarified for the third-party carriers that this is cost-effective for them, because if that patient had seen those three disciplines in their offices for three separate appointments, all three providers would have charged at level 5. By seeing the patient in the multidis-

come measures of the best possible care guidelines. United Healthcare did not involve itself in how the money was spent or how much was spent. If a clinic could provide care more cost-effectively, it could keep the difference. The other group that did this is the University of Michigan (unpublished data). The University of Michigan has a self-insurance program. It specified the guidelines to use and the outcomes measures. If a multidisciplinary clinic adheres to these, then whatever the costs, the insurance program will pay, but only once, up front, and the clinic needs to determine how to make the care cost-effective. I have no doubt that when the other payers see the results, they will want to adopt that payment model. With multimodality care becoming more recognized as best practice for advanced diseases like cancer, multidisciplinary clinics are opening up across the country. As Drs Krasna, Petrelli, and Salner explained, the principles stress the importance of continuity of care, coordination, and the involvement of the patient and caregivers, where appropriate, in the treatment and care planning process. In an upcoming issue, they will expand their discussion to focus on the NCCCP and its goals of increasing enrollment in clinical trials, reducing healthcare disparities, collecting and storing research samples, and linking computer systems nationally for research and results sharing. —Dawn Lagrosa

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PRACTICE MANAGEMENT

of having a physical place where patients always come for their care, then patients have an identified team and an identified place to go with any problems. Family members, likewise, see the team, often as embodied by the nurse navigator, as the focus for any issues. AS: I would agree. Team involvement gives patients a sense of confidence that their holistic needs are being addressed as opposed to one specialist who may be particularly focused on one

CASE STUDY

Multidisciplinary Tumor Board Case Study Treating a Patient with Unfavorable-risk Prostate Cancer Marc H. Siegelbaum, MD; Jason R. Citron, MD; James W. Eagan Jr, MD; Rima J. Couzi, MD The Cancer Institute at St. Joseph Medical Center offers a multidisciplinary clinic for its patients with genitourinary cancers. The following case is that of a 60-year-old man with a prostate-specific antigen value of 1.45 ng/dL, a clinical stage of T2bN0M0 Stage II, a biopsy positive for adenocarcinoma, and a Gleason score of 4 + 4 = 8 in one of his prostate cores. Despite his unfavorable-risk prostate cancer, this patient had a life expectancy of 20 years. The following commentaries reflect on the evidence and the thought processes behind this patient’s treatment from the views of the urologist, the pathologist, the medical oncologist, and the radiation oncologist.

CASE PRESENTATION Chief complaint: Symptoms of obstructive voiding.

nodule, but did not recommend further testing.

History of present illness: The patient was a 60-year-old man who had self-referred for a prostate checkup. He complained of obstructive symptoms, including weak stream, nocturia four times per night, urinary urgency, and frequency. According to the patient, a urologist he visited previously told him that he had a prostate

Medical history: Osteopenia.

Social history: Patient was divorced with no children. He quit smoking in 1977 and was an audiologist by trade. He does not get much exercise.

Surgical history: Tonsillectomy, bilateral inguinal hernia repair.

Medications: Alendronate, 70 mg/week; aspirin 81 mg/day.

Family history: Father: died of cryoglobulinemia. Mother: died of chronic obstructive pulmonary disease. Sibling: died of glioblastoma.

Allergies: No known allergies.

Urologist commentary The patient presented to the urologist for a prostate checkup. He was experiencing obstructive symptoms, including weak stream, nocturia four times per night, urinary urgency, and freMarc H. Siegelbaum, quency. He had preMD viously seen another urologist who, according to the patient, identified a prostate nodule but did not recommend any additional testing. On physical examination, the prostate felt firm, and it was recommended that the patient undergo a transrectal ultrasound and biopsy. Also recommended was a cystoscopy to evaluate his obstructive voiding symptoms. Six weeks later, he underwent a transDr Siegelbaum is Medical Director, Urologic Oncology Center, The Cancer Institute at St. Joseph Medical Center, Towson, Maryland. Dr Citron is Medical Director, Radiation Oncology Center, The Cancer Institute at St. Joseph Medical Center, Towson, Maryland. Dr Eagan is a pathologist at The Cancer Institute at St. Joseph Medical Center, Towson, Maryland. Dr Couzi is a medical oncologist at The Cancer Institute at St. Joseph Medical Center, Towson, Maryland. 14

rectal ultrasound and guided biopsy of the prostate as well as a cystoscopy. With ultrasound guidance, 12 biopsies were performed in the sextent configuration. The cystoscopic examination showed significant trilobar obstruction. Findings on uroflow examination were consistent with an obstructive voiding pattern. The biopsy results demonstrated a prostate size of 48.6 grams. Of the 12 core samples, one showed a Gleason score of 3 + 3 = 6; three showed a Gleason score of 3 + 4 = 7; one showed a Gleason score of 4 + 4 = 8; and seven of 12 showed a benign prostatic hypertrophy pattern only.

Pathologist commentary In patients with suspicious clinical or laboratory findings, core needle biopsy of the prostate has proved to be an accurate method for the diagnosis James W. Eagan Jr, of malignancy. AlMD though initially limited to a few random biopsies of one or both lobes, the advent of the “sextant biopsy” technique, wherein 12 or more biopsies are systematically taken from all areas of the gland, has led to increased diagnostic accuracy. In many cases, multiple biopsy cores will be involved by tumor, and a diagnosis of malignancy will be relatively straightforward. In some cases, however, few foci of tumor may be present, and these may be easily overlooked. Con-

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Physical examination: Firm prostate. Laboratory values: versely, a number of benign processes may mimic cancer, resulting in false-positive diagnoses for the unwary. Fortunately, a number of ancillary techniques, immunoperoxidase stains for specific markers in particular, have contributed to the pathologist’s ability to define minute tumor foci as well as to exclude “cancer mimics” from consideration. The finding of a minute focus of tumor in only one of multiple cores is of importance because a significant number of such cases will be found to have substantial amounts of tumor in subsequent prostatectomy specimens. Conversely, increasing amounts of tumor involvement in a biopsy set, whether measured by volume of tumor in individual cores or in total number of cores involved, has been correlated with increasingly adverse pathologic findings in subsequent prostatectomy specimens, such as margin involvement, extraprostatic extension, and seminal vesicle involvement.1 After a diagnosis of malignancy has been established, a second powerful predictive tool, the Gleason grading system,2 is used. This five-category system, based on morphologic architectural patterns of the tumor, provides a scale from pattern 1, the most well-differentiated, to pattern 5, the least well-differentiated. Moreover, because many tumors will display more than one pattern, the predictive value of the system was improved by adding the predominant pattern to the second most predominant pattern (eg, “Gleason 3 + 4 = 7”). In cases where only a single pattern is found, the pattern number is doubled

International Prostate Symptom Score: 8 Sexual Health Inventory for Men Score: 20 Prostate-specific antigen value: 1.45 ng/dL Computed tomography: No suspicious lymphadenopathy; enlarged prostate; small right renal cysts. (eg, “Gleason 3 + 3 = 6”). As the Gleason score increases, so does the likelihood of adverse pathologic findings in patients who proceed to prostatectomy, with the expected adverse effects on response to therapy and overall prognosis. In conjunction with the multiple cores involved on the right side, from base through apex, the Gleason 4 + 4 = 8 score in at least one core would suggest that the patient’s disease might pursue a more than usually aggressive course.

Urologist commentary The treatment of prostate cancer is controversial.3,4 This patient was a healthy 60-year-old man with a life expectancy of at least 20 years, who may or may not have had localized disease. By using the Partin tables,5 the patient’s chance of extension was determined to be 20%, and his chance of having lymph node involvement was determined to be 17%. His prostatespecific antigen (PSA) level was quite low, and his computed tomography (CT) scan suggested localized disease. His higher Gleason score in one core, Gleason 8, was worrisome, however.6 Accepted treatment options following the National Comprehensive Cancer Network (NCCN) guidelines included7: (1) radical prostatectomy (robotic or open); and (2) radiation therapy (external-beam radiation therapy [EBRT]/image-guided radiation therapy, brachytherapy). The forms of radiation could be used individually or in combination with or without hormonal downstaging. July/August 2009

patients with unfavorable-risk prostate cancer benefit from both a short course of neoadjuvant hormonal therapy before and during radiation,18 and adjuvant hormonal therapy at the completion of EBRT.19-21 Another issue is whether this patient will benefit from whole pelvic radiation therapy (WPRT). Initial reports from the Radiation Therapy Oncology Group (RTOG) 9413 trial showed a possible benefit with this approach when combined with neoadjuvant hormones.22 However, in addition to the evidence provided by the recently published European Groupe d’Etude des Tumeurs Uro-Génitales (GETUG)01,23 the update of this study has suggested that WPRT may not be of much benefit.24

