December 2010, Vol 3, No 8

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DECEMBER 2010

www.TheOncologyNurse.com

VOL 3, NO 8

GENETIC TESTING

CANCER CENTER PROFILE

Geisinger Medical Center’s Cancer Institute Joins the NCCCP

By Dawn Lagrosa

Multigene Signature Scores and Breast Cancer 2010

By Deena Damsky Dell, MSN, RN-BC, AOCN Clinical Nurse Specialist, Fox Chase Cancer Center, Philadelphia

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he addition of new biomarkers for establishing a prognosis for patients with breast cancer has been recommended in the 2010 edition of the American Joint Committee of Cancer’s Cancer Staging Handbook.1 Human epidermal growth factor receptor type 2 (HER2) status and multigene signature “scores” have been added to estrogen receptor (ER) and progesterone receptor (PR) determinations.1 So, where are we regarding multigene signature scores? At this time, two tests are commercially

available in the United States: Oncotype DX (Genomic Health) and MammaPrint (Agendia).

21-gene recurrence score assay Available since 2004, Oncotype DX uses a process called reverse-transcriptase polymerase chain reaction (RT-PCR) to look at 21 genes: 16 are linked to breast cancer and five are reference genes used for normalizing the expression of the cancer-related genes. The chosen genes have Continued on page 12

CONFERENCE NEWS

Mammography technologist Jessica Davis, RT(R) (M), is part of a multidisciplinary breast cancer care team working to improve access to screening, treatment, and research.

Oncology Nursing Society’s 11th Annual Advanced Practice Nursing Conference/ Institutes of Learning Orlando, Florida, November 11-14, 2010.

See who was there: page 8.

his past April, Geisinger Medical Center’s (GMC) Cancer Institute became one of 14 sites added to the National Cancer Institute Community Cancer Centers Program (NCCCP). Joining this national network of community cancer centers offers GMC the opportunity to expand its state-of-the-art cancer care and research in northeast Pennsylvania.

GMC is a part of Geisinger Health System (Geisinger), which serves a mostly rural population and has cancer centers in Danville, WilkesBarre, State College, and Hazleton. Geisinger takes pride in its innovative approach to healthcare delivery to this population, which also includes many elderly patients. In addition, a significant portion is underserved because of socioeconomic status and transportation problems. Thanjavur Ravikumar, MD, FACS, director of the Center for Surgical Innovation, and co-chair of the oncology service line at

T

Continued on page 18

Kimberly Gessner, Holly Gentry, and Marlene Ferguson display copies of The Council of Dads, a book by keynote speaker Bruce Feiler.

Inside

Journal of Oncology

NAVIGATION & SURVIVORSHIP

™

Lung Cancer Stereotactic Radiation for Non–small-cell Lung Cancers

Continuing Education Maintenance erapy in Patients with Advanced Non–small-cell Lung Cancer

Submit your cases online today at

Page 20

Page 30

www.myelomacases.com

Page 25

Fostering a Dialogue to Improve Patient Care & Outcomes

The Official Journal of the Academy of Oncology Nurse Navigators ® DECEMBER 2010

www.AONNonline.org

VOL 1, NO 7

CARE COORDINATION

City-wide Patient Navigation Network Coordinates Washington, DC, Cancer Care

By Karen Rosenberg

Leadership Council Lillie Shockney, RN, BS, MAS Johns Hopkins Breast Center Johns Hopkins University School of Medicine Baltimore, Maryland Sharon Gentry, RN, MSN, AOCN, CBCN Derrick L. Davis Forsyth Regional Cancer Center Winston-Salem, North Carolina Nicole Messier, RN Vermont Cancer Center Burlington, Vermont Pamela Matten, RN, BSN, OCN St. Joseph Hospital Orange, California Elaine Sein, RN, BSN, OCN, CBCN Fox Chase Cancer Center Partners Rockledge, Pennsylvania Tricia Strusowski, MS, RN Helen F. Graham Cancer Center Christiana Care Health System Newark, Delaware

T

he George Washington Cancer Institute (GWCI) recently received a $2.4 million grant from the DC Cancer Consortium to establish and coordinate a City-wide Patient Navigation Network (CPNN) in Washington, DC. The CPNN will create a seamless, cohesive framework for coordination of cancer care throughout the city to ensure that all city residents get appropriate cancer screening and treatment regardless of their ability to pay. The network will also help patients identify support services throughout the cancer continuum, including posttreatment survivorship.

