june 2010, vol 3, no 4

NEW ORLEANS—With the passage of the PatientProtection and Affordable Care Act, many changes are instore that will affect the field of oncology. Joseph S. Bailes,MD, chairman of the Government Relations Council andpast-president of the American Society of ClinicalOncology, described what oncology pharmacists can expectin his keynote address.

“Cancer is viewed in Washington as an area that needsmuch greater efficiency,” he said, predicting that essential-

©2010 Green Hill Healthcare Communications, LLC

Fostering a Dialogue to Improve Patient Care & Outcomes

Submit your cases online today at

www.myelomacases.com

In the healing garden. Back row left to right: Joy Dimagmaliw, RNC;Joann Signorino, RN-BC; Charlotte Bradley, RN, OCN; Robyn Rex, RN,OCN; Debora Velmer, RN, CCM; Patricia Molinelli, MS, RN, APN-C,AOCNS; Rita Messemer, RN; Janet Belmonte, RNC. Bottom row left toright: Amalia Apuzzio, RN-BC; Bozena Owsieniuk, RN; Erica Schermer;Kathy Wagle, PCT.

The Lead

er

in News a

nd

Meeting

Coverage

JUNE 2010 www.TheOncologyPharmacist.com VOL 3, NO 4

President Obama guaranteed Americans that after health reform became lawthey could keep their insurance plans and their doctors. It’s clear that thispromise cannot be kept. Insurers and physicians are already reshaping their

businesses as a result of Mr. Obama’s plan.The health-reform law caps how much insurers can spend on expenses and take

for profits. Starting next year, health plans will have a regulated “floor” on theirmedical-loss ratios, which is the amount of revenue they spend on medical claims.Insurers can only spend 20% of their premiums on running their plans if they offerpolicies directly to consumers or to small employers. The spending cap is 15% forpolicies sold to large employers.

This regulation is going to have its biggest impact on insurance sold directly toconsumers—what’s referred to as the “individual market.” These policies cost more

VIEWPOINT

No, You Can’t Keep YourHealth PlanInsurers and doctors are already consolidating their businesses in the wake of ObamaCare’s passage.

By Scott Gottlieb, MD

Continued on page 6Continued on page 6

CANCER CENTER PROFILE

Steeplechase Cancer CenterProvides Patient-centeredCare in Community SettingBy Karen Rosenberg

Steeplechase Cancer Center at Somerset Medical Center inSomerville, New Jersey, was established in 2007 in response tocommunity needs for easily accessible high-quality cancer care.

The center is named for the steeplechase horse race, held eachOctober in the neighboring community of Far Hills, New Jersey.Proceeds from the race are donated to the center and go to supportexpanded facilities and services.The cancer center occupies a large, state-of-the-art facility and offers

a full range of services. “It houses everything you need for diagnosis andtreatment of cancer in one place,” notes Joan Perrone, RPh, one of fourpharmacists who service the infusion center at Steeplechase. Somerset

Safe HandlingNational Safe HandlingInitiative An interview withTimothy Tyler, PharmD,FCSHP

page 26

CE CreditActive Surveillance as a Management Strategy for Low-risk Prostate Cancer

page 14

Conference NewsEPO Ordering Form ImprovesGuidelines Compliance, SavesPractices MoneyBased on a presentation by Siu-Fun Wong, PharmD

page 10

InsideCOMPLIMENTARY

Changes Ahead with HealthcareReform: What’s in Store for OncologyPharmacy?By Caroline Helwick

Conference News: HOPAThe following articles are based on presentations at the 6th AnnualConference of the Hematology/Oncology Pharmacy Association held in New Orleans, Louisiana, March 24-27, 2010.

Continued on page 8 Joseph S. Bailes, MD

TOP_June2010_v2_TOP 6/15/10 11:52 AM Page Cov1

Totect® Kit (dexrazoxane) for injection is

for intravenous infusion only. Totect is

indicated for the treatment of extravasation

resulting from intravenous anthracycline

chemotherapy.

TWO PRICE OPTIONS AVAILABLE

First and only FDA approved treatment for anthracycline extravasation.

Supplied as a convenient and accessible complete three day treatment kit for single patientuse, which should be proactively stocked on-site and infused as soon as possible andwithin 6 hours of an anthracycline extravasation.

Demonstrates 98% overall efficacy based on two biopsy-confirmed clinical trials1,2 inreducing or avoiding surgical intervention (i.e., surgical debridement, plastic surgery and their related costs), thereby reducing postponement of a patient’s chemotherapy treatments and the avoidance of long-term consequences.

Cited in nursing guidelines3,4 and oncology safety standards5.

For more information, call 866-478-8274 or visit our website at www.totect.comTo order Totect®, contact one of our authorized distributors.

ASD Healthcare(800) 746-6273

Cardinal Specialty(866) 677-4844

McKesson/OTN(800) 482-6700

Oncology Supply(800) 633-7555

US Oncology(888) 987-6679

1 Mouridsen HT et al. Treatment of anthracycline extravasation with savene (dexrazoxane).Results from two prospective clinical multicentre studies. Ann Oncol 2007; 18:546-550.2 Totect® package insert.3 Polovich M, White JM, Olsen, M (eds.). Chemotherapy and Biotherapy Guidelines and Recommenda-tions for Practice (ed 3). Pittsburgh, PA, Oncology Nursing Society, 2009.4 Alexander M, Corrigan A, Gorski L, Hankins J, Perucca R. (eds). Infusion Nurses Society Infusion Nursing an Evidence-Based Approach (ed 3). Boston, MA, Infusion Nurses Society, 2009.5 Jacobsen J., et al. American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards. Oncology Nursing Forum, 2009; 36:651-658.© 2010 TopoTarget USA. All rights reserved. TOT0111/4-10Totect and its logo mark are registered trademarks of TopoTarget A/SImage is copyright © Photo Researchers, Inc.

ARE YOU PREPARED?

Pharma Chemo Ad 4 23 10 indd 1 4/26/10 3:52:48 PM

TOP_June2010_v2_TOP 6/15/10 11:52 AM Page Cov2

Rx onlyTotect® is a registered trademark of TopoTarget A/SUS Patent No. 6,727,253B2NDC 38423-110-01

Manufactured by:Ben Venue Laboratories, Inc.Bedford, OH 44146

Hameln Pharmaceuticals GmbH31789 HamelnGermany

Manufactured for:TopoTarget A/SSymbion Science ParkFruebjergvej 3DK-2100 CopenhagenDenmark

TOT0111/4-10© 2010 TopoTarget USA

www.totect.com

Totect® – Brief prescribing information Please refer to the package insert for full prescribing information. Each Totect carton contains 10 vials of Totect® (dexrazoxane for injection) 500 mg and 10 vials of 50 mL diluent. Indication: Treatment of extravasation resulting from IV anthracycline chemotherapy. Dosage and administration: Totect is a cytotoxic drug. Vial contents must be mixed and diluted before use. Totect should not be mixed or administered with any other drug during the infusion. Administration of Totect should begin as soon as possible and within 6 hours following the anthracycline extravasa-tion. Totect should be given as an intravenous (IV) infusion once daily for 3 consecutive days. The dose of Totect is based on the patient’s body surface area: day one, 1000 mg/m2; day two, 1000 mg/m2; day three, 500 mg/m2. For patients with a body surface area of > 2 m2, a dose of 2000 mg should be given on days 1 and 2, and a dose of 1000 mg should be given on day 3. Treatment on Day 2 and Day 3 should start at the same hour (+/- 3 hours) as on the �rst day. The Totect dose should be reduced 50% for patients with creati-nine clearance values of <40 mL/minute. Cooling procedures such as ice packs should be removed from the a�ected area at least 15 minutes prior to Totect administration. Totect (dexrazoxane for injection) must be reconstituted with diluent supplied in the carton. The patient’s Totect dose is diluted in 0.9% 1000 mL NaCl prior to administration. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guide-lines on this subject have been published.3-5 Direct contact of Totect® with the skin or mucous membranes prior to and following reconstitution should be avoided. If contact occurs, wash immediately and thoroughly with water. Contraindications: None.Warnings and Precautions: Myelosuppression: treatment with Totect is asso-ciated with leukopenia, neutropenia, and thrombocytopenia. Hematological monitoring should be performed. Use in Pregnancy: Pregnancy Category D. Totect can cause fetal harm when administered to a pregnant woman. There is no adequate information about the use of Totect in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Adverse reactions: The most common adverse reactions (≥ 16%) are nausea, pyrexia, injection site pain and vomiting.

Drug Interactions: No drug interactions have been identi�ed. Based on anecdotal reports concurrent use of topical dimethyl sulfoxide (DMSO) at the site of tissue injury may reduce the benefit of Totect. Additionally, nonclinical studies using a mouse model that simulates extravasation of anthracyclines has shown that concomitant treat-ment with topical DMSO decreases the efficacy of systemic dexrazoxane. Use in Speci�c Populations: Nursing Mothers: Discontinue drug or nursing, taking into consideration the importance of drug to the mother. Renal Impairment: Reduce the Totect dose by 50% In patients with creatinine clearance values <40 mL/min. Pediatric Use: The safety and e�ectiveness of Totect in pediatric patients have not been established. Geriatric Use: This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Be-cause elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Overdosage: There are no data on overdosage. There is no known antidote for dexrazoxane. Carcinogenesis, Mutagenesis, Impairment of Fertility: The carcinogenic potential of dexrazoxane has not been investigated. Nevertheless, a study by the National Cancer Institute has reported that long term dosing with razoxane (the racemic mixture of dexrazoxane, ICRF-187, and its enantiomer ICRF-186) is associated with the development of malignancies in rats and possibly in mice. Dexrazoxane was not mutagenic to bacteria in vitro (Ames assay), but caused signi�cant chromosomal aberrations in mammalian cells in vitro. It also increased the formation of micronucleated polychromatic erythrocytes in mice. Thus, dexrazoxane is mutagenic and clastogenic. The possible adverse effects of Totect on the fertility of humans and experimental animals, male or female, have not been adequately studied. Testicular atrophy was seen with dexrazoxane administration at doses as low as 30 mg/kg weekly for 6 weeks in rats (about 1/5 the human dose on a mg/m2 basis) and as low as 20 mg/kg weekly for 13 weeks in dogs (about half the human dose on a mg/m2 basis).

Pharma Chemo Ad 4 23 10 indd 2 4/26/10 3:52:48 PM

TOP_June2010_v2_TOP 6/15/10 11:52 AM Page 1

EDITOR-IN-CHIEFPatrick Medina,PharmD, BCOPOklahoma UniversityCollege of PharmacyTulsa, OK

John F. Aforismo,BSc Pharm, RPh,FASCPRJ Health SystemsInternational, LLCWethersfield, CT

David Baribeault,RPh, BCOPBoston Medical CenterBoston, MA

Betty M. Chan,PharmD, BCOPUSC/Norris CancerHospitalLos Angeles, CA

Steven L.D’Amato, RPh,BCOPMaine Center for CancerMedicineScarborough, ME

Anjana Elefante,PharmD, BSc,BSc Pharm, RPhRoswell Park CancerInstituteBuffalo, NY

Beth Faiman, RN,MSN, APRN,BC, AOCN Cleveland Clinic TaussigCancer CenterCleveland, OH

ChristopherFausel, PharmDIndiana University Simon Cancer CenterIndianapolis, IN

Rebecca S. Finley,PharmD, MSJefferson School ofPharmacyPhiladelphia, PA

David C.Gammon, BS PharmUniversity ofMassachusetts Memorial HospitalWorcester, MA

Lew Iacovelli, BS,PharmD, BCOP,CPP Moses H. Cone HealthSystemGreensboro, NC

Dwight Kloth,PharmD, FCCP,BCOPFox Chase Cancer CenterPhiladelphia, PA

Jim Koeller, MSUniversity of Texas atAustinSan Antonio, TX

Christopher J.Lowe, PharmDNovant HealthWinston-Salem, NC

Emily Mackler,PharmD, BCOPUniversity of MichiganHealth System & Collegeof PharmacyAnn Arbor, MI

Laura BoehnkeMichaud,PharmD, BCOP,FASHPThe University of TexasM. D. Anderson CancerCenterHouston, TX

LeAnn BestNorris, PharmD,BCPS, BCOPSouth Carolina College ofPharmacyColumbia, SC

Steve Stricker,PharmD, MS,BCOPSamford UniversityMcWhorter School ofPharmacyBirmingham, AL

Timothy G. Tyler,PharmD, FCSHPDesert Regional MedicalCenterPalm Springs, CA

John M. Valgus,PharmD, BCOPUniversity of NorthCarolina Hospitals andClinicsChapel Hill, NC

Gary C. Yee,PharmD, FCCP,BCOPUniversity of NebraskaCollege of PharmacyOmaha, NE

Burt Zweigenhaft,BSBioPharma Partners LLCNew York, NY

Marlo Blazer, RPh, PharmDJames Cancer Hospital & Solove ResearchInstituteColumbus, OH

Heidi D. Gunderson, PharmD,BCOPMayo Clinic Cancer CenterRochester, MN

Kamakshi V. Rao, PharmD,BCOPUniversity of North Carolina Hospitals and ClinicsChapel Hill, NC

Editorial Board

2 June 2010 I VOL 3, nO 4 www.TheOncologyPharmacist.com


The American Society ofClinical Oncology (ASCO)annual meeting ended this

week but reports from the meetingare still appearing in the medicalwebsites and daily newspapers andnewscasts. New drugs and drugcombinations are showing prom-ise for many types of cancer. Asthese drugs become available forclinical practice, oncology phar-macists will be called upon to con-fer with other members of the

healthcare team and help determine which ones to usein our own practice and how best to use them. We willalso have responsibility to educate patients and theircaregivers about these new medications or combinationsof agents not previously given, how to prevent or man-age their possible adverse effects, and their potential forinteractions with other drugs or supplements they maybe taking. But our job does not end there. Many new therapies

come with high costs, and pharmacists will increasinglyhave to be involved in the discussion of cost-effectiveness

and comparative effectiveness and of practical issues, suchas how to ensure reimbursement and minimize waste.Reports from the annual meeting of the Hematology/Oncology Pharmacy Association provide examples of phar-macists’ approachs to these practical concerns.

The Oncology Pharmacist attempts to filter news fromASCO and other major meetings through a pharmacist’sperspective, presenting not only results of large clinicaltrials but also of smaller studies that do not get as muchattention, such as a study of a pharmacist/nurse model forsupportive care or of use of computerized physician orderentry to reduce prescribing errors.Finally, although many oncology pharmacists are

involved in clinical trials and research, there are limitedopportunities to publish their results. To help fill this gap,Green Hill Healthcare Communications will launch theJournal of Hematology Oncology Pharmacy later this year. Weinvite submissions of original research reports, reviews ofdisease state management and new drugs, case reports, andarticles on practical issues in pharmacy management relat-ed to the treatment of patients with hematologic or onco-logic malignancies. Please send inquiries about manuscriptpreparation to [email protected] and look for a callfor papers in late summer or early fall. �

June 2010 • VOL 3, nO 4

PUBLISHING STAFF

PublisherPhilip [email protected]

Editorial DirectorKaren [email protected]

Associate EditorDawn [email protected]

Director, Client ServicesJohn W. [email protected]

Production ManagerStephanie Laudien

Business ManagerBlanche [email protected]

Executive AdministratorAndrea Boylston

Circulation [email protected]

Editorial Contact:Telephone: 732-992-1891 Fax: 732-656-7938

EDITORIAL CORRESPONDENCE should be addressedto EDITORIAL DIRECTOR, The Oncology Pharmacist®,241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. E-mail: [email protected]. YEARLY SUBSCRIP-TION RATES: United States and possessions: individuals,$105.00; institutions, $135.00; single issues $17.00. Orders willbe billed at individual rate until proof of status is confirmed.Prices are subject to change without notice. Correspondenceregarding permission to reprint all or part of any article pub-lished in this journal should be addressed to REPRINT PER-MISSIONS DEPARTMENT, Green Hill HealthcareCommun i cations, LLC, 241 Forsgate Drive, Suite 205C,Monroe Twp, NJ 08831. The ideas and opinions expressed inThe Oncology Pharmacist® do not necessarily reflect those of theEditorial Board, the Editorial Director, or the Publisher.Publication of an advertisement or other product mention inThe Oncology Pharmacist® should not be construed as anendorsement of the product or the manufacturer’s claims.Readers are encouraged to contact the manufacturer withquestions about the features or limitations of the productsmentioned. Neither the Editorial Board nor the Publisherassumes any responsibility for any injury and/or damage to per-sons or property arising out of or related to any use of thematerial contained in this periodical. The reader is advised tocheck the appropriate medical literature and the product infor-mation currently provided by the manufacturer of each drug tobe administered to verify the dosage, the method and durationof administration, or contraindications. It is the responsibilityof the treating physician or other healthcare professional, rely-ing on independent experience and knowledge of the patient,to determine drug dosages and the best treatment for thepatient. Every effort has been made to check generic and tradenames, and to verify dosages. The ultimate responsibility, how-ever, lies with the prescribing physician. Please convey anyerrors to the Editorial Director. ISSN #1944-9607.

The Oncology Pharmacist® is published 8 times a year by GreenHill Healthcare Communications, LLC, 241 Forsgate Drive,Suite 205C, Monroe Twp, NJ 08831. Telephone:732.656.7935. Fax: 732.656.7938. Copyright ©2010 by GreenHill Healthcare Communications LLC. All rights reserved.The Oncology Pharmacist® logo is a registered trademark ofGreen Hill Healthcare Com munications, LLC. No part of thispublication may be reproduced or transmitted in any form orby any means now or hereafter known, electronic or mechani-cal, including photocopy, recording, or any informational stor-age and retrieval system, without written permission from thePublisher. Printed in the United States of America.

Green Hill Healthcare Communications LLCGreen Hill Healthcare Communications, LLCHGYour Innovative Partners in Medical Media™

™

241 Forsgate Drive, Suite 205CMonroe Twp, NJ 08831

EDITOR’S LETTER

CONTENTS

www.TheOncologyPharmacist.com June 2010 I VOL 3, nO 4 4

Patrick Medina,PharmD, BCOP

FEATURE ARTICLES9 Conference News: HOPA

Palonosetron reduces readmissions for CINV in patients receiving IP cisplatinEPO ordering form improves guidelines compliance, saves practices moneyOncology pharmacists can significantly reduce chemotherapy wasteStandardized forms facilitate COG treatment

11 Breast Cancer Concurrent trastuzumab with chemotherapy beats sequential use for HER2-positive breast cancerThree new drugs on the horizon for HER2-positive breast cancer

14 Continuing EducationActive surveillance as a management strategy for low-risk prostate cancer

22 Drug TherapyNew treatments for chronic idiopathic thrombocytopenic purpura. Part 2. Eltrombopag

26 Safe HandlingNational safe handling initiative serves as reminder of need for precautions when handling hazardous drugs

DEPARTMENTS16 News Notes

18 Oncology Drug CodesLung cancer

28 International News

28 Financial Planning

29 Meetings


www.BioOncology.com

© 2010 Genentech USA, Inc. All rights reserved. 10201400 Printed in USA.

At Genentech BioOncology, not only are we leading the fi ghtagainst cancer with innovative science, but we’re also dedicatedto supporting patients and others within the oncology community.

A commitment to patients — We created Genentech BioOncology™

Access Solutions™, a single source for all access and reimbursementissues, so healthcare providers can remain focused on patient care.

Reducing barriers to treatment — We help make treatment possiblefor patients in fi nancial need through our BioOncology Co-Pay CardProgram and ongoing charitable donations to various independentnonprofi t organizations in support of co-pay assistance.

A commitment to care — Our fi rst product was approved in 1985, and since then we have donated approximately $1.5 billion inmedicine to uninsured patients through the Genentech® Access to Care Foundation and other donation programs.

Our goal is to fundamentally change the way that cancer is treated by personalizing solutions to patient care.