Urologist commentary The team’s preference (as was the patient’s) was to perform a robotic prostatectomy, which would offer him a potential for cure and improved local control25 (Figure 2). The patient was counseled that if the margins were found to be positive, he might need adjuvant EBRT as well.26 He was also told that surgery would resolve his obstructive voiding symptoms.25 Medical oncologist commentary The median survival of men diagnosed with metastatic or locally advanced prostate cancer is 3.5 and 4.5 years, respectively. More than 50% of patients with highrisk cancer relapse Rima J. Couzi, MD after local therapy. Several trials are addressing new strategies with the hope of improving the prognosis of men diagnosed with prostate cancer. Neoadjuvant chemotherapy has been evaluated in several small phase 2 clinical trials.27,28 Although PSA responses were frequently observed, most studies failed to show pathologic complete responses. Neoadjuvant chemotherapy with docetaxel appears to be safe and feasible. The Cancer and Leukemia Group B (CALGB) is conducting a phase 3 randomized clinical trial, 90203, compar-

Figure 2. Robotic prostatectomy using the daVinci robot. July/August 2009

CASE STUDY

Radiation oncologist commentary Based on his PSA of 1.45 ng/dL, his clinical stage of T2bN0M0 Stage II, and his biopsy positive for adenocarcinoma with one of the cores having a Gleason score of 4 + 4 = 8, this patient Jason R. Citron, MD had unfavorablerisk prostate cancer.8 The standard treatment options for prostate cancer include active surveillance, radical prostatectomy, EBRT, and prostate brachytherapy seed implantation. Because he was a young man with a good life expectancy and an unfavorable cancer, I did not recommend watchful waiting.9 Nor did I recommend brachytherapy alone, because for someone with unfavorable-risk prostate cancer, this treatment has been found to be inferior compared with other options.10 If he had wanted to be treated with radiation, I would have recommended that he either receive definitive EBRT, or EBRT for 5 weeks followed by a prostate brachytherapy seed implant. Expected outcomes with either of these two approaches would be a 53% to 68% chance of long-term biochemical relapse-free survival.11,12 No randomized trials have compared these two approaches, but recent evidence suggests that dose escalation with EBRT results in improved biochemical relapse-free survival compared with lower doses of radiation.13-16 A combination of 5 weeks of EBRT with a brachytherapy implant does result in higher doses of radiation to the prostate compared with EBRT alone. However, no evidence proves that this combination will result in an improved outcome compared with EBRT alone and, in fact, it may result in an increase in toxicity.17 Modern radiation treatment utilizes intensity-modulated radiation therapy (IMRT). IMRT has been shown to be an extremely effective treatment for a patient with any prostate cancer risk classification, with a low incidence of late urinary and rectal toxicity.11 Figure 1 shows an axial CT slice of a typical treatment plan. In addition, evidence has shown that

Figure 1. Axial computed tomography slice of a typical radiation treatment plan. The bladder is contoured in yellow, the prostate in red, and the rectum in blue. Isodose curves are shown conforming well to treat the prostate and to avoid the bladder and rectum. ing neoadjuvant chemohormonal therapy followed by surgery with surgery alone in patients with high-risk localized prostate cancer. Patients are randomized to either 6 months of neoadjuvant androgen deprivation and chemotherapy with docetaxel (eight cycles at 75 mg/m2 every 3 weeks) followed by radical prostatectomy with lymph node dissection, or to radical prostatectomy alone. The primary end point of the study is 3-year biochemical progressionfree survival. The secondary end points include 5-year progression-free survival, prostate cancer–specific survival, and overall survival. Another phase 3 randomized study, the Therapy for High-Risk Localized Adenocarcinoma of the Prostate (DART) trial is being conducted by the National Cancer Institute of Canada. In this study, patients with high-risk disease are randomized to neoadjuvant androgen deprivation and radiotherapy with or without neoadjuvant and concurrent docetaxel. The role of adjuvant chemotherapy after surgery or radiotherapy is also being addressed in several clinical trials. A multi-institutional phase 2 study evaluated adjuvant docetaxel in 77 men with nonmetastatic prostate cancer who were at greater than 50% risk of relapse at 3 years after radical prostatectomy. The median progression-free survival of 15.7 months was longer than the nomogram-predicted rate for this patient population.29 This approach is being evaluated further in phase 3 randomized trials. The US Department of Veterans Affairs cooperative study No. 553 is a phase 3 trial randomizing patients with high-risk features after prostatectomy to observation or to adjuvant docetaxel for 18 weeks. Unfortunately, the TAX 3501 study, a large, randomized adjuvant postoperative trial, was closed early because of poor accrual. Participants were to be randomized to observation alone, leuprorelin acetate for 18 months, or leuprorelin acetate and docetaxel for 6 cycles. The impact of early use of chemotherapy alone or with hormonal or tar-

geted therapy on improvement in survival in high-risk patients remains to be established. Ongoing phase 3 trials will ultimately help define the role of chemotherapy in this setting. Because these results were not yet available, the team followed NCCN guidelines in the management of this patient. If he had been found to have positive margins at surgery, the options would have been either watchful waiting or proceeding with radiation therapy because the role of androgen-deprivation therapy with radiation therapy after surgery has not been established. Therefore, we encouraged him to consider participating in an adjuvant clinical trial.

Summary There is no one “right answer” when it comes to prostate cancer treatment. Using the multidisciplinary approach, the team of treating physicians and the patient quickly arrived at an individualized treatment plan. This approach allowed us to look at treatment from all angles and choose the most appropriate choice for this patient in a shorter period of time. Ultimately, this time-savings is most beneficial to the patient. In this case, the patient opted for a daVinci (robotic) prostatectomy. We felt that this potentially would be curative, and if not, it would afford him better local control. If surgical margins had been found to be positive, he would have needed adjuvant EBRT, as early postoperative treatment in the face of positive margins seems more beneficial in terms of recurrence (PSA failure) than later treatment. References 1. Epstein JI, Yang XJ. Prostate Biopsy Interpretation. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002:142-153. 2. Gleason DF, Mellinger GT; for the Veterans Administration Cooperative Urological Research Group. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol. 1974;111:58-64. 3. Johansson JE, Andren O, Andersson SO, et al. Natural history of early, localized prostate can-

Continued on page 18

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Case Study Continued from page 15

CASE STUDY

cer. JAMA. 2004;291:2713-2719. 4. Ohori M, Goad J, Wheeler J, et al. Can radical prostatectomy alter the progression of poorly differentiated prostate cancer? J Urol. 1994;152 (5 pt 2):1843-1849. 5. Partin AW, Mangold LA, Lamm DM, et al. Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology. 2001;58:843-848. 6. Lau WK, Bergstralh EJ, Bluet ML, et al. Radical prostatectomy for pathological Gleason 8 or greater prostate cancer: influence of concomitant pathological variables. J Urol. 2002;167: 117-122.

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7. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Prostate Cancer. V.2.2009. www.nccn.org/pro fessionals/physician_gls/PDF/prostate.pdf. Accessed July 7, 2009. 8. Chism DB, Hanlon AL, Horwitz EM, et al. A comparison of the single and double factor high-risk models for risk assignment of prostate cancer treated with 3D conformal radiotherapy. Int J Radiat Oncol Biol Phys. 2004;59:380-385. 9. Klotz L. Active surveillance for favorable risk prostate cancer: what are the results, and how safe is it? Semin Radiat Oncol. 2008;18:2-6. 10. D’Amico AV, Whittington R, Malkowicz SB,

Table 1: Frequencya of Important Treatment Emergent Adverse Events in the Randomized Study on an Every-3-Weeks Schedule (Continued) Percent of Patients ABRAXANE Paclitaxel Injection 260/30minb 175/3hc,d (n=229) (n=225)