Twenty-five separate institutions, including hospitals, cancer centers, and community organizations in the Washington, DC, area are members of

the network, and patient navigators are embedded at every site, said Steven Patierno, PhD, executive director of the GWCI.

and a secure Internet-based data collection process, which allows the navigators to upload their navigation logs and their patient interactions in real time.

“The CPNN will create a seamless, cohesive framework for coordination of cancer care throughout the city. ” —Steven Patierno, PhD

The program, he explained, provides training once a month to every navigator and every navigator’s supervisor. It also provides a central communications portal

Journal of Oncology Navigation & Survivorship™

He gave an example of how coordination of care works. “If a patient is seen at a community advocacy group that does Continued on page 2

NAVIGATION TRAINING

Center Provides Platform for Discussion of Cancer Survivorship, Navigation, and Policy

By Karen Rosenberg

Fast Neutron Radiotherapy

Breast Cancer Prolonging Chemotherapy in Metastatic Breast Cancer Improves Survival Page 44

©2010 Green Hill Healthcare Communications, LLC

Linda Fleisher, MPH, PhD(c) Fox Chase Cancer Center Cheltenham, Pennsylvania Susan M. Gardner, RN, CBEC, CBCN Valley Medical Center Renton, Washington Jay R. Swanson, RN, BSN, OCN Saint Elizabeth Cancer Institute Lincoln, Nebraska Carol Lewis, RN, BSN, OCN, CRNI Memorial Hermann The Woodlands, Texas

T

he Center for the Advancement of Cancer Survivorship, Navigation, and Policy (caSNP), a collaboration of the George Washington Cancer Institute (GWCI) and the university’s School of Public Health and Health Services Department of Health Policy, was established in 2009 with support from Pfizer and the Pfizer Foundation. The center’s goals are to advance patient navigation and cancer survivorship efforts both locally and nationally through training, research,

policy analysis, and education. caSNP grew out of the understanding that there is “overlap between patient navigation, survivorship, and policy and both of these intersect with local and national healthcare policy,” explained Steven Patierno, PhD, executive director of the GWCI. “We wanted to create a platform to talk about navigation and survivorship in the context of policy in a united program.”

The center offers training programs at three levels:

• Navigation training is designed for navigators, including nurses, social workers, and lay persons. Trainees from institutions across the country learn about barriers that affect their patients, are trained to launch or improve programs, and gain tools for implementing institutional change.

• Executive level training is designed for chief executive officers, chief financial officers, hospital adminis-

AONN Staff Sean T. Walsh Executive Director sean@AONNonline.org

GUIDE OUR PATH Start a Local, State, or Regional Affiliate, Join a Committee

www.AONNonline.org ©2010 Green Hill Healthcare Communications, LLC

Continued on page 2

between pages 34 and 35

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Announcing the first and only monoclonal antibody indicated for use in HER2+ metastatic gastric and gastroesophageal junction (GEJ) cancer Indication Herceptin is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease.

to drive outcomes in HER2+ metastatic gastric/GEJ cancer

Boxed WARNINGS Herceptin administration can result in sub-clinical and clinical cardiac failure.

The incidence and severity was highest in patients receiving Herceptin with anthracycline-containing chemotherapy regimens. In a pivotal adjuvant breast cancer trial, one patient who developed CHF died of cardiomyopathy Evaluate cardiac function prior to and during treatment. Discontinue Herceptin for cardiomyopathy Herceptin can result in serious and fatal infusion reactions and pulmonary toxicity.

