JOMCC | March/April 2009 Volume 2 Issue 2

© 2009 Green Hill Healthcare Communications, LLC

Current and Future Therapies for Non–small-cell Lung CancerCommentary by Konstantin H. Dragnev, MD

A Rational Approach to the Treatment of Advanced Non–small-cell Lung CancerReport from the Scripps Cancer Center’s 29th Annual Conference on ClinicalHematology & Oncology

Lung Cancer Drugs in Phase 3 and 4 Trials in the United States

Multidisciplinary Cancer Clinics: A Streamlined Approach toCancer Care in the Community SettingAn interview with Mark J. Krasna, MD

Battling Reimbursement Issues to Win the War on CancerTimothy G. Tyler, PharmD, FCSHP

Medications Used for the Treatment of Lung CancerICD-9-CM and J-codes, with FDA- and Compendia-approved uses and AWP-based and ASP + 6% pricing

March/April 2009 • Volume 2 • Number 2

IN THIS ISSUE

Business

Clinical tt

CLINICAL, BUSINESS, AND HEALTH ECONOMICINSIGHTS INTO PRACTICE MANAGEMENT

HG™

Join th

e JOM

CC

Edito

rial A

dvisory

Panel

• pag

e 26

Traditional educational activities (livemeetings or lectures, printed or Internet-based CME activities) may make you awareof new information, illuminate associated healthcare quality gaps, and may evenprovide you the rationale or evidence-based information for improving care of yourmultiple myeloma patients. However, theyusually do not offer any further support inthe successful application of the learningin your practice.

MedCases brings you an innovative,multifaceted opportunity to improve thequality of care of your multiple myelomapatients. This unique initiative combineseducation with practice-based application.You will:

Treat virtual patients in 6 onlineinteractive case simulations that offer up to 12 free AMA PRA Category 1 credits™. Learn about recent updates to the national guidelines and other current evidence, and how best to apply them in different patient scenarios.

Take the learning into your practice withthe unique Performance Improvement (PI) CME activity that offers up to 20 additional free AMA PRA Category 1 credits™. Step through an expert-led structured mechanism to identify, implement, and evaluate specific improvements in your practice.

The case simulations and PI-CME activity are now available at www.challengingcases.com

Supported by an educational grant from Millennium Pharmaceuticals, Inc.

Sponsored by

Multidisciplinary Cancer Care n 3

PublisherPhilip [email protected]

Editorial DirectorKaren [email protected]

Managing EditorDawn [email protected]

Production ManagerMarie RS Borrelli

Directors, Client ServicesJohn W. [email protected]

Russell [email protected]

Cristopher [email protected]

Business ManagerBlanche [email protected]

Executive AdministratorsThiel HennessyLisa Russo

TABLE OF CONTENTS

Mission Statement

Journal of Multidisciplinary CancerCare is a forum that provides oncolo-gists, nurses, pharmacists, and theirrespective cancer care team membersinsights into the diverse aspects of oncol-ogy management. As an authoritativeresource on the clinical, business, andregulatory changes affecting the oncologycare community, this journal offersexpert analysis of the dynamic natureand practical implications of currenttreatment, legislative, and reimburse-ment issues in the field.

6 Together We Are Stronger: Teamwork Combinesthe Clinical and Business Aspects of Cancer CareTimothy G. Tyler, PharmD, FCSHP

9 Current and Future Therapies for Non–small-cellLung CancerCommentary by Konstantin H. Dragnev, MD

15 A Rational Approach to the Treatment of AdvancedNon–small-cell Lung CancerReport from the Scripps Cancer Center’s 29th Annual Conference on Clinical Hematology & Oncology

21 Lung Cancer Drugs in Phase 3 and 4 Trials in theUnited States

Clinicalt

A Letter to Our Readerst

GH

4 n March/April 2009

EDITORIAL BOARD

John F. Aforismo, BSc, Pharm,RPh, FASCPR•J Health Systems InternationalOncology PharmacyScott E. Eggener, MDUniversity of ChicagoGenitourinary CancerBeth Faiman, RN, MSN, APRN, BC, AOCNCleveland Clinic TaussigCancer InstituteOncology NursingMehra Golshan, MDDana-Farber Cancer InstituteBreast CancerMark J. Krasna, MD St. Joseph Cancer InstituteThoracic SurgeryShaji K. Kumar, MDMayo ClinicHematologic MalignanciesTheodore F. Logan, MDIndiana UniversityMelanomaBeryl McCormick, MDMemorial Sloan-Kettering Cancer CenterRadiation OncologyLaura L. Morris, MDGoshen Center for Cancer CareSurgical OncologyRitu Salani, MDOhio State University Medical CenterGynecologic MalignanciesTimothy G. Tyler, PharmD, FCSHPComprehensive Cancer CenterDesert Regional Medical CenterOncology PharmacyGary C. Yee, PharmD, FCCP, BCOPUniversity of Nebraska Medical CenterOncology Pharmacy

TABLE OF CONTENTS

EDITORIAL CORRESPONDENCE should be addressed to EDITORIAL DIRECTOR, Journal of Multidisciplinary Cancer Care, 241 Forsgate Drive,Suite 205C, Monroe Twp, NJ 08831. E-mail: [email protected]. YEARLY SUBSCRIPTION RATES: United States and possessions: individ-uals, $105.00; institutions, $135.00; single issues $17.00. Orders will be billed at individual rate until proof of status is confirmed. Prices are subjectto change without notice. Correspondence regarding permission to reprint all or part of any article published in this journal should be addressed toREPRINT PERMISSIONS DEPARTMENT, Green Hill Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ08831. The ideas and opinions expressed in Journal of Multidisciplinary Cancer Care do not necessarily reflect those of the Editorial Board, theEditorial Director, or the Publisher. Publication of an advertisement or other product mentioned in Journal of Multidisciplinary Cancer Care shouldnot be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturer with ques-tions about the features or limitations of the products mentioned. Neither the Editorial Board nor the Publisher assumes any responsibility for anyinjury and/or damage to persons or property arising out of or related to any use of the material contained in this periodical. The reader is advised tocheck the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered toverify the dosage, the method and duration of administration, or contraindications. It is the responsibility of the treating physician or other health-care professional, relying on independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient.Every effort has been made to check generic and trade names, and to verify dosages. The ultimate responsibility, however, lies with the prescribingphysician. Please convey any errors to the Editorial Director. ISSN # applied for.

Journal of Multidisciplinary Cancer Care is published by Green Hill Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205C, MonroeTwp, NJ 08831. Telephone: 732.656.7935. Fax: 732.656.7938. Copyright ©2009 by Green Hill Healthcare Communications, LLC. All rightsreserved. Journal of Multidisciplinary Cancer Care is a trademark of Green Hill Healthcare Communications, LLC. No part of this publication maybe reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, orany informational storage and retrieval system, without written permission from the Publisher. Printed in the United States of America.

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

™

Businesst

23 Multidisciplinary Cancer Clinics: A StreamlinedApproach to Cancer Care in the Community SettingAn interview with Mark J. Krasna, MD

28 Battling Reimbursement Issues to Win the War on CancerTimothy G. Tyler, PharmD, FCSHP

31 Medications Used for the Treatment of Lung CancerICD-9-CM and J-codes, with FDA- and Compendia-approved uses andAWP-based and ASP + 6% pricing

7 News Notes

Abraxis Oncology® is a division of Abraxis BioScience, LLC. ©2008 Abraxis BioScience, LLC. All Rights Reserved. AO 1126 12/08

We’re here for you,so you can be there for your patients

ARC of Support is a comprehensive program that provides a broad range of services for health care professionals. This resource center has experienced representatives who are available to assist you with specific questions or issues about an Abraxis Oncology product. Just call 800.564.0216 Monday through Friday to access their help.

Information• Safety and efficacy data

• Product administration guidelines

• Coverage, coding, and

reimbursement information

Service• Assistance with claims review

and appeals process

• Benefit verification and prior authorization assistance

• Assistance for both uninsured and insured patients through the Abraxis Patient Access Program (APAP)

Support• Customer service representatives

• Reimbursement services representatives

• Trained health care professionals

• Live operators

Call the resource center today at 800.564.0216 to learn more.

ARC of Support is a comprehensive program that provides a broad range of services for health care professionals.

Call the ARC of Support™

Hotline at 800.564.0216

800.564.0216

GH


A Letter to Our Readers

Together We Are Stronger: Teamwork Combines the Clinical and Business Aspects of Cancer Care

If you are like most clinicians, you probably find yourself lagging behind in your reading and wouldnot even consider wading into the 1800 pages of the Outpatient Prospective Payment System(OPPS) rule for 2009 or the physician fee schedule rules published in Federal Register. Also, most of

us find it difficult enough to keep up with our own responsibilities, much less with things that onlyintersect our practice peripherally. At some point, you have to admit that you do not have the time,energy, or interest to keep up on every single aspect of care that impacts your patients. The Journal ofMultidisciplinary Cancer Care is a great nod to the idea that together we are stronger; or to get biblical(or nautical), a cord of many strands is not easily broken.

There are distinct advantages in the multidisciplinary approach. There are times when as a clinicianyou need to lean on others, sometimes very heavily. In my life, I have been leaned on by three disci-plines just while trying to write this introduction. I’ve been putting the documentation in place toensure that our patient accounting department knows that we got the replacement drug for a patientwe are treating. I’ve also been working with an IT analyst on an issue with the electronic medicalrecords system that is going live at my facility as I write. Lastly, I’ve been asked by the infectious diseasephysician to suggest a therapy for a chronic urinary tract infection and to explain the rationale for it tothe doctor and the patient.

This is a challenging time in healthcare. Healthcare expenditures are growing even as the economytanks around us. Many eyes are focusing on our standards of practice. Now more than ever, we need toknow what we do well and what we do not do well and then rely on those clinicians who know moreor are better at those functions or tasks than we are. I wish I did not know anything about reimburse-ment, but my brain is wired for clinical outcomes and financial accountability, so I was asked to writethe article on reimbursement for this issue. It is my hope that it will generate some interesting discus-sions among your colleagues across the healthcare spectrum.

Because this issue is focusing on lung cancer, I am pleased that my colleagues in other disciplines ofcancer care have written on the aspects of care that I do not know as well as they do. Our clinical arti-cles highlight recent reports on the approved and emerging targeted therapies, as well as promising noveltherapeutic agents, for non–small-cell lung cancer. Plus, for those of you thinking of implementing a mul-tidisciplinary approach in your practice, Dr Mark Krasna, a participant in the National Cancer Institute’sNational Community Cancer Center Program, explains how the approach works in his cancer center.

All of us on the editorial board and staff hope you enjoy this issue. We hope to hear from you andintegrate your ideas into future issues.

—Timothy G. Tyler, PharmD, FCSHPComprehensive Cancer InstituteDesert Regional Medical Center


Costs May Lead Cancer Patients and Survivors to Go Without Care

Two recent reports highlight the challenges cancerpatients and survivors face in paying for healthcare. Ina report presented at the American Association forCancer Research’s Science of Cancer Health Dispar-ities conference in February, National Cancer Instituteresearchers found that an estimated 2 million cancersurvivors are going without needed medical carebecause of economic considerations. Nearly 10% ofsurvivors do not fill prescriptions, nearly 8% pass onwhat they believe to be necessary general medical care,more than 11% skip needed dental care, and almost 3%forgo mental health services. Further, the researchersfound that Hispanic and African-American survivorsare twice as likely to forgo crucial care, and that finan-cial impediments were not limited to survivors withouthealth insurance.

A Kaiser Family Foundation and American CancerSociety report, Spending to Survive: Cancer PatientsConfront Holes in the Health Insurance System, high-lights how many patients amass high debt, file for per-sonal bankruptcy, or postpone or forgo necessary care.Among other factors, high cost-sharing, caps on bene-fits, and lifetime and annual maximums are highlight-ed as contributing to high out-of-pocket (OOP) costsafter cancer treatments begin. Patients also face obsta-cles to maintain coverage after they become ill. Andbecause many Americans depend on their employer forhealth insurance, patients who are unable to work mayfind themselves responsible for the full cost of monthlypremiums as well as OOP costs, all at a time when theirincomes have been reduced.

After patients go into remission, they may face higherpremiums even if they have a low risk of recurrence. Andif patients and survivors can no longer work and qualifyfor Social Security Disability Insurance payments, theymust wait 2 years before they are eligible for Medicare.

ASCO Guide Can HelpA new American Society of Clinical Oncology

(ASCO) guide, Managing the Cost of Cancer Care, canhelp patients and clinical staff to communicate about

the costs of cancer care. The guide can help patientsunderstand what costs to expect, a crucial step in prepar-ing for their disease’s financial impact. Included in theguide is a list of questions patients can ask their providersabout healthcare costs, such as those associated withmedication and treatment, office visits, transportation,living expenses, and long-term care. Information onresources for employment or health insurance problemsis also included, along with tips for organizing bills andexpenses, a list of financial resources available to peoplewith cancer, and a glossary of cancer treatment andfinancial terms. The guide can be downloaded atwww.cancer.net/managingcostofcare.

Seated Exercise Intervention for Lung Cancer Patients

A pilot study reported at the 9th National Conferenceon Cancer Nursing Research sought to assess the effectsof a seated exercise program on quality of life (QOL) andfatigue in lung cancer patients. Five participants random-ized to the intervention group received a video of low- tomoderate-intensity seated exercise programs and individ-ualized instructions about how to modify exercise inten-sity. They also were encouraged to perform the exercisesat least three times a week. Qualitative data of thepatients’ perceptions of QOL and fatigue were assessedafter 3 months. The researchers concluded that althoughtheir study group was small, their findings support theinclusion of a tailored exercise program duringchemotherapy education for patients with lung cancer.

Phase 3 Study Shows ImprovedProgression-free Survival inAdvanced NSCLC

Erlotinib in combination with bevacizumab asmaintenance therapy following initial treatment withbevacizumab plus chemo-therapy has been shown toextend progression-free survival significantly inadvanced non–small-cell lung cancer (NSCLC)patients. A preliminary safety analysis found thatadverse events were similar to those of previous beva-cizumab or erlotinib studies and no new safety signals

News Notes

GH


were observed.The ATLAS study was the second positive phase 3

trial of erlotinib as first-line maintenance therapy. TheSATURN study previously showed that erlotinibdelayed disease progression when given as a singleagent following chemotherapy.

Racial Disparities Examined in Lung Cancer Patients

Racial differences in the receipt of optimal therapy donot appear to affect outcomes, according to a recentstudy by Farjah and colleagues. Working from thehypothesis that there would be no significant evidenceof racial disparities among patients with early-stage lungcancer for whom surgical therapy is recommended, theresearchers analyzed data from the Surveillance,

Epidemiology, and End Results—Medicare database.They found that 14% fewer African-American patientsunderwent resection than their Caucasian counterparts.Further, even among patients who were recommendedsurgery, African-Americans underwent surgery less oftenthan whites. Surprisingly, although unadjusted 5-yearsurvival rates were lower for African-American patients,after adjustment, there was no significant associationbetween race and death. The researchers concluded thattheir finding points to distrust, beliefs, and perceptionsabout lung cancer and its treatment, and limited accessto care may play a dominant role in perpetuating racialdisparities. (Arch Surg. 2009;144:14-18.)

New Tumor Suppressor for Lung Cancer Identified

Researchers at the University of Cincinnati havefound that animals that did not express the proteinkinase C (PKC)-zeta gene developed more Ras-inducedlung cancer. This finding suggests that this gene acts as

a tumor suppressor, slowing Ras transformation andtumor development. This is significant because previ-ous research has established that the proto-oncogeneRas is abnormally expressed in up to 25% of lung can-cers. The researchers hope that this new understandingof the specific chain of events that lead to Ras-inducedlung cancers will enhance the ability to develop moretargeted therapies. (Galvez AS et al. Mol Cell Biol.2009;29:104-115.)

Microcoil Localization Helps in Removal of Small Lung Nodules

A new technique using microcoil localization ofsmall peripheral lung nodules enables their resectionusing fluoroscopically guided video-assisted thoraco-scopic surgery (VATS), with a low rate of interventionfor procedural complications. The technique uses com-puted tomography to place the fiber-coated surgicalmicrocoil at the precise location of the nodule to guidethe VATS removal. The authors propose that this tech-nique can be used to definitively determine if a noduleis malignant or benign. Further, this procedure allowsfor removal of the entire nodule and only a smallamount of surrounding tissue, thereby maintaining lungfunction and reducing recovery time. (Mayo JR et al.Radiology. 2009;250:576-585.)

Potential Biomarker Identified forLung Diseases Linked to Smoking

Researchers at Boston University have shown thatmicroRNAs (miRNAs) regulate the smoking-inducedgene-expression changes in airway epithelium. In com-paring smokers with never smokers, the researchersfound 28 miRNAs to be differentially expressed in smok-ers, with the majority being down-regulated. They alsoidentified a number of mRNAs whose expression level ishighly inversely correlated with miRNA expression invivo. The study suggests that these changes in miRNAexpression levels mediate some of the smoking-inducedgene-expression changes in airway epithelium, andtherefore, that miRNAs play a role in regulating hostresponse to environmental exposures and may con-tribute to the pathogenesis of smoking-related lung can-cer. It is hoped that these findings may lead to a new, rel-atively noninvasive biomarker for smoking-related lungdiseases. (Schembri F et al. Proc Natl Acad Sci U S A.Epub January 23, 2009.) n

The researchers concluded that theirfinding points to distrust, beliefs, andperceptions about lung cancer and itstreatment, and limited access to caremay play a dominant role in perpetuating racial disparities.