Brief Summary of Full Prescribing Information. WARNING ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available. ABRAXANE therapy should not be administered to patients with metastatic breast cancer who have baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE. Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS. INDICATION: ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. CONTRAINDICATIONS: ABRAXANE should not be used in patients who have baseline neutrophil counts of <1,500 cells/mm3. WARNINGS: Bone marrow suppression (primarily neutropenia) is dose dependent and a dose limiting toxicity. ABRAXANE should not be administered to patients with baseline neutrophil counts of <1,500 cells/mm3. Frequent monitoring of blood counts should be instituted during ABRAXANE treatment. Patients should not be retreated with subsequent cycles of ABRAXANE until neutrophils recover to a level >1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. The use of ABRAXANE has not been studied in patients with hepatic or renal dysfunction. In the randomized controlled trial, patients were excluded for baseline serum bilirubin >1.5 mg/dL or baseline serum creatinine >2 mg/dL. Pregnancy – Teratogenic Effects: Pregnancy Category D ABRAXANE can cause fetal harm when administered to a pregnant woman. Administration of paclitaxel protein-bound particles to rats on gestation days 7 to 17 at doses of 6 mg/m2 (approximately 2% of the daily maximum recommended human dose on a mg/m2 basis) caused embryo- and fetotoxicity, as indicated by intrauterine mortality, increased resorptions (up to 5-fold), reduced numbers of litters and live fetuses, reduction in fetal body weight and increase in fetal anomalies. Fetal anomalies included soft tissue and skeletal malformations, such as eye bulge, folded retina, microphthalmia, and dilation of brain ventricles. A lower incidence of soft tissue and skeletal malformations were also exhibited at 3 mg/m2 (approximately 1% of the daily maximum recommended human dose on a mg/m2 basis). There are no adequate and well-controlled studies in pregnant women using ABRAXANE. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with ABRAXANE. Use in Males Men should be advised to not father a child while receiving treatment with ABRAXANE (see PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility for discussion of effects of ABRAXANE exposure on male fertility and embryonic viability). Albumin (Human) ABRAXANE contains albumin (human), a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob Disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin. PRECAUTIONS: Drug Interactions No drug interaction studies have been conducted with ABRAXANE. The metabolism of paclitaxel is catalyzed by CYP2C8 and CYP3A4. In the absence of formal clinical drug interaction studies, caution should be exercised when administering ABRAXANE (paclitaxel protein-bound particles for injectable suspension) concomitantly with known substrates or inhibitors of CYP2C8 and CYP3A4 (see CLINICAL PHARMACOLOGY). Potential interactions between paclitaxel, a substrate of CYP3A4, and protease inhibitors (such as ritonavir, saquinavir, indinavir, and nelfinavir), which are substrates and/or inhibitors of CYP3A4, have not been evaluated in clinical trials. Hematology ABRAXANE therapy should not be administered to patients with baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of myelotoxicity, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE. Patients should not be retreated with subsequent cycles of ABRAXANE until neutrophils recover to a level >1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. In the case of severe neutropenia (<500 cells/mm3 for seven days or more) during a course of ABRAXANE therapy, a dose reduction for subsequent courses of therapy is recommended (see DOSAGE AND ADMINISTRATION). Nervous System Sensory neuropathy occurs frequently with ABRAXANE. The occurrence of grade 1 or 2 sensory neuropathy does not generally require dose modification. If grade 3 sensory neuropathy develops, treatment should be withheld until resolution to grade 1 or 2 followed by a dose reduction for all subsequent courses of ABRAXANE (see DOSAGE AND ADMINISTRATION). Injection Site Reaction Injection site reactions occur infrequently with ABRAXANE and were mild in the randomized clinical trial. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic potential of ABRAXANE has not been studied. Paclitaxel has been shown to be clastogenic in vitro (chromosome aberrations in human lymphocytes) and in vivo (micronucleus test in mice). ABRAXANE was not mutagenic in the Ames test or the CHO/HGPRT gene mutation assay. Administration of paclitaxel protein-bound particles to male rats at 42 mg/m2 on a weekly basis (approximately 16% of the daily maximum recommended human exposure on a mg/m2 basis) for 11 weeks prior to mating with untreated female rats resulted in significantly reduced fertility accompanied by decreased pregnancy rates and increased loss of embryos in mated females. A low incidence of skeletal and soft tissue fetal anomalies was also observed at doses of 3 and 12 mg/m2/week in this study (approximately 1% to 5% of the daily maximum recommended human exposure on a mg/m2 basis). Testicular atrophy/degeneration has also been observed in single-dose toxicology studies in rodents administered paclitaxel protein-bound particles at 54 mg/m2 and dogs administered 175 mg/m2 (see WARNINGS). Pregnancy – Teratogenic Effects: Pregnancy Category D (See WARNINGS section). Nursing Mothers It is not known whether paclitaxel is excreted in human milk. Following intravenous administration of carbon-14 labeled paclitaxel to rats on days 9 to 10 postpartum, concentrations of radioactivity in milk were higher than in plasma and declined in parallel with the plasma concentrations. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, it is recommended that nursing be discontinued when receiving ABRAXANE therapy. Pediatric Use The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated. Geriatric Use Of the 229 patients in the randomized study who received ABRAXANE, 11% were at least 65 years of age and <2% were 75 years or older. No toxicities occurred notably more frequently among elderly patients who received ABRAXANE. ADVERSE REACTIONS: The following table shows the frequency of important adverse events in the randomized comparative trial for the patients who received either single-agent ABRAXANE or paclitaxel injection for the treatment of metastatic breast cancer. Table 1: Frequencya of Important Treatment Emergent Adverse Events in the Randomized Study on an Every-3-Weeks Schedule Percent of Patients ABRAXANE Paclitaxel Injection 260/30minb 175/3hc,d (n=229) (n=225) Bone Marrow Neutropenia < 2.0 x 109/L < 0.5 x 109/L Thrombocytopenia < 100 x 109/L < 50 x 109/L Anemia < 11 g/dL < 8 g/dL Infections Febrile Neutropenia Bleeding

80 9

82 22

2 <1

3 <1

33 1 24 2 2

25 <1 20 1 2 (Continued)

Hypersensitivity Reactione All 4 12 0 2 Severef Cardiovascular Vital Sign Changesg Bradycardia <1 <1 Hypotension 5 5 3 4 Severe Cardiovascular Eventsf Abnormal ECG All patients 60 52 Patients with Normal Baseline 35 30 Respiratory Cough 7 6 Dyspnea 12 9 Sensory Neuropathy Any Symptoms 71 56 Severe Symptomsf 10 2 Myalgia/Arthralgia Any Symptoms 44 49 f 8 4 Severe Symptoms Asthenia Any Symptoms 47 39 f 8 3 Severe Symptoms Fluid Retention/Edema Any Symptoms 10 8 f Severe Symptoms 0 <1 Gastrointestinal Nausea Any symptoms 30 22 Severe symptomsf 3 <1 Vomiting Any symptoms 18 10 4 1 Severe Symptomsf Diarrhea Any Symptoms 27 15 Severe Symptomsf <1 1 Mucositis Any Symptoms 7 6 <1 0 Severe Symptomsf Alopecia 90 94 Hepatic (Patients with Normal Baseline) Bilirubin Elevations 7 7 Alkaline Phosphatase Elevations 36 31 AST (SGOT) Elevations 39 32 Injection Site Reaction <1 1 a Based on worst grade b ABRAXANE dose in mg/m2/duration in minutes c paclitaxel injection dose in mg/m2/duration in hours d paclitaxel injection pts received premedication e Includes treatment-related events related to hypersensitivity (e.g., ﬂushing, dyspnea, chest pain, hypotension) that began on a day of dosing. f Severe events are deﬁned as at least grade 3 toxicity g During study drug dosing. Myelosuppression and sensory neuropathy were dose related. Adverse Event Experiences by Body System Unless otherwise noted, the following discussion refers to the primary safety database of 229 patients with metastatic breast cancer treated with single-agent ABRAXANE in the randomized controlled trial. The frequency and severity of important adverse events for the study are presented above in tabular form. In some instances, rare severe events observed with paclitaxel injection may be expected to occur with ABRAXANE. Hematologic Neutropenia, the most important hematologic toxicity, was dose dependent and reversible. Among patients with metastatic breast cancer in the randomized trial, neutrophil counts declined below 500 cells/mm3 (Grade 4) in 9% of the patients treated with a dose of 260 mg/m 2 compared to 22% in patients receiving paclitaxel injection at a dose of 175 mg/m2. In the randomized metastatic breast cancer study, infectious episodes were reported in 24% of the patients treated with a dose of 260 mg/m2 given as a 30-minute infusion. Oral candidiasis, respiratory tract infections and pneumonia were the most frequently reported infectious complications. Febrile neutropenia was reported in 2% of patients in the ABRAXANE arm and 1% of patients in the paclitaxel injection arm. Thrombocytopenia was uncommon. In the randomized metastatic breast cancer study, bleeding episodes were reported in 2% of the patients in each treatment arm. Anemia (Hb <11 g/dL) was observed in 33% of patients treated with ABRAXANE in the randomized trial and was severe (Hb <8 g/dL) in 1% of the cases. Among all patients with normal baseline hemoglobin, 31% became anemic on study and 1% had severe anemia. Hypersensitivity Reactions (HSRs) In the randomized controlled metastatic breast cancer study, Grade 1 or 2 HSRs occurred on the day of ABRAXANE administration and consisted of dyspnea (1%) and flushing, hypotension, chest pain, and arrhythmia (all <1%). The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied. During postmarketing surveillance, rare occurrences of severe hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied. Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug. Cardiovascular Hypotension, during the 30-minute infusion, occurred in 5% of patients in the randomized metastatic breast cancer trial. Bradycardia, during the 30-minute infusion, occurred in <1% of patients. These vital sign changes most often caused no symptoms and required neither specific therapy nor treatment discontinuation. Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3% of patients in the randomized trial. These events included chest pain, cardiac arrest, supraventricular tachycardia, edema,thrombosis, pulmonary thromboembolism, pulmonary emboli, and hypertension. Cases of cerebrovascular attacks (strokes) and transient ischemic attacks have been reported rarely. Electrocardiogram (ECG) abnormalities were common among patients at baseline. ECG abnormalities on study did not usually result in symptoms, were not dose-limiting, and required no intervention. ECG abnormalities were noted in 60% of patients in the metastatic breast cancer randomized trial. Among patients with a normal ECG prior to study entry, 35% of all patients developed an abnormal tracing while on study. The most frequently reported ECG modifications were non-specific repolarization abnormalities, sinus bradycardia, and sinus tachycardia. Respiratory Reports of dyspnea (12%) and cough (6%) were reported after treatment with ABRAXANE in the randomized trial. Rare reports (<1%) of pneumothorax were reported after treatment with ABRAXANE. Rare reports of interstitial pneumonia, lung fibrosis, and pulmonary embolism have been received as part of the continuing surveillance of paclitaxel injection safety and may occur following ABRAXANE treatment. Rare reports of radiation pneumonitis have been received in paclitaxel injection patients receiving concurrent radiotherapy. There is no experience with the use of ABRAXANE with concurrent radiotherapy. Neurologic The frequency and severity of neurologic manifestations were influenced by prior and/or concomitant therapy with neurotoxic agents. In general, the frequency and severity of neurologic manifestations were dose-dependent in patients receiving single-agent ABRAXANE. In the randomized trial, sensory neuropathy was observed in 71% of patients (10% severe) in the ABRAXANE arm and in 56% of patients (2% severe) in the paclitaxel injection arm. The frequency of sensory neuropathy increased with cumulative dose. Sensory neuropathy was the cause of ABRAXANE discontinuation in 7/229 (3%) patients in the randomized trial. In the randomized comparative study, 24 patients (10%) treated with ABRAXANE developed Grade 3 peripheral neuropathy; of these patients, 14 had documented improvement after a median of 22 days; 10 patients resumed treatment at a reduced dose of ABRAXANE and 2 discontinued due to peripheral neuropathy. Of the 10 patients without documented improvement, 4 discontinued the study due to peripheral neuropathy. No incidences of grade 4 sensory neuropathies were reported in the clinical trial. Only one incident of motor neuropathy (grade 2) was observed in either arm of the controlled trial. Reports of autonomic neuropathy resulting in paralytic ileus have been received as part of the continuing surveillance of paclitaxel injection safety. Cranial nerve palsies have been reported during postmarketing surveillance of ABRAXANE. Because these events have been reported during clinical practice, true estimates of frequency cannot be made and a causal relationship to the events has not been established. Ocular/visual disturbances occurred in 13% of all patients (n=366) treated with ABRAXANE in single arm and randomized trials and 1% were severe. The severe cases (keratitis and blurred vision) were reported in patients in a single arm study who received higher doses than those recommended (300 or 375 mg/m2). These effects generally have been reversible. However, rare reports in the literature of abnormal visual evoked potentials in patients treated with paclitaxel injection have suggested persistent optic nerve damage. Arthralgia/Myalgia Forty-four percent of patients treated in the randomized trial experienced arthralgia/myalgia; 8% experienced severe symptoms. The symptoms were usually transient, occurred two or three days after ABRAXANE administration, and resolved within a few days. Hepatic Among patients with normal baseline liver function treated with ABRAXANE in the randomized trial, 7%, 36%, and 39% had elevations in bilirubin, alkaline phosphatase, and AST (SGOT), respectively. Grade 3 or 4 elevations in GGT were reported for 14% of patients treated with ABRAXANE and 10% of patients treated with paclitaxel injection in the randomized trial.