Discontinue Herceptin for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome Exposure to Herceptin during pregnancy can result in oligohydramnios, in some cases complicated by pulmonary hypoplasia and neonatal death

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Herceptin plus chemotherapy* extended median overall survival (OS) in HER2+ metastatic gastric and GEJ cancer1 In the ToGA trial†: •

The final overall survival analysis demonstrated a 13.5-month median OS with Herceptin + chemotherapy (cisplatin and either capecitabine or 5-fluorouracil) vs an 11.0-month median OS with chemotherapy alone1

•

The updated overall survival analysis demonstrated a 13.1-month median OS with Herceptin + chemotherapy (cisplatin and either capecitabine or 5-fluorouracil) vs an 11.7-month median OS with chemotherapy alone1

•

Herceptin should be administered until disease progression or unacceptable toxicity in HER2+ metastatic gastric and GEJ cancer

†

Trastuzumab in gastric cancer.

Final Median Overall Survival Analysis1

13.5

Hazard Ratio = 0.73 95% CI: 0.60-0.91 P=0.0038

11.0 Updated Median Overall Survival Analysis1‡

13.1 Hazard Ratio = 0.80 95% CI: 0.67-0.97

11.7 0

3

6

9

12

15

Months Herceptin plus chemotherapy* (n=298) Chemotherapy alone* (n=296) *Chemotherapy was cisplatin and either capecitabine or 5-FU. ‡ The updated analysis was conducted one year after the final analysis. No P value was associated with the updated analysis in the Herceptin Prescribing Information because there was no preplanned statistical testing for OS after the final analysis.

Additional Important Safety Information Exacerbation of chemotherapy-induced neutropenia has also occurred Detection of HER2 protein overexpression is necessary for selection of patients appropriate for Herceptin therapy The most common adverse reactions associated with Herceptin were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia Please see brief summary of full Prescribing Information, including Boxed WARNINGS and additional important safety information, on the following pages.

Reference: 1. Herceptin Prescribing Information. Genentech, Inc. October 29, 2010.

©2010 Genentech USA, Inc.

So. San Francisco, CA

All rights reserved.

10581800

11/10

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HERCEPTIN® (trastuzumab) Brief Summary For full Prescribing Information, see package insert.

WARNING: CARDIOMYOPATHY, INFUSION REACTIONS, EMBRYO-FETAL TOXICITY, and PULMONARY TOXICITY Cardiomyopathy Herceptin administration can result in sub clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving Herceptin with anthracycline containing chemotherapy regimens.

Evaluate left ventricular function in all patients prior to and during treatment with Herceptin. Discontinue Herceptin treatment in patients receiving adjuvant therapy and withhold Herceptin in patients with metastatic disease for clinically significant decrease in left ventricular function. [see Warnings and Precautions and Dosage and Administration] Infusion Reactions; Pulmonary Toxicity Herceptin administration can result in serious and fatal infusion reactions and pulmonary toxicity.

Symptoms usually occur during or within 24 hours of Herceptin administration. Interrupt Herceptin infusion for dyspnea or clinically significant hypotension.

Monitor patients until symptoms completely resolve.

Discontinue Herceptin for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. [see Warnings and Precautions] Embryo-Fetal Toxicity Exposure to Herceptin during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. [see Warnings and Precautions, Use in Specific Populations] INDICATIONS AND USAGE Adjuvant Breast Cancer Herceptin is indicated for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature [see Clinical Studies] breast cancer • as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel • with docetaxel and carboplatin • as a single agent following multi-modality anthracycline based therapy. Metastatic Breast Cancer Herceptin is indicated: • In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer • As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease. Metastatic Gastric Cancer Herceptin is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease. CONTRAINDICATIONS None. WARNINGS AND PRECAUTIONS Cardiomyopathy Herceptin can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death [see Boxed Warning: Cardiomyopathy]. Herceptin can also cause asymptomatic decline in left ventricular ejection fraction (LVEF).