One-year relative survival for lung cancer hasincreased slightly in the past 30 years, from 35%in 1975-1979 to 41% in 2000-2003, due largely

to better surgical and pharmacologic interventions.1

However, 5-year survival for all lung cancer stages com-bined is just 15%.1 When lung cancer is detected whilestill localized, 5-year survival is better (49%), but only16% of cases are diagnosed at this early stage.1

The World Health Organization classifies lung can-cer into two main groups on the basis of biology, ther-apy, and prognosis: non–small-cell lung cancer(NSCLC) and small-cell lung cancer (SCLC).2

NSCLC, which accounts for more than 85% of all lungcancers, includes two main types: nonsquamous carci-noma (eg, adenocarcinoma) and squamous cell carci-noma.2 SCLC accounts for the remaining 15% of lungcancers.3 This article focuses on approved and emerg-ing therapies for NSCLC.

Prognostic FactorsIn patients with NSCLC, prognostic factors indica-

tive of longer survival include early-stage disease, goodperformance status, no significant weight loss, andfemale gender; poor prognosis in NSCLC is predictedby immunohistologic factors that include mutation ofthe tumor suppression gene (p53) and the activation ofKRAS oncogenes.2

Standard Therapy for NSCLCFor patients with earlier stage (I or II) NSCLC, sur-

gery provides the best chance of cure.2 Unfortunately,only 30% of patients are candidates for curative sur-gery.4 Radiation therapy is also employed in NSCLC, asis chemotherapy.2

Chemotherapy has numerous applications inNSCLC, depending on disease stage and surgical eligi-bility. Following surgery for early-stage disease, adju-vant chemotherapy has been shown to improve sur-vival.2 In patients with stage III NSCLC that is notsurgically resectable, concurrent chemoradiation maybe superior to sequential chemotherapy.2 For stage IVdisease, which is rarely treated surgically, platinum-

based chemotherapy is the standard treatment.2

Regimens include carboplatin/paclitaxel, cisplatin/paclitaxel, cisplatin/vinorelbine, gemcitabine/cisplatin,and docetaxel/cisplatin.2 Nanoparticle-albumin-boundpaclitaxel can be substituted for paclitaxel to improvetherapeutic targeting. Antifolate therapy with peme-trexed may also be used in NSCLC.

The Table shows chemotherapy drugs approved for NSCLC by the US Food and Drug Admin-istration (FDA).5,6

Approved Targeted Therapies for AdvancedNSCLC

Specific, targeted therapies have been developed foradvanced NSCLC.2 Three of these agents, bevacizumab,erlotinib, and gefitinib, are FDA approved (Table).5,6

Bevacizumab. The recombinant monoclonal anti-body bevacizumab blocks vascular endothelial growthfactor (VEGF). Bevacizumab was approved by the FDAin 2007 for unresectable, locally advanced, recurrent,or metastatic nonsquamous NSCLC.2 Based on resultsfrom phase 2/3 clinical trials, the Eastern CooperativeOncology Group (ECOG) recommends bevacizumabplus paclitaxel and carboplatin, provided patients meetthe following selection criteria: advanced nonsqua-mous NSCLC, no history of hemoptysis, and nountreated central nervous system (CNS) metastasis.7

Patients treated with bevacizumab/paclitaxel/carbo-platin in ECOG trials achieved higher median overallsurvival ([OS] 12.3 vs 10.3 months, P = .003), medianprogression-free survival ([PFS] 6.2 vs 4.5 months, P<.001), and response rates (35% vs 15%, P <.001)compared with paclitaxel/carboplatin.7 The three-drugcombination, however, produced higher rates of clini-cally significant bleeding than did the two-drug regi-men—4.4% versus 0.7% (P <.001). Bevacizumabshould therefore be combined cautiously with any ther-apy that carries a high risk of thrombocytopenia andthus bleeding.2 Other important adverse events (AEs)include gastrointestinal (GI) perforation, non-GI fistu-la, esophagitis, and hypertension.7

Erlotinib. Erlotinib is an orally administered small-

Current and Future Therapies forNon–small-cell Lung CancerWith commentary by Konstantin H. Dragnev, MD (see page 14)

GH


Table. Drugs Approved by the FDA for NSCLC

Drug Approved indication Approval date

Chemotherapy

Gemcitabine (injectable) In combination with cisplatin for the first-line treatment

of patients with inoperable, locally advanced (stage IIIA

or IIIB) or metastatic (stage IV) NSCLC 1998

Vinorelbine (injectable) As a single agent or in combination with cisplatin for stage

IV NSCLC or first-line treatment of ambulatory patients with

unresectable, advanced NSCLC; in combination with cisplatin

for stage III NSCLC 1994, 2000

Docetaxel (injectable) As a single agent for locally advanced or metastatic NSCLC

after failure of prior platinum-based chemotherapy; in

combination with cisplatin for unresectable, locally advanced

or metastatic NSCLC not previously treated with chemotherapy 1999, 2002

Paclitaxel (injectable) In combination with cisplatin for the first-line treatment of

NSCLC in patients who are not candidates for potentially

curative surgery and/or radiation therapy 1998

Pemetrexed (injectable) In combination with cisplatin therapy for locally advanced or

metastatic nonsquamous NSCLC; as a single agent for locally

advanced or metastatic nonsquamous NSCLC after prior

chemotherapy 2004, 2008

Molecularly Targeted Therapy

Erlotinib (tablets) For the treatment of patients with locally advanced or

metastatic NSCLC after failure of at least 1 prior chemotherapy

regimen; not recommended for use with platinum-based

chemotherapy 2004

Gefitinib (tablets) As monotherapy for the continued treatment of locally

advanced or metastatic NSCLC after failure of both platinum-

based and docetaxel chemotherapies, for patients who are

benefiting or have benefited from gefitinib*; no benefit

from adding gefitinib to doublet, platinum-based

chemotherapy 2003, 2005

Bevacizumab (injectable) In combination with carboplatin and paclitaxel for first-line

treatment of unresectable, locally advanced, recurrent, or

metastatic nonsquamous NSCLC 2007

*Use other treatment options in advanced NSCLC populations that have received 1 or 2 prior chemotherapy regimens and are refractory or intolerantto their most recent regimen. NSCLC staging: stage III, locally advanced disease; stage IV, disease with distant metastases.Sources: References 5 and 6.


molecule tyrosine kinase inhibitor (TKI) with specificinhibitory activity of the epidermal growth factor recep-tor (EGFR).2 EGFR is detectable in 80% to 85% ofpatients with NSCLC, at widely varying levels of expres-sion. Inhibition of EGFR suppresses multiple tumor-cellfunctions, including proliferation and survival.2

Erlotinib was approved by the FDA in 2004 forpatients with locally advanced NSCLC who havefailed one or more prior chemotherapy regimens.2

Erlotinib may also be considered for off-label use firstline, as monotherapy or in combination with chemo-therapy, in a stratified subset of NSCLC patients whoexhibit an active EGFR mutation or gene amplificationand who have never smoked.2,8,9 However, combiningerlotinib with paclitaxel and carboplatin first line in anonstratified group of NSCLC patients did not confera survival advantage compared with dual therapy withpaclitaxel/carboplatin.10

In a phase 3 trial of NSCLC patients previouslytreated with one or two chemotherapy regimens,11

erlotinib monotherapy produced a response rate of8.9% versus <1% in the placebo group (P <.001); PFSwas 2.2 months and 1.8 months, respectively (P<.001), and OS was 6.7 months and 4.7 months,respectively (P <.001). Five percent of patients discon-tinued erlotinib because of toxic effects. Common AEsincluded skin rash, anorexia, nausea, and vomiting.Hepatically impaired patients taking erlotinib shouldbe closely monitored and therapy discontinued orinterrupted if changes in liver function are severe.2

Gefitinib. Gefitinib, another orally administeredTKI, received accelerated approval by the FDA in 2003as monotherapy for patients with locally advanced ormetastatic NSCLC after two failed chemotherapy regi-mens. This approval was based on two large phase 2studies, with tumor response rate being the surrogateend point in these trials. Subsequently, however, aphase 3 trial showed no improvement in survival withgefitinib compared with placebo, and in 2005, the FDAapproved new labeling for the drug, restricting its use topatients in clinical trials or still receiving benefit fromtreatment already initiated.12

Updates on Emerging Targeted TherapiesNumerous targeted therapies are under continued

investigation for advanced NSCLC, such as monoclon-al antibodies (eg, cetuximab and trastuzumab) andTKIs (eg, gefitinib, sunitinib, axitinib, and sorafenib),as well as novel combinations containing erlotinib andbevacizumab. Emerging therapies aim at variousongogenic targets, including EGFR activity, multipletyrosine kinase receptors, EGFR2 (HER2/neu), stem-

cell factor receptor, insulin-like growth factor receptor,and VEGF. At the 2008 Annual Meeting of theAmerican Society of Clinical Oncology (ASCO),investigators presented a number of studies on emerg-ing NSCLC therapies, which are summarized here.

Gefitinib. Lee and colleagues13 compared oral gefi-tinib 250 mg/day with intravenous docetaxel 75 mg/m2

every 3 weeks in 161 patients with advanced ormetastatic NSCLC previously treated with platinum-based chemotherapy. Treatment with gefitinib pro-duced significantly longer PFS than did docetaxel (P =.0441), along with a significantly improved overallresponse rate (28.1% vs 7.6%, P = .0007). There wereno significant differences between treatments in quali-ty of life and lung cancer symptom improvement rate.AEs, which were generally mild, were consistent withboth the underlying disease and the usual toxicity pro-files of the drugs. More severe AEs (grade 3/4) occurredin 21.0% and 27.6% of patients taking gefitinib anddocetaxel, respectively; one possible treatment-relateddeath occurred in the gefitinib arm. An event indica-tive of interstitial lung disease was observed in threepatients treated with gefitinib and three treated withdocetaxel.

Bevacizumab. Socinski and colleagues14 studied theincorporation of bevacizumab and erlotinib intochemotherapy and radiotherapy regimens for NSCLC.Patients received induction therapy with carboplatinAUC 6, paclitaxel 225 mg/m2, and bevacizumab 15mg/kg, on days 1 and 22. On day 43, they began receiv-ing continuation therapy with weekly carboplatinAUC 2 x 7 and paclitaxel 45 mg/m2 x 7 with 74 Gy ofthoracic radiotherapy. During this phase of therapy,cohort 1 (n = 5) received concurrent bevacizumab at10 mg/kg every 2 weeks; cohorts 2 and 3 (both n = 5)received the same dose of concurrent bevacizumab plusoral erlotinib 100 mg and 150 mg, respectively, 4 daysout of each week. As of the presentation date, an ini-tial set of 20 patients was evaluable, with one patientexperiencing grade 3/4 nonhematologic toxicity. Atotal of 44.4% of patients had objective responses, andnone progressed during induction. Tumor volumes andvolumes on positron-emission tomography significant-ly decreased following induction (P <.0002). Over theentire study, 33% of patients experienced grade 3esophagitis. During the concurrent therapy phase,grade 3 AEs included one pulmonary hemorrhagerequiring bevacizumab discontinuation, one case ofinterstitial pneumonitis, and two cases of esophagitis.One grade 5 hemorrhage occurred in a squamous cellcarcinoma patient. The authors concluded that addingbevacizumab and erlotinib to chemotherapy and radio-

therapy was feasible, but that esophagitis remains theprimary toxicity.

Dansin and colleagues15 reported preliminary resultsfrom the SAiL study, an open-label, single-arm trialevaluating the safety of first-line bevacizumab com-bined with standard chemotherapy regimens in 2000patients with locally advanced, metastatic, or recurrentnonsquamous NSCLC. Patients received a standardfirst-line platinum-based chemotherapy regimen for upto six cycles combined with bevacizumab. There were396 serious AEs (SAEs), of which 16% were bevacizu-mab-related. Most of these SAEs, (75.5%) resolved orimproved. Grade 3/4 hypertension was seen in 2.7% ofpatients. CNS progression of disease was observed in1.1% of patients, but no CNS hemorrhage was seenduring treatment; one patient diagnosed with brainmetastases after cessation of bevacizumab had a CNShemorrhage 26 weeks after the last dose. The studydemonstrated that bevacizumab-based therapy has awell-characterized safety profile in NSCLC, with nometastases-related cases of CNS hemorrhage to date.

Erlotinib. Erlotinib at a dose of 150 mg/day is cur-rently under investigation in the large-scale, open-label, nonrandomized, global TRUST study, whichincludes more than 6000 patients with advancedNSCLC who have failed on or were not candidates forchemotherapy/radiotherapy. Several reports fromTRUST were presented at ASCO 2008.

Groen and colleagues16 reported TRUST findingsfor 6708 patients. Data on best tumor response wereavailable for 5448 patients: fewer than 1% had a com-plete response (CR), 12% had a partial response (PR),and 56% had stable disease (SD). Median PFS was 14.1weeks. Among 6267 safety-evaluable patients, 52%had at least one AE of any cause. Only 4% had morethan one erlotinib-related SAE, of which the mostcommon was diarrhea (1%). Erlotinib-related AEsresulted in treatment discontinuation in 5% ofpatients, predominantly due to rash, which wasobserved in 70% of patients and was primarily mild(grade 1/2). The authors concluded that erlotinibwould be an effective option for patients withadvanced NSCLC.

Merimsky and colleagues17 assessed erlotinib in animportant subgroup of the TRUST study, ie, elderlypatients who had not received prior chemotherapy orradiotherapy. Such first-line use of erlotinib may beuseful in an elderly population, since prognosis in thisgroup is poor due to significant comorbidities and lowperformance status. At the time of reporting, interimdata were available for 451 elderly patients older than70 years. Moderate to severe AEs (grade 3 to 5) of any

cause were reported by 49% of patients; however, only7% had more than one treatment-related AE, and onlythree patients (<1%) died because of a treatment-relat-ed AE. Dose reductions were required in 16% ofpatients, CR occurred in 1%, PR in 8%, SD in 45%,and PFS of 16.4 weeks. The study authors concludedthat erlotinib would be valuable as a first-line treat-ment in the management of advanced NSCLC in el-derly patients.

Crinó and colleagues18 presented data on quality oflife, symptom control, and survival in the TRUSTstudy. In evaluable patients who received erlotinib assecond-line treatment (n = 2724), fewer than 1% hada CR, 13% had a PR, and 54% had SD. Median PFSwas 13.7 weeks for all patients, but was longer or short-er depending on better or worse performance status.The safety analysis showed that only 4% of patientsreported an erlotinib-related SAE. Erlotinib-relatedrash was reported in 71% of patients, with 84% of thosecases grade 1 or 2. Interestingly, PFS was significantlylonger in patients who experienced rash of any gradeversus those without rash. The study also showed thatpatients with a good performance status had better out-comes. The authors concluded that, due to its favorabletoxicity profile and efficacy, erlotinib would be a goodalternative as second-line treatment in NSCLC.

Cetuximab. Cetuximab, an EGFR inhibitor, isapproved for the treatment of metastatic colorectalcancer and head and neck cancer, but its use in treat-ment of lung cancer is currently being investigated. Inthe phase 3 FLEX trial, Pirker and colleagues19 assessedthe efficacy and safety of cetuximab in combinationwith cisplatin/vinorelbine (CV) compared with CValone in 1125 patients with advanced NSCLC anddetectable EGFR. Patients were randomized to twoarms: patients in arm A (n = 557) received a regimenevery 3 weeks of an initial dose of cetuximab 400mg/m2 then 250 mg/m2/wk plus cisplatin 80 mg/m2 onday 1 and vinorelbine 25 mg/m2 on days 1 and 8; thosein arm B (n = 568) received only the CV portion of theregimen. At the time of data presentation, median OSwas significantly improved in arm A versus arm B (11.3vs 10.1 months, respectively, P = .0441). The studyauthors concluded that since cetuximab plus CVshowed superior survival versus CV alone, it would bea clinically relevant choice for first-line treatment ofadvanced NSCLC.

Pirker and colleagues19 also included a preplannedracial subgroup analysis. Caucasians (n = 945) had sig-nificantly longer median OS when cetuximab wasincluded in treatment (arm A, 10.5 months) thanwithout cetuximab (arm B, 9.1 months, P = .0025); the

GH



difference was observed regardless of tumor histology—adenocarcinoma or squamous cell carcinoma. In thesubgroup of 121 Asian patients, median OS was 17.6months in arm A and 20.4 months in arm B, a non-significant difference.

Pilz and colleagues20 reported early phase 2 results onthe feasibility of using cetuximab combined with com-mon chemotherapy regimens in patients with locallyadvanced or metastatic NSCLC. All patients receivedcetuximab 400 mg/m2 as an initial dose then 250 mg/m2

weekly in combination with either (1) gemcitabine1000 mg/m2 on days 1 and 8 for two 3-weekly cycles fol-lowed by docetaxel 75 mg/m2 on day 1 for two cyclesevery 3 weeks; or (2) gemcitabine 1200 mg/m2 on days1 and 8 and carboplatin AUC 5 on day 1 for a maxi-mum of four cycles every 3 weeks. Among 142 patientsevaluable for toxicity, the addition of cetuximab didnot add to the known toxicity of chemotherapy in theinduction phase; cetuximab combinations were alsowell tolerated in the maintenance phase.

The Cancer and Leukemia Group B, led byGovindan and colleagues,21 compared chemotherapyand thoracic radiation with and without cetuximab ina randomized phase 2 study. The study reported resultsfor a total of 106 eligible patients with previouslyuntreated stage III NSCLC. Patients were randomizedto receive either thoracic radiation 70 Gy plus carbo-platin AUC 5 and pemetrexed 500 mg/m2 intravenous-ly on day 1 every 21 days for 4 cycles (arm A) or thesame radiation and chemotherapy regimen plus cetux-imab at a loading dose of 400 mg/m2 followed 1 weeklater by 250 mg/m2/wk for an additional 6 weeks (armB). All patients then received consolidation therapywith four additional cycles of pemetrexed 500 mg/m2

every 21 days. Preliminary data show that the inci-dence of grade 3 or higher AEs was relatively similar forboth treatment arms, except for skin rash, which wasmarkedly higher with the addition of cetuximab. Onepatient died of fatal hemoptysis. The study authorsconcluded that combining radiation with peme-trexed/carboplatin with or without cetuximab was bothfeasible and well tolerated.