Taking a broader view —char ting a unique course in cancer care


www.TheOncologyPharmacist.com6 June 2010 I VOL 3, nO 4

Cancer Center Profile

Steeplechase Cancer Center... Continued from cover

VIEWPOINT

No, You Can’t Keep Your Health Plan Continued from cover

to market. They also have higher med-ical costs, owing partly to selection byless healthy consumers.Finally, individual policies have high

start-up costs. If insurers cannot spendmore of their revenue getting plans ontrack, fewer new policies will be offered.This will hit WellPoint, one of the

biggest players in the individual market,particularly hard. The insurance compa-ny already has a strained relationshipwith the White House: Earlier thismonth Mr. Obama accused WellPoint ofsystemically denying coverage to breastcancer patients, though the facts don’tbear that out.Restrictions on how insurers can spend

money are compounded by simultaneousconstraints on how they can managetheir costs. Beginning in 2014, a new fed-eral agency will standardize insurancebenefits, placing minimum actuarial val-ues on medical policies. There are alsomandates forcing insurers to cover a lot ofexpensive primary-care services in full.At the same time, insurers are beingblocked from raising premiums—for now

by political jawboning, but the threat oflegislative restrictions looms.One of the few remaining ways to

manage expenses is to reduce the actu-al cost of the products. In health care,this means pushing providers to acceptlower fees and reduce their use of cost-ly services like radiology or other diag-nostic testing.To implement this strategy, compa-

nies need to be able to exert more con-trol over doctors. So insurers are tryingto buy up medical clinics and doctorpractices. Where they can’t ownproviders outright, they’ll maintainsmaller “networks” of physicians thatthey will contract with so they can man-age doctors more closely. That meanseven fewer choices for beneficiaries.Insurers hope that owning providers willenable health policies to offset the costof the new regulations.Doctors, meanwhile, are selling their

practices to local hospitals. In 2005,doctors owned more than two-thirds ofall medical practices. By next year, morethan 60% of physicians will be salaried

employees. About a third of those willbe working for hospitals, according tothe American Medical Association. Areview of the open job searches held byone of the country’s largest physician-recruiting firms shows that nearly 50%are for jobs in hospitals, up from about25% five years ago.Last month, a hospital I’m affiliated

with outside of Manhattan sent a note toits physicians announcing a new sub-sidiary it’s forming to buy up local medicalpractices. Nearby physicians are lining upto sell—and not just primary-care doc-tors, but highly paid specialists like ortho-pedic surgeons and neurologists. Similardevelopments are unfolding nationwide.Consolidated practices and salaried

doctors will leave fewer options forpatients and longer waiting times for rou-tine appointments. Like the insurers,physicians are responding to the econom-ic burdens of the President’s plan in oneof the few ways they’re permitted to.For physicians, the strains include

higher operating costs. The Obamahealth plan puts expensive new mandates

on doctors, such as a requirement to pur-chase IT systems and keep more records.Overhead costs already consume morethan 60% of the revenue generated by anaverage medical practice, according to a2007 survey by the Medical GroupManagement Association. At the sametime, reimbursement under Medicare isfalling. Some specialists, such as radiolo-gists and cardiologists, will see theirMedicare payments fall by more than10% next year. Then there’s the fact thatmedical malpractice premiums have risenby 10%-20% annually for specialists likesurgeons, particularly in states thathaven’t passed liability reform.The bottom line: Defensive business

arrangements designed to blunt Obama -Care’s economic impacts will mean lesspatient choice. �

Dr. Gottlieb, a former official at the Centers for Medicare& Medicaid Services, is a fellow at the AmericanEnterprise Institute and a practicing internist. He’s partnerto a firm that invests in health-care companies.

Reprinted with permission. © Scott Gottlieb. Originallyprinted in Opinion Journal. The Wall Street Journal.May 18, 2010.

Medical Center is the only full-servicehospital in the county, and “it’s an inte-gral part of the community,” she says.“We do community fundraisers and arewell supported by the community.” Kathleen Toomey, MD,

med ical director of the cancercenter, notes that patients arenot only able to get their careclose to home but are able tocontinue to see their own doc-tors. “The doctors who knowthe patients best are here andcan help coordinate their carewith the many specialists.”In addition to medical, radi-

ation, and surgical oncology,Steeple chase’s services include plasticsurgery, a breast care center, genetic

counseling, a cancer registry, clinical tri-als, rehabilitation medicine, palliativecare and pain management, and nutri-tion counseling. “Besides the clinical tri-als that are available to patients, there

are four multidisciplinarygroups [breast, prostate, co -lo rectal, and lung] that cometogether and discuss cases. Inthe case of breast and coloncancer, all new cases are dis-cussed in a multidisciplinaryforum,” Toomey says. TheTobacco Quitcenter is avail-able to help patients stopsmoking. Somerset Medical Center

is a clinical research affiliate of TheCancer Institute of New Jersey, allowing

patients access to clinical tri-als. Currently, patients areenrolled in treatment trialsfor breast, prostate, renal,bladder, and colorectal can-cers as well as chemotherapy-in duced peripheral neuropa-thy. There are also industryregistry trials in multiplemyeloma and chronic lym-phocytic leukemia and a largeannual screening trial forprostate cancer. “We accrued92 patients to trials last year, 23 on treat-ment trials and 69 on the screening trial,”Toomey notes. A complementary medicine suite pro-

vides a variety of services includingyoga, meditation, and massage. Otherresources include a patient library, anonsite wellness boutique, a survivorshipprogram, a healing garden, and educa-tional and support groups for patientsand their families. The Steeplechase Cancer Center

earned its 3-year Community Com -prehensive Cancer Program accredita-tion from the American College ofSurgeons in 2008, and it ranks in the99th percentile for patient-satisfactionscores in New Jersey.Inpatient services are provided at the

35-bed Paul R. Nardoni OncologyPavilion. Patient rooms have sofa bedsfor visitors wishing to stay overnight inaddition to amenities such as blanketwarmers, lounge chairs, showers, refrig-

erators, flat-screen televisions,and DVD/VHS players. Patricia Molinelli, MS, RN,

APN-C, AOCNS, is nursemanager of the inpatient andoutpatient oncology units. Shecame to the center from largeacademic medical centers inNew York and values the inti-macy afforded by working in asmaller setting. “I try to knowone thing that is important toevery patient,” she says. Care

at the center is patient-centered. AsMolinelli de scribes it, “I am the gate-keeper, the coordinator of all these orbits.The patient is the sun.” She views familymembers and other caregivers as “anextension of the patient” and takes careto provide for their comfort with a well-stocked pantry, games, and DVDs for vis-itor use. “We try to take a lot of the bur-den off the family,” she explains. She alsopoints to the latest technology in evi-dence throughout the center. “We rush toget whatever is available to reduce med-ical errors and increase patient safety.”Her current goal is to incorporate genet-ics into the cancer program.Other future plans include a new

interdisciplinary group for lymphoma,myeloma, and leukemias, and a headand neck group as well as gynecology-oncology and palliative care programs,and a men’s cancer support group. ADay of Hope is planned for cancer sur-vivor month. �

Left to right: radiation oncologist Joel Braver, MD; urologist Joel Fischer, MD, chair ofthe Prostate Cancer Institute; Kathleen Toomey, MD, medical director of theSteeplechase Cancer Center; and Katrina Losa, RN, director of the SteeplechaseCancer Center.

Joan Perrone, RPh

Patricia Molinelli,MS, RN, APN-C,

AOCNS


ALOXI® is a registered trademark of Helsinn Healthcare SA, Switzerland, used under license.

Distributed and marketed by Eisai Inc.

© 2010 Eisai Inc.

All rights reserved. Printed in USA. ALO00035-A 05/10

STARTS STRONG. LASTS LONG.

Indication

ALOXI® (palonosetron HCl) injection 0.25 mg is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy, and acute nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy.

Important Safety Information

• ALOXI is contraindicated in patients known to have hypersensitivity to the drug or any of its components

• Most commonly reported adverse reactions in chemotherapy-induced nausea and vomiting include headache (9%) and constipation (5%)

Please see the following brief summary of Full Prescribing Information.

References: 1. Gralla R, et al. Ann Oncol. 2003;14:1570-1577. 2. Eisenberg P, et al. Cancer. 2003;98:2473-2482. 3. Aapro MS, et al. Ann Oncol. 2006;17:1441-1449.

ALOXI® provides powerful CINV prevention that can’t be ignored.

ALOXI is the only IV 5-HT3 antiemetic specifi cally approved for the prevention of both acute and delayed CINV.• Powerful chemotherapy-induced nausea and vomiting (CINV) prevention in the fi rst 24 hours

and up to 5 days following moderately emetogenic chemotherapy1,2

• Powerful acute CINV prevention following highly emetogenic chemotherapy3

Eisai offers:• Contracting opportunities

• Reimbursement resources


ly all aspects of oncology will be affectedby healthcare reform. “This horse has leftthe barn, and they tied an awful lot to it,”he said of the act. “We will all be engagedin this, whether we like it or not.”

But this “engagement” does not haveto be negative, he indicated. The health-care reform act illustrates “the criticalrole that oncology pharmacy plays” inareas that include drug development and

usage, literature evaluation, develop-ment of pathways and guidelines, andcomparative effectiveness research(CER), he told attendees.

It is estimated that at least half the

compounds now in clinical developmentare oncolytics, and many are oral agentsthat will require strict monitoring. “Youare critical to this area,” he said.

Pharmacists will also be central play-ers in the merging of major medical andpharmacy benefits. This has many impli-cations; for example, it could affect howinstitutions will issue formularies, hesaid. Risk evaluation and mitigationstrategies, which the US Food and DrugAdministration is increasingly putting inplace for drug safety and monitoring, willfall under the auspices of pharmacy.Finally, “step therapy,” which is com-monly used in other diseases, may enteroncology, although Bailes said he doesnot see this “fitting in with how oncolo-gists practice.”

Evaluation of the medical literature isbecoming important in the developmentof compendia and in justifying or deny-ing the off-label use of drugs. “You willsee the Centers for Medicare &Medicaid Services doing a more criticalread of the clinical trial literature, espe-cially with regard to the study popula-tions. You will see this evolving fairlyrapidly as a way for Medicare to deal withcompendia problems,” he predicted.

Pathways and guidelines are beingincreasingly promoted by payers, institu-tions, and practices. It is unclear whatthis means for choice of treatments, butevidence-based development is critical,as is monitoring of compliance.

“You, the oncology pharmacists,will be at the center of these discus-sions in your institutions becauseyour work revolves around pharma-ceuticals,” he said.

CER will change practiceCER aims to assess how various drugs,

devices, therapies, or procedures com-pare in treating a disorder. It is a majorfocus of the movement to obtain value-based cancer care.

In oncology, the major focus is ondrugs and their cost implications. TheInstitute of Medicine has articulated100 priority topics for CER. How thisresearch is conducted will be veryimportant, and there is a need formethodology to compare studies.

In 2009-2010, CER received signifi-cant short-term funding ($1.1 billion)from the American Recovery andReinvestment Act. Current healthcarereform proposals would restructure thisinitiative and enhance long-term fund-ing. “This has become very politicized,”Bailes noted. “In restructuring, morestakeholders have been brought in andthey have an enormous say.”

The Congressional Budget Office hasestimated “trillions of dollars” in savings


Conference News

ALOXI® (palonosetron HCl) injection

BRIEF SUMMARY OF PRESCRIBING INFORMATION

INDICATIONS AND USAGE

Chemotherapy-Induced Nausea and VomitingALOXI is indicated for:• Moderately emetogenic cancer chemotherapy – prevention of acute and delayed nausea and vomiting associated with initial and repeat courses• Highly emetogenic cancer chemotherapy – prevention of acute nausea and vomiting associated with initial and repeat coursesDOSAGE AND ADMINISTRATIONRecommended DosingChemotherapy-Induced Nausea and VomitingDosage for Adults - a single 0.25 mg I.V. dose administered over 30 seconds. Dosing should occur approximately 30 minutes before the start of chemotherapy.Instructions for I.V. AdministrationALOXI is supplied ready for intravenous injection. ALOXI should not be mixed with other drugs. Flush the infusion line with normal saline before and after administration of ALOXI.Parenteral drug products should be inspected visually for particulate matter and discoloration before administration, whenever solution and container permit.CONTRAINDICATIONSALOXI is contraindicated in patients known to have hypersensitivity to the drug or any of its components. [see Adverse Reactions (6) in full prescribing information]WARNINGS AND PRECAUTIONSHypersensitivityHypersensitivity reactions may occur in patients who have exhibited hypersensitivity to other 5-HT3 receptor antagonists.ADVERSE REACTIONSBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not refl ect the rates reported in practice.In clinical trials for the prevention of nausea and vomiting induced by moderately or highly emetogenic chemotherapy, 1374 adult patients received palonosetron. Adverse reactions were similar in frequency and severity with ALOXI and ondansetron or dolasetron. Following is a listing of all adverse reactions reported by ≥ 2% of patients in these trials (Table 1).Table 1: Adverse Reactions from Chemotherapy-Induced Nausea and Vomiting Studies ≥ 2% in any Treatment Group

In other studies, 2 subjects experienced severe constipation following a single palonosetron dose of approximately 0.75 mg, three times the recommended dose. One patient received a 10 mcg/kg oral dose in a postoperative nausea and vomiting study and one healthy subject received a 0.75 mg I.V. dose in a pharmacokinetic study.In clinical trials, the following infrequently reported adverse reactions, assessed by investigators as treatment-related or causality unknown, occurred following administration of ALOXI to adult patients receiving concomitant cancer chemotherapy:Cardiovascular: 1%: non-sustained tachycardia, bradycardia, hypotension, < 1%: hypertension, myocardial ischemia, extrasystoles, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles and QT prolongation. In many cases, the relationship to ALOXI was unclear.Dermatological: < 1%: allergic dermatitis, rash.Hearing and Vision: < 1%: motion sickness, tinnitus, eye irritation and amblyopia.Gastrointestinal System: 1%: diarrhea, < 1%: dyspepsia, abdominal pain, dry mouth, hiccups and fl atulence.

General: 1%: weakness, < 1%: fatigue, fever, hot fl ash, fl u-like syndrome.Liver: < 1%: transient, asymptomatic increases in AST and/or ALT and bilirubin. These changes occurred predominantly in patients receiving highly emetogenic chemotherapy.Metabolic: 1%: hyperkalemia, < 1%: electrolyte fl uctuations, hyperglycemia, metabolic acidosis, glycosuria, appetite decrease, anorexia.Musculoskeletal: < 1%: arthralgia.Nervous System: 1%: dizziness, < 1%: somnolence, insomnia, hypersomnia, paresthesia.Psychiatric: 1%: anxiety, < 1%: euphoric mood.Urinary System: < 1%: urinary retention.Vascular: < 1%: vein discoloration, vein distention.Postmarketing ExperienceThe following adverse reactions have been identifi ed during postapproval use of ALOXI. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.Very rare cases (<1/10,000) of hypersensitivity reactions and injection site reactions (burning, induration, discomfort and pain) were reported from postmarketing experience of ALOXI 0.25 mg in the prevention of chemotherapy-induced nausea and vomiting.DRUG INTERACTIONSPalonosetron is eliminated from the body through both renal excretion and metabolic pathways with the latter mediated via multiple CYP enzymes. Further in vitro studies indicated that palonosetron is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4/5 (CYP2C19 was not investigated) nor does it induce the activity of CYP1A2, CYP2D6, or CYP3A4/5. Therefore, the potential for clinically signifi cant drug interactions with palonosetron appears to be low.Coadministration of 0.25 mg I.V. palonosetron and 20 mg I.V. dexamethasone in healthy subjects revealed no pharmacokinetic drug-interactions between palonosetron and dexamethasone.In an interaction study in healthy subjects where palonosetron 0.25 mg (I.V. bolus) was administered on day 1 and oral aprepitant for 3 days (125 mg/80 mg/80 mg), the pharmacokinetics of palonosetron were not signifi cantly altered (AUC: no change, Cmax: 15% increase).A study in healthy volunteers involving single-dose I.V. palonosetron (0.75 mg) and steady state oral metoclopramide (10 mg four times daily) demonstrated no signifi cant pharmacokinetic interaction.In controlled clinical trials, ALOXI injection has been safely administered with corticosteroids, analgesics, antiemetics/antinauseants, antispasmodics and anticholinergic agents.Palonosetron did not inhibit the antitumor activity of the fi ve chemotherapeutic agents tested (cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C) in murine tumor models.USE IN SPECIFIC POPULATIONSPregnancyTeratogenic Effects: Category BTeratology studies have been performed in rats at oral doses up to 60 mg/kg/day (1894 times the recommended human intravenous dose based on body surface area) and rabbits at oral doses up to 60 mg/kg/day (3789 times the recommended human intravenous dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to palonosetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, palonosetron should be used during pregnancy only if clearly needed.Labor and DeliveryPalonosetron has not been administered to patients undergoing labor and delivery, so its effects on the mother or child are unknown.Nursing MothersIt is not known whether palonosetron is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants and the potential for tumorigenicity shown for palonosetron in the rat carcinogenicity study, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric UseSafety and effectiveness in patients below the age of 18 years have not been established.Geriatric UsePopulation pharmacokinetics analysis did not reveal any differences in palonosetron pharmacokinetics between cancer patients ≥ 65 years of age and younger patients (18 to 64 years). Of the 1374 adult cancer patients in clinical studies of palonosetron, 316 (23%) were ≥ 65 years old, while 71 (5%) were ≥ 75 years old. No overall differences in safety or effectiveness were observed between these subjects and the younger subjects, but greater sensitivity in some older individuals cannot be ruled out. No dose adjustment or special monitoring are required for geriatric patients.Of the 1520 adult patients in ALOXI PONV clinical studies, 73 (5%) were ≥65 years old. No overall differences in safety were observed between older and younger subjects in these studies, though the possibility of heightened sensitivity in some older individuals cannot be excluded. No differences in effi cacy were observed in geriatric patients for the CINV indication and none are expected for geriatric PONV patients. However, ALOXI effi cacy in geriatric patients has not been adequately evaluated.Renal ImpairmentMild to moderate renal impairment does not signifi cantly affect palonosetron pharmacokinetic parameters. Total systemic exposure increased by approximately 28% in severe renal impairment relative to healthy subjects. Dosage adjustment is not necessary in patients with any degree of renal impairment.Hepatic ImpairmentHepatic impairment does not signifi cantly affect total body clearance of palonosetron compared to the healthy subjects. Dosage adjustment is not necessary in patients with any degree of hepatic impairment.RaceIntravenous palonosetron pharmacokinetics was characterized in twenty-four healthy Japanese subjects over the dose range of 3 – 90 mcg/kg. Total body clearance was 25% higher in Japanese subjects compared to Whites, however, no dose adjustment is required. The pharmacokinetics of palonosetron in Blacks has not been adequately characterized.OVERDOSAGEThere is no known antidote to ALOXI. Overdose should be managed with supportive care. Fifty adult cancer patients were administered palonosetron at a dose of 90 mcg/kg (equivalent to 6 mg fi xed dose) as part of a dose ranging study. This is approximately 25 times the recommended dose of 0.25 mg. This dose group had a similar incidence of adverse events compared to the other dose groups and no dose response effects were observed.Dialysis studies have not been performed, however, due to the large volume of distribution, dialysis is unlikely to be an effective treatment for palonosetron overdose. A single intravenous dose of palonosetron at 30 mg/kg (947 and 474 times the human dose for rats and mice, respectively, based on body surface area) was lethal to rats and mice. The major signs of toxicity were convulsions, gasping, pallor, cyanosis and collapse.PATIENT COUNSELING INFORMATIONSee FDA-Approved Patient Labeling (17.2) in full prescribing informationInstructions for Patients• Patients should be advised to report to their physician all of their medical conditions, any pain, redness, or swelling in and around the infusion site [see Adverse Reactions (6) in full prescribing information].• Patients should be instructed to read the patient insert.

Rx OnlyMfd by OSO Biopharmaceuticals, LLC, Albuquerque, NM, USA or Pierre Fabre, Médicament Production, Idron, Aquitaine, France and Helsinn Birex Pharmaceuticals, Dublin, Ireland.

ALOXI® is a registered trademark of Helsinn Healthcare SA, Switzerland, used under license.Distributed and marketed by Eisai Inc., Woodcliff Lake, NJ 07677.© 2009 Eisai Inc.All rights reserved. Printed in USA. AL449-A 08/09

EventALOXI

0.25 mg (N=633)

Ondansetron 32 mg I.V. (N=410)

Dolasetron 100 mg I.V.

(N=194)Headache 60 (9%) 34 (8%) 32 (16%)

Constipation 29 (5%) 8 (2%) 12 (6%)Diarrhea 8 (1%) 7 (2%) 4 (2%)Dizziness 8 (1%) 9 (2%) 4 (2%)Fatigue 3 (< 1%) 4 (1%) 4 (2%)

Abdominal Pain 1 (< 1%) 2 (< 1%) 3 (2%)Insomnia 1 (< 1%) 3 (1%) 3 (2%)

HOPA

Changes Ahead with Healthcare Reform... Continued from cover

Continued on page 9


NEW ORLEANS—A retrospectiveanalysis of healthcare resource utiliza-tion for patients with ovarian cancerreceiving intraperitoneal (IP) cisplatinchemo therapy identified a trendtoward more hospital readmissions forchemotherapy-induced nausea andvomiting (CINV) among patientsreceiving ondansetron prophylaxis, ascompared with palo nosetron.The study from Brigham and

Women’s Hospital (BWH) in Bostonwas presented by Ann McDonnell,PharmD, BCOP.Palonosetron was identified as a high-

expenditure drug by the PartnersHealthCare System Center for DrugPolicy, a center established by BWH’sintegrated healthcare system to study theeffectiveness of new drugs before or asthey are being introduced to the market.An evaluation of prior medication useidentified the gynecologic oncologygroup as the predominant prescriber ofpalonosetron at BWH, frequently forpatients receiving IP cisplatin.Palonosetron and ondansetron are

the two 5-hydroxytryptamine-3 (5-HT3) receptor antagonists included onthe BWH formulary. A literature reviewconcluded that these agents can be con-sidered clinically interchangeable (YehYV, et al. J Oncol Pharm Pract. May 7,2010. Epub ahead of print), but the costof generic ondansetron is several-fold lower than that of palonosetron,McDonnell pointed out.In March 2008, BWH instituted pro-

tocol guidelines that consisted ofondansetron for first-line use andpalonosetron for second-line use (Table).“When ondansetron became generic,the differences in cost became substan-tial. We changed practice to useondansetron first-line, but anecdotalreports from our healthcare providerssuggested that patients who receiveondansetron were more likely to haveadditional healthcare resource use due toCINV,” she said.The study aimed, therefore, to

describe the use of these agents inpatients receiving IP cisplatin and tocompare the two agents with regard toresource utilization.The investigators reviewed medical

records during three time periods: twoperiods prior to BWH guidelines(January through June 2006 forondansetron and October 2007through June 2008 for palonosetron)and one period after guideline imple-mentation for ondansetron (Marchthrough June 2008).The occurrence of CINV-related hos-

pital readmissions, emergency depart-

ment visits, and outpatient encounters(ie, clinic visits, telephone calls) within7 days after cisplatin administration wascompared. Reasons for healthcareresource use were determined by re view-ing medical charts. CINV-relatedresource use was defined as events associ-ated with dehydration due to nausea andvomiting, hypovolemia, hypo kalemia,constipation, shortness of breath, or syn-cope/collapse.