There is a 4−6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving Herceptin as a single agent or in combination therapy compared with those not receiving Herceptin. The highest absolute incidence occurs when Herceptin is administered with an anthracycline.

Withhold Herceptin for * 16% absolute decrease in LVEF from pre-treatment values or an LVEF value below institutional limits of normal and * 10% absolute decrease in LVEF from pretreatment values [see Dosage and Administration]. The safety of continuation or resumption of Herceptin in patients with Herceptin-induced left ventricular cardiac dysfunction has not been studied. Cardiac Monitoring Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan. The following schedule is recommended: • Baseline LVEF measurement immediately prior to initiation of Herceptin • LVEF measurements every 3 months during and upon completion of Herceptin • Repeat LVEF measurement at 4 week intervals if Herceptin is withheld for significant left ventricular cardiac dysfunction [see Dosage and Administration] • LVEF measurements every 6 months for at least 2 years following completion of Herceptin as a component of adjuvant therapy.

In Study 1, 16% (136/844) of patients discontinued Herceptin due to clinical evidence of myocardial dysfunction or significant decline in LVEF. In Study 3, the number of patients who discontinued Herceptin due to cardiac toxicity was 2.6% (44/1678). In Study 4, a total of 2.9% (31/1056) patients in the TCH arm (1.5% during the chemotherapy phase and 1.4% during the monotherapy phase) and 5.7% (61/1068) patients in the AC-TH arm (1.5% during the chemotherapy phase and 4.2% during the monotherapy phase) discontinued Herceptin due to cardiac toxicity. Among 32 patients receiving adjuvant chemotherapy (Studies 1 and 2) who developed congestive heart failure, one patient died of cardiomyopathy and all other patients were receiving cardiac medication at last follow-up. Approximately half of the surviving patients had recovery to a normal LVEF (defined as * 50%) on continuing medical management at the time of last follow-up. Incidence of congestive heart failure is presented in Table 1. The safety of continuation or resumption of Herceptin in patients with Herceptin-induced left ventricular cardiac dysfunction has not been studied.

Table 1 Incidence of Congestive Heart Failure in Adjuvant Breast Cancer Studies Incidence of CHF Study Regimen Herceptin Control 1 & 2a ACbAPaclitaxel+ Herceptin 2% (32/1677) 0.4% (7/1600) 3 ChemoAHerceptin 2% (30/1678) 0.3% (5/1708) 4 ACbADocetaxel+ Herceptin 2% (20/1068) 0.3% (3/1050) 4 Docetaxel+Carbo+ Herceptin 0.4% (4/1056) 0.3% (3/1050) a b

Includes 1 patient with fatal cardiomyopathy.

Anthracycline (doxorubicin) and cyclophosphamide

Table 2 Incidence of Cardiac Dysfunctiona in Metastatic Breast Cancer Studies

Study 5 (AC)b 5 (paclitaxel) 6

Incidence NYHA I−IV NYHA III−IV Herceptin Control Herceptin Control

Event Cardiac Dysfunction 28% 7% 19% 3% Cardiac Dysfunction 11% 1% 4% 1% Cardiac Dysfunctionc 7% N/A 5% N/A a Congestive heart failure or significant asymptomatic decrease in LVEF. b Anthracycline (doxorubicin or epirubicin) and cyclophosphamide. c Includes 1 patient with fatal cardiomyopathy.