ConclusionDespite advances in treatment, the mortality rate for

patients with lung cancer remains high, and improvedtreatment is a clinical priority. Molecularly targeteddrug therapies, alone or in combination withchemotherapy, show promise in NSCLC. Research ontargeted therapy is especially robust in advancedNSCLC, and three targeted drugs, erlotinib, gefitinib,

and bevacizumab, have been approved by the FDA foruse in this type of lung cancer. It is hoped that ongoingresearch will continue to discover and confirm appro-priate uses for targeted therapy in lung cancers. n

References1. American Cancer Society. Cancer Facts & Figures, 2006. www.can

cer.org/downloads/STT/CAFF2006PWSecured.pdf. Accessed October29, 2008.

2. National Comprehensive Cancer Network. NCCN Clinical PracticeGuidelines in Oncology: Non-Small Cell Lung Cancer. V.2.2009.www.nccn.org/professionals/physician_gls/PDF/nscl.pdf. AccessedOctober 29, 2008.

3. National Comprehensive Cancer Network. NCCN Clinical PracticeGuidelines in Oncology: Small Cell Lung Cancer. V.2.2009.www.nccn.org/professionals/physician_gls/PDF/sclc.pdf. AccessedOctober 29, 2008.

4. Carney DN, Hansen HH. Non-small-cell lung cancer—stalemate orprogress? N Engl J Med. 2000;343:1261-1262.

5. RxList: the Internet Drug Index. www.rxlist.com. Accessed Decem-ber 3, 2008.

6. US Food and Drug Administration. Drugs@FDA: FDA approveddrug products. www.accessdata.fda.gov/scripts/cder/drugsatfda. Ac-cessed December 3, 2008.

7. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone orwith bevacizumab for non-small cell lung cancer. N Engl J Med.2006;355:2542-2550.

8. Sequist LV, Joshi VA, Jänne PA, et al. Response to treatment and sur-vival of patients with non-small cell lung cancer undergoing somat-ic EGFR mutation testing. Oncologist. 2007;12:90-98.

9. Eberhard DA, Johnson BE, Amler LC, et al. Mutations in the epider-mal growth factor receptor and in KRAS are predictive and prognos-tic indicators in patients with non-small-cell lung cancer treatedwith chemotherapy alone and in combination with erlotinib. J ClinOncol. 2005;23:5900-5909.

10. Herbst RS, Prager D, Hermann R, et al. TRIBUTE: a phase III trialof erlotinib hydrochloride (OSI-774) combined with carboplatinand paclitaxel chemotherapy in advanced non-small-cell lung can-cer. J Clin Oncol. 2005;23:5892-5899.

11. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in pre-viously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123-132.

12. US Food and Drug Administration. FDA Alert: Gefitinib (marketedas Iressa) information. www.fda.gov/cder/drug/infopage/gefitinib/default.htm. Accessed February 20, 2009.

13. Lee D, Kim S, Park K, et al. A randomized open-label study of gefi-tinib versus docetaxel in patients with advanced/metastatic non-small cell lung cancer (NSCLC) who have previously receivedplatinium-based chemotherapy. J Clin Oncol. 2008;26(May 20suppl):Abstract 8025.

14. Socinski MA, Morris DE, Stinchcombe TE, et al. Incorporation ofbevacizumab (B) and erlotinib (Er) with induction (I) and concur-rent (C) carboplatin (Cb)/paclitaxel (P) and 74 Gy of thoracicradiotherapy in stage III non-small cell lung cancer (NSCLC). J ClinOncol. 2008;26(May 20 suppl):Abstract 7517.

15. Dansin E, Mezger J, Isla D, et al. Safety of bevacizumab-based thera-py as first-line treatment of patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC): MO19390 (SAiL).J Clin Oncol. 2008;26(May 20 suppl):Abstract 8085.

16. Groen H, Arrieta OG, Riska H, et al. The global TRUST study oferlotinib in advanced non-small-cell lung cancer (NSCLC). J ClinOncol. 2008;26(May 20 suppl):Abstract 19000.

17. Merimsky O, Cheng C, Reck M, et al. Erlotinib as 1st-line therapyfor elderly patients (pts) with advanced non-small cell lung cancer(NSCLC). J Clin Oncol. 2008;26(May 20 suppl):Abstract 19016.

18. Crinó L, Boyer M, Eberhardt WE, et al, on behalf of the TRUSTinvestigators. Second-line erlotinib in patients with advanced non-small-cell lung cancer (NSCLC): results from a large, open-labelstudy. J Clin Oncol. 2008;26(May 20 suppl):Abstract 19002.

19. Pirker R, Szczesna A, von Pawel J, et al. FLEX: a randomized, multi-center, phase III study of cetuximab in combination withcisplatin/vinorelbine (CV) versus CV alone in the first-line treat-ment of patients with advanced non-small cell lung cancer(NSCLC). J Clin Oncol. 2008;26(May 20 suppl):Abstract 3.

20. Pilz LR, Cicenas S, Eschbach C, et al. Feasibility of cetuximab in

combination with gemcitabine or docetaxel or carboplatin/gem-citabine for chemonaïve patients with advanced non-small cell lungcancer (NSCLC): observations from an ongoing randomized phaseII/III trial (GemTax IV). J Clin Oncol. 2008;26(May 20 suppl):Abstract 19005.

21. Govindan R, Bogart J, Wang X, et al. A phase II study of peme-trexed, carboplatin and thoracic radiation with or without cetux-imab in patients with locally advanced unresectable non-small celllung cancer: CALGB 30407—early evaluation of feasibility and tox-icity. J Clin Oncol. 2008;26(May 20 suppl):Abstract 7518.

GH


New technology, the explosion of biological andgenetic information, and the development of

novel therapeutic agents have significantly impactedthe treatment of cancer. The survival of patients withadvanced non–small-cell lung cancer (NSCLC) hasincreased in recent years. This is attributed toimproved cytotoxic chemotherapy, better supportivecare, and the introduction of targeted agents. Manymore treatment options are available, and the chal-lenge is the selection of the most appropriate regi-men for each patient.

Tumor histology is one easily obtainable charac-teristic that can be used to select chemotherapy. Forexample, pemetrexed is more effective than gem-citabine in patients with nonsquamous carcinoma ofthe lung. Molecular markers to assist in the selectionof chemotherapy are also being studied, such asERCC1 to predict sensitivity to cisplatin, or RRM1for gemcitabine. The results have not yet been vali-dated, and these remain a research tool, rather thana clinically useful aid.

Targeted agents are developed based on improvedunderstanding of the molecular mechanisms of cancer.The target is a molecule that should be critical for thesurvival or proliferation of cancer cells and should beexpendable for the normal cells. This is straightfor-ward in theory, but finding such unique targets has notbeen easy. Current targeted agents are not effective inall patients, and they all affect to some degree non-cancerous cells and tissues, causing toxicities.

Ideally, therapies for individual patients should beselected based on the presence of the target in theirtumors. For the available targeted agents for NSCLC,

however, there are no markers ready for use in the clin-ic. For antiangiogenic drugs, for example, the selectionis based on risks for toxicities. Ongoing studies mayexpand the range of patients who can receive regimenscontaining these agents. Even for drugs targeting well-studied molecules, such as the epidermal growth factorreceptor, there are no agreed upon markers that the cli-nician can use in everyday practice.

With the availability of many regimens, morepatients will be offered several lines of therapy. It maybe more important that patients are exposed to allthese agents at some point in the course of their treat-ment rather than the precise sequence of regimens.The economic impact of the high cost of the noveltreatments will invariably influence the choice oftherapy. Although the well-being of the patientremains the primary focus of the oncology team, eco-nomic realities will change our practice. It is likelythat more regulation by payers—insurance companiesand federal agencies—may soon affect our ability toselect therapy. As more targeted agents are developed,it is imperative that treatment choices become indi-vidualized and regimens are tailored to the specificmolecular characteristics of the tumor. Thus, anexpensive new drug will be used only in a patient whois likely to benefit from it. A patient whose tumor hasdifferent characteristics will be offered another regi-men. This will improve the cost/benefit ratio of noveltherapies and will ensure that all patients continue toreceive high-quality cancer care.

Commentary

Current and Future Therapies for Non–small-cellLung Cancer: The Clinician’s PerspectiveBy Konstantin H. Dragnev, MD*

*Norris Cotton Cancer Center, Dartmouth-HitchcockMedical Center, Lebanon, New Hampshire


SAN DIEGO—A leading expert in the treatmentof advanced lung cancer recently described somepromising novel therapeutic agents that when

combined could potentially improve upon the currentstandard chemotherapeutics by triggering apoptosisand slowing down tumor progression.

Ronald B. Natale, MD, gave this year’s LongmireLecture at the Scripps Cancer Center’s 29th AnnualConference on Clinical Hematology & Oncology.Natale is the senior research advisor and national direc-tor of the Lung Cancer Research Program for AptiumOncology and an attending physician at the Cedars-Sinai Outpatient Cancer Center in Los Angeles.

The lecture, which each year honors Dr William P.Longmire Jr, the surgeon who helped found theUniversity of California at Los Angeles School ofMedicine, was titled, “Treatment of AdvancedNSCLC: Chemotherapy, Biological Agents, and a NewHypothesis Regarding Their Interaction.” Natale’sreview first looked back to what worked and then for-ward to what improvements can be made in synergisticdrug therapy for non–small-cell lung cancer (NSCLC).

In the lecture, he touched on emerging agents forthe treatment of NSCLC and included combinationregimens that are currently approved by the US Food and Drug Administration (FDA); a review ofthe Eastern Cooperative Oncology Group (ECOG)4599 trial; the subsequent Avastin in Lung (AVAiL)trial; and data supporting the use of molecularly tar-geted therapies for NSCLC, such as the epidermalgrowth factor receptor (EGFR) tyrosine kinaseinhibitors (TKIs) gefitinib and erlotinib, whichNatale said represent “a new hypothesis and maybe anew paradigm that can produce an apoptotic responsein patients” (Table).

Combination Regimens in NSCLCCurrently, the FDA-approved combination regimens

for first-line treatment of advanced NSCLC are carbo-platin + paclitaxel + bevacizumab for patients with nobrain metastases and cisplatin/carboplatin + paclitaxel/docetaxel/gemcitabine for those with brain metastases.

Natale presented a chart showing that the 1-yearsurvival rates for cytotoxic, alkylating agents pre-1980were 12% to 15%; from 1980 to 1990, the cisplatin-based treatment increased the survival rate to 25%, andfrom 1990 to 2000, it increased further to 35% or morewith cisplatin + carboplatin-based treatments.

The ECOG Trial: Questions RemainBased on the findings of the ECOG 4599 trial, beva-

cizumab was approved in 2006 as a component of first-line therapy for patients with unresectable, locallyadvanced, recurrent or metastatic, nonsquamousNSCLC.1,2 Bevacizumab is a monoclonal antibodymade partially of murine protein from Chinese hamsterovary cells. It works by blocking the action of vascularendothelial growth factor (VEGF).

Natale said that patients with “undifferentiatedNSCLC” or “NSCLC not otherwise specified” wereincluded in ECOG 4599 and that the trial also includedpatients with adenocarcinoma of the lung; large-cellundifferentiated carcinoma of the lung; poorly differen-tiated or undifferentiated carcinoma; carcinoma not oth-erwise specified; and a large number of elderly subjects.

This study showed statistically significant progres-sion-free survival (PFS) and overall survival benefitswhen 15 mg/kg of bevacizumab was added to the stan-dard regimen of carboplatin + paclitaxel every 3 weekscompared with chemotherapy alone (25% improve-ment; hazard ratio, 0.80).

A Rational Approach to the Treatmentof Advanced Non–small-cell Lung CancerReport from Scripps Cancer Center’s 29th Annual Conference on Clinical Hematology & OncologyKristina Rebelo

GH


Natale, however, cited several problems with thetrial. “This trial started off ambitiously, but left manyquestions remaining.” He said the trial has been“debated and debated, but the primary problem withthe study was that clinicians knew which patients weregetting what drugs.” Other important questions raisedwere (a) whether a lower dose of bevacizumab wouldhave provided similar efficacy; and (b) whether beva-cizumab could have also enhanced the activity of otherchemotherapy regimens besides carboplatin + paclitax-el. Natale said that, despite its reported flaws, theECOG 4599 trial has led to changes in the standard ofpatient care in the United States.

The AVAiL study3 addressed some of the issuesraised by ECOG 4599 by randomizing 1043 patientswith NSCLC to gemcitabine + cisplatin, with or with-out either high-dose (15 mg/kg) or low-dose (7.5mg/kg) bevacizumab; this study confirmed that beva-cizumab improves PFS in patients with advanced, non-squamous NSCLC.

According to Natale, however, the AVAiL studyraised questions too, such as whether a higher dose ofbevacizumab is needed for lung cancer. He also urgedtreating oncologists to utilize pathology findings. “Weneed to talk to pathologists and get more patient tissue totry to nail down a diagnosis, and we need more molecu-lar studies for more valid parameters, not just histology.”

The Rationale for EGFR InhibitorsNatale explained that despite the importance of

chemotherapy in lung cancer treatment, it can be expect-ed that patients with advanced lung cancer will eventu-ally reach the “chemotherapy plateau,” and he stressed

the importance of adding novel agents at that point.He presented slides elucidating the basic concepts of

EGFR signaling pathways and how EGFR, a proteinwith a critical role in cell division that is often mutatedin tumors, is overexpressed in many solid tumors, includ-ing NSCLC,4 definitively documenting its role in thepathogenesis of some lung cancers. He said that tumorheterogeneity is a hallmark of lung cancer and “patientsmay require multiple drugs to attack multiple targets.”

Natale reviewed studies of the EGFR-TKIs, whichinclude gefitinib and erlotinib. He explained that thesemolecularly targeted agents provide a different mecha-nism of action from chemotherapy that can be muchmore specific in treatment of patients with NSCLCwho have EGFR mutations.5

“Gefitinib and erlotinib work very differently thanstandard chemotherapy and have a very different tox-icity profile,” he said, and therefore adding one of theseagents to standard chemotherapy should improvepatient survival. He noted too that “taking a pill oncea day that causes a mild-to-moderate skin rash and milddiarrhea may be at least as good as receiving toxicintravenous chemotherapy in some patients. Let’s testthis strategy in patients who are so debilitated fromtheir lung cancer that chemotherapy may not be thebest choice.”

He discussed two phase 2 trials in patients with pre-viously treated advanced NSCLC that suggested gefi-tinib is efficacious and less toxic than chemotherapy. A recently reported phase 3 study of patients with previously treated advanced NSCLC showed that gefitinib was noninferior in overall survival comparedwith docetaxel.6

Table. Generating a New Hypothesis of NSCLC Treatment

• EGFR-TKIs can produce an “apoptotic” response (>30% rapid, measurable tumor regression)in NSCLC.~10% of unselected patients~50% of never smokers (or “light” former smokers >15-year interval)~70% of patients with EGFR mutations

• EGFR-TKIs (gefitinib/erlotinib) can produce an “antiproliferative” effect in NSCLC.~40%-60% of unselected patients~30% of never smokers (or “light” former smokers >15-year interval)~10%-20% of patients with EGFR mutations

• EGFR-TKIs induce apoptotic effects that may be synergistic with chemotherapy; the antiproliferative effects are probably antagonistic.

NSCLC indicates non–small-cell lung cancer; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor.


Another Novel Agent Shows PromiseNatale next discussed studies of vandetanib, a once-

daily oral agent that selectively inhibits VEGF recep-tor, EGFR, and rearranged during transfection (RET)signaling.7 Improved PFS with vandetanib has beenshown in three phase 2 studies of patients withadvanced NSCLC. Two of these studies were in previ-ously treated patients (vandetanib 300 mg vs gefitinib;vandetanib 100 mg ± docetaxel vs docetaxel), and in one, it was used as first-line therapy (vandetanib 300mg ± paclitaxel + carboplatin vs paclitaxel + carbo-platin). Another study, however, found poorer PFSwith vandetanib 300 mg monotherapy compared withpacitaxel + carboplatin. Results of an exploratoryanalysis reported at the 2008 annual meeting of theAmerican Society of Clinical Oncology suggest thatlow baseline levels of circulating VEGF may be predic-tive of a PFS advantage in patients with NSCLC whoreceive vandetanib monotherapy. n

References1. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or

with bevacizumab for non-small-cell lung cancer. N Engl J Med.2006;355:2542-2550.

2. Cohen MH, Gootenberg J, Keegan P, et al. FDA drug approval sum-mary: bevacizumab (Avastin) plus carboplatin and paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer. Oncologist. 2007;12:713-718.

3. Reck M, von Pawel J, Zatloukal P, et al. Phase III trial of cisplatinplus gemcitabine with either placebo or bevacizumab as first-linetherapy for non-squamous non–small-cell lung cancer: AVAiL. J ClinOncol. 2009 Feb 2;Epub ahead of print.

4. Perez-Soler R, Chachoua A, Huberman M, et al. A phase II trial ofthe epidermal growth factor receptor (EGFR) tyrosine kinase inhibi-tor OSI-774, following platinum-based chemotherapy, in patients(pts) with advanced, EGFR-expressing, non-small cell lung cancer(NSCLC). Proc Am Soc Clin Oncol. 2001;20(suppl):Abstract 1235.

5. Comis RL. The current situation: erlotinib (Tarceva) and gefitinib(Iressa) in non-small cell lung cancer. Oncologist. 2005;10:467-470.