Trend toward increasedreadmissions with ondansetronHospital readmissions tended to be

greater with ondansetron: 2/39 (5.1%)patients, both CINV related, comparedwith 2/89 (2.3%), neither of which wasCINV related (P = .09 for CINV-relatedadmissions). One of the readmittedpatients had documented electrolyteimbalance, nausea and vomiting, anddehydration on day 7 of the chemother-apy cycle. This patient received oralondansetron only on the day of IP cis-platin during her hospital stay. The otherreadmitted patient received intravenousondansetron for 2 days and reporteddehydration 4 days after IP cisplatin.There were no CINV-related emer-

gency department visits. CINV-relatedoutpatient visits were documented infour (10.3%) patients receiving on -dansetron and seven (7.9%) patientsreceiving palonosetron (P = .657). Twiceas many of the ondansetron grouppatients (5.1% vs 2.3%) switched to thealternate 5-HT3 receptor antagonist.“To our knowledge this is the first real-

world comparison of healthcare resourceuse between patients given ondansetronor palonosetron for prophylaxis ofCINV,” McDonnell said. “Our analysisfound a trend toward a higher incidenceof CINV-related hospital readmissionswith ondansetron, though not statistical-ly significant, which is consistent withclinicians’ anecdotal reports.”These findings need to be confirmed

in prospective, randomized trials that

compare outcomes with single-dosepalo nosetron versus multiday ondan -setron therapies in the IP cisplatin popu-lation, she said. She noted that the dos-ing of ondansetron might have beensuboptimal in some cases; 27% ofpatients in this study received only 1 dayof ondans etron during their hospital stay.During the discussion, it was noted

that the dose of cisplatin that manypatients were given (100 mg/m2) is nowviewed as unacceptably high.Regardless, McDonnell emphasized

that oncologists at BWH were unhap-py with ondansetron. “It is a challengeto get our physicians to acceptondansetron for patients receiving IPcisplatin,” she said.

Palonosetron inhibits NK1 agonistresponsesIn a second presentation, Barbara

Slusher, PhD, chief scientific officer forthe Johns Hopkins Brain Science In -stitute NeuroTranslational Pro gram,

Baltimore, reported results of translation-al work showing that palonosetronuniquely inhibits neuro kinin-1 (NK1)agonist re sponses in vitro and in vivo.The same was not found for ondansetronor granisetron.Previous work has shown that

palonosetron exhibits allosteric bindingand positive cooperativity (Rojas C, etal. Anesth Analg. 2008;107:469-478) andtriggers receptor internalization and pro-longed inhibition of receptor function(Rojas C, et al. Eur J Pharmacol. 2010;626:193-199). NK1 receptor antagonistsare used to prevent delayed emesis.Palonosetron helps prevent delayed eme-sis as well. Slusher and her colleaguesinvestigated whether palonosetron indi-rectly antagonizes the NK1 pathway.“Our results provide a rationale for the

efficacy observed with palono setron indelayed emesis in the clinic,” Slushersaid. �

—CH

June 2010 I VOL 3, nO 4 9www.TheOncologyPharmacist.com

Conference News

Ondansetron Group Palonosetron Group

Day 2 Aprepitant 125 mg, oralDexamethasone 12 mg, IVOndansetron 24 mg, oral or IV

Aprepitant 125 mg, oralDexamethasone 12 mg, IVPalonosetron 0.24 mg, IV

Day 3 Aprepitant 80 mg, oralDexamethasone 12 mg, IVOndansetron 24 mg, oral or IV

Aprepitant 80 mg, oralDexamethasone 12 mg, IV

Day 4 Aprepitant 80 mg, oralDexamethasone 12 mg, oral

Aprepitant 80 mg, oralDexamethasone 12 mg, oral

Table. Dosing Regimens Used at Brigham and Women’s Hospital

Palonosetron Reduces Readmissions for CINV inPatients Receiving IP Cisplatin

Changes Ahead with HealthcareReform... Continued from page 8

if CER findings are tied to providerincentives, he added.The fiscal year 2011 budget is likely to

include additional funding for CER. TheAgency for Healthcare Research andQuality will be budgeted approximately$286 million, which is an increase of$261 million over fiscal year 2010.The Senate Finance Committee pro-

posal recommends that CER be governedby a nonprofit entity with a public/pri-vate board. It proposes long-term fundingfrom private insurers and a Medicaretrust fund on a per-member basis.

Language was added to ensure that CERnot be used as the sole basis for Medicarecoverage decisions. Coverage determina-tions must give weight to all relevantstudies and evidence, and to evidencesuggestive of benefits to specific subpopu-lations, “even if, on average, no suchbenefit is seen,” he said.“I think this will change over time,

however, as experience widens withCER and more become involved,” hepredicted. “Our view is that oncologyneeds to be part of the decision-makingprocess in CER.” �

Palonosetron uniquely inhibits neuro kinin-1 agonist re sponses in vitro and in vivo.


NEW ORLEANS—Oncology pharma-cists can save their institutions thou-sands of dollars annually by reducingchemotherapy waste, according to theexperience of the Veterans Affairs’North Texas Health Care System inDallas. Sarah Gressett Ussery, PharmD,described her institution’s chemotherapymonitoring and management.

“Our findings speak to the role of thehematology/oncology pharmacist inreviewing orders for their appropriate-ness, and knowing which drugs areexpensive,” Ussery told The OncologyPharmacist. “Having an oncology phar-macist in charge significantly reducedwaste. Before this, we were not evenaware of how much was wasted.”

Ussery and colleagues documentedchemotherapy waste over a 2-monthperiod in 2005 and found that 143chemotherapy doses were wasted, mostfrequently bevacizumab, docetaxel, gem-citabine, oxaliplatin, and rituximab. Thetotal cost of waste was $90,400, whichextrapolated to more than $500,000annually. Documenting waste again, thistime in a 2-month period in 2007, theyidentified 61 wasted doses costing$42,000, extrapolating to $250,000annually.

The reasons for drug waste were dis-ease progression (23%), symptomatictoxicity (18%), patient no-show(15%), wrong order or ordered tooearly (13%), treatment delay per

patient preference (12%), dose adjust-ment (8%), laboratory abnormality(8%), and other reason (3%).

Concerns over this waste precipitatedthe hiring of a hematology/oncologypharmacist who implemented a chemo -

therapy management program and pro-vided oversight. The key to this programwas to delay the preparation of expensivechemotherapies.

Waste was then calculated withthis program in place. Under the

chemo therapy management program,waste over a 2-month period wasonly $15, extrapolating to $90 annu-ally, Ussery reported. �

—CH


Conference News

EPO Ordering Form Improves Guidelines Compliance,Saves Practices MoneyNEW ORLEANS—Implementationof an explicit order form for darbe po et-in alfa significantly improved compli-ance with current guidelines and led tolarge cost savings, California pharma-cists report.

In July 2007, the Centersfor Medicare & Medicaid Ser -vices (CMS) implementedstricter guidelines for treatingchemotherapy-induced ane-mia with erythropoiesis-stimu-lating agents. “This changedthe prescribing requirementsand created some confusion,”said Siu-Fun Wong, PharmD,of the Hematology-OncologyMedical Group of OrangeCounty, Orange, California, who pre-sented the study at the meeting.

The lead author was her student,Stacy L. Yang, a PharmD candidate atWestern University of Health Sciences

College of Pharmacy in Pomona,California.

“We wanted to detect prescribingerrors in the daily encounters withpatients,” Wong said. To this end, the

investigators retrospectivelyreviewed cases in whichpatients received darbepoetinalfa between May 2008 andFebruary 2009. They discov-ered that in 50% of cases, thedrugs were not given inaccordance with the updatedCMS guidelines.

“There was a fairly highnoncompliance rate, andthis also was associated withloss of revenue,” Wong said.

In an effort to correct the high non-compliance event rate, they developed aDarbepoetin alfa (Aranesp) Admin -istration Order Form (AAOF), thenassessed compliance once it was institut-

ed. The form is quite explicit, although itis designed to be self-directed. Staffattended in-service training on its use.

The study evaluated guideline compli-ance before use of the AAOF, involving38 patients receiving 231 interventions.After implementation, 53 patients re -ceived 143 interventions.

Implementation of the AAOF signifi-cantly reduced noncompliance eventspertaining to initial dosing and mainte-nance dose frequency, the review found.

Prior to the AAOF, 27 (71.1%) of38 patients received an inappropriateinitial weight-based dose but this prac-tice occurred only in two (3.8%) of 53patients when the form was used (P<.001). Inappropriate dose frequencyoccurred at baseline in 41 (17.7%) of231 interventions, but with theAAOF, no cases occurred at all (P<.0001). There were no significantchanges in inappropriate dosing, dose

reduction, or dose escalation. In total, there were 19 inappropriate

documentations after the intervention,and in eight (15.1%) of 53 patients pro -viders did not use the AAOF. Failure todocument doses given or laboratory val-ues occurred in <5% of interventions,she added.

“Most important, better complianceimpacted reimbursement,” Wong said.The projected cost-avoidance analysisshowed that $72,611 per year was cap-tured by implementation of the form.

The projected number of noncompli-ance events per year was 132 beforeAAOF and just 18 after AAOF, repre-senting projected reimbursement lossesof $84,076 versus $11,465.

“Even with the declining use of darbe-poetin alfa, we saved the practice over$70,000,” she noted. �

—CH

Oncology Pharmacists Can Significantly ReduceChemotherapy Waste

Siu-Fun Wong,PharmD

NEW ORLEANS—The use of stan-dardized pediatric chemotherapy formscan improve safety by creating a consis-tent and streamlined method of orderingChildren’s Oncology Group (COG) trialprotocols and regimens, according toinvestigators from Memorial RegionalHospital and Joe DiMaggio Children’sHospital in Hollywood, Florida.

Wayne R. Shipman, RPh, and Mari -beth Arzola, PharmD, showcased theorder set they developed for this pur-pose. It consists of a preprinted chemo -therapy ordering form, preprinted med-ication administration record, andpreprinted pharmacy dispensing recordthat correspond to the 14 COG treat-ment protocols they use. The formsreflect the protocol for a complete planof care, they noted.

“Prior to the introduction of our stan-dardized pediatric order sets, we encoun-tered many mistakes in pediatric chemo -therapy orders, and these required

multiple pharmacy interventions. Afterthe introduction of the preprintedforms, there was a 93% reduction inchemotherapy transcribing and calcula-tions errors,” Arzola said.

These errors were mostly illegible orconfusing orders; wrong dosing; andcrossed out, altered, or incompleteorders, she explained.

“We decided to revamp the process,”she said. “We redid how we orderchemo therapy, dispense chemotherapy,and check chemotherapy on the medica-tion administration record.”

A multidisciplinary team (Chemo -therapy Safe Practice Committee) andthe oncology pharmacy team createdthe templates.

The standardized order set consists ofa COG protocol template (per tumorsite) for chemotherapy orders with amedication dose calculator, whichrequires two physician signatures; amedication administration record per

COG protocol; and a pharmacy triple-check form, which reflects the COGprotocol template and enables the phar-macist to interpret and verify thepatient’s plan of care.

The system is not perfect, theyacknowledged. Second signatures aresometimes missing, heights and weightsmay be inconsistent between the orderforms, incomplete forms are still sent tothe pharmacy, reasons for dose modifica-tions are sometimes lacking, and “cross-ing out” doses is still an issue.

But the order set has greatly improvedaccuracy in writing, checking, interpret-ing, and entering chemotherapy orders;has decreased pharmacy chemotherapypreparation turnaround times; hasincreased nursing chemotherapy admin-istration efficiency; and has shortenedlength of stay and throughput times forpediatric patients and their families. �

—CH

Standardized Forms Facilitate COGTreatment



Breast Cancer

SAN ANTONIO—Interim analysis of alarge trial of women treated withtrastuzumab for human epidermal growthfactor receptor type 2 (HER2)-positivebreast cancer before or after surgery indi-cates that concurrent use with a taxanemay improve overall survival (OS) anddisease-free survival (DFS) comparedwith sequential administration. Previoustrials have shown a large benefit oftrastuzumab but left open the question ofthe optimal timing of its use. (See, eg,the HERA trial: Piccart-Gebhart MJ. NEngl J Med. 2005;353:1659-1672.)

At the San Antonio Breast CancerSymposium in December 2009, EdithPerez, MD, director of the breast programat Mayo Clinic in Jacksonville, Florida,reported results of the N9831 trial thattested concurrent or sequential tras tu -zumab (San Antonio Breast CancerSymposium; 2009. Abstract 80). The

trial randomized women to one of threetreatment arms: doxorubicin/cyclophos-phamide then paclitaxel (control), dox-orubicin/cyclophospha mide, then pacli-taxel, then trastu zumab for 52 weeks(sequential therapy), or doxorubicin/cyclophosphamide, then paclitaxelplus trastuzumab for 12 weeks followedby trastuzumab for 40 weeks (concur-rent therapy).

Compared with the control regimen(n = 1097), sequential therapy (n =1087) was associated with a 30% benefitin DFS at a median of 5.5 years of follow-

up (estimated hazard ratio [HR], 0.70; log rank P = .0005). An additional 23%benefit in DFS occurred in the concur-rent therapy group (n = 949) when com-pared with the sequential arm at a medi-an follow-up of 5.3 years (estimated HR,0.77; log rank P = .019). Based on thespecific statistical methods designed for

interim analysis, however, this last differ-ence was not deemed to be significant.

Perez presented results comparingcontrol and concurrent thera-py for a median follow-up ofapproximately 3 years. Com -pared with the control arm,concurrent therapy was asso-ciated with a 52% benefit inDFS (adjusted HR, 0.48; P <.00001) and a 35% benefit inOS (unadjusted HR, 0.65; P= .0007).

Speaking with The On -cology Pharm a cist before herpresentation, Perez said she thought theN9831 trial results would change prac-tice patterns worldwide, especially incountries where the usual practice issequential therapy. Most observers feltthat the N9831 results made a goodcase for using concurrent trastuzumabwith the taxane, although most saidusing sequential therapy would not bebad practice.

Julie Gralow, MD, professor of med-ical oncology at the University ofWashington in Seattle, a coauthor ofN9831, noted that the interim results

involved less than one half of theplanned events for which the study waspowered to show a difference. She con-

cluded that the results werestill strong enough to recom-mend overlapping trastuzu -mab with a taxane.

Mark Pegram, MD, direc-tor of clinical research at the Sylvester Comp re hen -sive Cancer Center of theUni versity of Miami MillerSchool of Medicine inFlorida, said, “While maybenot completely technically

statistically significant…[the study is]so consistent with what was expected,based on all of the science, that I thinkit will be embraced fairly widely andfairly quickly.”

But Aman Buzdar, MD, of the M. D.Anderson Cancer Center in Houston,Texas, cautioned that physicians needto be familiar with using the drugstogether and have to follow patientsclosely. “Some of the toxicities are alsosynergistic when you combine chemo -therapeutic agents with antibody treat-ment,” he warned. �

Concurrent Trastuzumab with Chemotherapy BeatsSequential Use for HER2-positive Breast CancerBy Daniel M. Keller, PhD

Three New Drugs on the Horizon for HER2-positiveBreast Cancer

Three new drugs are in thepipeline to treat human epider-mal growth factor receptor

(HER) type 2-positive metastatic breastcancer (MBC). Two appear to have thepotential to provide incremental gains,and one looks like a game changer.

T-DM1The one getting the most attention at

recent oncology conferences is T-DM1,a first-in-class conjugate of the mono-clonal antibody trastuzumab and DM1,a derivative of maytansine. Maytansineis an antimicrotubule agent that provedtoo toxic to use alone a couple ofdecades ago. The key to taming it foruse today is a linker that attaches DM1to trastuzumab and is cleaved once thedrug has been internalized in cells over-expressing HER2, releasing the DM1inside. The drug is almost undetectablein the circulation (LoRusso P, et al. SanAntonio Breast Cancer Symposium;2009. Abstract 5099).

Ian Krop, MD, PhD, and coworkersreported on a phase 2 study of 110

patients with HER2-positive MBC pre-viously treated with an anthracycline, ataxane, capecitabine, lapatinib, andtrastuzumab. Patients received single-agent T-DM1 at a dose of 3.6 mg/kgintravenously every 3 weeks. Even in thispopulation of heavily pretreated patientswith more than 2 years of HER2-direct-ed therapy, the overall response rate(ORR) was 30%, more than 46% hadstable disease, and the clinical benefitrate (CBR) was 40% to 45%. The medi-an time to progression was 7.3 months(San Antonio Breast Cancer Sym -posium; 2009. Abstract 5090).

In another phase 2 study of 112heavily pretreated patients with MBC,T-DM1 showed good efficacy and tol-erability. The ORR was 26.7% by in de-pendent review and 38.9% by investi-gator assessment, with a medianprogression-free survival of 4.6 months(Vogel CL, et al. J Clin Oncol. 2009;27[15S]:Abstract 1017). In the 66patients in that trial who were previ-ously treated with lapatinib andtrastuzumab, T-DM1 produced very

similar re sponse rates (24.2% and34.8%, respectively).

The main adverse effects, as exempli-fied in the Krop study, were fatigue,nausea, and brief, transient thrombocy-topenia. Most have been grade 1 or 2.Phase 3 trials are ongoing, comparing T-DM1 to other combined therapies.

Carlos Arteaga, MD, professor ofmedicine at Vanderbilt University inNashville, Tennessee, is very positiveabout T-DM1, especially for heavilypretreated patients. “The conjugate hasshown remarkable activity as a thirdline in HER2-positive metastatic breastcancer,” he said.

Harold Burstein, MD, PhD, of Dana-Farber Cancer Institute in Boston,noted that T-DM1 may have efficacy asa single agent “because it is, in essence,chemotherapy plus trastuzumab.” And,he added, “It does not seem to cause sig-nificant alopecia, which is very excitingfor patients.”

Although some patients have donewell on trial for more than 1 year, and insome cases 2 years, Eric Winer, MD,

director of breast oncology at Dana-Farber, cautioned that “We have nottreated a sufficient number of patients foryears to know for certain that there isn’ta low level of cumulative toxicity.”

Adam Brufsky, MD, PhD, professor ofmedicine at the University of Pittsburgh,remains very optimistic about T-DM1.“It will have a major role in clinical prac-tice...at least be equivalent to cap -ecitabine/lapatinib with probably fewerside effects,” he said.

In a more general sense, the linkertechnology used to join DM1 withtrastuzumab may be applicable to usewith other monoclonal antibodiesagainst other tumor types, “the so-calledtargeted chemotherapy concept that hasbeen the Holy Grail for everybody for somany years,” according to Luca Gianni,MD, director of medical oncology andclinical pharmacology at Italy’s NationalTumor Institute in Milan.

NeratinibAnother drug in development is nera-

Continued on page 13

Edith Perez, MD

Concurrent use with a taxane may improve overallsurvival and disease-free survival compared withsequential administration.


Bayonne, New Jersey—Asdemand for their servicesgrew and it became increas-ingly clear that their prac-tice was becoming a region-al center for patients battlingcancer, the medical staff atColanta Hematology &Oncology Center made thedecision to build and openan outpatient infusion cen-ter that could adequatelyand comfortably serve theirpatients.The result was a state-of-

the-art infusion center with 20 reclinersin a patient-focused environment that isopen to serve patients 7 days a week. Themedical staff of three physicians and fournurses, led by practice administratorRomel Colanta, MD, now delivers abroad array of out patient oncology servic-es, including chemotherapy, albumin,anti emetic, and iron therapy infusions.Additionally, the infusion center staffprovides supportive cancer care services,including therapeutic phlebotomy, anti -biotic infusion, and electrolyte replace -ment. They also provide multidiscipli-nary infusion services for patientsreferred to the center by gastroenterolo-gists, neurologists, and infectious diseasespecialists.With the high volume of oncology

drugs required to treat their patientpanel, the medical staff at Colanta had tomake the decision as to how they wouldsupply their patients with oncology med-

ications. If they followed thetraditional practice of hema-tology and oncology pro -viders, they would “buy andbill” the medications, mean-ing they would have theresponsibility of sourcing andpurchasing the medications,storing them, preparing andsometimes compounding themfor patients, managing theinventory on an ongoing basis,and dealing with a bevy ofinsurance prior authorizationand reimbursement procedures

and requirements in order to get paid.Although buy and bill traditionally

had its benefits, including a substantialmargin paid by Medicare and other com-

mercial payers, changes that resultedfrom the Medicare Modernization Actlowered a margin that sometimes paidphysicians 40% over the cost of the drugto just 6%.The Colanta team decided there was a

better way. They knew they could out-

source the pharmacy func-tion to a pharmacy that washighly specialized in oncolo-gy medications. This phar-macy would prepare thedrugs under the highest clin-ical standards, deliver themjust in time for treatmentday (thereby eliminatingwaste), handle all the hasslesof insurance prior authoriza-tion and reimbursement,and free the center from thechallenges of safely storing and dispens-ing the drugs and the huge, capital-intensive “carry costs” that maintainingsuch an inventory requires.Dr Colanta and his colleagues

researched their options and chose

OncoMed—The Oncology Pharmacy.OncoMed is an oncology pharmacy,meaning that its sole business is oncolo-gy medications. Its specially trained andcertified oncology pharmacists work in atechnologically advanced pharmacy builtexclusively for oncology pharmaceuticalprescription processing and dispensing,including a USP <797>-compliant class5 clean room. To protect the supplychain and ensure a complete and fulldrug pedigree, all inventories are pur-chased directly from pharmaceuticalmanufacturers. The company’s “just-in-time treatment-day” service means thatoncologists and hematologists in anystate in the nation are guaranteed deliv-ery of medications and all therapy-specific administration supplies within24 hours of placing the order. Given theColanta Hematology & OncologyCenter’s close proximity to one ofOncoMed’s regional oncology pharmacysites, they were eligible to get same dayand even emergency stat dose deliverywhen needed.But what also set OncoMed apart from

specialty pharmacies thatconcentrate on more thanone class of pharmaceuticalsis the OncoMed care man-agement support team’s abil-ity to work with insurers toget the authorizations thatthe Colanta Hematology &Oncology Center’s pa tientsneed. OncoMed’s team in -cludes patient care naviga-tors and patient reimburse-ment specialists who have

extensive experience working with in -surers, oncology drug manufacturers, andmedical foundations. These specialistsalways know where to go to search forneeded funding for patients who arebanking on that expertise for theirrecovery.OncoMed has become a pivotal part-

ner to the Colanta Hematology & On -cology Center by owning the pharma-ceutical worry and letting the physiciansfocus solely on guiding their patients toremission.We sat down with Dr Colanta and

asked him about the new center and itspartnership with OncoMed.