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et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280: 969-974. 11. Zelefsky MJ, Chan H, Hunt M, et al. Longterm outcome of high dose intensity modulated radiation therapy for patients with clinically localized prostate cancer. J Urol. 2006;176(4 pt 1):1415-1419. 12. Sylvester JE, Grimm PD, Blasko JC, et al. 15year biochemical relapse free survival in clinical Stage T1-T3 prostate cancer following combined external beam radiotherapy and brachy-

Rare reports of hepatic necrosis and hepatic encephalopathy leading to death have been received as part of the continuing surveillance of paclitaxel injection safety and may occur following ABRAXANE treatment. Renal Overall 11% of patients experienced creatinine elevation, 1% severe. No discontinuations, dose reductions, or dose delays were caused by renal toxicities. Gastrointestinal (GI) Nausea/vomiting, diarrhea, and mucositis were reported by 33%, 27%, and 7% of ABRAXANE treated patients in the randomized trial. Rare reports of intestinal obstruction, intestinal perforation, pancreatitis, and ischemic colitis have been received as part of the continuing surveillance of paclitaxel injection safety and may occur following ABRAXANE treatment. Rare reports of neutropenic enterocolitis (typhlitis), despite the coadministration of G-CSF, were observed in patients treated with paclitaxel injection alone and in combination with other chemotherapeutic agents. Injection Site Reaction Injection site reactions have occurred infrequently with ABRAXANE and were mild in the randomized clinical trial. Recurrence of skin reactions at a site of previous extravasation following administration of paclitaxel injection at a different site, i.e., “recall”, has been reported rarely. Rare reports of more severe events such as phlebitis, cellulitis, induration, skin exfoliation, necrosis, and fibrosis have been received as part of the continuing surveillance of paclitaxel injection safety. In some cases the onset of the injection site reaction in paclitaxel injection patients either occurred during a prolonged infusion or was delayed by a week to ten days. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Asthenia Asthenia was reported in 47% of patients (8% severe) treated with ABRAXANE in the randomized trial. Asthenia included reports of asthenia, fatigue, weakness, lethargy and malaise. Other Clinical Events Rare cases of cardiac ischemia/infarction and thrombosis/embolism possibly related to ABRAXANE treatment have been reported. Alopecia was observed in almost all of the patients. Nail changes (changes in pigmentation or discoloration of nail bed) were uncommon. Edema (fluid retention) was infrequent (10% of randomized trial patients); no patients had severe edema. The following rare adverse events have been reported as part of the continuing surveillance of paclitaxel injection safety and may occur following ABRAXANE treatment: skin abnormalities related to radiation recall as well as reports of Stevens-Johnson syndrome, toxic epidermal necrolysis, conjunctivitis, and increased lacrimation. As part of the continuing surveillance of ABRAXANE, skin reactions including generalized or maculo-papular rash, erythema, and pruritis have been observed. Additionally, there have been case reports of photosensitivity reactions, radiation recall phenomenon, and in some patients previously exposed to capecitabine, reports of palmar-plantar erythrodysaesthesiae. Because these events have been reported during clinical practice, true estimates of frequency cannot be made and a causal relationship to the events has not been established. Accidental Exposure No reports of accidental exposure to ABRAXANE have been received. However, upon inhalation of paclitaxel, dyspnea, chest pain, burning eyes, sore throat, and nausea have been reported. Following topical exposure, events have included tingling, burning, and redness. OVERDOSAGE: There is no known antidote for ABRAXANE overdosage. The primary anticipated complications of overdosage would consist of bone marrow suppression, sensory neurotoxicity, and mucositis. DOSAGE AND ADMINISTRATION: After failure of combination chemotherapy for metastatic breast cancer or relapse within 6 months of adjuvant chemotherapy, the recommended regimen for ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) is 260 mg/m2 administered intravenously over 30 minutes every 3 weeks. Hepatic Impairment The appropriate dose of ABRAXANE for patients with bilirubin greater than 1.5 mg/dL is not known. Dose Reduction Patients who experience severe neutropenia (neutrophil <500 cells/mm3 for a week or longer) or severe sensory neuropathy during ABRAXANE therapy should have dosage reduced to 220 mg/m2 for subsequent courses of ABRAXANE. For recurrence of severe neutropenia or severe sensory neuropathy, additional dose reduction should be made to 180 mg/m2. For grade 3 sensory neuropathy hold treatment until resolution to grade 1 or 2, followed by a dose reduction for all subsequent courses of ABRAXANE. Preparation and Administration Precautions ABRAXANE is a cytotoxic anticancer drug and, as with other potentially toxic paclitaxel compounds, caution should be exercised in handling ABRAXANE. The use of gloves is recommended. If ABRAXANE (lyophilized cake or reconstituted suspension) contacts the skin, wash the skin immediately and thoroughly with soap and water. Following topical exposure to paclitaxel, events may include tingling, burning and redness. If ABRAXANE contacts mucous membranes, the membranes should be flushed thoroughly with water. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Limiting the infusion of ABRAXANE to 30 minutes, as directed, reduces the likelihood of infusion-related reactions (see PRECAUTIONS: Injection Site Reaction). No premedication to prevent hypersensitivity reactions is required prior to administration of ABRAXANE. Preparation for Intravenous Administration ABRAXANE is supplied as a sterile lyophilized powder for reconstitution before use. AVOID ERRORS, READ ENTIRE PREPARATION INSTRUCTIONS PRIOR TO RECONSTITUTION. Each mL of the reconstituted formulation will contain 5 mg/mL paclitaxel. 1. Aseptically, reconstitute each vial by injecting 20 mL of 0.9% Sodium Chloride Injection, USP. 2. Slowly inject the 20 mL of 0.9% Sodium Chloride Injection, USP, over minimum of 1 minute, using the sterile syringe to direct the solution flow onto the INSIDE WALL OF THE VIAL. 3. DO NOT INJECT the 0.9% Sodium Chloride Injection, USP, directly onto the lyophilized cake as this will result in foaming. 4. Once the injection is complete, allow the vial to sit for a minimum of 5 minutes to ensure proper wetting of the lyophilized cake/powder. 5. Gently swirl and/or invert the vial slowly for at least 2 minutes until complete dissolution of any cake/powder occurs. Avoid generation of foam. 6. If foaming or clumping occurs, stand solution for at least 15 minutes until foam subsides. Calculate the exact total dosing volume of 5 mg/mL suspension required for the patient: Dosing volume (mL) = Total dose (mg)/5 (mg/mL). The reconstituted suspension should be milky and homogenous without visible particulates. If particulates or settling are visible, the vial should be gently inverted again to ensure complete resuspension prior to use. Discard the reconstituted suspension if precipitates are observed. Discard any unused portion. Inject the appropriate amount of reconstituted ABRAXANE into an empty, sterile IV bag (plasticized polyvinyl chloride (PVC) containers, PVC or non PVC type IV bag). The use of specialized DEHP-free solution containers or administration sets is not necessary to prepare or administer ABRAXANE infusions. The use of an in-line filter is not recommended. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Stability Unopened vials of ABRAXANE are stable until the date indicated on the package when stored between 20°C to 25°C (68°F to 77°F), in the original package. Neither freezing nor refrigeration adversely affects the stability of the product. Stability of Reconstituted Suspension in the Vial Reconstituted ABRAXANE should be used immediately, but may be refrigerated at 2°C to 8°C (36°F to 46°F) for a maximum of 8 hours if necessary. If not used immediately, each vial of reconstituted suspension should be replaced in the original carton to protect it from bright light. Discard any unused portion. Stability of Reconstituted Suspension in the Infusion Bag The suspension for infusion prepared as recommended in an infusion bag should be used immediately, but may be stored at ambient temperature (approximately 25°C) and lighting conditions for up to 8 hours. HOW SUPPLIED: Product NDC No. No. 103450 68817-134-50 100 mg of paclitaxel in a single use vial, individually packaged in a carton. Storage Store the vials in original cartons at 20°C to 25°C (68°F to 77°F). Retain in the original package to protect from bright light. Handling and Disposal Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate. U.S. Patent Numbers: 5,439,686; 5,498,421; 6,096,331; 6,506,405; 6,537,579; 6,749,868; 6,753,006 REFERENCES: 1. Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs. Publication No. 83-2621. For sale by the Superintendent of Documents, US Government NIH Printing Office, Washington, DC 20402. 2. AMA Council Report. Guidelines for Handling Parenteral Antineoplastics. JAMA. 1985;253(11):1590-1592. 3. National Study Commission on Cytotoxic Exposure Recommendations for Handling Cytotoxic Agents. Available from Louis R Jeffrey, ScD, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences. 179 Longwood Avenue, Boston, Massachusetts 02115. 4. Clinical Oncology Society of Australia. Guidelines and Recommendations for Safe Handling of Antineoplastic Agents. Med J Australia. 1983;1:426-428. 5. Jones RB, et al: Safe Handling of Chemotherapeutic Agents: A Report from the Mount Sinai Medical Center. CA-A Cancer Journal for Clinicians. 1983; (Sept/Oct) 258-263. 6. American Society of Hospital Pharmacists Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs. Am J Hosp Pharm. 1990;47:1033-1049. 7. Controlling Occupational Exposure to Hazardous Drugs. (OSHA WORK-PRACTICE GUIDELINES.) Am J Health-Syst Pharm. 1996;53:1669-1686. 8. ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice. Pittsburgh, Pa: Oncology Nursing Society; 1999:32-41.