6. Kim ES, Hirsh V, Mok T, et al. Gefitinib versus docetaxel in previ-ously treated non-small-cell lung cancer (INTEREST): a randomisedphase III trial. Lancet. 2008;372:1809-1818.

7. Heymach JV, Hanrahan EO, Mann P, et al. Baseline VEGF as apotential predictive biomarker of vandetanib clinical benefit inpatients with advanced NSCLC. J Clin Oncol. 2008;26(May 20suppl):Abstract 8009.

APRIL

April 30-May 3Oncology Nursing Society 34th Annual CongressSan Antonio, TXwww.ons.org

MAY

3-612th World Congress on Cancer of the Skin 2009Tel Aviv, [email protected]

13-144th Annual Oncology Economics Forum: Access toInnovative Cancer Therapies in 2009Washington, DCwww.conferagroup.com

May 29-June 22009 ASCO Annual MeetingOrlando, FLwww.asco.org

JUNE

17-20HOPA 2009: Hematology/Oncology PharmacyAssociation 5th Annual ConferenceMiami, FLwww.hoparx.org

17-2010th International Lung Cancer CongressKohala Coast, HIwww.cancerlearning.com

22-262009 Pan Pacific Lymphoma ConferenceKohala Coast, [email protected]

24-26VIII Madrid Breast Cancer ConferenceMadrid, Spainwww.madridbreastcancer2009.com

25-27Supportive Care in Cancer MASCC/ISOO 2009International SymposiumRome, Italywww.mascc.org

Upcoming Meetings

She’s still fighting after surgery,radiation, and chemotherapy. How can you respond whenshe asks what’s next?

IMPORTANT SAFETY INFORMATIONThe use of ABRAXANE has not been studied in patients with hepatic orrenal dysfunction. In the randomized controlled trial, patients wereexcluded for baseline serum bilirubin >1.5 mg/dL or baseline serum creatinine >2 mg/dL.

ABRAXANE can cause fetal harm when administered to a pregnantwoman. Women of childbearing potential should be advised to avoidbecoming pregnant while receiving treatment with ABRAXANE.

Men should be advised to not father a child while receiving treatmentwith ABRAXANE.

It is recommended that nursing be discontinued when receivingABRAXANE therapy.

ABRAXANE contains albumin (human), a derivative of human blood.

Caution should be exercised when administering ABRAXANE concomitantly with known substrates or inhibitors of CYP2C8 andCYP3A4.

ABRAXANE therapy should not be administered to patients with metastaticbreast cancer who have baseline neutrophil counts of less than 1,500 cells/mm3. It is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE.

ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease orrelapse within 6 months of adjuvant chemotherapy. Priortherapy should have included an anthracycline unless clinically contraindicated.

WARNING: ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) should be administered under the supervision of a physician experienced inthe use of cancer chemotherapeutic agents. Appropriate management ofcomplications is possible only when adequate diagnostic and treatment facilities are readily available. ABRAXANE therapy should not be administered to patients withmetastatic breast cancer who have baseline neutrophil counts of lessthan 1,500 cells/mm3. In order to monitor the occurrence of bonemarrow suppression, primarily neutropenia, which may be severe andresult in infection, it is recommended that frequent peripheral bloodcell counts be performed on all patients receiving ABRAXANE. Note: An albumin form of paclitaxel may substantially affect a drug’sfunctional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS.

Patients should not be retreated with subsequent cycles of ABRAXANEuntil neutrophils recover to a level >1,500 cells/mm3 and plateletsrecover to a level >100,000 cells/mm3.

In the case of severe neutropenia (<500 cells/mm3 for 7 days or more)during a course of ABRAXANE therapy, a dose reduction for subsequentcourses is recommended.

Sensory neuropathy occurs frequently with ABRAXANE.

If grade 3 sensory neuropathy develops, treatment should be withhelduntil resolution to grade 1 or 2 followed by a dose reduction for allsubsequent courses of ABRAXANE.

Severe cardiovascular events possibly related to single-agent ABRAXANEoccurred in approximately 3% of patients in the randomized trial. Theseevents included chest pain, cardiac arrest, supraventricular tachycardia,edema, thrombosis, pulmonary thromboembolism, pulmonary embolism,and hypertension.

In the randomized metastatic breast cancer study, the most importantadverse events included alopecia (90%), neutropenia (all cases 80%;severe 9%), sensory neuropathy (any symptoms 71%; severe 10%),asthenia (any 47%; severe 8%), myalgia/arthralgia (any 44%; severe8%), anemia (all 33%; severe 1%), infections (24%), nausea (any 30%;

severe 3%), vomiting (any 18%; severe 4%), diarrhea (any 27%; severe<1%), and mucositis (any 7%; severe <1%).

Other adverse reactions have included ocular/visual disturbances (any13%; severe 1%), fluid retention (any 10%; severe 0%), hepatic dysfunction (elevations in bilirubin 7%, alkaline phosphatase 36%, AST[SGOT] 39%), renal dysfunction (any 11%; severe 1%), thrombocytopenia(any 2%; severe <1%), hypersensitivity reactions (any 4%; severe 0%),cardiovascular reactions (severe 3%), and injection site reactions(<1%). During postmarketing surveillance, rare occurrences of severehypersensitivity reactions have been reported with ABRAXANE.

give her for efficacy

In a pivotal phase III trial

ABRAXANE® delivered nearly double the overall response rate vs solvent-based paclitaxel1

21.5% vs 11.1%(P=.003) for all study patients. 195% CI, 16.2% to 26.7% for ABRAXANE. 195% CI, 6.9% to 15.1% for solvent-based paclitaxel. 1

15.5% vs 8.4%(P=NS) for study patients who failed combination chemotherapyor relapsed within 6 months of adjuvant chemotherapy.195% CI, 9.3% to 21.8% for ABRAXANE. 195% CI, 3.9% to 12.9% for solvent-based paclitaxel. 1

BOUND AND DETERMINED

The albumin-bound paclitaxel, ABRAXANE, eliminates the need for Cremophor® EL,*allowing delivery of a 49% higher dose vs solvent-based paclitaxel1

To learn more about ABRAXANE, visit our Web site at www.abraxane.comPlease see the Brief Summary of the ABRAXANE full prescribing information (includingboxed WARNING) on the next page.*Cremophor EL (polyoxyethylated castor oil) is a registered trademark of BASF Aktiengesellschaft.

Reference: 1. ABRAXANE [prescribing information]. Los Angeles, Calif: Abraxis Oncology, a division of Abraxis BioScience, Inc; August 2007.

ABRAXANE is a registered trademark of Abraxis BioScience, LLC. Abraxis Oncology® is a division of Abraxis BioScience, LLC.

©2008 Abraxis BioScience, LLC All Rights Reserved. AO 1127 12/08

WARNING ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available.

ABRAXANE therapy should not be administered to patients with metastatic breast cancer who have baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE.

Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS.

INDICATION:ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.

CONTRAINDICATIONS: ABRAXANE should not be used in patients who have baseline neutrophil counts of <1,500 cells/mm3.

WARNINGS: Bone marrow suppression (primarily neutropenia) is dose dependent and a dose limiting toxicity. ABRAXANE should not be administered to patients with baseline neutrophil counts of <1,500 cells/mm3. Frequent monitoring of blood counts should be instituted during ABRAXANE treatment. Patients should not be retreated with subsequent cycles of ABRAXANE until neutrophils recover to a level >1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3.

The use of ABRAXANE has not been studied in patients with hepatic or renal dysfunction. In the randomized controlled trial, patients were excluded for baseline serum bilirubin >1.5 mg/dL or baseline serum creatinine >2 mg/dL.

Pregnancy – Teratogenic Effects: Pregnancy Category D ABRAXANE can cause fetal harm when administered to a pregnant woman. Administration of paclitaxel protein-bound particles to rats on gestation days 7 to 17 at doses of 6 mg/m2 (approximately 2% of the daily maximum recommended human dose on a mg/m2 basis) caused embryo- and fetotoxicity, as indicated by intrauterine mortality, increased resorptions (up to 5-fold), reduced numbers of litters and live fetuses, reduction in fetal body weight and increase in fetal anomalies. Fetal anomalies included soft tissue and skeletal malformations, such as eye bulge, folded retina, microphthalmia, and dilation of brain ventricles. A lower incidence of soft tissue and skeletal malformations were also exhibited at 3 mg/m2 (approximately 1% of the daily maximum recommended human dose on a mg/m2 basis).

There are no adequate and well-controlled studies in pregnant women using ABRAXANE. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with ABRAXANE.

Use in MalesMen should be advised to not father a child while receiving treatment with ABRAXANE (see PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility for discussion of effects of ABRAXANE exposure on male fertility and embryonic viability).

Albumin (Human)ABRAXANE contains albumin (human), a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob Disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.

PRECAUTIONS: Drug InteractionsNo drug interaction studies have been conducted with ABRAXANE.

The metabolism of paclitaxel is catalyzed by CYP2C8 and CYP3A4. In the absence of formal clinical drug interaction studies, caution should be exercised when administering ABRAXANE (paclitaxel protein-bound particles for injectable suspension) concomitantly with known substrates or inhibitors of CYP2C8 and CYP3A4 (see CLINICAL PHARMACOLOGY).

Potential interactions between paclitaxel, a substrate of CYP3A4, and protease inhibitors (such as ritonavir,saquinavir, indinavir, and nelfinavir), which are substrates and/or inhibitors of CYP3A4, have not been evaluated in clinical trials.

HematologyABRAXANE therapy should not be administered to patients with baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of myelotoxicity, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE. Patients should not be retreated with subsequent cycles of ABRAXANE until neutrophils recover to a level >1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. In the case of severe neutropenia (<500 cells/mm3 for seven days or more) during a course of ABRAXANE therapy, a dose reduction for subsequent courses of therapy is recommended (see DOSAGE AND ADMINISTRATION).

Nervous SystemSensory neuropathy occurs frequently with ABRAXANE. The occurrence of grade 1 or 2 sensory neuropathy does not generally require dose modification. If grade 3 sensory neuropathy develops, treatment should be withheld until resolution to grade 1 or 2 followed by a dose reduction for all subsequent courses of ABRAXANE (see DOSAGE AND ADMINISTRATION).

Injection Site ReactionInjection site reactions occur infrequently with ABRAXANE and were mild in the randomized clinical trial. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration.

Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic potential of ABRAXANE has not been studied.

Paclitaxel has been shown to be clastogenic in vitro (chromosome aberrations in human lymphocytes) and in vivo (micronucleus test in mice). ABRAXANE was not mutagenic in the Ames test or the CHO/HGPRT gene mutation assay.

Administration of paclitaxel protein-bound particles to male rats at 42 mg/m2 on a weekly basis (approximately 16% of the daily maximum recommended human exposure on a mg/m2 basis) for 11 weeks prior to mating with untreated female rats resulted in significantly reduced fertility accompanied by decreased pregnancy rates and increased loss of embryos in mated females. A low incidence of skeletal and soft tissue fetal anomalies was also observed at doses of 3 and 12 mg/m2/week in this study (approximately 1% to 5% of the daily maximum recommended human exposure on a mg/m2 basis). Testicular atrophy/degeneration has also been observed in single-dose toxicology studies in rodents administered paclitaxel protein-bound particles at 54 mg/m2 and dogs administered 175 mg/m2 (see WARNINGS).

Pregnancy – Teratogenic Effects: Pregnancy Category D(See WARNINGS section).

Nursing MothersIt is not known whether paclitaxel is excreted in human milk. Following intravenous administration of carbon-14 labeled paclitaxel to rats on days 9 to 10 postpartum, concentrations of radioactivity in milk were higher than in plasma and declined in parallel with the plasma concentrations. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, it is recommended that nursing be discontinued when receiving ABRAXANE therapy.

Pediatric UseThe safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated.

Geriatric UseOf the 229 patients in the randomized study who received ABRAXANE, 11% were at least 65 years of age and <2% were 75 years or older. No toxicities occurred notably more frequently among elderly patients who received ABRAXANE.

ADVERSE REACTIONS:The following table shows the frequency of important adverse events in the randomized comparative trial for the patients who received either single-agent ABRAXANE or paclitaxel injection for the treatment of metastatic breast cancer.

Table 1: Frequency a of Important Treatment Emergent Adverse Events in the Randomized Study on an Every-3-Weeks Schedule

Percent of Patients ABRAXANE260/30minb

(n=229)

Paclitaxel Injection175/3hc,d

(n=225) Bone Marrow

Neutropenia< 2.0 x 109/L < 0.5 x 109/L

80 9

82 22

Thrombocytopenia < 100 x 109/L < 50 x 109/L

2 <1

3 <1

Anemia < 11 g/dL< 8 g/dL

331

25<1

Infections 24 20 Febrile Neutropenia 2 1 Bleeding 2 2

(Continued)

Table 1: Frequencya of Important Treatment Emergent Adverse Events in the Randomized Study on an Every-3-Weeks Schedule

(Continued)

Percent of Patients ABRAXANE260/30minb

(n=229)

Paclitaxel Injection175/3hc,d

(n=225)Hypersensitivity Reactione

All 4 12 Severef 0 2

CardiovascularVital Sign Changesg

Bradycardia <1 <1 Hypotension 5 5

Severe Cardiovascular Eventsf 3 4 Abnormal ECG

All patients 60 52Patients with Normal Baseline 35 30

RespiratoryCough 7 6Dyspnea 12 9

Sensory NeuropathyAny Symptoms 71 56Severe Symptomsf 10 2

Myalgia/ArthralgiaAny Symptoms 44 49Severe Symptomsf 8 4

AstheniaAny Symptoms 47 39Severe Symptomsf 8 3

Fluid Retention/EdemaAny Symptoms 10 8Severe Symptomsf 0 <1

GastrointestinalNausea

Any symptoms 30 22Severe symptomsf 3 <1

VomitingAny symptoms 18 10Severe Symptomsf 4 1

DiarrheaAny Symptoms 27 15Severe Symptomsf <1 1

MucositisAny Symptoms 7 6Severe Symptomsf <1 0

Alopecia 90 94Hepatic(Patients with Normal Baseline)

Bilirubin Elevations 7 7Alkaline Phosphatase Elevations 36 31AST (SGOT) Elevations 39 32

Injection Site Reaction <1 1a Based on worst gradeb ABRAXANE dose in mg/m2/duration in minutesc paclitaxel injection dose in mg/m2/duration in hoursd paclitaxel injection pts received premedicatione tsehc,aenpsyd,gnihsufl,.g.e(ytivitisnesrepyhotdetalerstnevedetaler-tnemtaertsedulcnI

pain, hypotension) that began on a day of dosing.f Severe events are defined as at least grade 3 toxicityg During study drug dosing.

Myelosuppression and sensory neuropathy were dose related.Adverse Event Experiences by Body System Unless otherwise noted, the following discussion refers to the primary safety database of 229 patients with metasttatic breast cancer treated with single-agent ABRAXANE in the randomized controlled trial. The frequency and severity of important adverse events for the study are presented above in tabular form. In some instances, rare severe events observed with paclitaxel injection may be expected to occur with ABRAXANE.

HematologicNeutropenia, the most important hematologic toxicity, was dose dependent and reversible. Among patients with metastatic breast cancer in the randomized trial, neutrophil counts declined below 500 cells/mm3 (Grade 4) in 9% of the patients treated with a dose of 260 mg/m2 compared to 22% in patients receiving paclitaxel injection at a dose of 175 mg/m2.

In the randomized metastatic breast cancer study, infectious episodes were reported in 24% of the patients treated with a dose of 260 mg/m2 given as a 30-minute infusion. Oral candidiasis, respiratory tract infections and pneumonia were the most frequently reported infectious complications. Febrile neutropenia was reported in 2% of patients in the ABRAXANE arm and 1% of patients in the paclitaxel injection arm.

Thrombocytopenia was uncommon. In the randomized metastatic breast cancer study, bleeding episodes were reported in 2% of the patients in each treatment arm.

Anemia (Hb <11 g/dL) was observed in 33% of patients treated with ABRAXANE in the randomized trial and was severe (Hb <8 g/dL) in 1% of the cases. Among all patients with normal baseline hemoglobin, 31% became anemic on study and 1% had severe anemia.

Hypersensitivity Reactions (HSRs)In the randomized controlled metastatic breast cancer study, Grade 1 or 2 HSRs occurred on the day of ABRAXANE administration and consisted of dyspnea (1%) and flushing, hypotension, chest pain, and arrhythmia (all <1%). The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied.

During postmarketing surveillance, rare occurrences of severe hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied. Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug.

Cardiovascular Hypotension, during the 30-minute infusion, occurred in 5% of patients in the randomized metastatic breast cancer trial. Bradycardia, during the 30-minute infusion, occurred in <1% of patients. These vital sign changes most often caused no symptoms and required neither specific therapy nor treatment discontinuation.

Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3% of patients in the randomized trial. These events included chest pain, cardiac arrest, supraventricular tachycardia, edema,thrombosis, pulmonary thromboembolism, pulmonary emboli, and hypertension. Cases of cerebrovascular attacks (strokes) and transient ischemic attacks have been reported rarely.

Electrocardiogram (ECG) abnormalities were common among patients at baseline. ECG abnormalities on study did not usually result in symptoms, were not dose-limiting, and required no intervention. ECG abnormalities were noted in 60% of patients in the metastatic breast cancer randomized trial. Among patients with a normal ECG prior to study entry, 35% of all patients developed an abnormal tracing while on study. The most frequently reported ECG modifications were non-specific repolarization abnormalities, sinus bradycardia, and sinus tachycardia.