In Study 4, the incidence of NCI-CTC Grade 3/4 cardiac ischemia/infarction was higher in the Herceptin containing regimens: (AC-TH: 0.3% (3/1068) and TCH 0.2% (2/1056)) as compared to none in AC-T. Infusion Reactions Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion included nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia. [see Adverse Reactions] In postmarketing reports, serious and fatal infusion reactions have been reported. Severe reactions which include bronchospasm, anaphylaxis, angioedema, hypoxia, and severe hypotension, were usually reported during or immediately following the initial infusion. However, the onset and clinical course were variable including progressive worsening, initial improvement followed by clinical deterioration, or delayed post-infusion events with rapid clinical deterioration. For fatal events, death occurred within hours to days following a serious infusion reaction. Interrupt Herceptin infusion in all patients experiencing dyspnea, clinically significant hypotension, and intervention of medical therapy administered, which may include: epinephrine, corticosteroids, diphenhydramine, bronchodilators, and oxygen. Patients should be evaluated and carefully monitored until complete resolution of signs and symptoms. Permanent discontinuation should be strongly considered in all patients with severe infusion reactions. There are no data regarding the most appropriate method of identification of patients who may safely be retreated with Herceptin after experiencing a severe infusion reaction. Prior to resumption of Herceptin infusion, the majority of patients who experienced a severe infusion reaction were pre-medicated with antihistamines and/or corticosteroids. While some patients tolerated Herceptin infusions, others had recurrent severe infusion reactions despite pre-medications. Embryo-Fetal Toxicity Herceptin can cause fetal harm when administered to a pregnant woman. In post-marketing reports, use of Herceptin during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise women of the potential hazard to the fetus resulting from Herceptin exposure during pregnancy and provide contraception counseling to women of childbearing potential. [see Use in Specific Populations, Patient Counseling Information].

Pulmonary Toxicity Herceptin use can result in serious and fatal pulmonary toxicity. Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions [see Warnings and Precautions]. Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity. Exacerbation of Chemotherapy-Induced Neutropenia In randomized, controlled clinical trials the per-patient incidences of NCI CTC Grade 3−4 neutropenia and of febrile neutropenia were higher in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received Herceptin and those who did not. [see Adverse Reactions] HER2 Testing Detection of HER2 protein overexpression is necessary for selection of patients appropriate for Herceptin therapy because these are the only patients studied and for whom benefit has been shown. Due to differences in tumor histopathology, use FDAapproved tests for the specific tumor type (breast or gastric/ gastroesophageal adenocarcinoma) to assess HER2 protein overexpression and HER2 gene amplification. Tests should be performed by laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance, including use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results. Several FDA-approved commercial assays are available to aid in the selection of breast cancer and metastatic gastric cancer patients for Herceptin therapy. Users should refer to the package inserts of specific assay kits for information on the Intended Use, and the validation and performance of each assay. Limitations in assay precision make it inadvisable to rely on a single method to rule out potential Herceptin benefit.

Treatment outcomes for adjuvant breast cancer (Studies 2 and 3) and for metastatic breast cancer (Study 5) as a function of IHC and FISH testing are provided in Tables 8 and 10. Assessment of HER2 protein overexpression and HER2 gene amplification in metastatic gastric cancer should be performed using FDA-approved tests specifically for gastric cancers due to differences in gastric vs. breast histopathology, including incomplete membrane staining and more frequent heterogeneous expression of HER2 seen in gastric cancers.

Study 7 demonstrated that gene amplification and protein overexpression were not as well correlated as with breast cancer. Treatment outcomes for metastatic gastric cancer (Study 7), based on HER2 gene amplification (FISH) and HER2 protein overexpression (IHC) test results are provided in Table 12. ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: • Cardiomyopathy [see Warnings and Precautions] • Infusion reactions [see Warnings and