ABRAXANE, Abraxis, and Abraxis Oncology are registered trademarks of Abraxis BioScience, LLC. Abraxis Oncology® is a division of Abraxis BioScience, LLC. ©2009 Abraxis BioScience, LLC. All Rights Reserved. AO 1304 08/07 Printed in USA

therapy; Seattle experience. Int J Radiat Oncol Biol Phys. 2007;67:57-64. 13. Dearnaley DP, Sydes MR, Graham JD, et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet Oncol. 2007;8:475-487. 14. Kuban DA, Tucker SL, Dong L, et al. Longterm results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys. 2008;70:67-74. 15. Zietman AL, DeSilvio ML, Slater JD, et al. Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA. 2005;294:12331239. 16. Peeters ST, Heemsbergen WD, Koper PC, et al. Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol. 2006;24:1990-1996. 17. Lee WR, Bae K, Lawton C, et al. Late toxicity and biochemical recurrence after externalbeam radiotherapy combined with permanentsource prostate brachytherapy: analysis of Radiation Therapy Oncology Group study 0019. Cancer. 2007;109:1506-1512. 18. Roach M 3rd, Bae K, Speight J, et al. Shortterm neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol. 2008;26:585-591. 19. Bolla M, Collette L, Blank L, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002;360:103-106. 20. Horwitz EM, Bae K, Hanks GE, et al. Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol. 2008;26:2497-2504. 21. Pilepich MV, Winter K, Lawton CA, et al. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma—long-term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys. 2005;61:1285-1290. 22. Roach M 3rd, DeSilvio M, Lawton C, et al. Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol. 2003;21:1904-1911. 23. Pommier P, Chabaud S, Lagrange JL, et al. Is there a role for pelvic irradiation in localized prostate adenocarcinoma? Preliminary results of GETUG-01. J Clin Oncol. 2007;25:5366-5373. 24. Lawton CA, DeSilvio M, Roach M 3rd, et al. An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys. 2007;69:646-655. 25. Smith JA Jr, Herrell SD. Robotic assisted laparoscopic prostatectomy: do minimally invasive approaches offer significant advantages? J Clin Oncol. 2005;23:8170-8175. 26. Thompson IM Jr, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA. 2006;296:2329-2335. 27. Febbo PG, Richie JP, George DJ, et al. Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer. Clin Cancer Res. 2005;11:52335240. 28. Driecer R, Magi-Galluzzi C, Zhou M, et al. Phase II trial of neoadjuvant docetaxel before radical prostatectomy for locally advanced prostate cancer. Urology. 2004;63:1138-1142. 29. Kibel AS, Rosenbaum E, Kattan MW, et al. Adjuvant weekly docetaxel for patients with high risk prostate cancer after radical prostatectomy: a multi-institutional pilot study. J Urol. 2007;177:1777-1781.

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Multidisciplinary Care for Thoracic Surgery Patients, Delivered Daily, Improves Pain Control ORLANDO—Apparently, thoracic surgeons and pain and palliative medicine specialists can teach each other a thing or two, and patients reap the benefits. A daily multidisciplinary approach to managing thoracic surgery (lung cancer) patients resulted in improved pain control and lower treatment cost than conventional treatment, in a study presented at the annual meeting of the American Society of Clinical Oncology. Furthermore, the improvements “carried over” for 6 months after the program ended, suggesting that the surgeon’s education was long-lasting. “Surgeons do not have specialized training in pain management. Our study was driven by the desire to improve pain management and patient outcomes by working as a team,” said principal investigator Michael D. Adolph, MD, assistant clinical professor, pain and palliative medicine service, James Cancer Hospital and Solove Research Institute, Ohio State University Medical Center, Columbus, Ohio. The 8-month program ended because it was no longer really necessary, he said. The surgical team learned from the pain and palliative medicine (PPM) service how to recognize those patients who needed PPM consults, and they also became more comfortable with developing pain management plans themselves. The PPM service also learned from the surgeons, he added. “The surgeons taught us that not all chest surgery patients are alike. We learned that patients with thoracotomies and rib resections have considerably more pain than those with thorascopic surgery, and patients discharged with chest tubes in place have significantly more pain and symptoms than patients whose tubes are removed,” he said.