RespiratoryReports of dyspnea (12%) and cough (6%) were reported after treatment with ABRAXANE in the randomized trial. Rare reports (<1%) of pneumothorax were reported after treatment with ABRAXANE. Rare reports of interstitial pneumonia, lung fibrosis, and pulmonary embolism have been received as part of the continuing surveillance of paclitaxel injection safety and may occur following ABRAXANE treatment. Rare reports of radiation pneumonitis have been received in paclitaxel injection patients receiving concurrent radiotherapy. There is no experience with the use of ABRAXANE with concurrent radiotherapy.

NeurologicThe frequency and severity of neurologic manifestations were influenced by prior and/or concomitant therapy with neurotoxic agents.

In general, the frequency and severity of neurologic manifestations were dose-dependent in patients receiving single-agent ABRAXANE. In the randomized trial, sensory neuropathy was observed in 71% of patients (10% severe) in the ABRAXANE arm and in 56% of patients (2% severe) in the paclitaxel injection arm. The frequency of sensory neuropathy increased with cumulative dose. Sensory neuropathy was the cause of ABRAXANE discontinuation in 7/229 (3%) patients in the randomized trial. In the randomized comparative study, 24 patients (10%) treated with ABRAXANE developed Grade 3 peripheral neuropathy; of these patients,14 had documented improvement after a median of 22 days; 10 patients resumed treatment at a reduced dose of ABRAXANE and 2 discontinued due to peripheral neuropathy. Of the 10 patients without documented improvement, 4 discontinued the study due to peripheral neuropathy.

No incidences of grade 4 sensory neuropathies were reported in the clinical trial. Only one incident of motor neuropathy (grade 2) was observed in either arm of the controlled trial.

Reports of autonomic neuropathy resulting in paralytic ileus have been received as part of the continuing surveillance of paclitaxel injection safety.

Cranial nerve palsies have been reported during postmarketing surveillance of ABRAXANE. Because these events have been reported during clinical practice, true estimates of frequency cannot be made and a causal relationship to the events has not been established.

Ocular/visual disturbances occurred in 13% of all patients (n=366) treated with ABRAXANE in single arm and randomized trials and 1% were severe. The severe cases (keratitis and blurred vision) were reported in patients in a single arm study who received higher doses than those recommended (300 or 375 mg/m2). These effects generally have been reversible. However, rare reports in the literature of abnormal visual evoked potentials in patients treated with paclitaxel injection have suggested persistent optic nerve damage.

Arthralgia/MyalgiaForty-four percent of patients treated in the randomized trial experienced arthralgia/myalgia; 8% experienced severe symptoms. The symptoms were usually transient, occurred two or three days after ABRAXANE administration, and resolved within a few days.

HepaticAmong patients with normal baseline liver function treated with ABRAXANE in the randomized trial, 7%, 36%,and 39% had elevations in bilirubin, alkaline phosphatase, and AST (SGOT), respectively. Grade 3 or 4 elevations in GGT were reported for 14% of patients treated with ABRAXANE and 10% of patients treated with paclitaxel injection in the randomized trial.

Rare reports of hepatic necrosis and hepatic encephalopathy leading to death have been received as part of the continuing surveillance of paclitaxel injection safety and may occur following ABRAXANE treatment.

RenalOverall 11% of patients experienced creatinine elevation, 1% severe. No discontinuations, dose reductions, or dose delays were caused by renal toxicities.

Gastrointestinal (GI)Nausea/vomiting, diarrhea, and mucositis were reported by 33%, 27%, and 7% of ABRAXANE treated patients in the randomized trial.

Rare reports of intestinal obstruction, intestinal perforation, pancreatitis, and ischemic colitis have been received as part of the continuing surveillance of paclitaxel injection safety and may occur following ABRAXANE treatment. Rare reports of neutropenic enterocolitis (typhlitis), despite the coadministration of G-CSF, were observed in patients treated with paclitaxel injection alone and in combination with other chemotherapeutic agents.

Injection Site ReactionInjection site reactions have occurred infrequently with ABRAXANE and were mild in the randomized clinical trial. Recurrence of skin reactions at a site of previous extravasation following administration of paclitaxel injection at a different site, i.e., “recall”, has been reported rarely. Rare reports of more severe events such as phlebitis, cellulitis, induration, skin exfoliation, necrosis, and fibrosis have been received as part of the continuing surveillance of paclitaxel injection safety. In some cases the onset of the injection site reaction in paclitaxel injection patients either occurred during a prolonged infusion or was delayed by a week to ten days.

Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration.

AstheniaAsthenia was reported in 47% of patients (8% severe) treated with ABRAXANE in the randomized trial. Asthenia included reports of asthenia, fatigue, weakness, lethargy and malaise.

Other Clinical EventsRare cases of cardiac ischemia/infarction and thrombosis/embolism possibly related to ABRAXANE treatment have been reported. Alopecia was observed in almost all of the patients. Nail changes (changes in pigmentation or discoloration of nail bed) were uncommon. Edema (fluid retention) was infrequent (10% of randomized trial patients); no patients had severe edema.

The following rare adverse events have been reported as part of the continuing surveillance of paclitaxel injection safety and may occur following ABRAXANE treatment: skin abnormalities related to radiation recall as well as reports of Stevens-Johnson syndrome, toxic epidermal necrolysis, conjunctivitis, and increased lacrimation. As part of the continuing surveillance of ABRAXANE, skin reactions including generalized or maculo-papular rash, erythema, and pruritis have been observed. Additionally, there have been case reports of photosensitivity reactions, radiation recall phenomenon, and in some patients previously exposed to capecitabine, reports of palmar-plantar erythrodysaesthesiae. Because these events have been reported during clinical practice, true estimates of frequency cannot be made and a causal relationship to the events has not been established.

Accidental ExposureNo reports of accidental exposure to ABRAXANE have been received. However, upon inhalation of paclitaxel,dyspnea, chest pain, burning eyes, sore throat, and nausea have been reported. Following topical exposure,events have included tingling, burning, and redness.

OVERDOSAGE:There is no known antidote for ABRAXANE overdosage. The primary anticipated complications of overdosage would consist of bone marrow suppression, sensory neurotoxicity, and mucositis.

DOSAGE AND ADMINISTRATION:After failure of combination chemotherapy for metastatic breast cancer or relapse within 6 months of adjuvant chemotherapy, the recommended regimen for ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) is 260 mg/m2 administered intravenously over 30 minutes every 3 weeks.

Hepatic ImpairmentThe appropriate dose of ABRAXANE for patients with bilirubin greater than 1.5 mg/dL is not known.

Dose ReductionPatients who experience severe neutropenia (neutrophil <500 cells/mm3 for a week or longer) or severe sensory neuropathy during ABRAXANE therapy should have dosage reduced to 220 mg/m2 for subsequent courses of ABRAXANE. For recurrence of severe neutropenia or severe sensory neuropathy, additional dose reduction should be made to 180 mg/m2. For grade 3 sensory neuropathy hold treatment until resolution to grade 1 or 2,followed by a dose reduction for all subsequent courses of ABRAXANE.

Preparation and Administration PrecautionsABRAXANE is a cytotoxic anticancer drug and, as with other potentially toxic paclitaxel compounds, caution should be exercised in handling ABRAXANE. The use of gloves is recommended. If ABRAXANE (lyophilized cake or reconstituted suspension) contacts the skin, wash the skin immediately and thoroughly with soap and water. Following topical exposure to paclitaxel, events may include tingling, burning and redness. If ABRAXANE contacts mucous membranes, the membranes should be flushed thoroughly with water.

Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Limiting the infusion of ABRAXANE to 30 minutes, as directed, reduces the likelihood of infusion-related reactions (see PRECAUTIONS: Injection Site Reaction).

No premedication to prevent hypersensitivity reactions is required prior to administration of ABRAXANE.

Preparation for Intravenous AdministrationABRAXANE is supplied as a sterile lyophilized powder for reconstitution before use. AVOID ERRORS, READ ENTIRE PREPARATION INSTRUCTIONS PRIOR TO RECONSTITUTION.

Each mL of the reconstituted formulation will contain 5 mg/mL paclitaxel.

1. Aseptically, reconstitute each vial by injecting 20 mL of 0.9% Sodium Chloride Injection, USP.

2. Slowly inject the 20 mL of 0.9% Sodium Chloride Injection, USP, over minimum of 1 minute, using the sterile syringe to direct the solution flow onto the INSIDE WALL OF THE VIAL.

3. DO NOT INJECT the 0.9% Sodium Chloride Injection, USP, directly onto the lyophilized cake as this will result in foaming.

4. Once the injection is complete, allow the vial to sit for a minimum of 5 minutes to ensure proper wetting of the lyophilized cake/powder.

5. Gently swirl and/or invert the vial slowly for at least 2 minutes until complete dissolution of any cake/powder occurs. Avoid generation of foam.

6. If foaming or clumping occurs, stand solution for at least 15 minutes until foam subsides.

Calculate the exact total dosing volume of 5 mg/mL suspension required for the patient: Dosing volume (mL) = Total dose (mg)/5 (mg/mL).

The reconstituted suspension should be milky and homogenous without visible particulates. If particulates or settling are visible, the vial should be gently inverted again to ensure complete resuspension prior to use.Discard the reconstituted suspension if precipitates are observed. Discard any unused portion.

Inject the appropriate amount of reconstituted ABRAXANE into an empty, sterile IV bag (plasticized polyvinyl chloride (PVC) containers, PVC or non PVC type IV bag). The use of specialized DEHP-free solution containers or administration sets is not necessary to prepare or administer ABRAXANE infusions. The use of an in-line filter is not recommended.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

StabilityUnopened vials of ABRAXANE are stable until the date indicated on the package when stored between 20°C to 25°C (68°F to 77°F), in the original package. Neither freezing nor refrigeration adversely affects the stability of the product.

Stability of Reconstituted Suspension in the VialReconstituted ABRAXANE should be used immediately, but may be refrigerated at 2°C to 8°C (36°F to 46°F) for a maximum of 8 hours if necessary. If not used immediately, each vial of reconstituted suspension should be replaced in the original carton to protect it from bright light. Discard any unused portion.

Stability of Reconstituted Suspension in the Infusion BagThe suspension for infusion prepared as recommended in an infusion bag should be used immediately, but may be stored at ambient temperature (approximately 25°C) and lighting conditions for up to 8 hours.

HOW SUPPLIED:Product NDCNo. No.103450 68817-134-50 100 mg of paclitaxel in a single use vial, individually packaged in a carton.

StorageStore the vials in original cartons at 20°C to 25°C (68°F to 77°F). Retain in the original package to protect from bright light.

Handling and DisposalProcedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on thissubject have been published.1-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

U.S. Patent Numbers: 5,439,686; 5,498,421; 6,096,331; 6,506,405; 6,537,579; 6,749,868; 6,753,006

REFERENCES:1. Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs. Publication No. 83-2621. For sale by the

Superintendent of Documents, US Government NIH Printing Office, Washington, DC 20402.2. AMA Council Report. Guidelines for Handling Parenteral Antineoplastics. JAMA, 1985; 253(11):1590-1592.3. National Study Commission on Cytotoxic Exposure Recommendations for Handling Cytotoxic Agents. Available from

Louis R Jeffrey, ScD, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences. 179 Longwood Avenue, Boston, Massachusetts 02115.

4. Clinical Oncology Society of Australia. Guidelines and Recommendations for Safe Handling of Antineoplastic Agents. Med J Australia, 1983; 1:426-428.

5. Jones RB, et al: Safe Handling of Chemotherapeutic Agents: A Report from the Mount Sinai Medical Center. CA-A Cancer Journal for Clinicians, 1983; (Sept/Oct) 258-263.

6. American Society of Hospital Pharmacists Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs. Am J Hosp Pharm, 1990; 47:1033-1049.

7. Controlling Occupational Exposure to Hazardous Drugs. (OSHA WORK-PRACTICE GUIDELINES.) Am J Health-Syst Pharm, 1996; 53:1669-1686.

8. ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice. Pittsburgh, Pa: Oncology Nursing Society; 1999:32-41.

ABRAXANE is a registered trademark of Abraxis BioScience, LLC. Abraxis Oncology® is a division of Abraxis BioScience, LLC.©2008 Abraxis BioScience, LLC. All Rights Reserved.AO 1127 8/07

®

Brief Summary of Full Prescribing Information.

Rx Only


Drug name, developer(s) Study Status

Abraxane (paclitaxel protein- • Abraxane/carboplatin vs Taxol/carboplatin Recruitingbound particles); Abraxis Bioscience as first-line therapy in advanced NSCLC

Affinitak • Chemotherapy/carboplatin/paclitaxel vs carboplatin/ ActiveIsis Pharmaceuticals, Eli Lilly paclitaxel/Affinitak in advanced, previously untreated NSCLC

Aflibercept • Aflibercept vs placebo in patients treated with second-line Recruitingsanofi-aventis docetaxel after failure of one platinum-based therapy for

locally advanced/metastatic NSCLC

AG3340 • Prinomastat in combination with gemcitabine/cisplatin in ActiveAgouron Pharmaceuticals advanced NSCLC

Alimta (pemetrexed) • Pemetrexed/carboplatin/bevacizumab followed by RecruitingEli Lilly maintenance pemetrexed/bevacizumab vs paclitaxel/

carboplatin/bevacizumab followed by maintenancebevacizumab in stage IIIB or IV nonsquamous NSCLC

• Maintenance pemetrexed/best supportive care vs best Activesupportive care immediately following induction treatment for advanced NSCLC

• Pemetrexed/cisplatin/radiotherapy followed by consolidation Recruitingpemetrexed vs etoposide/cisplatin/radiotherapy followed byconsolidation cytotoxic chemotherapy of choice in unresectable,locally advanced, stage III NSCLC other than predominantly squamous cell histology

Amrubicin • Comparing amrubicin vs topotecan in extensive/limited and RecruitingPharmion sensitive/refractory SCLC after failure of first-line chemotherapy

Avastin (bevacizumab) • Comparing bevacizumab therapy with/without erlotinib after ActiveGenentech completion of chemotherapy with bevacizumab for the first-

line treatment of locally advanced/recurrent/metastatic NSCLC• Bevacizumab/Tarceva compared with Tarceva alone for Active

treatment of advanced NSCLC after failure of standard first-line chemotherapy

• Avastin/chemotherapy for treatment of metastatic, locally Recruitingadvanced, and unresectable colorectal cancer and locally advanced/ metastatic NSCLC (excluding predominant squamous cell histology)

Lung Cancer Drugs in Phase 3and 4 Trials in the United StatesNew drugs and combinations are being studied for the treatment of non–small-cell and small-cell lung cancer.Ongoing trials and those currently recruiting patients are listed below.

GH


Drug name, developer(s) Study Status

Genasense (oblimersen); Genta • Docetaxel vs docetaxel/Genasense in previously treated NSCLC Active

Mage-3 recombinant pharmaccine • Cancer immunotherapeutic GSK1572932A as adjuvant therapy RecruitingGlaxoSmithKline for mage-A3-positive NSCLC

• GSK1572932A antigen-specific cancer immunotherapeutic as Recruitingadjuvant therapy in patients with resectable mage-A3-positve NSCLC

NOV-002 • NOV-002/paclitaxel/carboplatin vs paclitaxel/carboplatin RecruitingNovelos Therapeutics alone for advanced NSCLC

Onconase (ranpirnase) • Onconase/doxorubicin vs doxorubicin for malignant pleural/ ActiveAlfacell peritoneal mesothelioma with no more than one prior

chemotherapy regimen

Stimuvax; Merck, EMD Serono • Cancer vaccine Stimuvax in unresectable stage III NSCLC Recruiting

Sutent (sunitinib) • Efficacy/safety study of sunitinib in advanced/metastatic RecruitingPfizer NSCLC treated with erlotinib

Tarceva (erlotinib) • Bevacizumab/Tarceva compared with Tarceva alone for advanced ActiveGenentech, OSI Pharmaceuticals NSCLC after failure of standard first-line chemotherapy

• Comparing bevacizumab therapy with/without erlotinib after Activecompletion of chemotherapy with bevacizumab for the first-line treatment of locally advanced/recurrent/metastatic NSCLC

• Erlotinib or placebo following concurrent docetaxel/ Recruitingcarboplatin/thoracic radiotherapy in inoperable stage III NSCLC

Taxotere (docetaxel) • RRM1/ERCC1 directed customized chemotherapy vs standard Recruitingsanofi-aventis of care for first-line treatment of advanced NSCLC

Thalomid (thalidomide) • Carboplatin/paclitaxel/thoracic radiotherapy with/ ActiveCelgene without thalidomide in stage III NSCLC

Xyotax (polyglutamate paclitaxel) • Paclitaxel poliglumex/carboplatin vs paclitaxel/carboplatin for RecruitingCell Therapeutics chemonaïve advanced NSCLC in women with estradiol >30 pg/mL

• CT-2103 vs docetaxel for the second-line treatment of NSCLC Active• CT-2103 vs gemcitabine or vinorelbine for PS = 2 patients Active

with chemonaïve advanced NSCLC• CT-2103/carboplatin vs paclitaxel/carboplatin for Active

PS = 2 patients with chemonaïve advanced NSCLC• Paclitaxel poliglumex/carboplatin vs paclitaxel/carboplatin for Recruiting

chemonaïve advanced NSCLC in women with estradiol >25 pg/mL

Zactima (vandetanib) • Zactima/pemetrexed vs pemetrexed alone in locally ActiveAstraZeneca advanced/metastatic NSCLC

• Zactima vs Tarceva in locally advanced/metastatic NSCLC after Activefailure of at least one chemotherapy

Zolinza (vorinostat) • Oral suberoylanilide hydroxamic acid in advanced malignant pleural RecruitingMerck mesothelioma previously treated with systemic chemotherapy

NSCLC indicates non–small-cell lung cancer; PS, performance status; SCLC, small-cell lung cancer.


Journal of Multidisciplinary Cancer Care(JOMCC): What are the advantages of a multidiscipli-nary treatment approach for patients with cancer and

their healthcare providers?