Why did your infusion center chooseto partner with OncoMed?The buy-and-bill model that oncolo-

gists have always worked under is nolonger viable. Physicians can’t make anoffice run on a 6% margin. Under buyand bill, the average sales price (ASP) +6% methodology can very quickly go toASP + 4%, +2%, or -2% if we run intoany obstacles in getting reimbursed. Andwith expensive drugs like chemotherapy,we cannot take that risk. Plus, OncoMedhelps patients get funding for medicationeven after the patient’s insurer hasdenied coverage.

In addition to this new center, younow have two additional sites in NewJersey. How has the partnership withOncoMed enabled you to successfullylaunch and grow the center?When we opened, 90% of what we

infused in the clinic was oncolytics. As wehave grown, we infuse a far broader arrayof medications. The backbone of our prac-tice is still chemotherapy, but we haveincreased our nononcolytic infusions. For

New Jersey Hematology and Oncology Center Partners with OncoMed


Evolution inOncology Practice Management

PART2OF A SERIES

OncoMed providedfunding and

editorial support for this article

www.OncoMed.net

ADVERTORIAL

“The partnership with OncoMed has enabledus to make better use of our capital.”

——Romel Colanta, MDPractice Administrator

Colanta Hematology & Oncology Center

The outpatient infusion center at Colanta Hematology & Oncology Center comfortably servespatients.

Kevin Askari, RPhPresident and Chief Clinical PharmacistOncoMed

Burt ZweigenhaftCEO, OncoMed

� �� TOP_June2010_v2_TOP 6/15/10 11:53 AM Page 12


Breast Cancer

To learn more about OncoMed or to request a presentation, contact OncoMed at 1-877-662-6633, extension 1298 or [email protected], or go to www.oncomed.net.

patients referred by gastro -intestinal practitioners, we in -fuse infliximab, and for thosereferred by infectious diseasephysicians, we provide antibi-otic infusions. Some of thosedrugs are still viable [underbuy and bill], but not all. Wehave been able to devotemoney that has traditionallygone to purchasing medica-tion and instead ex pand ourservices. The partnership withOncoMed has enabled us tomake better use of our capital.

How does the medication orderingand fulfillment process work withOncoMed?Having an efficient and focused

process in place is very important. Wehave been able to institute a processwhere we have someone devoted tobeing our liaison with OncoMed. When

a patient comes in and his orher benefits are precertified,we send the person’s caseinformation to OncoMed,and the drugs are sent to usdirectly, along with all theadministration supplies. Weget them on a next-daybasis, or sooner if needed,and everything is clearlylabeled with patient-specificinformation. That makes ahuge difference to us whendealing with Onco Med ver-

sus some specialty pharmacies that someinsurers have imposed upon us to use,which get the drugs wrong, ship themlate, and have no idea of the correctadministration supplies.

How does the relationship withOncoMed allow you and your team tofocus on what is important?I will give you a “before-and-after”

example. Before weworked with Onco -Med, 50% or more ofour time was spent onmanaging drug costsand reimbursement.We had five peoplemanaging pharmacyat the three loca-tions; we have beenable to reduce thatnumber of employeesto one. Before, wehad to continuallymake sure that wewere not underwateron drugs, as reim-bursement rates and times fluctuated.OncoMed has made it possible to notdevote time and effort on that.

Based on your experience, whatwould you say about OncoMed to he -matologists and oncologists considering

such a move?It is definitely a relationship that every

infusion center or oncologist has toexplore. When dealing with narrowingreimbursement margins and delayedreimbursement, ultimately it will be ben-eficial to switch to OncoMed. �

Continued from page 12

EVOLUTION IN ONCOLOGY PRACTICE MANAGEMENT™

Pharmacists filling orders at the OncoMed facility.

Ellen Scharaga, RPhSenior Vice PresidentOncoMed

� ��

tinib, an oral small molecule, pan-ERBBirreversible tyrosine kinase (TK) in -hibitor, meaning it inhibits the TKs asso-ciated with the HER1, HER2, and HER4cell surface receptors. The consensusamong oncologists is that neratinib showsgood activity as a single agent as well as incombination with trastuzu mab afterprogression on trastuzumab. “There isactivity of neratinib in both trastuzu mab-and lapatinib-pretreated [patients],”said Debu Tripathy, MD, director ofthe Women’s Cancer Program at theUniversity of Southern California inLos Angeles.

In the past, the most prevalent con-cern about neratinib was the high inci-dence of diarrhea; however, at the SanAntonio Breast Cancer Symposium inDecember 2009, researchers said that thediarrhea is manageable with medicationand appears to diminish in frequency andseverity over several weeks of treatment.In a small phase 1/2 study using 240

mg/day of neratinib, Awada and cowork-ers found a 100% incidence of diarrheaamong patients with MBC who werepreviously treated with lapatinib and a93% incidence if no prior lapatinib expo-sure. ORRs were 43% if no prior lapa-tinib and 25% with prior exposure. CBRswere 57% and 50%, respectively (SanAntonio Breast Cancer Symposium;2009. Abstract 5095).Burstein and coworkers found the

same incidence of early-onset diarrheausing 240 mg/day of neratinib andreported that it could be controlledwith antidiarrheal medications and

dose reductions. Vomiting occurred in29% of patients. The drug appeared tohave acceptable cardiovascular safety,with no grade 3/4 toxicity that wasconsidered related to neratinib. In acohort of 67 patients, only 3% had aleft ventricular ejection fraction <50%(San Antonio Breast Cancer Sym -posium; 2009. Abstract 5096).

Both Burstein and Gabriel Horto -bagyi, MD, of The University of TexasM. D. Anderson Cancer Center inHouston, commented that studies indi-cate that the response rate to neratinibis probably higher than to lapatinib insimilar groups of patients. “We aremuch more excited about neratinibnow than we are about lapatinib,” saidHortobagyi.Thinking ahead, Sandra Swain, MD,

medical director of the WashingtonCancer Institute at Washington Hos -pital Center in Washington, DC, saiddiarrhea is manageable with neratinibin the metastatic setting, but it may be“a significant problem if you’re going totake it in the adjuvant setting.”

PertuzumabPertuzumab is a recombinant mono-

clonal antibody that inhibits dimeriza-tion of HER2 with itself (homodimers)and with other HER receptors (het-erodimers), thereby preventing theactivation of HER signaling pathways.It has limited potency alone butappears to synergize with trastuzumab.A group led by Jose Baselga, MD,

director of the Vall d’HebronInstitute of Oncology in Barcelona,Spain, enrolled patients with HER2-positive MBC whose disease had pro-gressed on trastuzumab in a phase 2

trial. Patients received pertuzumab alone(840 mg loading dose then 420 mg every3 weeks) and, if their disease progressed,trastuzumab was added. In the pertuzu -mab-only group (n = 29), the ORR was3% and the CBR was 10%. For the com-bined therapy group (n = 16), ORR was21%, and CBR was 43% (San AntonioBreast Cancer Symposium; 2009. Ab -stract 5114).Baselga stressed the need for “total

HER2 blockade,” involving both thehomodimer and heterodimer signalingpathways. He speculated that eithertrastuzumab or lapatinib would block thehomodimer pathway but not the het-erodimer one. “Half the problem is equalto the whole problem,” he said.Arteaga commented that as the pro-

portion of HER2/HER3 heterodimersincreases, the tumor becomes more sen-sitive to pertuzumab, which blocks het-erodimerization. In addition, HER3 haspowerful phosphorylating activity forHER2, driving HER2 activity.Brufsky believes dimers involving

HER3 are “an extremely important tar-get” not only in breast cancer but also inlung (HER1/HER3), ovarian (HER3/HER4), and other tumors, and, thus, per-tuzumab may have activity in thosetumors as well. �

—DMK

Three New Drugs on the Horizon... Continued from page 11

The consensus among oncologists is that neratinibshows good activity as a single agent as well as incombination with trastuzu mab after progression ontrastuzumab.



CONTINUING EDUCATION

The number of American men dying ofprostate cancer has decreased 30%over the past 25 years, but it remains

the second leading cause of cancer death. In2009, an estimated 192,280 new cases ofpro s tate cancer were diagnosed and 27,360men died of the disease.1 There is no univer-sally accepted strategy for screening, diagno-sis, and treatment of prostate cancer.2 Theintroduction and widespread use of prostate-

specific antigen (PSA) screening, however,has led to an increasing number of menbeing diagnosed with prostate cancer eachyear. Almost 50% of these cancers have bio-logical characteristics associated with a lowrisk of cancer progression.3 The challengefacing patients and physicians is accuratelydetermining which men have cancers with asignificant risk of progression or metastaseswhom would benefit from treatment, com-pared with those unlikely to be impacted bythe cancer during their natural lifespan.Although radical prostatectomy (RP) and

radiation therapy are effective treatments,they can result in serious long-term sideeffects such as urinary problems and erectiledysfunction. As a result, clinicians are inter-ested in management strategies that offer thepossibility of delaying, obviating, or minimiz-ing the impact of treatment to avoid havingpatients undergo unnecessary treatment.3One strategy is active surveillance (AS) withselective delayed intervention.3 AS involvescharacterizing the cancer using all availabletools, determining whether the patient is agood candidate for AS, and frequently evalu-ating the cancer and overall health of thepatient to determine if, and, when treatmentmay be warranted.2

Current clinical practice guidelinesBecause many prostate cancers detected

through PSA screening may not requireimmediate treatment, the American Uro - lo gical Association and National Com p re -hensive Cancer Network (NCCN) recom-mend that during discussion of treatmentap proaches for cancer clinicians include ASas an option for men with low-risk prostatecancer who have a life expectancy of lessthan 10 years.4,5 In addition, a new “verylow risk” category has been added to the

updated NCCN guidelines using a modifi-cation of the Epstein criteria for clinicallyinsignificant prostate cancer (Table). AS isoffered and recommended for men in thiscategory when life expectancy is less than20 years.5

Multicenter study examines activesurveillanceStudies have assessed the safety and effica-

cy of AS for low-risk localized prostate can-cer.2,3,6 One multicenter, retrospective studyevaluated the actuarial rates and predictors ofremaining on AS, the incidence of diseaseprogression, and the pathologic findings ofdelayed RP.3

Patient criteriaEach man in a cohort of 262 men from four

institutions was offered multiple options butultimately chose AS. All patients met the fol-lowing criteria for eligibility3:• 75 years of age or younger• PSA 10 ng/mL or less• Clinical stage T1 to T2a• Biopsy Gleason sum 6 or less• Three or fewer positive cores at diagnos-tic biopsy

• No single core with >50% cancer• Repeat biopsy before AS (restaging)• No treatment for 6 months following therepeat biopsy.

Patient assessmentAS was defined as starting on the date of

the second biopsy. Evaluation of patientprogress included office visits, review ofgeneral health and urinary symptoms, digi-tal rectal examinations, and PSA screen-ings every 6 to 12 months. Biopsies wereroutinely recommended within 18 monthsof starting AS and subsequently every 1 to 3

Active Surveillance as a ManagementStrategy for Low-risk Prostate CancerBy Scott E. Eggener, MDAssistant Professor of Surgery/Urology, University of Chicago Medical Center, Chicago, Illinois

PROGRAM TOP3 • RELEASE DATE: JUNE 15, 2010 • EXPIRATION DATE: JUNE 15, 2011

ESTIMATED TIME TO COMPLETE: 1.0 HOUR

CONTINUING PHARMACY EDUCATION ACCREDITATION AND CONTACT HOURS STATEMENTVeritas Institute for Medical Education, Inc is accredited by the Accreditation Council forPharmacy Education as a provider of continuing pharmacy education. This program(UPN 0394-0000-10-004-H01-P) is acceptable for 1.0 Contact Hours. Initial releasedate: June 15, 2010. A statement of credit will be available online to participants whosuccessfully complete the program, learning assessment (>70%), and program evalu-ation form. There is no registration or processing fees.

METHOD OF PARTICIPATION1. Read the article in its entirety2. Log on to www.TheOncologyPharmacist.com3. Click on “CE Credits”4. Click on “Click here to complete the posttest and obtain a CE certificate online”5. Register to participate6. Enter program number TOP37. Complete and submit the CE posttest and CE Activity Evaluation and Request forCredit Form online

8. Print your Statement of CompletionThis activity is provided free of charge to participants.

FINANCIAL DISCLOSURESVeritas Institute for Medical Education, Inc. is required to dis-close to the activity audience the relevant financial relation-ships of the planners and faculty involved in the develop-

ment of CE content. An individual has a relevant financial relationship if he or she hasa financial relationship in any amount occurring in the last 12 months with a commer-cial interest whose products or services are discussed in the CE activity content overwhich the individual has control. In addition, all faculty are expected to openly discloseany unlabeled/unapproved/investigational uses of drugs or devices discussed in thisactivity. Disclosures are as follows:• Scott E. Eggener, MD, has nothing to disclose.• David Frame, PharmD, has nothing to disclose.

The staffs of Veritas Institute for Medical Education, Inc. and Green Hill HealthcareCommunications, LLC have nothing to disclose.

DISCLAIMERThe opinions expressed in this activity are those of the presenters and do not necessar-ily reflect the opinions or recommendation of Veritas Institute for Medical Education, Inc.

Copyright © 2010 Veritas Institute for Medical Education, Inc. All rights reserved.

EDITORIAL BOARDScott E. Eggener, MDAssistant Professor ofSurgery/UrologyUniversity of Chicago MedicalCenter5841 South Maryland Ave,MC6038Chicago, IL 60637

David Frame, PharmDClinical Hematology/Oncology/BMT SpecialistAssistant Professor ofPharmacyUniversity of Michigan428 Church StreetAnn Arbor, MI 48109

PLANNING COMMITTEEGloria MuiMedical DirectorVeritas Institute for MedicalEducation, Inc.611 Route 46 West Hasbrouck Heights, NJ 07604

Julie Ann TagliareniCME DirectorVeritas Institute for MedicalEducation, Inc.611 Route 46 West Hasbrouck Heights, NJ 07604

Anne L. FingerPresidentVeritas Institute for MedicalEducation, Inc.611 Route 46 West Hasbrouck Heights, NJ 07604

Dawn LagrosaAssociate EditorGreen Hill HealthcareCommunications, LLC241 Forsgate DriveMonroe Twp, NJ 08831

Karen RosenbergEditorial DirectorGreen Hill HealthcareCommunications, LLC241 Forsgate DriveMonroe Twp, NJ 08831

Eileen Koutnik-Fotopoulos77A Beers StreetKeyport, NJ 07735

STATEMENT OF NEEDWith the introduction and widespread use of prostate-specific antigen screening, the number of men beingdiagnosed with prostate cancer has increased. Almost50% of these cancers, however, have biological char-acteristics associated with a low risk of cancer pro-gression. As a result, clinicians are interested in man-agement strategies that offer the possibility ofdelaying, obviating, or minimizing the impact of treat-ment to avoid having patients undergo unnecessarytreatment. Oncology nurses and pharmacists shouldbe aware of the most recent data regarding one suchstrategy, active surveillance with selective delayedintervention, so that they may discuss it with patientsdiagnosed with various types of prostate cancer.

TARGET AUDIENCERegistered pharmacists and other interestedhealth care professionals, especially those caringfor cancer patients

LEARNING OBJECTIVESAfter completing this activity, the reader should bebetter able to:• Discuss active surveillance with selectivedelayed intervention with patients diagnosedwith prostate cancer

• Appropriately select candidates for active surveil-lance based on disease characteristics at diagnosis

• Evaluate patient progress to determine if, and,when treatment may be warranted



years or prompted by a change in clini-cal status, a sign of possible disease pro-gression. Magnetic resonance imaging(MRI) of the prostate was selectivelyused at diagnosis and every 1 to 3 yearsafter starting AS. In isolated cases,MRI findings warranted biopsy earlierthan was scheduled.

Study resultsForty-three (16%) patients elected

active treatment, with a median follow-up of 29 months. The 2- and 5-year prob-abilities of remaining on AS were 91%and 75%, respectively. Of the 43 patientsundergoing delayed treatment, 41 (95%)were without disease progression at amedian of 23 months following treat-ment. The most commonly reported rea-sons for stopping AS included upgrading(35%) or higher volume of cancer (16%)on surveillance biopsy or a change in

patient preference (14%). The activetreatment choices among the cohortwere RP for 26 (61%) patients, radiationtherapy for 13 (30%), cryotherapy forone (2%), and androgen deprivation forthree (7%).

Patients with cancer on the secondbiopsy (hazard ratio [HR], 2.23; 95% con-fidence interval [CI], 1.23-4.06, P = .007)and a greater number of cancerous coresfrom the two biopsies combined (P =

.002) were more likely to undergo treat-ment. Bone metastases developed in onepatient 38 months after starting AS. Age,PSA, clinical stage, prostate volume, andthe number of total biopsy cores were notpredictive of outcome.

Clinical implications of ASThis study demonstrates that for

select patients with low-risk prostate

www.TheOncologyPharmacist.com


COMMENTARY

Active Surveillance as a Management Strategy forLow-risk Prostate Cancer: A Pharmacist’sPerspectiveDavid Frame, PharmDClinical Hematology/Oncology/BMT Specialist and Assistant Professor of Pharmacy, University of Michigan, Ann Arbor

Eggener discussed the role of activesurveillance (AS) in the treat-ment of prostate cancer, address-

ing an important option that is oftenoverlooked. We must remember thatthe Hippocratic oath is to do no harm.The potential of causing harm by per-forming a radical prostatectomy isvery real and can even result in mor-tality. A Canadian study exploringcomplications occurring within 30 daysafter radical prostatectomy among11,010 men who underwent this surgerybetween 1990 and 1999 showed a low,but clinically significant, 0.5% mortalityrate with another 20.4% having one ormore complications within these 30days.1 Other risks associated with thisprocedure are deep vein thrombosis andherniation, and the most common sideeffects are impotence and incontinence,which may be long-term and signifi-cantly affect quality of life. Because ofthese risks of radical prostatectomy, it isessential to consider AS if these sideeffects could be spared without increas-ing the risk of mortality from the cancerin individuals diagnosed with low- orvery-low-risk prostate cancer.

Prostate cancer is the second lead-ing cause of cancer death in men,effecting 192,280 men and accountingfor approximately 25% of all new cancerdiagnoses in men in 2009. Given thesenumbers, even low percentages ofunnecessary procedures could result in asignificant increase in the percentage ofunnecessary complications. To this end,the American Cancer Society (ACS)revised its recommendations on prostatecancer screening in March of this year.2The revised recommendations are par-tially based on two large trials thatsought to determine whether prostatecancer screening with prostate-specific

antigen (PSA) levels and digital rectalexamination (DRE) saves lives.3,4 Inthe American study, more than 76,000men were randomized to receive “usualcare” or to have annual PSA tests for 6years, and DREs every year for 4 years.Overall, no significant difference inprostate cancer death rates was demon-strated between the two groups after 7 to10 years of follow-up.3 In the Europeantrial, 182,000 men were stratified toeither a control group or a screeninggroup.4 Men in the screening group hadPSA tests every 4 years and, on average,two DREs during that period. In -terestingly, after approximately a 9-yearfollow-up, the researchers found thatscreening did reduce the rate of prostatecancer death by 20% but also was asso-ciated with a high risk of overdiagnoses.It is important to realize that muchlonger maturity is required before thesestudies can be fully analyzed. The reasonfor these studies, as pointed out byEggener, is to help further determinewhether finding pro state cancer earlytruly leads to de creased mortality. Someprostate cancers grow slowly and maynever cause any problems, whereasothers are more aggressive. This dis-tinction, how ever, cannot necessarilybe de termined by the standard PSAand DRE screening tools.

Based on all of the current informa-tion, the ACS recommends that menwithout high risk who have no symp-toms at 50 years of age and are in rela-tively good health with a life expectan-cy of 10 years or more, use decision-making tools to help them make aninformed choice about testing. Menwith no symptoms who are not expect-ed to live more than 10 years (because ofage or poor health) should not beoffered prostate cancer screening at

all.2 So for those readers unsure of theappropriateness of the revised Am er -ican Urological Association andNational Comprehensive Cancer Net -work (NCCN) recommendations toinclude AS in discussions of treatmentapproaches for men with low-riskprostate cancer who have a life ex -pectancy of less than 10 years or 20 yearsin the very-low-risk category, they seemto pale in comparison with the newACS screening guidelines.