Benefit of multidisciplinary programs not easy to demonstrate In 1995, the SUPPORT study done to understand prognoses and preferences for outcomes and risks of treatments (JAMA. 1995;274:1591-1598) failed to substantiate improved end-oflife care and pain control through an educational approach that sought to identify preferences and to enhance communications. The investigators of that study suggested that other “proactive measures” might be more effective. In 2006, the National Institutes of Health described one such proactive measure—transdisciplinary collaboration, an intraorganizational partnership in which participants work together within a single organization to maximize basic or clinical research. Adolph and colleagues hypothesized that daily transdisciplinary care of July/August 2009

patients that involved both the thoracic surgery service and a consultative palliative care team would result in measurable and sustained clinical outcomes. Their observational study compared outcomes from two time periods for 1188 thoracic surgery patients being

ice clinic was available for continuity of care in cancer survivorship.

Results sustained after collaboration period ended Patients were surveyed soon after hospital discharge, either by telephone or

A daily multidisciplinary approach to managing thoracic surgery (lung cancer) patients resulted in improved pain control and lower treatment cost than conventional treatment. The improvements “carried over” for 6 months after the program ended. treated for lung cancer at their National Cancer Institute–approved cancer hospital. There were three study cohorts: (1) period 1 patients (n = 660), who were treated before the 8-month daily collaborative transdisciplinary care period; (2) patients treated during the collaborative care period (n = 250) of February 2007 to November 2007; and (3) period 2 patients (n = 528), who were treated between November 2007 and July 2008, after the 8-month program ended. The study compared period 1 with period 2 patients. The average patient was a 60-yearold white man, although more than 40% of the patients were women. For the 8-month collaborative period, the hospital’s PPM service had “face-to-face” contact with the thoracic surgery service, either as consultants on the complex cases or less formally in lesser cases. Inpatients were selected for PPM consultations on the basis of advanced or inoperable malignancy, preexisting chronic pain, or uncontrolled symptoms, especially postoperative pain. Consensus plans were developed for all patients. “The surgical service educated the PPM service by providing detailed descriptions of surgical procedures and anticipated postoperative care needs,” Adolph said. “We had daily conversations about every patient on the service, and the PPM actually saw the most severe patients. The outcome of those discussions helped facilitate the patient’s transition to home care.” Pain was managed according to principles of the World Health Organization analgesic ladder. The proportion of patients receiving postoperative epidural analgesia was similar in all periods. Ambulatory follow-up in the PPM serv-

mail. Compared with period 1 patients receiving standard care, the period 2 patients reported significantly greater satisfaction with pain control. On a scale of 0-10, the scores were 9.0 versus 9.5, respectively (P <.0001), Adolph said. Period 2 patients were also significantly more likely to be appropriately referred to hospice when their cancer was inoperable (P = .027). They also

had significantly shorter case-adjusted lengths of hospital stay (P = .004), and significantly less expensive care when surgery was not required (P = .002). Interestingly, the patients’ satisfaction with doctors and nurses was not significantly different between the periods. This probably reflects the fact that these patients were seriously ill, in the hospital, and undergoing surgery for the lifethreatening diagnosis they just received, Adolph suggested. “There are a host of emotions and psychological factors” that no doubt override the potential differences in satisfaction, he said. Pain control in the thoracic surgery patients also exceeded that seen in other surgical divisions during the same period, he added. “We wondered whether other services might also improve, whether all the doctors became better educated as the result of our program,” he said, “but the data showed, in fact, that the thoracic surgery service outstripped the other three surgical services in pain satisfaction, which suggests this is indeed a team-focused phenomenon.” The surgeons “drove this outcome,” he emphasized. “The transdisciplinary program was a short-term activity with a long-term effect.” —CH

Financial and Clinical Outcomes in an Acute Palliative Care Unit

cute palliative care units (APCUs) can produce reimbursement outcomes consistent with the American acute care model. In a study at the University of Texas M.D. Anderson Cancer Center, Elsayem and colleagues found reimbursement to be comparable with the rest of the community cancer center. The researchers reviewed all admissions to the APCU over the past 5 fiscal years for demographic information, length of stay, discharges, survival, hospital billings, and collection of charges, and compared these with the rest of the institution. In that time period, 2510 unique patients were admitted, with a median age of 59 years and a median length of stay in the APCU of 8 days. Just over half were women (51%). Professional collections ranged

from 42% to 47% of charges for the APCU, versus 32% to 38% for the rest of the cancer center and were stable over the 5-year period. Hospital collections were 47% to 51% of charges for the APCU, versus 55% to 57% for the rest of the cancer center. The payer mix included commercial (46%), Medicare (30%), Medicaid (5%), mixed (5%), indigent (8%), and others (6%). The researchers concluded that the APCU is as viable as any other clinical program in their institution. Although further research is needed to investigate possible reasons for lack of APCUs in cancer centers, this study helps break down the financial barrier for establishing APCUs (Abstract e20518). —DL

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CONFERENCE NEWS

Conference News

Continued from cover reliable early detection test, and fewer than 20% of patients are diagnosed in the early stages before the disease has spread beyond the ovaries. As a result, the overall survival rate is only about 46%.

Ovarian Cancer National Alliance The Ovarian Cancer National Alliance (OCNA), established in 1997, unites individuals and organizations at the local, state, and regional levels to advance ovarian cancer research, improve healthcare practices, and help raise public awareness of the disease and its symptoms. Chief executive officer Karen Kaplan, MPH, ScD, says, “Talking about it is the key. We have to raise awareness among women and the men who care about them.” The alliance’s activities fall into three broad areas: • Awareness: OCNA seeks to increase awareness of the symptoms of ovarian cancer and the importance of early recognition and treatment. • Education: OCNA serves as a resource for survivors and works to educate healthcare professionals about the diagnosis of ovarian cancer and the importance of referral to a gynecologic oncologist. • Advocacy: OCNA focuses on legislative issues of importance to the ovarian cancer community. It advocates at the federal level for (1) adequate funding for ovarian cancer research and awareness programs, and (2) legislation that will improve quality of life and access to care for cancer patients. A central part of OCNA’s educational efforts is its Survivors Teaching Students: Saving Women’s Lives program, which is supported by the Entertainment Industry Foundation. In this program, ovarian cancer survivors of diverse backgrounds go into medical school classrooms to share their experiences with cancer diagnosis and treatment with third-year medical students during their gynecology rotation. The program has been expanded to include nurses, nurse practitioners, physician assistants, and residents. Journal of Multidisciplinary Cancer Care recently spoke with participants in the Survivors Teaching Students: Saving Women’s Lives program.

Survivors share their stories Five-year survivor Alice, a 5-year survivor, was in her late 30s when she was diagnosed with ovarian cancer. Based on her experiences in two different treatment centers, she has become a firm believer in the importance of doctor–patient communication and the need to involve patients in decision making. Her medical treatment was excellent, but she felt that communication between doctors and patients and between doctors in different specialties could be improved. “I find that when people are dissatisfied with their care, it often comes down to communication,” she observed. Alice had a nurse who explained everything clearly and was the person to contact if she had any questions. Other women she has spoken with, however, have found that “the lines of communication are not always so clear.” Although they understand the need to prioritize patients’ calls, many women feel that sometimes “they have to make a pitch to get attention, to get someone to return calls.” She also noted that different practices and different departments have different ways of handling communication, which can make it difficult to keep track of whom to contact in different practices. “Having one point person to go to would make life a lot easier,” she said. Alice also felt that some patients with ovarian cancer are not referred to other services, such as pain management and nutrition, as readily as patients with other cancers. “It seems that sometimes referrals are not made quickly enough. One woman I know reported pain to her oncologist for 7 months before advocating for herself and asking for a referral to a pain management clinic,” she said. Becoming involved in patient support and advocacy groups, such as the OCNA, has helped Alice cope with the ovarian cancer experience and overcome the isolation she felt when she was first diagnosed. She finds that the information on treatment advances she has obtained by attending OCNA conferences has helped her in making decisions about her own treatment. Ovarian cancer survivors have unique needs, she has found. “Not everyone gets their 5-year clean bill of