Mark J. Krasna (MJK): The major advantage ofmultidisciplinary care for patients is that they have atrue one-stop shopping approach. They no longer haveto go from physician office to physician office, whichcan take anywhere from weeks to months and cover ahuge geographic distance, which obviously is very dif-ficult for the patient. Besides convenience, thisapproach also has advantages in terms of quality ofcare. If the patient is seen at one time, in one place, byone team of physicians, that patient now has access toall the specialties he or she needs and gets all of theinput at one place. That means that the patient knowsthat the entire medical team has a consensus on whatis the right care and that there is one treatment planthat can be delivered in a timely fashion.

JOMCC: With all its advantages, why hasn’t the multi-disciplinary approach been more widely adopted?

MJK: The number one limitation is simply the lackof a physical facility that would allow all the providersto meet in one place. Number two is the lack of theinfrastructure in terms of how to house doctors andmake sure that everyone can do the appropriate billing.Number three is how to get everybody on the samepage to do what’s right for the patient. Obviously,everyone wants to do that, but the challenge is how tofacilitate it. Cancer centers, whether they be academicor in the community, generally have a hard timeanswering those needs. You need to build a cancer cen-ter that not only has the physical space but also has theinfrastructure to provide all the necessary support.

There are significant reimbursement issues as well.You have to make sure that patients are getting theapprovals for consultations with more than one physi-cian. Let’s say, for example, that they are going to see amedical, surgical, and radiation oncologist for lungcancer. They have to get a preauthorization for consul-tation for all three of those specialists. That is definite-ly doable, but it’s another challenge that has to betaken into consideration by the administrators who arerunning that cancer center to make sure that they areadhering to all the appropriate Medicare guidelines andstill able to do what they need to do.

JOMCC: Please explain how a patient with lung cancer,for example, would be treated in a multidisciplinary clinic.

Multidisciplinary Cancer Clinics: A Streamlined Approach to CancerCare in the Community SettingAn interview with Mark J. Krasna, MD

Dr Krasna is Medical Director of St. Joseph Cancer Institutein Towson, MD, and principal investigator, Catholic HealthInitiatives National Community Cancer Center Programsites.

Patients with cancer often require treatment by medical, surgical, and radiation oncolo-gists. Those treated in the community setting—as the vast majority of patients aretoday—usually have to schedule individual appointments with these specialists at theirseparate offices. In this interview, Mark J. Krasna, MD, explains the advantages of multi-disciplinary cancer clinics, in which medical, surgical, and radiation oncologists work as ateam in one facility and together develop a consensus on a patient’s treatment plan. Heillustrates this approach with a description of how a patient with lung cancer would betreated in a multidisciplinary clinic.Mark J. Krasna, MD

MJK: In the current era, about 90% of patients withlung cancer will get multimodality therapy. For stage IBpatients or higher, there is a role for chemotherapy aftersurgery. Stage III patients who have local, regionaltumors that are potentially resectable will getchemotherapy, radiation therapy, and surgery, whereasfor those with stage III tumors that are not resectable,there’s a role for chemotherapy and radiation. Today,even 50% of patients with stage IV disease who are get-ting chemotherapy will eventually get radiation too

because they have a brain or bone metastasis that needspalliation. So of the 190,000 patients who will be diag-nosed with lung cancer this year, 150,000 to 170,000will get more than one type of therapy.

Therefore, the best approach for every patient is tosee the entire team before any therapy has begun sothat there is a true prospective evaluation of thepatient, and the patient gets an opinion from each ofthe specialists before any therapy is started. Thatshould be the standard of care in both community andacademic medical centers. At St. Joseph CancerInstitute, all the team members typically see every newpatient with lung cancer. The unique approach is thatwe all, as a team, give our input upfront.

This approach couldn’t work without what I call anurse coordinator, or what others may call a navigator.Each of our disease sites has a nurse coordinator whohelps patients coordinate their medical, radiation, andsurgical oncology visits and treatments. We have navi-gators as well, but they are more focused on the sur-vivorship or the palliative side of cancer care.

JOMCC: Please describe your cancer center and how it works.

MJK: The Cancer Institute at St. Joseph MedicalCenter, a member of Catholic Health Initiatives, wasdesigned specifically to provide multidisciplinary can-cer care with facilities for all the different specialties. Itwas truly built around the patient experience. In addi-tion to the thoracic oncology center, there are centersspecializing in breast, hepatobiliary, colorectal, gyneco-logic, and urologic oncology as well as a medical oncol-

ogy center and a radiation oncology center.Taking lung cancer as an example, a patient newly

diagnosed with what is thought to be stage III disease isfirst seen by a nurse technician, who gets the patient’svital signs and brings the patient into one of the multi-disciplinary clinic rooms. The patient stays in the sameroom the whole time of their visit and the physicianteam rotates around the patient. The medical oncolo-gist sees the patient first with the nurse coordinator.Then the nurse brings in the radiation oncologist fol-lowed by the surgical oncologist. So during that onevisit, the patient sees three medical specialists plus thenurse coordinator plus the navigator, plus the dietitianif necessary. A patient who is considered a potentialclinical trial candidate will also see the research nurse.By the time the patient leaves, follow-up appointmentsand any additional tests have been scheduled.

That same day, we have a multidisciplinary confer-ence and discuss every single patient before any treat-ment is begun. The advantages for the patient are huge.Not only does he or she, in one visit, experience thisconsensus approach, but the amount of time saved forthe patient is immeasurable. The best part is that whenthe consensus is reached, we can then initiate treat-ment, usually within 2 weeks from the date of their firstvisit. That kind of multidisciplinary approach is veryhard to replicate without the commitment of the physi-cians, the staff, and a committed nurse coordinator, butif it can be done, it really takes multidisciplinary care tothe next level.

It is because of this model that St. Joseph CancerInstitute was chosen by the National Cancer Institute(NCI) to be part of the National Community CancerCenters Program (NCCCP) pilot [see sidebar, page 25].The NCCCP is an opportunity to demonstrate thatyou don’t have to be an NCI-designated cancer centerto deliver high-quality cancer care. The basics that arenecessary to define your ability to function like anNCCCP site are multidisciplinary care as a paradigm,outreach to minority populations, and enrollment ofpatients in clinical trials.

JOMCC: It has been said that doctors in communitypractice may be reluctant to refer their patients to clinicaltrials because they would lose that patient. Have you foundthat to be the case, and, if so, what can be done about it?

MJK: It is one of the main barriers to enrollment inclinical trials in community settings. If a medical oncol-ogist is treating a patient in his or her private office set-ting, that physician not only has a personal interest inand relationship with the patient, but also a financial

GH


The best approach for every patient is to see the entire team before any therapy has begun so that there is a trueprospective evaluation of the patient.


NCI Community Cancer Centers Program Pilot: A 1-Year Update

The National Cancer Institute (NCI) CommunityCancer Centers Program (NCCCP) is a proposed

national network of community cancer centersdesigned to bring the latest scientific advances andthe highest level of innovative and integrated, multi-specialty care to many more cancer patients in thecommunities where they live. The goals of the pro-gram are as follows:

• Draw more patients into clinical trials in com-munity-based settings

• Reduce cancer healthcare disparities• Explore standards for collecting and storing can-

cer research specimens• Link to national computer networks for con-

ducting research and sharing results.Approximately 85% of American cancer patients

are diagnosed at community hospitals and physicianoffices. For most, especially senior citizens and minori-ties, treatment at a major cancer center is unrealisticbecause of location/travel, distance from family andother support systems, or economic reasons. Currentlyin the pilot stage, this program provides state-of-the-art cancer care to patients in 16 community hospitalsin 14 states, with the goal of expanding nationwideafter successful completion in 2010.

NCCCP was established to encourage collabora-tion between private-practice medical, surgical, andradiation oncologists and NCI research and NCI-des-ignated cancer centers, which are based at largeresearch universities. Currently, pilot program sitesare exploring ways to share information, via electron-ic medical records, to improve patient care. Thesesites also are researching new and enhanced ways toassist, educate, and better treat the needs of under-served populations, including elderly, rural, inner-city, and low-income patients as well as racial andethnic groups with unusually high cancer rates.

In addition, NCCCP pilot sites have been tasked tostudy how community hospitals nationwide could mosteffectively develop and implement a national databaseof voluntarily provided electronic medical records acces-sible to cancer researchers. The sites also are studyingmethods of expanding and standardizing the collectionof blood and tissue specimens voluntarily obtained.

Begun in 2007, considerable progress has been

made to date. Sites have launched an effort focusedon three phase 3 clinical trials—breast, colorectal,and lung—that has increased the patient accrual rateto each. Further, many pilot sites have created collab-orations with NCI-designated cancer centers andother academic biomedical research institutions.Formal agreements have been made with NCI’sCommunity Networks Program, reducing disparitiesamong racial and ethnic minorities as well as under-served populations through community-based educa-tion, training, and research.

NCCCP pilot sites are implementing NCI recom-mendations for snap-frozen and formalin-fixed tissuesand other samples, which should improve the quality ofspecimens used in research. Five pilot sites have appliedto The Cancer Genome Atlas Prospective SpecimenCollection initiative, which should help accelerate thelarge-scale genome sequencing of cancers.

Four pilot sites have begun use of electronic records,seven sites are adopting caBIG clinical trials tools, andone site is adopting caTissue. NCI’s caBIG (cancerBiomedical Informatics Grid) is an information net-work that enables researchers, physicians, and patientsto share data and knowledge. caTissue is caBIG’s tissuebank repository tool for biospecimen inventory, track-ing, and basic annotation.

For community practitioners, NCCCP offers onlinetools to enhance clinical practice and research. A mul-tidisciplinary care assessment tool describes case plan-ning, physician engagement, coordination of care, infra-structure, and financial considerations for care in thecommunity setting. A uniform chemotherapy consentform template is available for modification for individ-ual practice use. And a genetic counseling assessmenttool defines the minimal genetic counseling servicerequirements to guide improvements. These tools canbe downloaded at http://ncccp.cancer.gov/index.htm.

Pilot program sites are exploringways to share information, viaelectronic medical records, toimprove patient care.

incentive to keep all the patient’s therapy at that center.If the patient is enrolled in the clinical trial but thatrequires the patient to be referred elsewhere, that’s a dis-incentive. I think it’s probably the number one barrier,

but it’s one that can be overcome. There are many clin-ical trials that can be opened in the private practice orcommunity cancer setting, which should obviate thatissue. In addition, there are many private and oncologygroup practices that do encourage patient participation

in clinical trials and actively recruit. One of the main goals of NCCCP is to increase

accrual in clinical trials and specifically to increaseaccrual of minorities and disparate populations intoclinical trials. Again that can only be done by the com-munity medical oncologist working with the communi-ty cancer center. It’s very hard for a single practice todo that on its own. As part of this NCCCP pilot, thereare 16 hospitals as part of 10 programs and they areactually accruing more patients now on clinical trialsthan before, because they’ve all made a conscious effortto do so and to enlist community oncologists’ help toaccrue these patients. The way to do that is to openmore clinical trials in the community setting so thatyou don’t necessarily need to refer all the patients outto an NCI-designated cancer center. The benefit forthe patients is they’re still getting access to clinical tri-als but may not have to travel to a facility farther fromtheir homes. n

GH

One of the main goals of NCCCP is toincrease accrual in clinical trials andspecifically to increase accrual of minorities and disparate populationsinto clinical trials.

To serve on the editorial advisory panel, please complete the form below and fax to: 732-656-7938or e-mail to [email protected] member information

First name Last name Credentials

Title Company

Address

E-mail Phone

Join the JOMCC Editorial Advisory Panel

Journal of Multidisciplinary Cancer Care is seeking oncologists, nurses, pharmacists, medical and

pharmacy directors, P&T Committee members, andexperts in healthcare legislation who are interested in

joining our editorial advisory panel and assisting in maintaining the high quality of articles published.

Panel members will occasionally be asked to contributearticles or commentaries, review manuscripts, or

participate in interviews or roundtable discussions.

Articles fall into three main categories: Clinical, Business, HealthEconomics. These main categories are represented from the different vantage points of all stakeholders in healthcare and aredivided into many subcategories, including (but not limited to):

u Administration/management u Radiation oncologyu Breast cancer u Other solid tumorsu Finance/economics u Health policy/reformu Gastrointestinal cancers u Hematologic malignanciesu Genitourinary cancers u Lung canceru Gynecologic malignancies u Melanomau Health information technology u Pediatric oncologyu Pharmacoeconomics: cost-benefit analysis, cost-effectivenessu Reimbursement: Medicare/Medicaid, health insurance,

prior authorization

OncologyTheOncologyPharmacist

The

PharmacistThe Official Newspaper of Record for the

Hem/Onc Pharmacist™

FREE CE newslettersat www.COEXM.com

Interactive online presentations withpolling questions at www.COEXM.com

FREE CE newslettersat www.COEXM.com

www.COEXM.com strives to provide the most up-to-date clinical information thatwill improve cancer care and outcomes for patients through specialty products,

across multimedia platforms, reaching multiple stakeholders and customers.

Current activities at www.COEXM.com include:• Considerations in Multiple Myeloma: Health Economics • Perspectives on the Treatmentof Colorectal Cancer • Perspectives on the Treatment of CTCL and PTCL • Developments inthe Treatment of Metastatic Breast Cancer • Perspectives on the Treatment of Lung Cancer

ON DEMANDFREE CONTINUING EDUCATION CREDITS

FREE • ACCREDITED • EVIDENCE-BASED • CLINICALLY RELEVANT • INSTANT CERTIFICATION

Registered participants will receive email announcementsas new educational activities become available.

December 2008 • Vol. 1 • No. 8

INTRODUCTION

© 2008 Center of Excellence Media, LLCCE

Cred

its

Offere

d

PublisherPhilip Pawelko

[email protected]

Editorial DirectorSusan Berry

[email protected]

Copy EditorBonnie Nickel

Senior Production ManagerAlaina Pede

Directors of Client ServicesJohn W. [email protected]

Russell [email protected]

Circulation [email protected]

Business ManagerBlanche Marchitto

Executive AdministratorsThiel Hennessy

Lisa Russo

Jointly sponsored by Medical Learning Institute, Inc. and Center of Excellence Media, LLC

Visit us at:www.coexm.com

Supported byan educational grant from

Colorectal Cancer Update:New Strategies inSupportive Care

IN THIS ISSUE:

• Metastatic Colorectal Cancer Update: Reports from the 2008 Gastrointestinal Cancers Symposium

• Supportive Care Strategies for Patients withChemotherapy-Induced Neuropathy

Virginia Chih-Yi Sun, RN, MSN, ANPNursing and Research Education Division of Population Sciences, City of Hope, Duarte, CA

A Supplement to

In the United States, colorectal cancer(CRC) is estimated to be the third most

commonly diagnosed cancer and the thirdmost common cause of cancer deathamong both men and women.1 The inci-dence rates of CRC have declined by near-ly 26% from 1984 to 2004, mainly due toearly detection of polyps before progres-sion to cancer.2 Surgery can cure about 90%of CRCs when the disease is found early,and 5-year survival rates have risen from51% (1975-1977) to 65% (1996-2003).1

About 50% to 60% of patients diagnosedwith CRC will develop metastatic disease,most commonly in the liver or lung.3 Five-year survival rates in patients withmetastatic liver disease who do not under-go surgery approach zero. With resectionof liver metastases, 5-year survival rates areapproximately 25% to 50%.3,4 In some

cases, chemotherapy can be used to shrinkunresectable tumors to facilitate surgery.It also remains the mainstay of treatmentfor patients with inoperable CRC.

Over the past decade, therapeuticoptions for patients with metastatic col-orectal cancer (MCRC) have expanded,due in large part to the development andapproval of more effective chemothera-peutic agents and new biologic therapies.However, these novel treatments are asso-ciated with unique toxicity profiles thatpose distinct nursing management chal-lenges. As integral members of the cancercare team, oncology nurses must remaincognizant of effective strategies for manag-ing specific treatment-related toxicities, sothat patients with MCRC are better able tocontinue with appropriate treatmentswhile maintaining quality of life.

REGISTER TODAY AT www.COEXM.com

© 2008 Center of Excellence Media, LLC

MULTIDISCIPLINARY TEAM PRESENTATIONS BY

Dear Colleague:

It is my distinct pleasure to offer this newsletter entitled “Considerations in MultipleMyeloma: Side Effect Management,” the fifth issue in a series of newsletters featuring top-ics relevant to your multidisciplinary team approach to caring for patients with multiplemyeloma (MM).

Together with a faculty of hematologists/oncologists, oncology nurses, and oncologypharmacists, we focus our discussion on one topic for each newsletter. Previous issuesfocused on patients with renal dysfunction, treatment-naive patients, difficult-to-treat pop-ulations of MM patients, and health economics. T his issue will focus on the side effectsassociated with various agents and treatment regimens used to treat MM.

It is our sincere hope that the information presented here is of value to you in your careof patientswith MM.

Sincerely,

Sagar Lonial, MDAssociate Professor of Hematology and OncologyEmory University

Supported by aneducational grant from

MillenniumPharmaceuticals, Inc.

LETTER TO OUR READERS

November/December 2008 • Volume 1 • Number 5

Editor in ChiefSagar Lonial, MDEmory University

Jointly sponsored by CME Consultants and Center of Excellence Media.