It should also be noted that in therevised NCCN guidelines the recom-mendation for AS for the very-low-riskgroup with less than 20 years expectedsurvival is a category 2B recommenda-tion, which means the recommendationis based on lower level evidence andthere is not a uniform consensus amongcommittee members.5 I believe that asignificant question that needs to be fur-ther explored is the potential risk ofAS, that is, the risk of developingadvanced cancer due to inadequatediagnosis, classification, or follow-upof these patients. A Scandinavian trialcomparing AS with radical prostatec-tomy in localized prostate cancerdemonstrated a relative risk of 0.65 forboth 12-year disease-specific mortality(P = .03) and distant metastasis (P =.006).6 The Epstein criteria for pre-dicting pathologically insignificantprostate cancer have been shown tomisdiagnose in as many as 8% of casesof nonorgan-confined disease uponpostsurgical findings.7

Finally, it is very important that ifpatients agree to AS, they must com-mit to regularly scheduled examina-tions, including repeat biopsies.Cancer progression is suggested whenmore core biopsies are positive, whenno single core has less than 50% can-

cer by volume, when the Gleasonscore increases to 4 or 5, or whenPSA doubling time is less than 3years. Although “trigger” points forintervention are suggested, thesehave also not been validated withgood clinical trials. Because it is like-ly that many patients will be on AS,pharmacists must fully understandthe potential benefits as well as theunanswered questions with thisapproach. In the near future, AS willlikely be revisited, because manyongoing studies are evaluating genet-ic components as they relate to dis-ease-risk classification.

References1. Alibhai SM, Leach M, Tomlinson G, et al. 30-

day mortality and major complications afterradical prostatectomy: influence of age andcomorbidity. Natl Cancer Inst. 2005;97:1525-1532.

2. American Cancer Society. Prostate cancer:early detection. 2010. www.cancer.org/docroot/CRI/content/CRI_2_6x_Prostate_Cancer_Early_Detection.asp?sitearea=&level=.Accessed April 15, 2010.

3. Andriole GL, Grubb RL, Buys SS, et al; for thePLCO Project Team. Mortality results from arandomized prostate-cancer screening trial. NEngl J Med. 2009;360:1310-1319.

4. Schroder FH, Hugosson J, Roobol MJ, et al; forthe ERSPC Investigators. Screening andprostate-cancer mortality in a randomizedEuropean study. N Engl J Med. 2009;360:1320-1328.

5. National Comprehensive Cancer Network.Clinical Practice Guidelines in Oncology: ProstateCancer. V.1.2010. www.nccn.org/professionals/physician_gls/PDF/prostate.pdf. AccessedApril 15, 2010.

6. Bill-Axelson A, Holmberg L, Filen F, et al; forthe Scandinavian Prostate Cancer GroupStudy Number 4. Radical prostatectomy versuswatchful waiting in localized prostate cancer:The Scandinavian Prostate Cancer Group-4randomized trial. J Natl Cancer Inst. 2008;100:1144-1154.

7. Jeldes C, Suardi N, Waltz J, et al. Validation ofthe contemporary Epstein criteria for insignif-icant prostate cancer in European men. EurUrol. 2008;54:1306-1313.



cancer, AS with judicious monitoringappears to be safe, durable, and associ-ated with a low risk of systemic progres-sion within the first 5 years. My col-leagues and I strongly recommend asecond biopsy before considering AS,because cancer detected at restagingbiopsy and a higher number of coreswith cancer are linked with a lowerlikelihood of remaining on AS.3

The success of any AS program relieson accurate disease characterization atdiagnosis. Because this study specifiedstrict clinical and pathologic inclusioncriteria and required a second biopsybefore starting AS, we were able to iden-tify a cohort of men with a low risk of

cancer progression. The rate of discon-tinuing AS was about 5% per year, lowerthan that of similar studies, largely dueto the strict inclusion criteria. Further -more, it is crucial that all men partici-pating in an AS program be counseledon the low but real risk of potentiallylife-threatening cancer progression.3Early to intermediate-term data forappropriately selected AS patients sug-gest metastasis rates are consistently lessthan 1%, with follow-ups ranging from 2to 8 years.2 To minimize the risk, westrongly recommend a restaging biopsy.This proactive approach ex cludes up to30% of patients considered for AS basedon the initial diagnostic biopsy, mini-

mizes the risk of Gleason grade samplingerror, and predicts the likelihood of con-tinuing on AS.3

Studies indicate that AS is used as atreatment strategy in only 10% ofpatients with newly diagnosed prostatecancer.2,3 Our findings as well as thosefrom other researchers show that ASshould be discussed and considered forappropriately selected patients.2,3,6

Multiple limitations of this study, how-ever, warrant consideration. Based on theshort-term follow-up of this study (medi-an, 29 months) and of other studies(median, 22-64 months), caution shouldbe exercised in extrapolating thesefindings to justify AS as a long-termmanagement strategy. Extended follow-up is mandatory to address this con-cern.3 The data in this study provide anobservational experience, which willcontinue to provide insights into thenatural history of low-risk prostate can-cer, generalized rates of delayed treat-ment given the variable practice pat-terns, overall cancer-specific successrates, and causes of death.3

Whereas a strength of this study is themulti-institutional cohort, this has alsoled to variations in the intensity of follow-up, diagnostic and restaging strat -

egies, occurrence of surveillance bio psies,pathologic assessment, and in dicationsfor treatment.3 Therefore, gen eralizing ofthe findings to include other populationsshould be done with caution. The mostcommon reason for stopping AS in thisstudy was the outcome of a surveillancebiopsy; in other AS studies it was patientpreference or increasing PSA alone,underscoring the variable nature of cur-rently available series and need for pre-specified study methodology.3

My view on AS is to appropriatelyselect patients, discuss initial observa-tion as an option, monitor frequently(based on serial prostate biopsies), and,if necessary, implement active therapywhile the disease is still at a highly cur-able stage. Most men will not requirean intervention, and those who do canbenefit from a period when quality oflife and cancer-related outcomes do notappear to be compromised. �

References1. American Cancer Society. What are the key statis-

tics about prostate cancer? March 3, 2010.www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_prostate_cancer_36.asp?sitearea=. Accessed March 12, 2010.

2. Large MC, Eggener SE. Active surveillance forlow-risk localized prostate cancer. Oncology(Williston Park). 2009;23:974-979.

3. Eggener SE, Mueller A, Berglund RK, et al. Amulti-institutional evaluation of active surveil-lance for low risk prostate cancer. J Urol.2009;181:1635-1641.

4. American Urological Association. Prostate-Specific Antigen: Best Practice Statement: 2009Update. Linthicum, MD: American UrologicalAssociation Education and Research Inc; 2009.

5. National Comprehensive Cancer Network.Clinical Practice Guidelines in Oncology: ProstateCancer. V.1.2010. www.nccn.org/professionals/physician_gls/PDF/prostate.pdf. Accessed March12, 2010.

6. Klotz L, Zhang L, Lam A, et al. Clinical resultsof long-term follow-up of a large, active surveil-lance cohort with localized prostate cancer. JClin Oncol. 2010;28:126-131.

Eileen Koutnik-Fotopoulos contributed to the prepara-tion of this manuscript.

CONTINUING EDUCATION

CASE STUDY

A66-year-old man who had been undergoing annual prostate-specific antigen (PSA)-based prostate cancer screen-ing had a normal digital rectal examination (DRE) but a PSA level of 6.4 ng/mL. PSA testing was repeated 1month later and found to be 6.2 ng/mL. Prostate biopsy revealed two of 12 cores with Gleason 6 prostate cancer,

encompassing 20% of each core. He had excellent sexual and urinary function. His medical history showed moderate obe-sity and medication-controlled hypertension. After meeting with multiple specialists and considering his options, he elect-ed to proceed with active surveillance (AS) and, therefore, underwent a restaging 12-core biopsy. No cancer was identi-fied and he formally entered AS. For 6 years, he underwent evaluations every 6 months without a significant change inhealth status, DRE, or PSA (range, 4.3 ng/mL-7.1 ng/mL). Surveillance biopsies performed every 12 to 18 months did notshow a higher-grade or higher-volume cancer and ranged from zero to two cores with cancer. Seven years following theinitiation of AS, the patient experienced a myocardial infarction, underwent the placement of two coronary stents, andwas started on clopidogrel and aspirin. He continues routine surveillance of his prostate cancer with annual evaluations.

Source: Reference 5.

• Clinical stage T1c

• Biopsy Gleason score ≤6

• Presence of disease in fewer than three biopsy cores

• ≤50% prostate cancer involvement in any core

• Prostate-specific antigen density <0.15 ng/mL/g

Table. Modified Epstein Criteria for Clinically InsignificantProstate Cancer

Americans’ BehaviorsRegarding Skin Cancer

Most people express concern aboutskin cancer and believe it is important toprotect their skin; however, their atti-tudes and behaviors do not necessarilyreflect these concerns, according to anew survey by the American Academyof Dermatology. A survey of more than7000 Americans between January 12 andJanuary 31, 2010, found encouragingnews as well as areas for patient educa-tion. Although 75% said they would doanything to prevent skin cancer; 28%said they never check moles and skinblemishes for changes, 59% have neverbeen checked for skin cancer by ahealthcare professional, and 70% do not

apply sunblock on the average day. Inaddition, 72% said that a tan makes peo-ple look more attractive, 66% said a tanmakes people look healthier, and 60%agreed that sun exposure is good for you.

Breast MRI AccreditationProgram

In May 2010, the American College ofRadiology Committee on Breast Mag -netic Resonance Imaging (MRI) Ac -creditation launched its Breast MRIAccreditation Program (BMRAP). Thisprogram enables facilities to improve andmaintain the quality of their breast MRIservices through a peer-review assessmentof their processes, equipment, and thequality of their images. BMRAP sets

quality standards for providers and willhelp them continuously improve theirpatient care by evaluating the qualifica-tions of personnel, equipment perform-ance, effectiveness of quality controlmeasures, and image quality. For facilitiesthat solely offer breast MRI services,BMRAP fulfills the accreditation require-ments under the Medicare Improvementsfor Patients and Providers Act

Medicaid Rolls Likely toExpand

The Patient Protection and Afford -able Care Act will add an estimated 15.9million Americans to the Medicaid rollsby 2019, according to a new KaiserFamily Foundation report. In addition,

the report estimates that 11 millionlow-income Americans will no longerbe uninsured. The Urban In stitute,which prepared the report for the KaiserFamily Foundation, projected enroll-ment at two levels of participation. The“enhanced outreach scenario” increasesthose numbers to 22.8 million peopleadded to Medicaid and 17.5 millionpeople newly insured.

The cost of these expansions is esti-mated to be $464.7 billion by 2019. Only$443.5 billion will be covered by the fed-eral government; state governments willneed to pay the remainder. Under theenhanced scenario, the cost rises to $575billion, with $532 billion paid by the fed-eral government. �

News Notes

Active Surveillance as a Management Strategy... Continued from page 15


A Newsletter Series for Cancer Care Professionals

Center of Excellence Media, along with Editor-in-ChiefSagar Lonial, MD, of Emory University, are pleased tooffer your multidisciplinary cancer team this series ofnewsletters focusing on the challenges of treatingpatients with multiple myeloma.

SAGAR LONIAL, MDAssociate Professor of

Hematology and Oncology Emory University School of Medicine

� Earn Continuing Education Credits �

Each newsletter will feature:

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

• Front-line therapy• Maintenance Settings• Transplant Settings• Retreatment Settings

• Non-Transplant Patients• Cytogenetics• Side Effect Management• Bone Health

• Contributions from thought-leadingphysicians, nurses, and pharmacists

• Continuing Education credits availableto physicians, nurses, and pharmacists

Presents the Third Annual Curriculum for CONSIDERATIONS IN MULTIPLE MYELOMA

PARTICIPATE TODAY at www.COEXM.com

8-part newsletter series

CASE STUDY DISCUSSIONS:

For complete learning objectives and accreditation information, please refer to each activity.

Target AudienceThese activities were developed for physicians, nurses, and pharmacists.

These activities are jointly sponsored by



Medications Used for the Treatment of Lung Cancer

Current MedicareFDA- code price allowableapproved Compendia listed (AWP-based (ASP + 6%), CPT

generic (Brand) HCPCS code: for off-label use for pricing), effective effective administrationname code description lung cancer lung cancera 6/1/10 4/1/10-6/30/10 codes

amifostine J0207: injection, � $564.95 $327.96 96374(Ethyol) amifostine, 500mgbevacizumab J9035: injection, � $66.99 $57.57 96413, 96415(Avastin) bevacizumab, 10 mgcarboplatin J9045: injection, � $48.55 $5.31 96409, 96413, 96415(Paraplatin) carboplatin, 50 mgcetuximab J9055: injection, � $57.60 $49.73 96413, 96415(Erbitux) cetuximab, 10 mgcisplatin J9060: cisplatin, powder � $4.33 $1.98 96409, 96413, 96415(Platinol AQ) or solution, per 10 mgcisplatin J9062: cisplatin, 50 mg � $21.66 $9.91 96409, 96413, 96415(Platinol AQ)cyclophosphamide J8530: cyclophosphamide, � $2.09 $0.84 N/A(Cytoxan) oral, 25 mgcyclophosphamide J9070: cyclophosphamide, � $10.57 $4.35 96409, 96413, 96415(Cytoxan) 100 mg (All 100 mg NDCs

inactive—500 mg NDCs used to calculate code price)

cyclophosphamide J9080: cyclophosphamide, � $21.15 $8.69 96409, 96413, 96415(Cytoxan) 200 mg (All 200 mg NDCs

inactive—500 mg NDCs used to calculate code price)

cyclophosphamide J9090: cyclophosphamide, � $52.87 $21.73 96409, 96413, 96415(Cytoxan) 500 mg

O N C O L O G Y D R U G C O D E SSupplied by: RJ Health Systems

Lung cancer forms in tissues of the lung, usuallyin the cells lining the air passages. The twomain types are small-cell lung cancer and non–small-cell lung cancer. The following sectionwill assist healthcare professionals and payers byproviding appropriate coding, billing, and reim-bursement information associated with themanagement of lung cancer.The following sections include:• Associated ICD-9-CM codes used for theclassification of lung cancer

• Drugs that have been FDA-approved in thetreatment of lung cancer

• Drugs that are compendia listed for off-labeluse for lung cancer based on clinical studiesthat suggest beneficial use in some cases.Please note: if a check mark appears in theFDA column, it will NOT appear in thecompendia off-label use column

• Corresponding HCPCS/CPT codes and codedescriptions

• Current Code Price (AWP-based pricing)• Most recent ASP plus 6% (Medicare allow-able), if applicable

• Possible CPT Administration Codes for eachmedication

Associated ICD-9-CM Codes Used for Lung Cancer

162 Malignant neoplasm of trachea, bronchus, and lung162.0 Trachea

Cartilage of tracheaMucosa of trachea

162.2 Main bronchusCarinaHilus of lung

162.3 Upper lobe, bronchus or lung162.4 Middle lobe, bronchus or lung162.5 Lower lobe, bronchus or lung162.8 Other parts of bronchus or lung

Malignant neoplasm of contiguous or overlapping sites of bronchus or lung whose point of origin cannot be determined

162.9 Bronchus and lung, unspecified






cyclophosphamide J9091: cyclophosphamide, � $95.21 $43.46 96409, 96413, 96415(Cytoxan) 1.0 gramcyclophosphamide J9092: cyclophosphamide, � $171.35 $86.92 96409, 96413, 96415(Cytoxan) 2.0 gramdocetaxel J9171: injection, � $23.87 $17.85 96413(Taxotere) docetaxel, 1 mgdoxorubicin HCl J9000: injection, doxorubicin � $13.20 $3.04 96409(Adriamycin) hydrochloride, 10 mgerlotinib J8999b: prescription drug, � NDC N/A N/A(Tarceva) oral, chemotherapeutic, not level

otherwise specified pricingetoposide J8560: etoposide, � $47.64 $28.26 N/A(Vepesid) oral, 50 mgetoposide J9181: injection, etoposide, � $0.53 $0.49 96413, 96415(Toposar) 10 mggefitinib J8565: gefitinib, � $68.08 none N/A(Iressa) oral, 250 mg reportedgemcitabine J9201: injection, gemcitabine � $173.83 $145.10 96413(Gemzar) hydrochloride, 200 mghydroxyurea J8999b: prescription drug, � NDC NDC N/A(Hydrea) oral, chemotherapeutic, level level

not otherwise specified pricing pricinghydroxyurea S0176: hydroxyurea, � $1.28 S0176 not N/A(Hydrea) oral, 500 mg payable by

Medicareifosfamide J9208: injection, � $56.40 $30.76 96413, 96415(Ifex) ifosfamide, 1 gramirinotecan J9206: injection, � �$31.50 $9.15 96413, 96415(Camptosar) irinotecan, 20 mgmechlorethamine HCl J9230: injection, � $178.71 $154.50 96409(Mustargen) mechlorethamine hydrochloride

(nitrogen mustard), 10 mgmethotrexate J8610: methotrexate, � $3.61 $0.16 N/A

oral, 2.5 mgmethotrexate sodium J9250: methotrexate sodium, � $0.29 $0.21 96372, 96374, 96401,

5 mg 96409, 96450methotrexate sodium J9260: methotrexate sodium, � $2.86 $2.10 96372, 96374, 96401,

50 mg 96409, 96450mitomycin J9280: mitomycin, � �$67.20 $20.36 96409(Mutamycin) 5 mgmitomycin J9290: mitomycin, � �$218.40 $81.43 96409(Mutamycin) 20 mgmitomycin J9291: mitomycin, � �$300.00 $162.87 96409(Mutamycin) 40 mgpaclitaxel J9265: injection, � $16.50 $11.46 96413, 96415(Taxol) paclitaxel, 30 mgpaclitaxel J9264: injection, � �$11.20 $9.43 96413protein-bound paclitaxel protein-boundparticles particles, 1 mg(Abraxane)panitumumab J9303: injection, � �$101.85 $87.23 96413, 96415(Vectibix) panitumumab, 10 mg







PO BOX 290616, Wethersfield, CT 06109 T: (860) 563-1223 • F: (860) 563-1650

www.RJHealthSystems.com

This information was supplied by:

pemetrexed J9305: injection, � $60.67 $50.63 96409(Alimta) pemetrexed, 10 mgporfimer sodium J9600: injection, porfimer � $3,317.04 $2,934.28 96409(Photofrin) sodium, 75 mgprocarbazine J8999b: prescription drug, � NDC NDC N/A(Matulane) oral, chemotherapeutic, level level

not otherwise specified pricing pricingprocarbazine S0182: procarbazine HCl, � $55.68 S0182 not N/A(Matulane) oral, 50 mg payable by

Medicaretamoxifen J8999b: prescription drug, � NDC NDC N/A(Nolvadex) oral, chemotherapeutic, level level

not otherwise specified pricing pricingtamoxifen S0187: tamoxifen citrate, � $1.89 S0187 not N/A(Nolvadex) oral, 10 mg payable by

Medicareteniposide Q2017: injection, teniposide, � $376.55 $324.55 96413, 96415(Vumon) 50 mgtopotecan J8705: topotecan, � $89.73 $74.66 N/A (Hycamtin) oral, 0.25 mgtopotecan J9350: injection topotecan, � $1,306.10 $1,058.90 96413(Hycamtin) 4 mgtrastuzumab J9355: injection, � $78.26 $66.42 96413, 96415(Herceptin) trastuzumab, 10 mgvinBLAStine J9360: injection, � $3.18 $1.02 96409

vinblastine sulfate, 1 mgvinCRIStine J9370: vincristine sulfate, � $7.22 $4.31 96409(Vincasar) 1 mgvinCRIStine J9375: vincristine sulfate, � $14.44 $8.62 96409(Vincasar) 2 mgvinCRIStine J9380: vincristine sulfate, � $36.10 $21.54 96409(Vincasar) 5 mgvinorelbine tartrate J9390: injection, � $42.60 $10.05 96409(Navelbine) vinorelbine tartrate, per 10 mg

aCompendia references available upon request.

bWhen billing a non-classified medication using a CMS 1500 claim form you must include both the HCPCS code (ie, J8999 for Tarceva) in Column 24D and the drug name, strength, and National DrugCode (NDC) in Box 19 in order to ensure appropriate reimbursement.

ReferencesHCPCS Level II Expert 2010 • Current Procedural Terminology (CPT) 2010 • ICD-9-CM for Professionals Volumes 1 & 2 2010 • The Drug Reimbursement Coding and Pricing Guide by RJ HealthSystems International, LLC, Volume 7, Number 2, 2nd Quarter 2010 • FDA-approved indication (from product’s prescribing information) • National Cancer Institute® • www.ReimbursementCodes.compowered by RJ Health Systems International, LLC, Wethersfield, Connecticut • CMS (Centers for Medicare and Medicaid Services)—Medicare Allowable 2nd Quarter 2010 (effective dates 4/1/10-6/30/10).

Prices listed herein are effective as of June 1, 2010.

ASP indicates average sales price; AWP, average wholesale price; CMS, Centers for Medicare & Medicaid Services; CPT, Current Procedural Terminology; FDA, US Food and Drug Administration; HCPCS,Healthcare Common Procedure Coding System; NDC, National Drug Code.