Precautions] • Embryo-fetal Toxicity [see Warnings and Precautions] • Pulmonary toxicity [see Warnings and Precautions] • Exacerbation of chemotherapy-induced neutropenia [see Warnings and Precautions] The most common adverse reactions in patients receiving Herceptin in the adjuvant and metastatic breast cancer setting are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia. Adverse reactions requiring interruption or discontinuation of Herceptin treatment include CHF, significant decline in left ventricular cardiac function, severe infusion reactions, and pulmonary toxicity [see Dosage and Administration]. In the metastatic gastric cancer setting, the most common adverse reactions (* 10%) that were increased (* 5% difference) in the Herceptin arm as compared to the chemotherapy alone arm were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia. The most common adverse reactions which resulted in discontinuation of treatment on the Herceptin-containing arm in the absence of disease progression were infection, diarrhea, and febrile neutropenia. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adjuvant Breast Cancer Studies The data below reflect exposure to Herceptin across three randomized, openlabel studies, Studies 1, 2, and 3, with (n= 3355) or without (n= 3308) trastuzumab in the adjuvant treatment of breast cancer. The data summarized in Table 3 below, from Study 3, reflect exposure to Herceptin in 1678 patients; the median treatment duration was 51 weeks and median number of infusions was 18. Among the 3386 patients enrolled in Study 3, the median age was 49 years (range: 21 to 80 years), 83% of patients were Caucasian, and 13% were Asian.

Table 3 Adverse Reactions for Study 3, All Gradesa : Adverse Reaction

1 Year Herceptin Observation (n= 1678) (n=1708)

Cardiac Hypertension 64 (4%) Dizziness 60 (4%) Ejection Fraction Decreased 58 (3.5%) Palpitations 48 (3%) Cardiac Arrhythmiasb 40 (3%) Cardiac Failure Congestive 30 (2%) Cardiac Failure 9 (0.5%) Cardiac Disorder 5 (0.3%) Ventricular Dysfunction 4 (0.2%) Respiratory Thoracic Mediastinal Disorders Cough 81 (5%) Influenza 70 (4%) Dyspnea 57 (3%) URI 46 (3%) Rhinitis 36 (2%) Pharyngolaryngeal Pain 32 (2%) Sinusitis 26 (2%) Epistaxis 25 (2%) Pulmonary Hypertension 4 (0.2%) Interstitial Pneumonitis 4 (0.2%) Gastrointestinal Disorders Diarrhea 123 (7%) Nausea 108 (6%) Vomiting 58 (3.5%) Constipation 33 (2%) Dyspepsia 30 (2%) Upper Abdominal Pain 29 (2%) Musculoskeletal & Connective Tissue Disorders Arthralgia 137 (8%) Back Pain 91 (5%) Myalgia 63 (4%) Bone Pain 49 (3%) Muscle Spasm 46 (3%) Nervous System Disorders Headache 162 (10%) Paraesthesia 29 (2%) Skin & Subcutaneous Tissue Disorders Rash 70 (4%) Nail Disorders 43 (2%) Pruritis 40 (2%) General Disorders Pyrexia 100 (6%) Edema Peripheral 79 (5%) Chills 85 (5%) Aesthenia 75 (4.5%) Influenza-like Illness 40 (2%) Sudden Death 1 (0.06%) Infections Nasopharyngitis 135 (8%) UTI 39 (3%) Immune System Disorders Hypersensitivity 10 (0.6%) Autoimmune Thyroiditis 4 (0.3%) a

35 (2%) 29 (2%) 11 (0.6%) 12 (0.7%) 17 (1%) 5 (0.3%) 4 (0.2%) 0 (0%) 0 (0%) 34 (2%) 9 (0.5%) 26 (2%) 20 (1%) 6 (0.4%) 8 (0.5%) 5 (0.3%) 1 (0.06%) 0 (0%) 0 (0%) 16 (1%) 19 (1%) 10 (0.6%) 17 (1%) 9 (0.5%) 15 (1%) 98 (6%) 58 (3%) 17 (1%) 26 (2%) 3 (0.2%) 49 (3%) 11 (0.6%) 10 (0.6%) 0 (0%) 10 (0.6%) 6 (0.4%) 37 (2%) 0 (0%) 30 (2%) 3 (0.2%) 0 (0%) 43 (3%) 13 (0.8%) 1 (0.06%) 0 (0%)

The incidence of Grade 3/4 adverse reactions was <1% in both arms for each listed term.