CME/

CECr

edits

Offere

d

Considerations in Multiple Myeloma:Side Effect Management

www.coexm.com

Lillian Chou, PharmD Charise Gleason, MSN, ANP-BC, AOCNP NewYork-Presbyterian Hospital Emory University

Cindy Ippoliti, PharmD Lisa C. Smith, MSN, FNP, AOCNCornell Medical Center Cancer Center of the Carolinas

CoeTOPHouseAd.V6:House Ad 1/20/09 5:04 PM Page 1

GH


Amid uncertain financial markets and recordhousing foreclosures, what will happen to can-cer care reimbursement is not the issue foremost

in most minds. The war on cancer has been waging bypresidential decree since 1971 when President Nixonissued the famous proclamation that made cancer pub-lic enemy number one and created the National CancerInstitute to combat it. There were decidedly few effec-tive drug therapies at that time and, although surgeryand radiation were available, the modern clinicianwould cringe at the often excessive techniques used.

We have come a long way since then—most, but notall of it good. Surgical techniques have improved, and

technology is available throughout the surgical suite,from robotic assistance to laparoscopic interventions.Radiation has dramatically improved delivery and pro-tection with intensity-modulated radiation therapy(IMRT) and 3-D conformal imaging. We not only havemore effective chemotherapy agents, we have mono-clonal antibodies and advanced supportive care med-ications. There are even oral therapies effective in tar-geting certain cancers. All major pharmaceuticalcompanies have cancer as a focus and invest billions in

trying to find the next edge in fighting this collectionof diseases called “the big C,” as John Wayne onceremarked. Patients no longer need to anticipate longand dreary hospital stays to receive chemotherapy. Thevast majority are treated as outpatients in doctors’offices or in hospital outpatient clinics. Arguably, all ofthe above allow for the best and most advanced cancercare provided on the planet. It only takes money—lotsand lots of money.

The two most expensive line items for any oncologypractice or hospital cancer clinic are drugs and people.Good people are essential. In oncology, the more train-ing an individual has, the higher the pay grade.Pharmacists, who used to be employed exclusively inthe hospital basement, have been migrating to outpa-tient clinics and are now beginning to be found even inlarger private physician practices. Physician practicestoo are morphing and either becoming larger or closingtheir doors. By and large, gone is the time of a success-ful one- or two-physician practice. The economies ofscale needed to compete are forcing smaller practices toband together or enter into a service agreement witharea hospital providers.

Some office practices are dividing sites of care, keep-ing reasonably profitable third-party payers and send-ing HMO or Medicaid patients to the local hospital.Not every physician practice is doing this, but thefinancial pressures will force a reduction in profit orquality, or both, if some solution is not found. Hospitalstoo are forced to undergo cost cutting or find somemeans of remaining solvent. For nonprofit hospitals,the opportunity to purchase drugs under 340B or dis-proportionate share pricing makes a tremendous differ-ence. If a hospital qualifies, they can buy oncologydrugs at the same low price as the federal government,which, by law, automatically gets the best price. If ahospital cannot qualify for 340B pricing, cost cuts oradded revenue streams must be found.

Battling Reimbursement Issues to Win the War on CancerTimothy G. Tyler, PharmD, FCSHP

Dr Tyler is Director of Pharmacy Services for theComprehensive Cancer Center, Desert Regional MedicalCenter, Palm Springs, CA.

Pharmacists, who used to be employedexclusively in the hospital basement, havebeen migrating to outpatient clinics andare now beginning to be found even inlarger private physician practices.


The government as the largest payer did somemaneuvering and through legislation (Omnibus Bud-get Reconciliation Act of 1997 and MedicareModernization Act of 2003) created a fee schedule forMedicare Part B (the physician office setting) and anoutpatient prospective payment system (OPPS) forMedicare Part A (the hospital outpatient clinic). TheOPPS or Ambulatory Payment Classification (APC)system can be thought of as generally similar to whenthe Centers for Medicare & Medicaid Services (CMS)introduced diagnosis-related groups to hospitals. Theidea was that an admitting diagnosis would have a setreimbursement. If the hospital could treat and dis-charge that patient for less than that predeterminedrate, they made money; if not, they lost money. TheOPPS-APC system is similar in that it establishes buck-ets or ranges and procedures; drugs get assigned intolike categories and that becomes the reimbursementrate. Once the outliers are removed, the claims submit-ted to CMS are used to populate a database. A hospi-tal’s cost report is then applied to this database, andCMS claims it can determine that hospital’s costs. Thisis contentious at present, and many groups have beenworking to convince CMS that their formulas havebeen flawed since the program’s inception. The con-sensus is that since any costs lower than the $60 thresh-old are bundled (in the OPPS system but not the physi-cian’s fee schedule) and not separately payable, theoverhead associated with each “bundled” item is notrepresented. The result is that CMS grossly underesti-mates the overhead needed to provide these drugs in ahospital outpatient setting.

This appears complex but, in reality, it is quite sim-ple. At the end of the day—regardless of where youpractice—all your expenses must be less than all yourrevenue. If not, the practice must find other solutionsor the hospital must determine to subsidize care oreventually discontinue that service line.

All clinicians should keep in mind that they canaffect the bottom line. By that I mean that every nurse,pharmacist, or physician should be conscious of waste,salvage what can be salvaged, and be prudent with allresources at their disposal. But as reimbursement is putunder the microscope, it will soon be beyond the pru-dent nurse or pharmacist to make an impact, as savinga few dollars will no longer be enough. A time is com-ing where there is no more manipulation or cost cut-

ting, and a decision will have to be made whether to abandon certain patient payer types or close thedoors altogether.

In my own region of Southern California, this isbeginning to occur. I work near a private, not-for-profithospital that has a foundation endowment in excess of$150 million and frequently has donations from a veryaffluent community to assist with building and otherprograms. Late last year, this hospital announced that itwould no longer be accepting Medicaid patients. Thisraises the question that if it cannot absorb the lowered

reimbursement rate of state-funded Medicaid, who can?I see their decision as a harbinger of similar futureevents, one that CMS will need to pay attention to asMedicare beneficiaries’ access to care will be affected.

If the environment that the physician oncologypractice and hospital outpatient cancer clinic findthemselves in does not improve, there are certain to beserious deliberations about which patients can contin-ue to be accepted and even whether the current busi-ness model makes sense and will remain viable. Thelaws that were passed in 1997 and 2003 have begun tohave impacts, and they are for the most part at oddswith the current model most of us use to treat patientswith cancer.

The time is fast approaching when we will need to give clear guidance to our representatives inWashington as to what is happening with the treat-ment of cancer patients and the tough decisions we arebeing forced to consider. Let us hope that the oncologycare we are so proud of does not become so expensivethat we cannot afford to continue to offer it. We areengaged in a war—the war on cancer that stands at 38years and counting. We are fighting to win. Let us hopethat we will be allowed to see a day in the near futurewhen reimbursement is not the biggest thing thathealthcare providers have to worry about. n

A time is coming where there is no more manipulation or cost cutting, and a decision will have to be madewhether to abandon certain patientpayer types or close the doors altogether.

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

™

To begin receiving issues of The Oncology Nurse, register online at www.theoncologynurse.com

Register to receive your subscription atNO CHARGE today!

Written by and for oncology nurses offering you the following:

• Concise reviews of hot topics in the peer-reviewed liter-ature by clinical specialists with key point ‘takeaways’

• Coverage of key research studies and on-the-scenereports from oncology medical meetings

• Continuing education articles at no charge and post-tests,offering you a convenient way to obtain contact hours

• Interviews with renowned thought leaders in the oncology nursing community

• A “Policy Watch” column covering legislation and policychanges that affect cancer care in your areas of practice

• Articles of special interest to student nurses,your future colleagues


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

The section includes:• Associated ICD-9-CM codes used for the

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

treatment of lung cancer• Drugs included in the NCCN (National

Comprehensive Cancer Network) Drugs and Biologics Compendium for off-label use in lung cancer. NCCN is recognized by the Centers for Medicare and Medicaid Services (CMS) as a referencing source

• Corresponding HCPCS/CPT codes and code descriptions

• Current code price (AWP-based pricing)• Most recent ASP + 6% (Medicare allowable)• Possible CPT administration codes for each

medication

Medications Used for the Treatment of Lung Cancer

Lung cancer forms in tissues of thelung, usually in the cells lining theair passages. The two main types

are small-cell lung cancer and non–small-cell lung cancer. This section willassist healthcare professionals and payersby providing appropriate coding, billing,and reimbursement information associat-ed with the management of lung cancer.

GH


NCCN Drugs Current MedicareFDA- and Biologics code price allowableapproved Compendium– (AWP- (ASP + 6%), CPT

Generic (brand) HCPCS code: for lung approved for based effective administrationname code description cancer lung cancer pricing) 1/1/09-3/31/09 codes

bevacizumab J9035: injection, 96413,(Avastin) bevacizumab, 10 mg 3 $68.75 $57.38 96415

carboplatin J9045: injection, 96409,(Paraplatin) carboplatin, 50 mg 3 $85.10 $5.75 96413, 96415

cetuximab J9055: injection, 96413, (Erbitux) cetuximab, 10 mg 3 $60.00 $49.75 96415

cisplatin J9060: cisplatin, powder 96409,(Platinol-AQ) or solution, per 10 mg 3 $4.51 $2.23 96413, 96415

cisplatin 96409,(Platinol-AQ) J9062: cisplatin, 50 mg 3 $22.56 $11.14 96413, 96415

cyclophosphamide J8530: cyclophosphamide,(Cytoxan) oral, 25 mg 3 $2.09 $0.92 N/A

cyclophosphamide J9090: cyclophosphamide, 96409,(Cytoxan) 500 mg 3 $31.60 $14.50 96413, 96415

cyclophosphamide J9091: cyclophosphamide, 96409, (Cytoxan) 1 g 3 $56.90 $29.00 96413, 96415

cyclophosphamide J9092: cyclophosphamide, 96409, (Cytoxan) 2 g 3 $52.50 $58.00 96413, 96415

docetaxel J9170: injection,(Taxotere) docetaxel, 20 mg 3 $459.33 $336.94 96413

doxorubicin HCl J9000: injection, doxorubicin(Adriamycin) hydrochloride, 10 mg 3 $13.75 $3.79 96409

erlotinib J8999*: prescription drug, NDC (Tarceva) oral, chemotherapeutic, level

not otherwise specified 3 pricing N/A N/A

etoposide J8560: etoposide,(Vepesid) oral, 50 mg 3 $47.64 $29.57 N/A

etoposide J9181: injection,(Toposar) etoposide, 10 mg 3 $0.55 $0.48 96413, 96415

gefitinib J8565: gefitinib,(Iressa) oral, 250 mg 3 $70.91 N/A N/A

gemcitabine J9201: injection, gemcitabine (Gemzar) hydrochloride, 200 mg 3 $172.41 $138.19 96413

ifosfamide J9208: injection,(Ifex) ifosfamide, 1 g 3 $58.75 $33.50 96413, 96415

irinotecan J9206: injection,(Camptosar) irinotecan, 20 mg 3 $32.81 $21.72 96413, 96415

mechlorethamine HCl J9230: injection,(Mustargen) mechlorethamine hydrochloride,

(nitrogen mustard), 10 mg 3 $177.29 $147.18 96409

mesna J9209: injection,(Mesnex) mesna, 200 mg 3 $19.50 $5.83 96365, 96374

methotrexate J8610: methotrexate, oral, 2.5 mg 3 $3.56 $0.16 N/A


NCCN Drugs Current MedicareFDA- and Biologics code price allowableapproved Compendium– (AWP- (ASP + 6%), CPT

Generic (brand) HCPCS code: for lung approved for based effective administrationname code description cancer lung cancer pricing) 1/1/09-3/31/09 codes

methotrexate sodium J9250: methotrexate sodium, 3 $0.24 $0.21 96372, 96374, 5 mg 96401, 96409,

96450

methotrexate sodium J9260: methotrexate sodium, 3 $2.38 $2.30 96372, 96374, 50 mg 96401, 96409,

96450

mitomycin (Mutamycin) J9280: mitomycin, 5 mg 3 $70.00 $15.30 96409



paclitaxel J9265: injection, paclitaxel, 3

(Taxol) 30 mg $21.38 $7.56 96413, 96415

paclitaxel protein-bound J9264: injection, paclitaxelparticles (Abraxane) protein-bound particles, 1 mg 3 $11.29 $9.07 96413

pemetrexed J9305: injection, (Alimta) pemetrexed, 10 mg 3 $60.21 $48.22 96409

porfimer sodium J9600: injection,(Photofrin) porfimer sodium, 75 mg 3 $3,276.45 $2,595.68 96409

topotecan J8705: topotecan,(Hycamtin) oral, 0.25 mg 3 $84.43 $69.89 N/A

topotecan J9350: injection topotecan, (Hycamtin) 4 mg 3 $1,229.00 $939.34 96413

vinBLAStine J9360: injection, (Velban) vinblastine sulfate, 1 mg 3 $3.31 $0.79 96409

vinCRIStine (Vincasar) J9370: vincristine sulfate, 1 mg 3 $10.00 $6.42 96409



vinorelbine tartrate J9390: injection,(Navelbine) vinorelbine tartrate, per 10 mg 3 $44.38 $15.70 96409

*When billing a nonclassified medication using a CMS 1500 claim form, you must include both the HCPCS code (ie, J8999 for Tarceva) in column 24D andthe drug name, strength, and NDC in box 19 to ensure appropriate reimbursement.

References

• HCPCS Level II Expert; 2009 • CPT 2009; 2008 • ICD-9-CM for Professionals, Volumes 1 & 2; 2009 • The Drug Reimbursement Coding and Pricing Guide, Vol6, No 1; R•J Health Systems International LLC; 1st Quarter 2009 • FDA-approved indication (from products' prescribing information) • NCCN •www.ReimbursementCodes.com powered by R•J Health Systems International, LLC, Wethersfield, Connecticut • CMS-Medicare allowable 1st Quarter 2009(effective dates 1/1/09-3/31/09).

Prices listed herein are effective as of March 3, 2009.

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

GH


This information was supplied by:

The Most Comprehensive HCPCS/CPT Drug and Product Reimbursement Coding and Pricing Service Available!

ReimbursementCodes.com is an online HCPCS/CPT reimbursement coding and pricing service that provides up-to-date reimbursement information.

You have the ability to accurately match reimbursement to the corresponding date of service for every claim!• Drugs which are injected subcutaneously, intramuscularly, or intravenously• Selected orally administered chemotherapeutic and antiemetic agents• Nutritional agents and ostomy care products• Drugs administered via nebulizers or other DME equipment• Radiopharmaceuticals

Plus a fast and efficient avenue to HCPCS/CPT coding and reimbursement information!• In billable units matching the CMS- and AMA-established reimbursement code description• A validated pricing methodology• Includes all price changes that have occurred for each code, along with the effective date of the change(s)• Radiopharmaceuticals

Does your revenue stream run as productively as possible? Contact R•J Health Systems, and mention Journal of Multidisciplinary Cancer Care.

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

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

INDICATIONS AND USAGE Non-Hodgkin’s Lymphoma (NHL) Rituxan®

(rituximab) is indicated for the treatment of patients with: Relapsed or refractory,low-grade or follicular, CD20-positive, B-cell NHL as a single agent; Previouslyuntreated follicular, CD20-positive, B-cell NHL in combination with CVPchemotherapy; Non-progressing (including stable disease), low-grade, CD20-positive B-cell NHL, as a single agent, after first-line CVP chemotherapy;Previously untreated diffuse large B-cell, CD20-positive NHL in combination withCHOP or other anthracycline-based chemotherapy regimens. WARNINGS ANDPRECAUTIONS Infusion Reactions Rituxan can cause severe, including fatal,infusion reactions. Severe reactions typically occurred during the first infusion withtime 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, or anaphylactoid events. Premedicatepatients with an antihistamine and acetaminophen prior to dosing. Institutemedical management (e.g., glucocorticoids, epinephrine, bronchodilators, oroxygen) for infusion reactions as needed. Depending on the severity of theinfusion reaction and the required interventions, consider resumption of theinfusion at a minimum 50% reduction in rate after symptoms have resolved.Closely monitor the following patients: those with preexisting cardiac orpulmonary conditions, those who experienced prior cardiopulmonary adversereactions, and those with high numbers of circulating malignant cells(≥25,000/mm3). [See Boxed Warning, Warnings and Precautions, AdverseReactions.] Tumor Lysis Syndrome (TLS) Rapid reduction in tumor volumefollowed by acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, orhyperphosphatemia, can occur within 12–24 hours after the first infusion. FatalTLS cases have occurred after administration of Rituxan. A high number ofcirculating malignant cells (≥25,000/mm3) or high tumor burden confers a greaterrisk of TLS after rituximab. Consider prophylaxis for TLS in patients at high risk.Correct electrolyte abnormalities, monitor renal function and fluid balance, andadminister supportive care, including dialysis as indicated. [See Boxed Warning.]Severe Mucocutaneous Reactions Mucocutaneous reactions, some with fataloutcome, can occur in patients treated with Rituxan. These reactions includeparaneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis,vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of thesereactions has varied from 1–13 weeks following Rituxan exposure. DiscontinueRituxan in patients who experience a severe mucocutaneous reaction. The safetyof readministration of Rituxan to patients with severe mucocutaneous reactionshas not been determined. [See Boxed Warning, Adverse Reactions.] ProgressiveMultifocal Leukoencephalopathy (PML) JC virus infection resulting in PMLand death can occur in Rituxan-treated patients with hematologic malignancies or with autoimmune diseases. The majority of patients with hematologicmalignancies diagnosed with PML received Rituxan in combination withchemotherapy or as part of a hematopoietic stem cell transplant. The patients withautoimmune diseases had prior or concurrent immunosuppressive therapy. Mostcases of PML were diagnosed within 12 months of their last infusion of Rituxan.Consider the diagnosis of PML in any patient presenting with new-onsetneurologic manifestations. Discontinue Rituxan and consider discontinuation orreduction of any concomitant chemotherapy or immunosuppressive therapy inpatients who develop PML. [See Boxed Warning, Adverse Reactions.] Hepatitis BVirus (HBV) Reactivation Hepatitis B Virus (HBV) reactivation with fulminanthepatitis, hepatic failure, and death can occur in patients with hematologicmalignancies treated with Rituxan. The median time to the diagnosis of hepatitiswas approximately 4 months after the initiation of Rituxan and approximately onemonth after the last dose. Screen patients at high risk of HBV infection beforeinitiation of Rituxan. Closely monitor carriers of hepatitis B for clinical andlaboratory signs of active HBV infection for several months following Rituxantherapy. Discontinue Rituxan and any concomitant chemotherapy in patients whodevelop viral hepatitis, and institute appropriate treatment including antiviraltherapy. Insufficient data exist regarding the safety of resuming Rituxan in patientswho develop hepatitis subsequent to HBV reactivation. [See Adverse Reactions.]Other Viral Infections The following additional serious viral infections, eithernew, reactivated, or exacerbated, have been identified in clinical studies orpostmarketing reports. The majority of patients received Rituxan in combinationwith chemotherapy or as part of a hematopoietic stem cell transplant. These viralinfections included cytomegalovirus, herpes simplex virus, parvovirus B19,varicella zoster virus, West Nile virus, and hepatitis C. In some cases, the viralinfections occurred as late as one year following discontinuation of Rituxan andhave resulted in death. [See Adverse Reactions.] Cardiovascular Discontinueinfusions for serious or life-threatening cardiac arrhythmias. Perform cardiacmonitoring during and after all infusions of Rituxan for patients who developclinically significant arrhythmias or who have a history of arrhythmia or angina.[See Adverse Reactions.] Renal Severe, including fatal, renal toxicity can occurafter Rituxan administration in patients with hematologic malignancies. Renaltoxicity has occurred in patients with high numbers of circulating malignant cells(≥25,000/mm3) or high tumor burden who experience tumor lysis syndrome andin patients with NHL administered concomitant cisplatin therapy during clinicaltrials. The combination of cisplatin and Rituxan is not an approved treatmentregimen. Use extreme caution if this non-approved combination is used in clinicaltrials and monitor closely for signs of renal failure. Consider discontinuation ofRituxan for patients with a rising serum creatinine or oliguria. Bowel Obstructionand Perforation Abdominal pain, bowel obstruction and perforation, in some

WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME(TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVEMULTIFOCAL LEUKOENCEPHALOPATHY (PML)Infusion Reactions: Rituxan administration can result in serious,including fatal infusion reactions. Deaths within 24 hours of Rituxaninfusion have occurred. Approximately 80% of fatal infusion reactionsoccurred in association with the first infusion. Carefully monitorpatients during infusions. Discontinue Rituxan infusion and providemedical treatment for Grade 3 or 4 infusion reactions [see Warningsand Precautions, Adverse Reactions]. Tumor Lysis Syndrome (TLS):Acute renal failure requiring dialysis with instances of fatal outcomecan occur in the setting of TLS following treatment of non-Hodgkin’slymphoma (NHL) patients with Rituxan [see Warnings and Precautions,Adverse Reactions]. Severe Mucocutaneous Reactions: Severe,including fatal, mucocutaneous reactions can occur in patientsreceiving Rituxan [see Warnings and Precautions, Adverse Reactions].Progressive Multifocal Leukoencephalopathy (PML): JC virus infectionresulting in PML and death can occur in patients receiving Rituxan [seeWarnings and Precautions, Adverse Reactions].

cases leading to death, can occur in patients receiving Rituxan in combinationwith chemotherapy. In postmarketing reports, the mean time to documentedgastrointestinal perforation was 6 (range 1–77) days in patients with NHL.Perform a thorough diagnostic evaluation and institute appropriate treatment forcomplaints of abdominal pain, especially early in the course of Rituxan therapy.[See Adverse Reactions.] Immunization The safety of immunization with live viralvaccines following Rituxan therapy has not been studied and vaccination with livevirus vaccines is not recommended. For NHL patients, the benefits of primary orbooster vaccinations should be weighted against the risks of delay in initiation ofRituxan therapy. Laboratory Monitoring Because Rituxan binds to all CD20-positive B lymphocytes (malignant and non-malignant), obtain complete bloodcounts (CBC) and platelet counts at regular intervals during Rituxan therapy andmore frequently in patients who develop cytopenias [see Adverse Reactions]. Theduration of cytopenias caused by Rituxan can extend months beyond thetreatment period. ADVERSE REACTIONS The most common adverse reactions ofRituxan (incidence ≥25%) observed in patients with NHL are infusion reactions,fever, chills, infection, asthenia, and lymphopenia. The most important seriousadverse reactions of Rituxan are infusion reactions, tumor lysis syndrome,mucocutaneous toxicities, hepatitis B reactivation with fulminant hepatitis, PML,other viral infections, cardiac arrhythmias, renal toxicity, and bowel obstructionand perforation. Clinical Trials Experience Non-Hodgkin’s LymphomaBecause clinical trials are conducted under widely varying conditions, adversereaction rates observed in the clinical trials of a drug cannot be directly comparedto rates in the clinical trials of another drug and may not reflect the rates observedin practice. The data described below reflect exposure to Rituxan in 1606patients, with exposures ranging from a single infusion up to 6–8 months. Rituxanwas studied in both single-agent and active-controlled trials (n = 356 and n =1250). These data were obtained in adults with low-grade, follicular, or DLBCLNHL. Most patients received Rituxan as an infusion of 375 mg/m2 per infusion,given as a single agent weekly for up to 8 doses, in combination withchemotherapy for up to 8 doses, or following chemotherapy for up to 16 doses.Infusion Reactions In the majority of patients with NHL, infusion reactionsconsisting of fever, chills/rigors, nausea, pruritus, angioedema, hypotension,headache, bronchospasm, urticaria, rash, vomiting, myalgia, dizziness, orhypertension occurred during the first Rituxan infusion. Infusion reactions typicallyoccurred within 30 to 120 minutes of beginning the first infusion and resolvedwith slowing or interruption of the Rituxan infusion and with supportive care(diphenhydramine, acetaminophen, and intravenous saline). The incidence ofinfusion reactions was highest during the first infusion (77%) and decreased witheach 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. Theoverall incidence of infections was 31% (bacterial 19%, viral 10%, unknown 6%,and fungal 1%). [See Warnings and Precautions.] In randomized, controlledstudies where Rituxan was administered following chemotherapy for thetreatment of follicular or low-grade NHL, the rate of infection was higher amongpatients who received Rituxan. In diffuse large B-cell lymphoma patients, viralinfections occurred more frequently in those who received Rituxan. Cytopeniasand hypogammaglobulinemia In patients with NHL receiving rituximabmonotherapy, NCI-CTC Grade 3 and 4 cytopenias were reported in 48% ofpatients. These included lymphopenia (40%), neutropenia (6%), leukopenia (4%),anemia (3%), and thrombocytopenia (2%). The median duration of lymphopeniawas 14 days (range, 1–588 days) and of neutropenia was 13 days (range, 2–116days). A single occurrence of transient aplastic anemia (pure red cell aplasia) andtwo occurrences of hemolytic anemia following Rituxan therapy occurred duringthe single-arm studies. In studies of monotherapy, Rituxan-induced B-celldepletion occurred in 70% to 80% of patients with NHL. Decreased IgM and IgGserum levels occurred in 14% of these patients. Single-Agent Rituxan Adversereactions in Table 1 occurred in 356 patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL treated in single-arm studies ofRituxan administered as a single agent. Most patients received Rituxan 375 mg/m2

weekly for 4 doses.Table 1Incidence of Adverse Events 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 andup to 6 months after Rituxan infusion. Rituxan in Combination WithChemotherapy Adverse reactions information below is based on 1250 patientswho received Rituxan in combination with chemotherapy or followingchemotherapy. Rituxan in Combination With Chemotherapy for Low-GradeNHL In Study 4, patients in the R-CVP arm experienced a higher incidence ofinfusional toxicity and neutropenia compared to patients in the CVP arm. Thefollowing adverse reactions occurred more frequently (≥5%) in patients receivingR-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 reactionswere reported more frequently (≥5%) in patients receiving Rituxan following CVPcompared to patients who received no further therapy: 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 thatoccurred more frequently (≥2%) in the Rituxan arm compared with those whoreceived no further therapy (4% vs. 1%). Rituxan in Combination With

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

Any Adverse Events 99 57Body as a Whole 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 System 67 48Lymphopenia 48 40Leukopenia 14 4Neutropenia 14 6Thrombocytopenia 12 2Anemia 8 3

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

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

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

Metabolic and Nutritional Disorders 38 3

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

Digestive System 37 2Nausea 23 1Diarrhea 10 1Vomiting 10 1

Nervous System 32 1Dizziness 10 1Anxiety 5 1

Musculoskeletal System 26 3Myalgia 10 1Arthralgia 10 1

Cardiovascular System 25 3Hypotension 10 1Hypertension 6 1

Chemotherapy for DLBCL In Studies 6 and 7, the following adverse reactions,regardless of severity, were reported more frequently (≥5%) in patients age ≥60years receiving R-CHOP as compared to CHOP alone: pyrexia (56% vs. 46%), lungdisorder (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 3and 4 adverse reactions and serious adverse reactions. In Study 7, a review ofcardiac toxicity determined that supraventricular arrhythmias or tachycardiaaccounted 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 morefrequently among patients in the R-CHOP arm compared with those in the CHOParm: thrombocytopenia (9% vs. 7%) and lung disorder (6% vs. 3%). Other Grade3 or 4 adverse reactions occurring more frequently among patients receiving R-CHOP were viral infection (Study 7), neutropenia (Studies 7 and 8), and anemia(Study 8). Immunogenicity As with all therapeutic proteins, there is a potentialfor immunogenicity. The observed incidence of antibody (including neutralizingantibody) positivity in an assay is highly dependent on several factors includingassay sensitivity and specificity, assay methodology, sample handling, timing ofsample collection, concomitant medications, and underlying disease. For thesereasons, comparison of the incidence of antibodies to Rituxan with the incidenceof 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%) patientswith low-grade or follicular NHL receiving single-agent Rituxan. Three of the fourpatients had an objective clinical response. The clinical relevance of HACAformation in rituximab treated patients is unclear. Postmarketing ExperienceThe following adverse reactions have been identified during postapproval use ofRituxan in hematologic malignancies. Because these reactions are reportedvoluntarily from a population of uncertain size, it is not always possible to reliablyestimate their frequency or establish a causal relationship to drug exposure.Decisions to include these reactions in labeling are typically based on one or moreof 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, hyperviscositysyndrome in Waldenstrom’s macroglobulinemia. Cardiac: fatal cardiac failure.Immune/Autoimmune Events: uveitis, optic neuritis, systemic vasculitis, pleuritis,lupus-like syndrome, serum sickness, polyarticular arthritis, and vasculitis with rash. Infection: viral infections, including progressive multifocalleukoencephalopathy (PML), increase in fatal infections in HIV-associatedlymphoma, and a reported increased incidence of Grade 3 and 4 infections inpatients 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 withRituxan. USE IN SPECIFIC POPULATIONS Pregnancy Category C: There areno adequate and well-controlled studies of rituximab in pregnant women.Postmarketing data indicate that B-cell lymphocytopenia generally lasting lessthan six months can occur in infants exposed to rituximab in-utero. Rituximab wasdetected postnatally in the serum of infants exposed in-utero. Non-Hodgkin’slymphoma is a serious condition that requires treatment. Rituximab should beused during pregnancy only if the potential benefit to the mother justifies thepotential risk to the fetus. Reproduction studies in cynomolgus monkeys atmaternal exposures similar to human therapeutic exposures showed no evidenceof teratogenic effects. However, B-cell lymphoid tissue was reduced in theoffspring of treated dams. The B-cell counts returned to normal levels, andimmunologic function was restored within 6 months of birth. Nursing Mothers Itis not known whether Rituxan is secreted into human milk. However, Rituxan issecreted in the milk of lactating cynomolgus monkeys, and IgG is excreted inhuman milk. Published data suggest that antibodies in breast milk do not enterthe neonatal and infant circulations in substantial amounts. The unknown risks tothe infant from oral ingestion of Rituxan should be weighed against the knownbenefits of breastfeeding. Pediatric Use The safety and effectiveness of Rituxanin pediatric patients have not been established. Geriatric Use Diffuse Large B-Cell NHL Among patients with DLBCL evaluated in three randomized, active-controlled trials, 927 patients received Rituxan in combination with chemotherapy.Of these, 396 (43%) were age 65 or greater and 123 (13%) were age 75 orgreater. No overall differences in effectiveness were observed between thesepatients and younger patients. Cardiac adverse reactions, mostly supraventriculararrhythmias, occurred more frequently among elderly patients. Serious pulmonaryadverse reactions were also more common among the elderly, includingpneumonia and pneumonitis. Low-Grade or Follicular Non-Hodgkin’sLymphoma 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 todetermine whether they respond differently from younger subjects.OVERDOSAGE There has been no experience with overdosage in human clinicaltrials. Single doses of up to 500 mg/m2 have been given in dose-escalationclinical trials. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis,Impairment of Fertility No long term animal studies have been performed toestablish the carcinogenic or mutagenic potential of Rituxan or to determinepotential effects on fertility in males or females. PATIENT COUNSELINGINFORMATION Patients should be provided the Rituxan Medication Guide andprovided an opportunity to read prior to each treatment session. Because cautionshould be exercised in administering Rituxan to patients with active infections, it isimportant that the patient’s overall health be assessed at each visit and anyquestions resulting from the patient’s reading of the Medication Guide bediscussed. Rituxan is detectable in serum for up to six months followingcompletion of therapy. Individuals of childbearing potential should use effectivecontraception during treatment and for 12 months after Rituxan therapy.

Revised 9/2008 (4835505)Jointly Marketed by: Biogen Idec Inc. 5200 Research Place San Diego, CA 92122Genentech USA, Inc. 1 DNA Way South San Francisco, CA 94080-4990

©2008 Biogen Idec Inc. and Genentech, Inc. 7140917 October 2008

For previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens

When planning a treatment course for DLBCL

Take the essential path toward improved survival

47% INCREASEin 7-year OS in GELA* trial1,2

RITUXAN+CHOP isproven to prolongsurvival in DLBCL

0

0.2

0.4

0.6

0.8

1.0

Years

Cum

ulat

ive

Prop

ortio

n Su

rviv

ing

0 1 32 4 5 7 86

R-CHOP (n=202)CHOP† (n=197)p=0.0004

0

0.2

0.4

0.6

0.8

1.0

Years

Cum

ulat

ive

Prop

ortio

n Su

rviv

ing

0 1 32 4 5 7 86

R-CHOP (n=202)CHOP† (n=197)p=0.0004

• At 7 years, 8 cycles of RITUXAN+CHOP increased overall survival (OS) from 36% to 53% compared with CHOP alone1

• At 5 years, 8 cycles of RITUXAN+CHOP increased OS from 46% to 58% compared with CHOP alone5

BOXED WARNINGS and Additional Important Safety InformationThe most important serious adverse reactions of RITUXAN are fatal infusionreactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions,progressive multifocal leukoencephalopathy (PML), hepatitis B reactivation withfulminant hepatitis, other viral infections, cardiovascular events, renal toxicity, andbowel obstruction and perforation. The most common adverse reactions of RITUXAN(incidence ≥25%) observed in patients with NHL are infusion reactions, fever, chills,infection, asthenia, and lymphopenia.5

RITUXAN in Combination with CHOP Chemotherapy for DLBCL: The followingadverse reactions, regardless of severity, were reported more frequently (≥5%) inpatients age ≥60 years receiving R-CHOP as compared to CHOP alone: pyrexia (56% vs46%), lung disorder (31% vs 24%), cardiac disorder (29% vs 21%), and chills (13% vs4%). In the GELA LNH 98-5 study, a review of cardiac toxicity determined thatsupraventricular arrhythmias or tachycardia accounted for most of the difference incardiac disorders (4.5% for R-CHOP vs 1.0% for CHOP).5

The following Grade 3 or 4 adverse reactions occurred more frequently among patientsin the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs7%) and lung disorder (6% vs 3%). Other Grade 3 or 4 adverse reactions reported morefrequently among patients receiving R-CHOP were viral infection (GELA LNH 98-5study), neutropenia (GELA LNH 98-5 and MInT studies), and anemia (MInT study).5

Please see brief summary of prescribing information on adjacent page.Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion.*GELA (Groupe d’Etude des Lymphomes de l’Adulte) LNH 98-5 trial: A Phase III trial of 399 previouslyuntreated elderly (age ≥60 years) DLBCL patients.3,4

†CHOP: Cyclophosphamide, doxorubicin, vincristine, and prednisone.

References: 1. Coiffier B, Feugier P, Mounier N, et al. Long-term results of the GELA study comparing R-CHOPand CHOP chemotherapy in older patients with diffuse large B-cell lymphoma show good survival in poor-riskpatients. J Clin Oncol. 2007;25(suppl 18S):443s. Abstract 8009. 2. Coiffier B, Feugier P, Mounier N, et al.Long-term results of the GELA study comparing R-CHOP and CHOP chemotherapy in older patients with diffuselarge B-cell lymphoma show good survival in poor-risk patients. Paper presented at: 43rd American Society ofClinical Oncology Annual Meeting; June 1-5, 2007; Chicago, Ill. Abstract 8009. 3. Coiffier B, Lepage E, BrièreJ, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235-242. 4. Data on file, Genentech, Inc. 5. RITUXAN® (Rituximab)full prescribing information, Genentech, Inc., 2008.

PROVE N. POWE R FU L.

©2008 Genentech, Inc., and Biogen Idec Inc. All rights reserved.3 Printed in USA on Recycled Paper 8957001 April 2008

JOMCC | March/April 2009 Volume 2 Issue 2

Documents

Transcript of JOMCC | March/April 2009 Volume 2 Issue 2