health and not everyone will Table. Symptoms of Ovarian Cancer live happily ever after. Many will have recurrences. Longterm survivorship issues is an Bloating emerging field, and I don’t want Pelvic or abdominal pain us to be left out. We have a lot Difficulty eating or feeling full quickly of the same needs and we have a lot of different needs as other Urinary symptoms (urgency or frequency) cancer survivors, but we are still Additional symptoms may include fatigue, survivors.” indigestion, back pain, pain with intercourse, Alice participates in the Survivors Teaching Students constipation, and menstrual irregularities. program, which she says is “one of my favorite things to do.” One thing that she hopes to accomplish months. Now I’ve become a strong is to make healthcare providers more advocate for ovarian cancer awareness.” aware that although the incidence of She was instrumental in launching the ovarian cancer increases with age, it can Survivors Teaching Students program affect younger women and women from at the University of California, San different ethnic and racial groups. Diego and continues her efforts to raise “Doctors do not expect to see pre- awareness among the public and healthmenopausal women of color with ovari- care professionals. “Women tend to an cancer. One day in the infusion rationalize and delay seeking treatment. room, the woman on my right was 42, Women need to be empowered. The and the woman on my left was 36, all of silence needs to be broken. Medical us being treated for ovarian cancer. I’m professionals need to think of ovarian hoping that after these medical students cancer first instead of last. If a woman become doctors, when someone who says there is something going on, looks like me reports new and persistent believe her because we tend to listen to symptoms, they will remember my story, our bodies.” that sometimes the unexpected happens, and that they will consider and A lasting impression rule out ovarian cancer a little earlier in Joanna Hofmann, RN, EdD, ANP/ the process.” GNP-BC, a professor at the HunterBellevue School of Nursing in New York, says that participating in the Two-and-a-half-year survivor Peg had an eye-opening encounter Survivors Teaching Program was “an with Western medicine when she was amazing experience” for her graduating diagnosed with stage I ovarian cancer nurse practitioner students. “Students just before her 60th birthday. She had no remembered what they heard and kept medical insurance, so, in addition to her getting information on their own aftermedical issues, she had to learn to deal ward. Hearing the survivors’ stories was with the intricacies of getting coverage a thousand times better than teaching through county and state resources. with a case study…. I think it has made “Most of my adult life, I turned to alter- a lasting impression. It will work native healing,” she said, and at first she throughout their careers and will help a attributed the symptoms she was feeling lot of people.” to a recent fall. She was fortunate to find a gynecologist who helped her get coun—Karen Rosenberg ty medical coverage and a quick referral to a gynecologic oncologist who, withFor more information about out hesitation, scheduled surgery immediately. “I have learned how important ovarian cancer and the Survivors timely referral to a gynecologic oncoloTeaching Students program, go gist is. Patients with ovarian cancer have to the Ovarian Cancer National better outcomes when they are treated Alliance web site by a specialist.” Peg says “I was stressed into this www.ovariancancer.org. Western medical world in about 6 To serve on the editorial advisory panel, please complete the form below and fax to 732-656-7938 or e-mail to Karen@greenhillhc.com.

Join the JOMCC Editorial Advisory Panel Journal of Multidisciplinary Cancer Care is seeking oncologists, nurses, pharmacists, medical and pharmacy directors, P&T Committee members, and experts in healthcare legislation who are interested in joining our editorial advisory panel and assisting in maintaining the high quality of articles published. Panel members will occasionally be asked to contribute articles or commentaries, review manuscripts, or participate in interviews or roundtable discussions.

July/August 2009

Articles fall into three main categories: Clinical, Business, Health Economics. These main categories are divided into many subcategories, including (but not limited to): Administration/management Radiation oncology Breast cancer Other solid tumors Finance/economics Health policy/reform Gastrointestinal cancers Hematologic malignancies Genitourinary cancers Lung cancer Gynecologic malignancies Melanoma Health information technology Pharmacoeconomics: cost-benefit analysis, cost-effectiveness Reimbursement: Medicare/Medicaid, health insurance,prior authorization

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ONCOLOGY DRUG CODES

Oncology Drug Codes Medications Used for the Treatment of Genitourinary Cancers The following sections include: • Associated ICD-9-CM codes used for the classification of genitourinary cancers • Drugs that have been FDA-approved in the treatment of genitourinary cancers. Please note: if a check mark appears in the FDA column it will NOT appear in the compendia section even if a drug is included in the NCCN (National Comprehensive Cancer Network) Drugs & Biologics Compendium • Drugs included in the NCCN Drugs & Biologics Compendium for off-label use in genitourinary cancers. NCCN is recognized by the Centers for Medicare & Medicaid Services (CMS) as a referencing source • Corresponding HCPCS/CPT codes and code descriptions • Current Code Price (AWP-based pricing) • Most recent ASP plus 6% (Medicare allowable) • Possible CPT Administration Codes for each medication.

Generic (brand) name

HCPCS code: code description

altretamine (Hexalen)

J8999*: prescription drug, oral, chemotherapeutic, not otherwise specified

anastrozole (Arimidex)

J8999*: prescription drug, chemotherapeutic, oral, not otherwise specified

anastrozole (Arimidex)

Ovarian Cancer The following section will assist healthcare professionals and payers by providing appropriate coding, billing, and reimbursement information associated with the management of ovarian cancer.

Associated ICD-9-CM Codes Used for Ovarian Cancer 183 Malignant neoplasm of ovary and other uterine adnexa 183.0 Ovary 183.2 Fallopian tube Oviduct Uterine tube 183.3 Broad ligament Mesovarium Parovarian region 183.4 Parametrium Uterine ligament NOS Uterosacral ligament 183.5 Round ligament 183.8 Other specified sites of uterine adnexa Tubo-ovarian Utero-ovarian Malignant neoplasm of contiguous or overlapping sites of ovary and other uterine adnexa whose point of origin cannot be determined 183.9 Uterine adnexa, unspecified

FDAapproved for ovarian cancer

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

Current code price (AWPbased pricing)

Medicare allowable (ASP + 6%), effective 7/1/09-9/30/09

CPT administration codes

NDC level pricing

N/A

NDC level pricing

N/A

S0170: anastrozole, oral, 1 mg

$12.81

S0170: not payable by Medicare

N/A

bevacizumab (Avastin)

J9035: injection, bevacizumab, 10 mg

$68.75

$57.43

96413, 96415

bleomycin (Blenoxane)

J9040: injection, bleomycin sulfate, 15 units

$46.33

$30.89

96401, 96409

capecitabine (Xeloda)

J8520: capecitabine, oral, 150 mg

$7.35

$5.72

N/A

capecitabine (Xeloda)

J8521: capecitabine, oral, 500 mg

$24.50

$19.02

N/A

July/August 2009

G REEN H ILL H EALTHCARE C OMMUNICATIONS

ONCOLOGY DRUG CODES 24

FDAapproved for ovarian cancer

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

Current code price (AWPbased pricing)

Medicare allowable (ASP + 6%), effective 7/1/09-9/30/09

CPT administration codes

Generic (brand) name

HCPCS code: code description

carboplatin (Paraplatin)

J9045: injection, carboplatin, 50 mg

$85.10

$5.22

96409, 96413, 96415

cisplatin (Platinol AQ)

J9060: cisplatin, powder or solution, per 10 mg

$4.51

$2.32

96409, 96413, 96415

cisplatin (Platinol AQ)

J9062: cisplatin, 50 mg

$22.56

$11.60

96409, 96413, 96415

cyclophosphamide oral (Cytoxan)

J8530: cyclophosphamide, oral, 25 mg

$2.09

$0.90

cyclophosphamide injection (Cytoxan)

J9090: cyclophosphamide, 500 mg

$31.60

$20.09

96409, 96413, 96415

cyclophosphamide injection (Cytoxan)

J9091: cyclophosphamide, 1.0 gm

$56.90

$40.18

96409, 96413, 96415

cyclophosphamide injection (Cytoxan)

J9092: cyclophosphamide, 2.0 gm

$52.50

$80.35

96409, 96413, 96415

dactinomycin (Cosmegen)

J9120: injection, dactinomycin, 0.5 mg

$654.08

$543.73

96409

docetaxel (Taxotere)

J9170: injection, docetaxel, 20 mg

$467.37

$344.65

96413

doxorubicin HCl (Adriamycin)

J9000: injection, doxorubicin hydrochloride, 10 mg

$13.75

$3.58

96409

doxorubicin HCl liposome (Doxil)

J9001: injection, doxorubicin hydrochloride all lipid formulations, 10 mg

$565.63

$456.99

96413

etoposide (Etopophos, Toposar)

J9181: injection, etoposide, 10 mg

$0.55

$0.45

96413, 96415

etoposide (VePesid)

J8560: etoposide, oral, 50 mg

$47.64

$30.35

N/A

gemcitabine (Gemzar)

J9201: injection, gemcitabine hydrochloride, 200 mg

$172.41

$141.29

hydroxyurea (Hydrea)

J8999*: prescription drug, oral, chemotherapeutic, not otherwise specified

NDC level pricing

N/A

hydroxyurea (Hydrea)

S0176: hydroxyurea, oral, 500 mg

$1.28

S0176: not payable by Medicare

N/A

ifosfamide (Ifex)

J9208: injection, ifosfamide, 1 g

$58.75

$30.03

96413, 96415

irinotecan (Camptosar)

J9206: injection, irinotecan, 20 mg

$32.82

$14.96

96413, 96415

letrozole (Femara)

J8999*: prescription drug, oral, chemotherapeutic, not otherwise specified

NDC level pricing

leuprolide (Lupron Depot)

J9217: leuprolide acetate (for depot suspension), 7.5 mg

$367.25

megestrol (Megace)

J8999*: prescription drug, oral, chemotherapeutic, not otherwise specified

NDC level pricing

N/A

megestrol (Megace)

S0179: megestrol acetate, oral 20 mg

$0.66

S0179: not payable by Medicare

N/A

melphalan oral (Alkeran oral)