Higher level grouping term.

The data from Studies 1 and 2 were obtained from 3206 patients, of whom 1635 received Herceptin; the median treatment duration was 50 weeks. The median age was 49 years (range: 24−80); 84% of patients were White, 7% Black, 4% Hispanic, and 4% Asian. In Study 1, only Grade 3−5 adverse events, treatment-related Grade 2 events, and Grade 2−5 dyspnea were collected during and for up to 3 months following protocol-specified treatment. The following non-cardiac adverse reactions of Grade 2−5 occurred at an incidence of at least 2% greater among patients randomized to Herceptin plus chemotherapy as compared to chemotherapy alone: arthralgia (31% vs. 28%), fatigue (28% vs. 22%), infection (22% vs. 14%), hot flashes (17% vs. 15%), anemia (13% vs.

7%), dyspnea (12% vs. 4%), rash/desquamation (11% vs. 7%), neutropenia (7% vs. 5%), headache (6% vs. 4%), and insomnia (3.7% vs. 1.5%). The majority of these events were Grade b

2 in severity. In Study 2, data collection was limited to the following investigator-attributed treatment-related adverse reactions: NCI-CTC Grade 4 and 5 hematologic toxicities, Grade 3−5 non-hematologic toxicities, selected Grade 2−5 toxicities associated with taxanes (myalgia, arthralgias, nail changes, motor neuropathy, sensory neuropathy) and Grade 1−5 cardiac toxicities occurring during chemotherapy and/ or Herceptin treatment. The following non-cardiac adverse reactions of Grade 2−5 occurred at an incidence of at least 2% greater among patients randomized to Herceptin plus chemotherapy as compared to chemotherapy alone: arthralgia (11% vs. 8.4%), myalgia (10% vs. 8%), nail changes (9% vs. 7%), and dyspnea (2.5% vs. 0.1%). The majority of these events were Grade 2 in severity. Safety data from Study 4 reflect exposure to Herceptin as part of an adjuvant treatment regimen from 2124 patients receiving at least one dose of study treatment [AC-TH: n = 1068; TCH: n = 1056]. The overall median treatment duration was 54 weeks in both the AC-TH and TCH arms. The median number of infusions was 26 in the AC-TH arm and 30 in the TCH arm, including weekly infusions during the chemotherapy phase and every three week dosing in the monotherapy period. Among these patients, the median age was 49 years (range 22 to 74 years). In Study 4, the toxicity profile was similar to that reported in Studies 1, 2, and 3 with the exception of a low incidence of CHF in the TCH arm.

Metastatic Breast Cancer Studies The data below reflect exposure to Herceptin in one randomized, open-label study, Study 5, of chemotherapy with (n=235) or without (n=234) trastuzumab in patients with metastatic breast cancer, and one single-arm study (Study 6; n=222) in patients with metastatic breast cancer. Data in Table 4 are based on Studies 5 and 6.

Among the 464 patients treated in Study 5, the median age was 52 years (range: 25−77 years). Eighty-nine percent were White, 5% Black, 1% Asian and 5% other racial/ethnic groups.

All patients received 4 mg/kg initial dose of Herceptin followed by 2 mg/kg weekly. The percentages of patients who received Herceptin treatment for * 6 months and * 12 months were 58% and 9%, respectively. Among the 352 patients treated in single agent studies (213 patients from Study 6), the median age was 50 years (range 28−86 years), 86% were White, 3% were Black, 3% were Asian, and 8% in other racial/ethnic groups. Most of the patients received 4 mg/kg initial dose of Herceptin followed by 2 mg/kg weekly. The percentages of patients who received Herceptin treatment for * 6 months and * 12 months were 31% and 16%, respectively.