Continued from page 19


Current activities at www.COEXM.com include:

� ��

��

��

��

��

��

��

��

�� CONTINUING EDUCATION CREDITS

��

��


Characterized by thrombocytope-nia and bleeding manifestations,particularly mucocutaneous,

idio pathic thrombocytopenic purpura(ITP) is an autoimmune disorder seenin both adults and children. Althoughthe majority of ITP cases in children areconsidered acute and typically resolvewithin 6 months often without therapy,adult ITP is generally chronic andrequires therapeutic interventions toraise platelet counts.1ITP can be associated with other dis-

orders, including malignancy and infec-tions, and is referred to as secondaryITP. However, the etiology of primaryITP is still largely unclear.1,2 Productionof antiplatelet autoantibodies leading toplatelet destruction by macrophages,coupled with the inhibition of mega -karyocyte platelet production, leads toan overall decrease in platelet counts inpatients with ITP. Several studies havealso demonstrated that antibody pro-duction may be driven by T-cell and B-

cell clones. Because of the risk of hem-orrhagic complications associated withsevere thrombocytopenia, the generalgoal in the treatment of patients severe-ly affected with ITP is to maintainplatelet counts at or above 30 ¥ 109/L to50 ¥ 109/L.Corticosteroids have long been the

first-line treatment and are consideredthe standard of care for the initial man-agement of ITP. Response rates to corti-costeroids range from 50% to 75%; how-ever, this response is often short-term,and only up to 30% of patients have aprolonged response.1,3 Intravenous im -munoglobulin (IVIG) is often the nextstep in the treatment of ITP after failureof corticosteroid therapy or developmentof hemorrhagic complications. Althoughsplenectomy remains the most effectiveand possibly curative option for chronicITP, with two thirds of patients having asustained response,4 the postsurgicalperiod can be complicated with infec-tions, and many questions still remain

regarding optimal timing and patientselection.3 Refractory ITP is defined aspersistent thrombocytopenia after initialtreatment including splenectomy thatrequires further treatment to maintain asafe platelet count. For these patients,options available include rituximab,danazol, cyclophosphamide, im muno-suppressive agents (eg, cyclo sporine, aza-thioprine), mycophenolate mofetil, andvinca alkaloids, all of which exhibit vary-ing degrees of effectiveness and adverseevent profiles.1,4Despite several effective treatment

strategies for patients with chronic orrelapsed ITP, a need for more salvagetreatment options has prompted addi-tional research on the biology of throm-bopoiesis. This research has led to thedevelopment of agents that work bystimulating the production of platelets,in contrast to traditional therapies,which aim at inhibiting the productionof antiplatelet antibodies. Endogenousthrombopoietin (TPO) is synthesized in

the liver, releases into the circulation,and binds to TPO receptors on stemcells, progenitor cells, and platelets.Activation of these receptors leads todownstream signaling pathways and,ultimately, to proliferation of megakary-ocytes, thus increasing the release ofplatelets into the bloodstream. Mostpatients with ITP have low or normallevels of endogenous TPO,5 despite thecompensatory reaction that normallyoccurs—increasing TPO levels in situa-tions with low platelet counts.Initial clinical trials using thrombo -

poietin analogs were halted due toimmunogenicity reactions and antibodyformation leading to secondary throm-bocytopenia and bleeding.6 Second-generation thrombopoiesis-stimulatingagents that developed out of this set-back have provided two new commer-cially available agents, which have min-imal immunogenicity and are notstructurally similar to endogenous TPO.Romiplostim was the first thrombo -poiesis-stimulating agent approved bythe US Food and Drug Administration,followed closely by eltrombopag for thetreatment of patients with chronic ITPwho have insufficient response to corti-costeroids, IVIG, or splenectomy. El -tro m bopag is a small-molecule, nonpep-tide TPO receptor–agonist that binds tothe transmembrane domain of humanTPO receptors, thus inducing prolifera-tion and differentiation of cells in themegakaryocytic lineage.7

Eltrombopag in the treatment ofITPThe results of two multicenter, ran-

domized, double-blind, placebo-con-trolled trials have served as the platformfor approval of eltrombopag for use inrefractory ITP. The initial trial was aphase 2 dose-ranging trial designed toassess whether eltrombopag could safelyincrease platelet counts. This studyincluded 118 patients with at least a 6-month history of ITP, who were at least18 years of age (median age, 50 years),had received at least one previous ther-apy (47% with prior splenectomy), andhad a platelet count <30 ¥ 109/L (48%had platelet count ≤15 ¥ 109/L) atenrollment. Patients were enrolled in a1:1:1:1 manner into the placebo, 30-mg,50-mg, or 75-mg eltrombopag groups tobe taken orally once per day for up to 6weeks. Maintenance immunosuppres-sive therapy, mainly glucocorticoids,with stable doses was allowed, but other


Drug Therapy

New Treatments for Chronic IdiopathicThrombocytopenic Purpura. Part 2. EltrombopagBy Starla J. Sweany, PharmD, BCOPThe University of Texas M. D. Anderson Cancer Center, Houston

Monitoring parameters

Laboratory values Recommendation

Complete blood count, including platelet count; peripheral blood smear

Weekly until stable platelet count (>50 ¥ 109/L) achieved, thenmonthly thereafter

Liver function tests, including AST, ALT, and bilirubin Prior to initiation, every 2 weeks during dose adjustment, and monthly once stable dose achieved

• If abnormal laboratory value, repeat in 3 to 5 days; followingconfirmation of abnormality, monitor weekly until resolution, stabilization, or return to baseline

• Discontinue therapy if ALT ≥3 ¥ ULN and:• Progressive, or• Persistent (≥4 weeks), or• Accompanied by increased direct bilirubin, or• Accompanied by clinical symptoms

Dose adjustment

Platelet count Recommendation

<50 ¥ 109/L after at least 2 weeks of therapy Increase daily dose by 25 mg, up to a maximum of 75 mg daily

≥200 ¥ 109/L to ≤400 ¥ 109/L anytime during therapy Decrease daily dose by 25 mg; allow 2 weeks before assessingeffects of new dose

>400 ¥ 109/L Stop eltrombopag; monitor platelets twice weekly and reinitiate therapy at a daily dose reduced by 25 mg when platelets are <150 ¥ 109/L

>400 ¥ 109/L after 2 weeks of therapy at lowest dose (25 mg) Discontinue therapy

ALT indicates alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal.

Source: Reference 7.

Table 1. Dosing and Monitoring Eltrombopag Therapy



www.ValueBasedCancer.com

��

� ��

��

A new publication for your new vocabulary

��

NCCN Roundtable: Clinical andEconomic Issues Impacting Cancer Care Delivery “Collision course” in sight

©2010 Engage Healthcare Communications, LLCContinued on page 24

Baltimore, MD—A long-held businesstruism is that “if you can’t measure it,you can’t manage it.” The application of this belief to the oncology setting was demonstrated at a session of theAssociation of Community Cancer Cen ters’ (ACCC) 36th Annual NationalMeeting. Kimberly Bergstrom, PharmD,chief clinical officer for McKessonSpecialty Care Solutions, told attendeesof the growing importance of developingand using standardized chemotherapytreatment regimens, and of the tools that

can benchmark performance and fostercompliance with treatment guidelines.Public and private payers are mov-

ing to control exploding healthcarecosts, Dr Bergstrom told attendees,and because increased cost controlwas inevitable, it is in providers’interest to get a seat at the table. “It is an important topic, because

this is one of those things, if we don’tget a handle on it, it’s going to happento us,” she said. “People and groupsand organizations are going to startdictating how we provide cancer care,and we can’t let that happen.”

Hollywood, FL—Clinical practiceguidelines issued by the NationalComprehensive Cancer Network(NCCN) are followed by conscien-tious oncologists in their everydaypractice, but they are developedbased on clinical efficacy and withoutregard to costs. At a roundtable heldduring the NCCN’s 15th AnnualConference, moderator CliffordGoodman, PhD, Senior Vice Presidentat The Lewin Group, predicted, “Theappropriate use of evidence-basedguidelines is on a collision coursewith the financial nonsustainability ofthe healthcare system.”

Dr Goodmanalluded to a levelof frustration thathas never beenhigher in cancercare. “Too manypatients are stilldying young. Weneed innovations and a cure,” he said.But the inadequacy of current treat-ments for cancer is no longer the mainproblem. Equally challenging, he sug-gested, is finding a means to pay forthe ever-costlier care that threatens tobankrupt the healthcare system. As society struggles to find solu-

tions, “the ground is shaking beneathus,” Dr Goodman commented.

Continued on page 8



By Audrey Andrews

SEER-Medicare Database AnalysisConfirms Expensive ProstateCancers Gaining SupremacyBut cost-effectiveness of this move remains to be determined

San Francisco, CA—The popularity ofminimally invasive radical prostatec-tomy (MIRP), intensity-modulatedradiation therapy (IMRT), and ofbrachytherapy combined with IMRTfor prostate cancer started to take offafter 2002, a new database analysishas confirmed.At the American Society of Clinical

Oncology’s 2010 Genitourinary Can -cers Symposium, Paul L. Nguyen,MD, presented the results of histeam’s analysis of data from theSurveillance, Epidemiology and EndResults (SEER)-Medicare database.Dr Nguyen, director of Prostate

Brachytherapy, Dana-Farber/Brigham

and Women’s Hospital, HarvardMedical School, Boston, and his co-investigators found MIRP jumpedfrom 1.5% of radical prostatectomies(RPs) in 2002 to 28.7% in 2005. Theyalso found that IMRT soared from8.7% of external radiation treatmentsfor prostate cancer to 81.7%. In addi-

By Rosemary Frei, MSc

New Tools Arriving to Measure andManage Chemotherapy CareBusiness, clinical concerns now connected in value-focused approach By Daniel Denvir

Breast Cancer Survival Improves,Thanks to New Therapies

The 2010 Genitourinary CancersSymposium: Progress in Multi -disciplinary Management was heldMarch 5-7 in San Francisco. All ses-sions emphasized a multidisciplinaryap proach to care; a number of thembrought out the cost and value issuesassociated with caring for genitouri-nary cancers.

Value-Based Cancer Carewill be at the ASCO Annual Meeting, June 4-8, in Chicago. Please visit us at booth 18121

Barcelona—Survival for patients withmetastatic breast cancer has improveddramatically in the last 20 years, espe-cially in the subgroup of patients withHER2-positive tumors, according toresearch presented at the 7th European

Breast Cancer Confer ence (EBCC7).This improvement, the researcherssuggest, is due to in creased use ofanthracyclines and the rise of targetedtherapies.“There is no doubt that trastuzu -

mab (Herceptin), which targets theHER2 gene, is the most important

By Colin Gittens


��

Photo by © ASCO/Todd Buchanan 2009

value-focused

payers

cost control

clinical practiceguidelines

cost effectiveness

efficacy

NCCN Roundtable: Clinical andEconomic Issues Impacting Cancer Care Delivery “Collision course” in sight

©2010 Engage Healthcare Communications, LLCContinued on page 24

Baltimore, MD—A long-held businesstruism is that “if you can’t measure it,you can’t manage it.” The application of this belief to the oncology setting was demonstrated at a session of theAssociation of Community Cancer Cen ters’ (ACCC) 36th Annual NationalMeeting. Kimberly Bergstrom, PharmD,chief clinical officer for McKessonSpecialty Care Solutions, told attendeesof the growing importance of developingand using standardized chemotherapytreatment regimens, and of the tools that

can benchmark performance and fostercompliance with treatment guidelines.Public and private payers are mov-

ing to control exploding healthcarecosts, Dr Bergstrom told attendees,and because increased cost controlwas inevitable, it is in providers’interest to get a seat at the table. “It is an important topic, because

this is one of those things, if we don’tget a handle on it, it’s going to happento us,” she said. “People and groupsand organizations are going to startdictating how we provide cancer care,and we can’t let that happen.”

Hollywood, FL—Clinical practiceguidelines issued by the NationalComprehensive Cancer Network(NCCN) are followed by conscien-tious oncologists in their everydaypractice, but they are developedbased on clinical efficacy and withoutregard to costs. At a roundtable heldduring the NCCN’s 15th AnnualConference, moderator CliffordGoodman, PhD, Senior Vice Presidentat The Lewin Group, predicted, “Theappropriate use of evidence-basedguidelines is on a collision coursewith the financial nonsustainability ofthe healthcare system.”

Dr Goodmanalluded to a levelof frustration thathas never beenhigher in cancercare. “Too manypatients are stilldying young. Weneed innovations and a cure,” he said.But the inadequacy of current treat-ments for cancer is no longer the mainproblem. Equally challenging, he sug-gested, is finding a means to pay forthe ever-costlier care that threatens tobankrupt the healthcare system. As society struggles to find solu-

tions, “the ground is shaking beneathus,” Dr Goodman commented.

Continued on page 8



By Audrey Andrews

SEER-Medicare Database AnalysisConfirms Expensive ProstateCancers Gaining SupremacyBut cost-effectiveness of this move remains to be determined

San Francisco, CA—The popularity ofminimally invasive radical prostatec-tomy (MIRP), intensity-modulatedradiation therapy (IMRT), and ofbrachytherapy combined with IMRTfor prostate cancer started to take offafter 2002, a new database analysishas confirmed.At the American Society of Clinical

Oncology’s 2010 Genitourinary Can -cers Symposium, Paul L. Nguyen,MD, presented the results of histeam’s analysis of data from theSurveillance, Epidemiology and EndResults (SEER)-Medicare database.Dr Nguyen, director of Prostate

Brachytherapy, Dana-Farber/Brigham

and Women’s Hospital, HarvardMedical School, Boston, and his co-investigators found MIRP jumpedfrom 1.5% of radical prostatectomies(RPs) in 2002 to 28.7% in 2005. Theyalso found that IMRT soared from8.7% of external radiation treatmentsfor prostate cancer to 81.7%. In addi-

By Rosemary Frei, MSc

New Tools Arriving to Measure andManage Chemotherapy CareBusiness, clinical concerns now connected in value-focused approach By Daniel Denvir

Breast Cancer Survival Improves,Thanks to New Therapies

The 2010 Genitourinary CancersSymposium: Progress in Multi -disciplinary Management was heldMarch 5-7 in San Francisco. All ses-sions emphasized a multidisciplinaryap proach to care; a number of thembrought out the cost and value issuesassociated with caring for genitouri-nary cancers.

Value-Based Cancer Carewill be at the ASCO Annual Meeting, June 4-8, in Chicago. Please visit us at booth 18121

Barcelona—Survival for patients withmetastatic breast cancer has improveddramatically in the last 20 years, espe-cially in the subgroup of patients withHER2-positive tumors, according toresearch presented at the 7th European

Breast Cancer Confer ence (EBCC7).This improvement, the researcherssuggest, is due to in creased use ofanthracyclines and the rise of targetedtherapies.“There is no doubt that trastuzu -

mab (Herceptin), which targets theHER2 gene, is the most important

By Colin Gittens


��

Photo by © ASCO/Todd Buchanan 2009

targeted therapies



Drug Therapy

treatments for ITP had to be discontin-ued at least 2 weeks before enrollment.In the 109 patients evaluated for

efficacy data, the primary end point(platelets ≥50 ¥ 109/L on day 43) wasachieved in 11%, 28%, 70%, and 81%in the placebo, 30-mg, 50-mg, and 75-mg groups, respectively. By day 15 oftherapy, more than 80% of patients inthe 50-mg and 75-mg groups hadreached platelet counts ≥50 ¥ 109/L.Platelet counts rose to ≥200 ¥ 109/L in28 patients (26%), at which time eltro m- bopag was discontinued. After cessationof therapy, platelet counts re turned tonear baseline levels within 2 weeks. Theincidence of bleeding also de creased asplatelet counts increased, particularly inthe patients receiving the 50-mg and 75-mg doses of eltrombopag.8A phase 3 trial was conducted as a fol-

low-up to assess the efficacy, safety, andtolerability of eltrombopag 50 mg orallyonce per day compared with placebo.Inclusion criteria were similar in the twostudies. The 114 patients enrolled wererandomized 2:1 to eltrombopag therapyfor up to 6 weeks or placebo. Eltrom -bopag could be increased to 75 mg dailyafter 3 weeks if platelet counts had notreached 50 ¥ 109/L. The primary end point (platelets ≥50

¥ 109/L after 6 weeks of therapy) wasreached by more patients in the eltrom-b opag arm than the placebo arm (59%vs 16%, P <.0001). Of the 34 patientswho received a dose increase to 75 mg,29% met the primary end point; how-ever, none of these patients reachedplatelet counts ≥200 ¥ 109/L. Prior his-tory of splenectomy, concomitant drugsfor ITP, or baseline platelet count ≤15 ¥109/L did not have a significant effecton response rates to eltrombopag com-pared with placebo. As is the goal in thetreatment of ITP, a significant reductionin bleeding symptoms was seen in thetreatment group compared with the

placebo group (39% vs 60%, P = .029).As seen in the phase 2 trial, plateletcounts returned to baseline followingdiscontinuation of eltrombopag, as didthe risk for bleeding complications.9

Dosing, administration, and toxicityEltrombopag should be started at a

dose of 50 mg orally once per day on anempty stomach (1 hour before or 2hours after a meal) and should be sepa-rated by at least 4 hours from antacids,calcium-rich food, and supplementscontaining polyvalent cations (iron,calcium, magnesium, aluminum, seleni-um, and zinc).7 Patients of East-Asiandecent (Chinese, Japanese, Korean, andTaiwanese) should be started at 25 mgorally daily because of pharmacokineticdata showing this population had a 70%increased exposure compared with non-Asian subjects. Moderate to severehepatic impairment (as determined byChild-Pugh criteria) will require dosereduction of eltrombopag to 25 mg oral-ly once per day. The lowest dose ofeltrombopag should be used to maintaina platelet count >50 ¥ 109/L. Doseadjustments and monitoring parameterscan be found in Table 1.Because eltrombopag is metabolized

by cytochrome P450 (CYP) 1A2,CYP2C8, and several uridine diphos-phate-glucuronosyltransferases, patientsreceiving concomitant therapy withmoderate or strong inhibitors of thesemetabolizers and eltrombopag should bemonitored closely for signs and symp-toms of excessive eltrombopag expo-sure. In vitro studies also show thateltrombopag is an inhibitor of theorganic anion transporting polypeptide1B1 and can increase systemic exposureto drugs that use this transport system,such as atorvastatin, fluvastatin, prava - statin, rosuvastatin, methotrexate,nateflinide, repaglinide, and rifampin.Although no specific dose reductions

have been given, caution should be usedwith administering these drugs con-comitantly.7The most common adverse effects

associated with eltrombopag use wereheadache, nausea, vomiting, and diar-rhea. Adverse events associated with the50-mg dose of eltrombopag combinedfrom the two randomized studies aresummarized in Table 2. The incidence ofgrade 3/4 adverse events during treat-ment in both studies was similar forpatients receiving eltrombopag andplacebo, 11 (7%) versus five (7%).8,9 Re ticulin fiber deposition, withoutcytopenias, was reported in the bonemarrow biopsies of seven patients. Thisobservation prompted the manufacturerto warn prescribers to monitor patientsclosely by examining peripheral bloodsmears and to discontinue therapy if thepatient develops new or worsening mor-phologic abnormalities or cytopenias.7Thrombotic complications have alsobeen observed in patients receivingeltrombopag and are likely a result ofexcessive increases in platelet counts.

Distribution programPromacta Cares is a restricted distri-

bution program that was designed topromote risk-benefit decisions beforeeltrombopag is dispensed to patients aswell as to require prescribers to reportbaseline and periodic safety informationfor each patient enrolled. Before distri-bution of eltrombopag, each prescribermust complete a one-time enrollmentform, which can be found on the Pro -macta Cares website.10 In addition, acompleted enrollment form and patientbaseline form must be sent in for eachpatient before the patient can receivethe medication. Twice yearly, a consult-ant from Promacta Cares will contactthe prescriber to collect safety informa-tion, verify the patient is still receivingeltrombopag, and verify whether thepatient should continue therapy. Tohelp establish long-term data regardingsafety and use, registered prescribersmust report any adverse events to theprogram. In particular, the risk for hepa-totoxicity, bone marrow reticulin forma-tion and fibrosis, worsened thrombocy-topenia upon cessation of therapyleading to serious hemorrhage, throm-boembolic/thrombotic complications,and increased risk or progression ofhematologic malignancies are the focusof the registry program. In addition toproper counseling regarding the use andside effects of eltrombopag, a mandato-ry medication guide must be distributedto each patient and can be found on thePromacta Cares website.10

ConclusionWith up to 10% of ITP patients

developing refractory disease, the needfor agents to reduce mortality frombleeding complications in this popula-tion has encouraged many researchersto delve into new mechanisms in thepathogenesis of ITP. Second-generationthrombopoiesis-stimulating agents weredeveloped to provide an additionalmechanism of increasing platelets bystimulating the production of plateletsin the bloodstream. Eltrombopag hasshown substantial efficacy in maintain-ing platelets above 50 ¥ 109/L inpatients with chronic ITP in two ran-domized controlled trials. Its long-termefficacy has not been established, how-ever, as the duration of these trials wasonly 6 weeks. Several ongoing studiesare looking at long-term use of eltrom-bopag in patients with chronic ITP.Preliminary data from the EltrombopagExtended Dosing Study (EXTEND)have shown that 73% of patients withbaseline platelets <30 ¥ 109/L achievedplatelet counts ≥50 ¥ 109/L during amedian treatment duration of 151 days,and the adverse event profile was similarto that in previous studies.11 The studyalso seeks to determine whether taper-ing of concomitant medications forITP will maintain platelet countswhile on eltrombopag, thus allowingpatients to receive less corticosteroidtherapy. Based on these favorable re -sults, the use of eltrombopag and romi-plostim is currently being studied inother disease states causing thrombo-cytopenia, including myelodysplastic syndrome and chemotherapy-inducedthrombocytopenia.12-14 Con tinued re -search in the use of thrombopoiesis-stimulating agents may identify whichpatients are more likely to respond tothese therapies as well as determinewhether these agents should be used asfrontline therapy. �

References1. Cines DB, Blanchette VS. Immune thrombocy-

topenic purpura. N Engl J Med. 2002;346:995-1008.