J8600: melphalan, oral, 2 mg

$5.63

$4.68

N/A

G REEN H ILL H EALTHCARE C OMMUNICATIONS

NDC level pricing $198.87

N/A

96413

N/A

96402

July/August 2009

FDAapproved for ovarian cancer

Current code price (AWPbased pricing)

Medicare allowable (ASP + 6%), effective 7/1/09-9/30/09

CPT administration codes

Generic (brand) name

HCPCS code: code description

melphalan injection (Alkeran injection)

J9245: injection, melphalan hydrochloride, 50 mg

$2003.78

$1624.60

96409, 96413

oxaliplatin (Eloxatin)

J9263: injection, oxaliplatin, 0.5 mg

$12.26

$9.61

96413, 96415

paclitaxel (Taxol)

J9265: injection, paclitaxel, 30 mg

$21.25

$7.72

96413, 96415

pemetrexed (Alimta)

J9305: injection, pemetrexed, 10 mg

$60.21

$49.46

tamoxifen (Nolvadex)

J8999*: prescription drug, oral, chemotherapeutic, not otherwise specified

NDC level pricing

N/A

tamoxifen (Nolvadex)

S0187: tamoxifen citrate, oral, 10 mg

$1.89

S0187: not payable by Medicare

N/A

thiotepa (Thiotepa)

J9340: injection, thiotepa, 15 mg

$143.75

$97.35

topotecan injection (Hycamtin)

J9350: injection, topotecan, 4 mg

$1257.89

$981.08

96413

vinBLAStine

J9360: injection, vinblastine sulfate, 1 mg

$3.31

$1.01

96409

vinCRIStine (Vincasar PFS)

J9370: vincristine sulfate, 1 mg

$9.90

$5.70

96409

vinCRIStine (Vincasar PFS)

J9375: vincristine sulfate, 2 mg

$19.80

$11.40

96409

vinCRIStine (Vincasar PFS)

J9380: vincristine sulfate, 5 mg

$49.50

$28.49

96409

vinorelbine (Navelbine)

J9390: injection, vinorelbine tartrate, per 10 mg

$44.38

$13.14

96409

Prostate Cancer

96409

51720, 96409

Associated ICD-9-CM Code Used for Prostate Cancer

The following section will assist healthcare professionals and payers by providing appropriate coding, billing, and reimbursement information associated with the management of prostate cancer.

FDAapproved for prostrate cancer

185 Malignant neoplasm of prostate Excludes: seminal vesicles (187.8)

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

Current code price (AWPbased pricing)

Medicare allowable (ASP + 6%), effective 7/1/09-9/30/09

CPT administration codes

Generic (brand) name

HCPCS code: code description

bicalutamide (Casodex)

J8999*: prescription drug, oral, chemotherapeutic, not otherwise specified

carboplatin (Paraplatin)

J9045: injection, carboplatin, 50 mg

$85.10

$5.22

96409, 96413, 96415

cisplatin (Platinol AQ)

J9060: cisplatin, powder or solution, per 10 mg

$4.51

$2.32

96409, 96413, 96415

cisplatin (Platinol AQ)

J9062: cisplatin, 50 mg

$22.56

$11.60

96409, 96413, 96415

Degarelix

J9999*: not otherwise classified, antineoplastic drugs OR C9399: unclassified drugs or biological

July/August 2009

ONCOLOGY DRUG CODES

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

NDC level pricing

N/A

96402

G REEN H ILL H EALTHCARE C OMMUNICATIONS

ONCOLOGY DRUG CODES

FDAapproved for prostrate cancer

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

Current code price (AWPbased pricing)

Medicare allowable (ASP + 6%), effective 7/1/09-9/30/09

CPT administration codes

Generic (brand) name

HCPCS code: code description

docetaxel (Taxotere)

J9170: injection, docetaxel, 20 mg

estradiol (Estrace)

J8499*: prescription drug, oral, nonchemotherapeutic, not otherwise specified

NDC level pricing

N/A

estramustine (Emcyt)

J8999*: prescription drug, oral, chemotherapeutic, not otherwise specified

NDC level pricing

N/A

etoposide (Etopophos)

J9181: injection, etoposide, 10 mg

$0.55

$0.45

96413, 96415

etoposide (VePesid)

J8560: etoposide, oral, 50 mg

$47.64

$30.35

N/A

flutamide (Eulexin)

J8999*: prescription drug, oral, chemotherapeutic, not otherwise specified

NDC level pricing

goserelin (Zoladex)

J9202: goserelin acetate implant, per 3.6 mg

$469.99

$196.05

histrelin (Vantas)

J9225: histrelin implant (Vantas), 50 mg

$6250.00

$1579.32

ketoconazole (Nizoral)

J8499*: prescription drug, oral, nonchemotherapeutic, not otherwise specified

leuprolide (Lupron Depot, Eligard)

J9217: leuprolide acetate (for depot suspension), 7.5 mg

$367.25

$198.87

mitoxantrone (Novantrone)

J9293: injection, mitoxantrone hydrochloride, per 5 mg

$126.94

$68.36

nilutamide (Nilandron)

J8999*: prescription drug, oral, chemotherapeutic, not otherwise specified

NDC level pricing

prednisone

J7506: prednisone, oral, per 5 mg

triptorelin (Trelstar LA, Trelstar Depot)

J3315: injection, triptorelin pamoate, 3.75 mg

zoledronic acid (Zometa)

J3487: injection (Zometa), zoledronic acid, 1 mg

$467.37

NDC level pricing

$344.65

NDC level pricing

96413

N/A

NDC level pricing

96372, 96402 11981, 11982, 11983 N/A

NDC level pricing

96402

96409, 96413 N/A

$0.05

$0.04

N/A

$756.25

$161.82

96372, 96402

$268.96

$217.37

96365, 96374

*When billing a nonclassified medication using a CMS 1500 claim form you must include both the HCPCS code (ie, J8999 for Tamoxifen) in column 24D and the drug name, strength, and National Drug Code (NDC) in box 19 to ensure appropriate reimbursement. References • HCPCS Level II Expert, 2009 • CPT 2009; 2008 • ICD-9-CM for Professionals Volumes 1 & 2; 2009 • The Drug Reimbursement Coding and Pricing Guide, Vol 6, No 3; RJ Health Systems International LLC; 3rd Quarter 2009 • FDA-approved indication (from products' prescribing information) • NCCN • National Cancer Institute • www.ReimbursementCodes.com powered by RJ Health Systems International, LLC., Wethersfield, Connecticut • CMS-Medicare allowable 3rd Quarter 2009 (effective dates 7/1/09-9/30/09). Prices listed herein are effective as of July 1, 2009. ASP indicates average sales price; AWP, average wholesale price; CMS, Centers for Medicare & Medicaid Services; CPT, Current Procedural Terminology; FDA, US Food and Drug Administration; HCPCS, Healthcare Common Procedure Coding System; NCCN, National Comprehensive Cancer Network.

This information was supplied by:

PO BOX 290616, Wethersfield, CT 06109 T: (860) 563-1223 • F: (860) 563-1650 • www.RJHealthSystems.com 26

G REEN H ILL H EALTHCARE C OMMUNICATIONS

MORE ONCOLOGY DRUG CODES ONLINE Bladder Cancer Kidney Cancer Testicular Cancer Uterine Cancer

www.jomcc.com July/August 2009

Meetings List 21-23 WASHINGTON, DC 8th International Congress on Targeted Therapies in Cancer www.cancerlearning.com

8-9

6-7 SAN FRANCISCO, CALIFORNIA ASCO Electronic Health Records Symposium www.asco.org

DALLAS, TEXAS 2009 Cancer Center Business Summit www.cancerbusinesssummit.com

8-10 SAN FRANCISCO, CALIFORNIA 2009 Breast Cancer Symposium www.asco.org

September 2009

11-12 ST. LOUIS, MISSOURI Translational Advances in Radiation Oncology and Cancer Imaging Symposium www.astro.org

11-12 SEATTLE, WASHINGTON Fifth Annual Multidisciplinary Interactive Thoracic Oncology Conference www.thecbce.com

11-12 CHICAGO, ILLINOIS 3rd Annual Perspectives in Genitourinary Oncology: A Case-based Approach to Enhance Patient Management of Prostate, Renal and Bladder Cancers www.imedex.com

24-25 NEW YORK, NEW YORK 8th Annual International Conference on Ovarian Cancer www.mskcc.org

October 2009

1-4 CHICAGO, ILLINOIS Lynn Sage Breast Cancer Symposium www.lynnsagebreastcancer.org

2-4 SAN DIEGO, CALIFORNIA 3rd Annual Conference on New Technologies & Innovative Treatment Strategies for GU Malignancies www.cityofhope.org

GEMZAR姞 (GEMCITABINE HCl) FOR INJECTION 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

July/August 2009

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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. 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.

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