2. Cines DB, McMillan R. Pathogenesis of chronicthrombocytopenia purpura. Curr Opin Hematol.2007;14:511-514.

3. Godeau B, Provan D, Bussel J. Immune thrombo-cytopenic purpura in adults. Curr Opin Hematol.2007;14:535-556.

4. Kojouri K, Vesely SK, Terrell DR, George JN.Splenectomy for adult patients with idiopathicthrombocytopenic purpura: a systematic review toassess long-term platelet count responses, predic-tion of response, and surgical complications.Blood. 2004;104:2623-2634.

5. Porcelijn L, Folman CC, Bossers B, et al. Thediagnostic value or thrombopoietin level mea -surements in thrombocytopenia. Thomb Haemost.1998;79:1101-1105.

6. Li J, Yang C, Xia Y, et al. Thrombocytopeniacaused by the development of antibodies tothrombopoietin. Blood. 2001;98:3241-3248.

7. Promacta (eltrombopag) [package insert].Research Triangle Park, NC: GlaxoSmithKline;2008.

New Treatments for Chronic Idiopathic Thrombocytopenic... Continued from page 22

ALT indicates alanine aminotransferase; AST, aspartate aminotransferase.

Sources: References 8 and 9.

Eltrombopag 50 mg (n = 106) Placebo (n = 67)

Event n (%) n (%)

Headache 9 (8) 10 (15)

Nausea 6 (6) 2 (4)

Vomiting 4 (4) 2 (3)

Diarrhea 4 (4) 3 (4)

Myalgia 3 (3) 1 (1)

Constipation 2 (2) 2 (3)

Increased ALT 2 (2) 0

Increased AST 2 (2) 0

Arthralgia 2 (2) 4 (6)

Table 2. Adverse Events Associated with the Use of Eltrombopag



TARGET AUDIENCEThis activity is intended for hematologists, oncologists and others whoare involved with the care of patients with Chronic LymphocyticLeukemia (CLL).

STATEMENT OF NEEDCLL is the most common type of leukemia in the United States, withover 15,000 new cases per year, characterized by the accumulation ofmonoclonal B cells in the bone marrow, peripheral blood, and lymphoidtissue. Primarily a disease of the elderly, the median survival for CLLvaries substantially: many patients survive more than 10 years after diagnosis, but a subset of symptomatic patients have shorter lifeexpectancies—in the range of 1.5 to 6 years. The clinical/research bodyof knowledge in CLL is rapidly changing and represents a challenge forthe whole treatment team.

EDUCATIONAL OBJECTIVESOn completion of this activity, participants should be able to:

• List the essential steps in diagnosis and treatment planning of theCLL patient

• Select CLL treatment regimens based on patient characteristics• Define data supporting the benefit/risk ratio of upfront, relapsed,

and refractory CLL setting• Define strategies to manage fludarabine-resistant CLL• Describe emerging therapies in CLL

www.coexm.com/ace02.aspLOG ON TODAY TO PARTICIPATE

Release Date: April 29, 2010Expiration Date: April 28, 2011

In collaboration with

FACULTYNeil E. Kay, MD Professor Department of Medicine Mayo ClinicRochester, Minnesota

Michael Keating, MDCourse ChairProfessor of Medicine �Deputy Department Chairman�Department of Leukemia�M.D. Anderson Cancer Center�Houston, Texas

This activity has been approved for 1.5 AMA PRA Category 1 Credits™. For further information and to participate, please go to: www.coexm.com/ace02.asp

This activity is supported by an educational grant fromGenentech BioOncology and Biogen Idec.

Chronic Lymphocytic LeukemiaThe Essentials of Patient Care


April 2010 was the second Nat -ional Safe Handling Month, acampaign designed to further

education about the risks associatedwith handling hazardous drugs and safe-ty measures that can preventexposure to these agents. Theinitiative was supported by anunrestricted educational grantprovided by Carmel Pharma,Inc, the maker of the PhaSealclosed-system drug transferdevice (CSTD) and includ-ed regional and nationaleducational activities. TheOncology Pharmacist recentlyspoke with Timothy Tyler,PharmD, FCSHP, director ofpharmacy services, Comp rehensive Can -cer Center, Desert Regional MedicalCenter, Palm Springs, California, abouthis institution’s decision to implement aCSTD to protect their personnel.

Why is there still a need to raiseawareness of safe handling?The 2004 National Institute for

Occupational Safety and Health(NIOSH) alert raised awareness of theproblem, but NIOSH has no executiveenforcement arm. The US Phar m a -copeia (USP) <797> regulations areenforceable, but who is going to enforcethem? We are all trying to comply, butwe know from listservs and what we hearfrom our colleagues that there are facili-ties that are not fully complying with allof the USP <797> regulations.And a lot of questions remain. For

instance, CSTDs are mentioned in theNIOSH alert and briefly in USP <797>.We know that if these devices are trulyclosed systems, they are effective inreducing contamination, but some ofthem are filtered, not truly closed, and

we don’t know if that’s acceptable. There’s also the question of how much

contamination—if any—is acceptable.At what level are we going to get intotrouble? There may be multiple thresh-

olds, and until we can say thisis the unsafe level at whichsome percentage of the popu-lation will be at risk for devel-oping a malignancy, peopleare going to ask why theyshould spend large sums ofmoney to comply when it maynot be necessary. The two-pronged approach is to eitherprovide reimbursement fromthe payers, Medicare, Medi -caid, and the third-party pay-

ers, for using CSTDs or to be able todemonstrate the level at which contam-ination will cause harm. So, the barriers to compliance with

the standards are basically cost andthe fact that we don’t know whatexactly the safety threshold is. We’rerunning a business with very littlemargin left these days in healthcare.There are a lot of issues with reim-bursement, so the idea of addinganother expense when we’re not posi-tive about the level of risk is notattractive to hospital or businessadministrators. I think people willdivide into those who say “if there’sany potential risk, we want to offerpersonal protective equipment for allof our staff to be on the safe side,” andthose who say “we don’t have themoney for this unless you can demon-strate that there’s a defined risk.” Oneof the reasons for an awareness monthis to keep raising this issue with thepeople who are actually involved inhandling of the cytotoxins and otherhazardous drugs.

At your own institution you decid-ed to use a CSTD. What led to thatdecision?Data from a study conducted at the

Huntsman Cancer Center in Salt LakeCity, Utah, were instrumental in mak-ing that decision. The Huntsman studyshowed a significant reduction in sur-face contamination and positive urinesamples from pharmacists, technicians,and nurses after implementation of thePhaSeal system (Wick C, et al. Am J Health Syst Pharm. 2003;60:2314-2320). In 2000, we had just moved intoa fairly low-volume, brand new facilityand had only one pharmacy technicianpreparing chemotherapy. We thoughtwe were doing everything right anddecided to do wipe testing to docu-ment it. Much to our surprise, we didtest positive, which made me believethat even under the very best circum-stances, you can still have contamina-tion. When we tested again after 6months of use of the PhaSeal system,all areas tested showed a reduction incontamination.

Did the staff accept the new devicereadily?We surveyed the nurses and techni-

cians after the first week of use andthey said it slowed them down, butafter 60 days of use that was no longerthe case. It just became part of ourstandard operating procedure. It isimportant though to train new person-nel how to use the system appropriate-ly. It does require a concerted effortwith everyone from administration topharmacy to nursing agreeing on whatthe important issues are, doing thetraining, and sticking to it, makingsure that the product is being usedappropriately.

What are some of the remainingissues with safe handling?Of course the 800-pound gorilla in

the room is that nearly all of thechemotherapy vials or hazardous drugvials that come to doctors’ offices andclinics come contaminated on theoutside. The manufacturers have saidtheir hands are tied. They’re con-cerned that if they put vials throughan extra washing that gets rid of thatcontamination, they’d be heating thevials, and the US Food and DrugAdministration would then requirethem to do studies to prove that theyhaven’t damaged the drug inside. TheHematology/Oncology Pharmacy As -sociation and other organizations arelooking into this situation.As I mentioned before, the cost of

CSTDs remains a concern too. Ithink probably the only way it’s goingto be solved is by mandating the useof some system. And that cost has tobe reimbursed by the payer community—by Medicare, Medicaid, or third-party insurance companies. We needlegislative involvement and we needto lobby the payer community to con-vince them that this is a legitimateuse of technology to keep employeessafe. As Luci Power stated in an edi-torial, “demand clean vials” (PowerLA. Am J Health Syst Pharm. 2005;62:471). �


Safe Handling

8. Bussel JB, Cheng G, Saleh MN, et al.Eltrombopag for the treatment of chronic idio-pathic thrombocytopenic purpura. N Engl J Med.2007;357:2237-2247.

9. Bussell JB, Provan D, Shamsi T, et al. Effect ofeltrombopag on platelet counts and bleedingduring treatment of chronic idiopathic throm-bocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373:641-648.

10. Promacta Cares. www.promactacares.com. Ac -cessed September 1, 2009.

11. Bussel JB, Cheng G, Kovaleva L, et al. Long-term

safety and efficacy of oral eltrombopag for thetreatment of subjects with idiopathic thrombocy-topenic purpura (ITP): preliminary data from theEXTEND study. Blood (Annual MeetingAbstracts). 2007;110:Abstract 566.

12. Tiu RV, Sekeres MA. The role of AMG-531 inthe treatment of thrombocytopenia in idio-pathic thrombocytopenic purpura andmyelodysplastic syndromes. Expert Opin BiolTher. 2008;8:1021-1030.

13. GlaxoSmithKline. Eltrombopag treatment ofthrombocytopenia in subjects with advanced

myelodysplastic syndrome (MDS) or secondaryacute myeloid leukemia after MDS (sAML/MDS). Clinicaltrials.gov identifier: NCT009 03422. http://clinicaltrials.gov/ct2/show/NCT00903422?term=eltrombopag&rank=11. AccessedSept ember 1, 2009.

14. Amgen, Inc; M.D. Anderson Cancer Center.AMG 531 in patients with advanced malignancyreceiving treatment with carboplatin. Clinical tri-als.gov identifier: NCT00147225. http://clinicaltrials.gov/ct2/show/NCT00147225?term=romiplostim&rank=6. Accessed September 1, 2009.

National Safe Handling Initiative Serves asReminder of Need for Precautions when HandlingHazardous DrugsBy Karen Rosenberg

Timothy Tyler,PharmD, FCSHP

For more information on safe handling ofhazardous drugs, please view the archivedSafe Handling Awareness Day CE webinar atwww.carmelpharmausa.com/CE. Free CEcredit for this archived webinar is availablefor pharmacists, pharmacy technicians,nurses, and risk managers.

DRUG THERAPY

New Treatments for Chronic Idiopathic Thrombocytopenic... Continued from page 24

Medicare covers only 56% of the costsof administering chemotherapy andproviding infusion room services toelderly patients, according to a study ofcancer care in community practices.

Did You Know?


COMING SOON!

HEMATOLOGYONCOLOGYPHARMACY

JOURNAL OF

��$� �*#� ��!��"�"�&��'�� %"�� "� �� )�!��"��#$#� ��$��" �$�� "��"��"�##��#��$��"�#��"��!"��$��$$ !��#��%��%$�� $��$��$ ��

• Pharmacology research• Pharmacokinetic research• Pharmacodynamic research• Pharmacoeconomic research• Cost-comparative and

cost-effectiveness research• Chemotherapy safe handling• Formulary design• Therapeutic and clinical pathway design

��"��%""��$�)��!$�� #%��##� �#�� "��$ "��(!�"$��&�# ")�� "��! #�$� �#��!��#��#%��$�$ ��$ "��"�� "�� #��"�$� ��#��#%��$��%#�"�!$#�$ �[email protected]�

�

� ��



International News

CEP17 Breast Cancer TumorsAre More Likely to Respondto AnthracyclinesBARCELONA—Breast cancer patientswith the chromosome enumerationprobe 17 (CEP17) alpha satellite abnor-mality are more likely to have good out-comes from chemotherapy involvinganthracycline antibiotics than womenwithout the abnormality, according tonew data released at the Seventh Euro -pean Breast Cancer Conference.

John Bartlett, MD, with the Uni -versity of Edinburgh in Scotland present-ed the results of a meta-analysis of fouradjuvant breast cancer trials thatenrolled a total of nearly 3000 women.

Women with CEP17 tumors that weretreated with anthracyclines were roughlytwo thirds more likely to survive withoutrecurrent cancer than those who did notreceive anthracyclines. Recurrence-freesurvival was 67%, and overall survivalwas 63%.

Prior research by the same investiga-tors had shown that duplication ofCEP17 predicts sensitivity to anthracy-clines. “CEP17 can be readily assessed influorescent in situ hybridization analysisof human epidermal growth factor recep-tor type 2 [HER2] status and may repre-

sent a clinically useful biomarker for theselection of patients likely to benefitfrom anthracycline-containing thera-pies,” Bartlett pointed out.

He added that the research is impor-tant because there has been conflictingevidence on the best way to predictresponse to anthracyclines and because ithas not been clear whether any of theknown biomarkers like HER2 and topo - isomerase 2 alpha were accurate indica-tors of response to these drugs.

High BMI Is No Reason toExclude Prostate CancerPatients from MinimallyInvasive SurgeryBARCELONA—Minimally invasiveprostate cancer surgery known asrobotic-assisted laparoscopic prostatec-tomy (RALP) is an effective and safetreatment option in obese patients,investigators announced at the 25thAnniversary European Association ofUrology Congress.

David Samadi, MD, and colleagues atMount Sinai Medical Center in NewYork presented results in 1112 men whounderwent RALP by a single surgeon. Ofthe study population, 870 patients had alow body mass index (BMI; <30) and

242 patients had a high BMI (≥30).The results showed similar perioper-

ative, pathologic, oncologic, and func-tional outcomes in the two groups.Continence and potency rates werealso similar.

Samadi noted that surgeons havevoiced concern that obese patientsmight develop worse outcomes thannonobese patients because surgery is technically more challenging in this population. “Surgeons shouldapproach these cases with more con-fidence,” he said.

Breast Cancer Patients Prefer“Buddy System” toPhotographs WhenDiscussing ReconstructionBARCELONA—Women with breastcancer say they would rather meet withother patients who have undergonebreast reconstructive surgery than viewclinical photographs before theydecide on the particulars of their pro-cedure, new data show.

Clinical photographs are the surgeons’preferred method for showing patientspreoperatively the outcomes of varioustypes of breast reconstruction.

Anushka Chaudhry, MD, with

Frenchay Breast Care Centre in Bristol,United Kingdom, interviewed 30 womenwho were planning to undergo recon-structive procedures at her institution.All patients were seen at the center’sdedicated breast reconstruction clinic.

In addition to viewing clinical pho-tographs of their surgeon’s breastreconstruction procedures, patientswere offered the opportunity to meetface-to-face with other women whohad undergone similar procedures ortalk to them by telephone or e-mail.Contact between the women was madeby the breast cancer nurse.

Twenty-five women reported that theypreferred meeting other patients to “sim-ply seeing clinical photographs.” Theother five women said that they, too, pre-ferred meeting other women who hadundergone reconstructive surgery butthat contact by phone or e-mail was bestfor them.

“A key part of the decision-makingprocess is support, and patients areoften the best advocates for others atthis time of great personal anguish,”Chaudhry said.

She reported the findings at theSeventh European Breast CancerConference. �

Reports from the European Breast CancerConference and the European Association of UrologyCongress

Are you tired of the poor interestrates your bank is offering?Have you had it with bank fees?

Are you worried your bank could fail?Perhaps, it’s time you consider switch-ing to a credit union.

More than 90 million Americansbelong to a credit union, according tothe Credit Union National Association.A credit union is a financial cooperativethat offers a wide array of services similarto those offered by banks, such as check-ing and saving accounts, credit cardswith low interest rates and low or noannual fees, and loans.

Nowadays, membership is not limitedto specialized groups because theNational Credit Union Administration(NCUA) has relaxed its regulations onjoining. NCUA is an indepedent feder-al organization that supervises and char- t ers credit unions, as well as insures par-ticipants’ savings. Each credit unionserves what is called their “field of mem-

bership”—that is the commonalitybetween the members, according toNCUA. You may be eligible to join acredit union based on your:

• Employer—many employers spon-sor their own credit unions

• Geographic location—many creditunions serve anyone who lives in aparticular geographic area

• Family—most credit unions allowmembers’ families to join

• Membership in a group, such as achurch, labor union, school, oralumni.

Here are some advantanges of belong-ing to a credit union:

• Credit unions are not-for-profitorganizations. The profits incurredby the credit union directly benefitits members, and NCUA insuresdeposits up to $250,000.

• The biggest distinction betweencredit unions and banks is thatcredit unions are owned and run by

its members. Therefore, if you havean account with a credit union, youare a member and owner. As amember, you have a say in how thecredit union is run and can vote ona board of directors.

• Interest rates, for example, on carloans, mortgages, and money mar-ket accounts, are often attractivelylow. Credit unions can offer theselower interest rates because they areexempted from most state and fed-eral income taxes. Additionally,credit unions are in a better posi-tion to lend money because they arenot as tangled up in the subprimecredit crisis, compared with com-mercial banks.

• Fees can be fewer and lower. Cus -tomer fees generated by bankshelp generate profits. Creditunions, however, charge nominalfees or no fees at all for many oftheir services.

• Minimum balance requirements arelow. Most credit unions require adeposit of $5 to $25 to join, open anaccount, and be eligible for freechecking. Banks, however, typicallyrequire a larger deposit to open anaccount and often require a mini-mum balance for free checking.

If you decide to join a credit union,keep in mind that you may have limitedaccess to branch offices and automatedteller machines (ATMs). However,many credit unions have formed a net-work of “shared branch” locationsthroughout the country that memberscan use without incurring ATM fees.Before opening an account, visit yourcredit union’s website for ATM loca-tions. It is also a good idea to talk withyour credit union to make sure you havea full understanding of their services.

To learn more about whether a cred-it union is right for you, visit NCUA’swebsite at www.ncua.gov. �

FINANCIAL PLANNING

Is It Time to Jump on the Credit Union Bandwagon?By Eileen Koutnik-Fotopoulos



Meetings

adverse reactions were defined by any of the following adverse events occurring during or within 24 hours of the start of infusion: nausea, pyrexia, chills, hypotension, vomiting,and dyspnea. In Study 9, the following Grade 3 and 4 adverse reactions occurred more frequently in R-FC–treated patients compared to FC-treated patients: infusion reactions (9% in R-FC arm), neutropenia (30% vs. 19%), febrile neutropenia (9% vs. 6%), leukopenia (23% vs. 12%), and pancytopenia (3% vs. 1%). In Study 10, the following Grade 3 or 4 adverse reactions occurred more frequently in R-FC–treated patients compared to FC-treated patients: infusion reactions (7% in R-FC arm), neutropenia (49% vs. 44%), febrile neutropenia (15% vs. 12%), thrombocytopenia (11% vs. 9%), hypotension (2% vs. 0%), and hepatitis B (2% vs. <1%). Fifty-nine percent of R-FC–treated patients experienced an infusion reaction of any severity. Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Rituxan with the incidence of antibodies to other products may be misleading. Using an ELISA assay, anti-human anti-chimeric antibody (HACA) was detected in 4 of 356 (1.1%) patients with low-grade or follicular NHL receiving single-agent Rituxan. Three of the four patients had an objective clinical response. The clinical relevance of HACA formation in Rituxan-treated patients is unclear. Postmarketing Experience The following adverse reactions have beenidentified during post-approval use of Rituxan in hematologic malignancies. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to Rituxan. Hematologic: prolongedpancytopenia, marrow hypoplasia, and late-onset neutropenia, hyperviscosity syndrome in Waldenstrom’s macroglobulinemia. Cardiac: fatal cardiac failure.: Immune/Autoimmune Events: uveitis, optic neuritis, systemic vasculitis, pleuritis, lupus-like syndrome, serum sickness, polyarticular arthritis, and vasculitis with rash. Infection: viralinfections, including progressive multifocal leukoencephalopathy (PML), increase in fatal infections in HIV-associated lymphoma, and a reported increased incidence of Grade 3 and 4 infections in patients with previously treated lymphoma without known HIV infection. Neoplasia: disease progression of Kaposi’s sarcoma.: Skin: severe mucocutaneousreactions. Gastrointestinal: bowel obstruction and perforation. Pulmonary: fatalbronchiolitis obliterans and pneumonitis (including interstitial pneumonitis). DRUGINTERACTIONS Formal drug interaction studies have not been performed with Rituxan. In patients with CLL, Rituxan did not alter systemic exposure to fludarabine or cyclophosphamide. USE IN SPECIFIC POPULATIONS Pregnancy Category C: There are no adequate and well-controlled studies of rituximab in pregnant women. Postmarketing data indicate that B-cell lymphocytopenia generally lasting less than six months can occur in infants exposed to rituximab in-utero. Rituximab was detected postnatally in the serum of infants exposed in-utero. Non-Hodgkin’s lymphoma is a serious condition that requires treatment. Rituximab should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Reproduction studies in cynomolgus monkeys at maternal exposures similar to human therapeutic exposures showed no evidence of teratogenic effects. However, B-cell lymphoid tissue was reduced in the offspring of treated dams. The B-cell counts returned to normal levels, and immunologic function was restored within 6 months of birth. Nursing Mothers It is not known whether Rituxan is secreted into human milk.However, Rituxan is secreted in the milk of lactating cynomolgus monkeys, and IgG is excreted in human milk. Published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts. The unknown risks to the infant from oral ingestion of Rituxan should be weighed against the known benefits of breast-feeding. Pediatric Use The safety and effectiveness of Rituxan in pediatric patients have not been established. Geriatric Use Diffuse Large B-Cell NHL Amongpatients with DLBCL evaluated in three randomized, active-controlled trials, 927 patients received Rituxan in combination with chemotherapy. Of these, 396 (43%) were age 65 or greater and 123 (13%) were age 75 or greater. No overall differences in effectiveness were observed between these patients and younger patients. Cardiac adverse reactions, mostly supraventricular arrhythmias, occurred more frequently among elderly patients. Serious pulmonary adverse reactions were also more common among the elderly, including pneumonia and pneumonitis. Low-Grade or Follicular Non-Hodgkin’s Lymphoma Clinical studies of Rituxan in low-grade or follicular, CD20-positive, B-cell NHL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. Chronic Lymphocytic LeukemiaAmong patients with CLL evaluated in two randomized active-controlled trials, 243 of 676 Rituxan-treated patients (36%) were 65 years of age or older; of these, 100 Rituxan-treated patients (15%) were 70 years of age or older. In exploratory analyses defined by age, there was no observed benefit from the addition of Rituxan to fludarabine and cyclophosphamide among patients 70 years of age or older in Study 9 or in Study 10; there was also no observed benefit from the addition of Rituxan to fludarabine and cyclophosphamide among patients 65 years of age or older in Study 10 [see Clinical Studies]. Patients 70 years or older received lower dose intensity of fludarabine andscyclophosphamide compared to younger patients, regardless of the addition of Rituxan. In Study 9, the dose intensity of Rituxan was similar in older and younger patients, however in Study 10 older patients received a lower dose intensity of Rituxan. The incidence of Grade 3 and 4 adverse reactions was higher among patients receiving R-FC who were 70 years or older compared to younger patients for neutropenia [44% vs. 31% (Study 9); 56% vs. 39% (Study 10)], febrile neutropenia [16% vs. 6% (Study 9)], anemia [5% vs. 2% (Study 9); 21% vs. 10% (Study 10)], thrombocytopenia [19% vs. 8% (Study 10)], pancytopenia [7% vs. 2% (Study 9); 7% vs. 2% (Study 10)] and infections [30% vs. 14% (Study 10)]. OVERDOSAGE There has been no experience with overdosage in human clinical trials. Single doses of up to 500 mg/m2 have been administered in clinical trials. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term animal studies have been performed to establish the carcinogenicor mutagenic potential of Rituxan or to determine potential effects on fertility in males or females. PATIENT COUNSELING INFORMATION Patients should be provided theRituxan Medication Guide and provided an opportunity to read prior to each treatment session. It is important that the patient’s overall health be assessed at each visit and the risks of Rituxan therapy and any questions resulting from the patient’s reading of the Medication Guide be discussed. Rituxan is detectable in serum for up to six months following completion of therapy. Individuals of childbearing potential should use effective contraception during treatment and for 12 months after Rituxan therapy.

Revised 02/2010 (4851501)

Jointly Marketed by:Biogen Idec Inc. 5200 Research Place San Diego, CA 92122Genentech USA, Inc. 1 DNA Way South San Francisco, CA 94080-4990

©2010 Biogen Idec Inc. and Genentech, Inc. 7140919 February 2010

RITUXAN® (Rituximab) Brief summary—Please consult full prescribing information.

INDICATIONS AND USAGE Non-Hodgkin’s Lymphoma (NHL) Rituxan® (rituximab) isindicated for the treatment of patients with: Relapsed or refractory, low-grade orfollicular, CD20-positive, B-cell NHL as a single agent; Previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy; Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, afterfirst-line CVP chemotherapy; Previously untreated diffuse large B-cell, CD20-positiveNHL in combination with CHOP or other anthracycline-based chemotherapy regimens.Chronic Lymphocytic Leukemia (CLL) Rituxan® (rituximab) is indicated, in combination with fludarabine and cyclophosphamide (FC), for the treatment of patientswith previously untreated and previously treated CD20-positive CLL. Limitations of useRituxan is not recommended for use in patients with severe, active infections.WARNINGS AND PRECAUTIONS Infusion Reactions Rituxan can cause severe,including fatal, infusion reactions. Severe reactions typically occurred during the firstinfusion with time to onset of 30–120 minutes. Rituxan-induced infusion reactions andsequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm,pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction,ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death. Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medicalmanagement (e.g. glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusionreactions as needed. Depending on the severity of the infusion reaction and the requiredinterventions, temporarily or permanently discontinue Rituxan. Resume infusion at aminimum 50% reduction in rate after symptoms have resolved. Closely monitor thefollowing patients: those with pre-existing cardiac or pulmonary conditions, those whoexperienced prior cardiopulmonary adverse reactions, and those with high numbers ofcirculating malignant cells (≥25,000/mm3). [See Boxed Warning, Warnings and Precautions, Adverse Reactions.] Tumor Lysis Syndrome (TLS) Acute renal failure,hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis,some fatal, can occur within 12–24 hours after the first infusion of Rituxan in patientswith NHL. A high number of circulating malignant cells (≥25,000/mm3) or high tumor burdenconfers a greater risk of TLS. Administer aggressive intravenous hydration and anti-hyperuricemic therapy in patients at high risk for TLS. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated. [See Boxed Warning.] Severe Mucocutaneous Reactions Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with Rituxan. Thesereactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoiddermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of these reactions has varied from 1–13 weeks following Rituxan exposure. Discontinue Rituxan in patients who experience a severe mucocutaneous reaction. The safety ofreadministration of Rituxan to patients with severe mucocutaneous reactions has notbeen determined. [See Boxed Warning, Adverse Reactions.] Progressive MultifocalLeukoencephalopathy (PML) JC virus infection resulting in PML and death can occur in Rituxan-treated patients with hematologic malignancies or with autoimmune diseases.The majority of patients with hematologic malignancies diagnosed with PML receivedRituxan in combination with chemotherapy or as part of a hematopoietic stem celltransplant. The patients with autoimmune diseases had prior or concurrentimmunosuppressive therapy. Most cases of PML were diagnosed within 12 months oftheir last infusion of Rituxan. Consider the diagnosis of PML in any patient presentingwith new-onset neurologic manifestations. Evaluation of PML includes, but is not limitedto, consultation with a neurologist, brain MRI, and lumbar puncture. Discontinue Rituxanand consider discontinuation or reduction of any concomitant chemotherapy orimmunosuppressive therapy in patients who develop PML. [See Boxed Warning, Adverse Reactions.] Hepatitis B Virus (HBV) Reactivation Hepatitis B virus (HBV) reactivation with fulminant hepatitis, hepatic failure, and death can occur in patients with hematologicmalignancies treated with Rituxan. The median time to the diagnosis of hepatitis wasapproximately 4 months after the initiation of Rituxan and approximately one month afterthe last dose. Screen patients at high risk of HBV infection before initiation of Rituxan.Closely monitor carriers of hepatitis B for clinical and laboratory signs of active HBVinfection for several months following Rituxan therapy. Discontinue Rituxan and anyconcomitant chemotherapy in patients who develop viral hepatitis, and instituteappropriate treatment including antiviral therapy. Insufficient data exist regarding thesafety of resuming Rituxan in patients who develop hepatitis subsequent to HBVreactivation. [See Adverse Reactions.] Infections Serious, including fatal, bacterial,fungal, and new or reactivated viral infections can occur during and up to one yearfollowing the completion of Rituxan-based therapy. New or reactivated viral infectionsincluded cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis B and C. Discontinue Rituxan for serious infections and institute appropriate anti-infective therapy. [See Adverse Reactions.] CardiovascularDiscontinue infusions for serious or life-threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of Rituxan for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina. [See Adverse Reactions.] Renal Severe, including fatal, renal toxicity can occur after Rituxanadministration in patients with NHL. Renal toxicity has occurred in patients whoexperience tumor lysis syndrome and in patients with NHL administered concomitantcisplatin therapy during clinical trials. The combination of cisplatin and Rituxan is not anapproved treatment regimen. Monitor closely for signs of renal failure and discontinueRituxan in patients with a rising serum creatinine or oliguria. Bowel Obstruction and Perforation Abdominal pain, bowel obstruction and perforation, in some cases leadingto death, can occur in patients receiving Rituxan in combination with chemotherapy. Inpostmarketing reports, the mean time to documented gastrointestinal perforation was 6(range 1–77) days in patients with NHL. Perform a thorough diagnostic evaluation andinstitute appropriate treatment for complaints of abdominal pain. [See Adverse Reactions.] Immunization The safety of immunization with live viral vaccines followingRituxan therapy has not been studied and vaccination with live virus vaccines is notrecommended. Laboratory Monitoring In patients with lymphoid malignancies, duringtreatment with Rituxan monotherapy, obtain complete blood counts (CBC) and platelet

WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)Infusion Reactions: Rituxan administration can result in serious, including fatal infusion reactions. Deaths within 24 hours of Rituxan infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Carefully monitor patients during infusions. Discontinue Rituxan infusion and provide medical treatment for Grade 3 or 4 infusion reactions [see Warnings and Precautions, Adverse Reactions]. s Tumor Lysis Syndrome (TLS): Acute renal failure requiring dialysis with instances of fatal outcome can occur in the setting of TLS following treatment of non-Hodgkin’s lymphoma (NHL) patients with Rituxan [see Warnings and Precautions, Adverse Reactions].s Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan [see Warnings and Precautions, Adverse Reactions]. s Progressive Multifocal Leukoen cephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving Rituxan [see Warnings and Precautions, Adverse Reactions].s

counts prior to each Rituxan course. During treatment with Rituxan and chemotherapy,obtain CBC and platelet counts at weekly to monthly intervals and more frequently in patients who develop cytopenias. [See Adverse Reactions]. The duration of cytopeniasscaused by Rituxan can extend months beyond the treatment period. ADVERSEREACTIONS The most common adverse reactions of Rituxan (incidence ≥25%)observed in clinical trials of patients with NHL were infusion reactions, fever, lymphopenia, chills, infection, and asthenia. The most common adverse reactions of Rituxan (incidence ≥25%) observed in clinical trials of patients with CLL were: infusion reactions and neutropenia. Clinical Trials Experience in Lymphoid MalignanciesBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to Rituxan in 2282 patients, with exposures ranging from a single infusion up to 6–8 months. Rituxan was studied in both single-agent and active-controlled trials (n = 356 and n = 1926). The population included 679 patients with low-grade follicular lymphoma, 927 patients with DLBCL, and 676 patients with CLL. Most NHL patients received Rituxan as infusion of 375 mg/m2 per infusion, given as a single agent weekly for up to 8 doses, in combination with chemotherapy for up to 8 doses, or following chemotherapy for up to 16 doses. CLL patients received Rituxan 375 mg/m2 as an initial infusion followed by 500 mg/m2 for up to 5 doses, in combination withfludarabine and cyclophosphamide. Seventy-one percent of CLL patients received 6 cycles and 90% received at least 3 cycles of Rituxan-based therapy. Infusion Reactions In the majority of patients with NHL, infusion reactions consisting of fever,schills/rigors, nausea, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, dizziness, or hypertension occurred during the first Rituxan infusion. Infusion reactions typically occurred within 30 to 120 minutes of beginning the first infusion and resolved with slowing or interruption of the Rituxan infusion and with supportive care (diphenhydramine, acetaminophen, and intravenous saline). The incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion. [See Boxed Warning, Warnings and Precautions.] Infections Serious infections (NCI CTCAE Grade 3 or 4), including sepsis,occurred in less than 5% of patients with NHL in the single-arm studies. The overall incidence of infections was 31% (bacterial 19%, viral 10%, unknown 6%, and fungal 1%). [See Warnings and Precautions.] In randomized, controlled studies where Rituxanwas administered following chemotherapy for the treatment of follicular or low-grade NHL, the rate of infection was higher among patients who received Rituxan. In diffuse large B-cell lymphoma patients, viral infections occurred more frequently in those who received Rituxan. Cytopenias and hypogammaglobulinemia In patients with NHL areceiving rituximab monotherapy, NCI-CTC Grade 3 and 4 cytopenias were reported in 48% of patients. These included lymphopenia (40%), neutropenia (6%), leukopenia (4%), anemia (3%), and thrombocytopenia (2%). The median duration of lymphopenia was 14 days (range, 1–588 days) and of neutropenia was 13 days (range, 2–116 days). A single occurrence of transient aplastic anemia (pure red cell aplasia) and two occurrences of hemolytic anemia following Rituxan therapy occurred during the single-arm studies. In studies of monotherapy, Rituxan-induced B-cell depletion occurred in 70% to 80% of patients with NHL. Decreased IgM and IgG serum levels occurred in 14% of these patients. Relapsed or Refractory, Low-Grade NHL Adverse reactions in Table 1occurred in 356 patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL treated in single-arm studies of Rituxan administered as a single agent. [See Clinical Studies.] Most patients received Rituxan 375 mg/m2 weekly for 4 doses.Table 1Incidence of Adverse Reactions in ≥5% of Patients with Relapsed or Refractory, Low-Grade or Follicular NHL, Receiving Single-agent Rituxan (N = 356)a,b

aAdverse reactions observed up to 12 months following Rituxan. bAdverse reactions graded for severity by NCI-CTC criteria.

In these single-arm Rituxan studies, bronchiolitis obliterans occurred during and up to 6 months after Rituxan infusion. Previously Untreated Low-Grade NHL In Study 4,Lpatients in the R-CVP arm experienced a higher incidence of infusional toxicity and neutropenia compared to patients in the CVP arm. The following adverse reactions occurred more frequently (≥5%) in patients receiving R-CVP compared to CVP alone: rash (17% vs. 5%), cough (15% vs. 6%), flushing (14% vs. 3%), rigors (10% vs. 2%), pruritus (10% vs. 1%), neutropenia (8% vs. 3%), and chest tightness (7% vs. 1%). In Study 5, the following adverse reactions were reported more frequently (≥5%) in patients receiving Rituxan following CVP compared to patients who received no furthertherapy: fatigue (39% vs. 14%), anemia (35% vs. 20%), peripheral sensory neuropathy (30% vs. 18%), infections (19% vs. 9%), pulmonary toxicity (18% vs. 10%), hepato-biliary toxicity (17% vs. 7%), rash and/or pruritus (17% vs. 5%), arthralgia (12% vs. 3%), and weight gain (11% vs. 4%). Neutropenia was the only Grade 3 or 4 adverse reaction that occurred more frequently (≥2%) in the Rituxan armcompared with those who received no further therapy (4% vs. 1%). [See Clinical Studies.] DLBCL In Studies 6 and 7, [L see Clinical Studies]s the following adverse reactions,regardless of severity, were reported more frequently (≥5%) in patients age ≥60 yearsreceiving R-CHOP as compared to CHOP alone: pyrexia (56% vs. 46%), lung disorder (31% vs. 24%), cardiac disorder (29% vs. 21%), and chills (13% vs. 4%). Detailed safety data collection in these studies was primarily limited to Grade 3 and 4 adverse reactions and serious adverse reactions. In Study 7, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R-CHOP vs. 1.0% for CHOP). The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs. 7%) and lung disorder (6% vs. 3%). Other Grade 3 or 4 adverse reactions occurring more frequently among patients receiving R-CHOP were viral infection (Study 7), neutropenia (Studies 7 and 8), and anemia (Study 8). CLL The data below reflectexposure to Rituxan in combination with fludarabine and cyclophosphamide in 676 patients with CLL in Study 9 or Study 10 [see Clinical Studies]. The age range was s30–83 years and 71% were men. Detailed safety data collection in Study 9 was limited to Grade 3 and 4 adverse reactions and serious adverse reactions. Infusion-related

All Grades (%) Grade 3 and 4 (%)

Any Adverse Events 99 57Body as a Wholey 86 10

Fever 53 1Chills 33 3Infection 31 4Asthenia 26 1Headache 19 1Abdominal Pain 14 1Pain 12 1Back Pain 10 1Throat Irritation 9 0Flushing 5 0

Heme and Lymphatic Systemy p y 67 48Lymphopenia 48 40Leukopenia 14 4Neutropenia 14 6Thrombocytopenia 12 2Anemia 8 3

Skin and Appendagespp g 44 2Night Sweats 15 1Rash 15 1Pruritus 14 1Urticaria 8 1

All Grades (%) Grade 3 and 4 (%)

Respiratory Systemp y y 38 4Increased Cough 13 1Rhinitis 12 1Bronchospasm 8 1Dyspnea 7 1Sinusitis 6 0

Metabolic and NutritionalDisorders 38 3

Angioedema 11 1Hyperglycemia 9 1Peripheral Edema 8 0LDH Increase 7 0

Digestive Systemg y 37 2Nausea 23 1Diarrhea 10 1Vomiting 10 1

Nervous Systemy 32 1Dizziness 10 1Anxiety 5 1

Musculoskeletal Systemy 26 3Myalgia 10 1Arthralgia 10 1

Cardiovascular Systemy 25 3Hypotension 10 1Hypertension 6 1

June 30-July 3BARCELONA, SPAIN12th World Congress onGastrointestinal Cancerwww.esmo.org

8-11 RANCHO PALOS VERDES, CA 11th International Lung CancerCongresswww.cancerlearning.com

16-17 WASHINGTON, DC10th International Congress onGenitourinary Malignancieswww.cancerlearning.com

22-25 LA JOLLA, CANinth International Congress on theFuture of Breast Cancerwww.cancerlearning.com

JUNE/JULY

15-17 BORDEAUX, FRANCECongress of the European Society ofSurgical Oncologywww.ecco-org.eu

1-3 WASHINGTON, DCBreast Cancer Symposiumwww.asco.org

5-8 MONTREAL, QUEBEC18th International Congress onPalliative Carewww.pal2010.com

SEPTEMBER

JULY

OCTOBER

©iS

tockp

ho

to.c

om

/Sa

mu

el B

urt

©iS

tockp

ho

to.c

om

/Sa

mu

el B

urt

©iS

tockp

ho

to.c

om

/Sam

ue

l B

urt

©iS

tockphoto

.com

/Sam

uel B

urt


CLL8 TRIAL (N=817) REACH TRIAL (N=552)RITUXAN-NAIVE PATIENTS

8.3month

improvementin median

PFS

5.0month

improvementin median

PFS

In first-line CLL1.7-year follow-up

39.8 monthsR-FC

31.5 monthsFC

vs

In relapsed/refractory* CLL2.1-year follow-up

26.7 monthsR-FC

21.7 monthsFC

vs

DRIVING BETTEROUTCOMESRITUXAN+FC improved median PFS in first-line and previously treated CLL1,2

In the CLL8 trial2

RITUXAN+FC more than doubled CR in first-line CLL compared with FC alone (36% vs 17%; p<0.0001)

In the REACH trial2

Patients who responded to RITUXAN+FC (n=167) maintained their responses for nearly 2 years longer (48 months vs 27 months; p=0.0294) than those treated with FC alone (n=134)

NOW IN THE TREATMENT OFCHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

IndicationRITUXAN® (Rituximab) is indicated, in combination with fludarabine and cyclophosphamide (FC), for the treatment of patients with previously untreated and previously treated CD20-positive CLL.RITUXAN is not recommended for use in patients with severe, active infections.

BOXED WARNINGS RITUXAN administration can result in serious, including fatal, adverse reactions. These include infusion reactions,

tumor lysis syndrome (TLS), severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (PML)

Warnings and Precautions RITUXAN can also result in serious, including fatal, adverse reactions. These include hepatitis B reactivation with fulminant hepatitis and hepatic failure resulting in death; other infections, including bacterial, fungal, new or reactivated viral infections; cardiovascular events; severe, including fatal, renal toxicity; and abdominal pain, bowel obstruction and perforation, in some cases leading to death

Additional Important Safety Information The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with CLL were infusion reactions and neutropenia. Most patients treated with R-FC experienced at least one Grade 3 or 4 adverse reaction. The most frequently reported Grade 3 or 4 adverse reaction was neutropenia

In clinical trials, CLL patients 70 years of age or older who received R-FC had more Grade 3 and 4 adverse reactions compared with younger CLL patients who received the same treatment

For additional safety information, please see following page for brief summary of full prescribing information, including BOXED WARNINGS.Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion.

* In the REACH trial, patients had received 1 prior therapy. Patients who had previously received RITUXAN or both fludarabine and cyclophosphamide, either sequentially or in combination, were excluded from the trial, as were fludarabine-refractory patients; alkylator-refractory patients were permitted.2

R=RITUXAN; FC=fludarabine and cyclophosphamide; PFS=progression-free survival; CR=complete response.

Treatment considerationsThese trials were not designed or powered to detect a significant difference in PFS by age category. However, exploratory analyses defined by age suggest no observed benefit with the addition of RITUXAN to FC chemotherapy in previously untreated CLL patients 70 years of age or older and in previously treated CLL patients 65 years of age or older.1

©2010 Genentech USA, Inc., and Biogen Idec Inc. All rights reserved. 10021501 May 2010

References: 1. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2010. 2. Data on file, Genentech, Inc.


june 2010, vol 3, no 4

Documents

infusion center

rn janet belmonte

rnbc bozena owsieniuk

rnbc charlotte bradley

health plans

rn erica schermerkathy

new jersey

health reform