Table 4 Per-Patient Incidence of Adverse Reactions Occurring in * 5% of Patients in Uncontrolled Studies or at Increased Incidence in the Herceptin Arm (Studies 5 and 6)

M ( d

In

d

B

Inflamm

Herceptin Single + Paclitaxel Herceptin ACb a Agent Paclitaxel Alone + ACb Alone n = 352 n = 91 n = 95 n = 143 n = 135 Body as a Whole Pain 47% 61% 62% 57% 42% Asthenia 42% 62% 57% 54% 55% Fever 36% 49% 23% 56% 34% Chills 32% 41% 4% 35% 11% Headache 26% 36% 28% 44% 31% Abdominal pain 22% 34% 22% 23% 18% Back pain 22% 34% 30% 27% 15% Infection 20% 47% 27% 47% 31% Flu syndrome 10% 12% 5% 12% 6% Accidental injury 6% 13% 3% 9% 4% Allergic reaction 3% 8% 2% 4% 2% Cardiovascular Tachycardia 5% 12% 4% 10% 5% Congestive 7% 11% 1% 28% 7% heart failure Digestive Nausea 33% 51% 9% 76% 77% Diarrhea 25% 45% 29% 45% 26% Vomiting 23% 37% 28% 53% 49% Nausea and vomiting 8% 14% 11% 18% 9% Anorexia 14% 24% 16% 31% 26% Heme & Lymphatic Anemia 4% 14% 9% 36% 26% Leukopenia 3% 24% 17% 52% 34% Metabolic Peripheral edema 10% 22% 20% 20% 17% Edema 8% 10% 8% 11% 5% Musculoskeletal Bone pain 7% 24% 18% 7% 7% Arthralgia 6% 37% 21% 8% 9% Nervous Insomnia 14% 25% 13% 29% 15% Dizziness 13% 22% 24% 24% 18% Paresthesia 9% 48% 39% 17% 11% Depression 6% 12% 13% 20% 12% Peripheral neuritis 2% 23% 16% 2% 2% Neuropathy 1% 13% 5% 4% 4% Respiratory Cough increased 26% 41% 22% 43% 29% Dyspnea 22% 27% 26% 42% 25% Rhinitis 14% 22% 5% 22% 16% Pharyngitis 12% 22% 14% 30% 18% Sinusitis 9% 21% 7% 13% 6% Skin Rash 18% 38% 18% 27% 17% Herpes simplex 2% 12% 3% 7% 9% Acne 2% 11% 3% 3% < 1% Urogenital Urinary tract infection 5% 18% 14% 13% 7% a Data for Herceptin single agent were from 4 studies, including 213 patients from Study 6. b Anthracycline (doxorubicin or epirubicin) and cyclophosphamide.

Tract Inf R

Impairm N

P

For Studie o

TON_December 2010_FINAL_v2_TON 12/8/10 11:48 AM Page 3

Metastatic Gastric Cancer The data below are based on the exposure of 294 patients to Herceptin in combination with a fluoropyrimidine (capecitabine or 5-FU) and cisplatin (Study 7). In the Herceptin plus chemotherapy arm, the initial dose of Herceptin 8 mg/kg was administered on Day 1 (prior to chemotherapy) followed by 6 mg/kg every 21 days until disease progression. Cisplatin was administered at 80 mg/m2 on Day 1 and the fluoropyrimidine was administered as either capecitabine 1000 mg/m2 orally twice a day on Days 1-14 or 5-fluorouracil 800 mg/m2/day as a continuous intravenous infusion Days 1 through 5. Chemotherapy was administered for six 21-day cycles. Median duration of Herceptin treatment was 21 weeks; median number of Herceptin infusions administered was eight.

b

c

Studies 1 and 2 regimens: doxorubicin and cyclophosphamide followed by paclitaxel (ACAT) or paclitaxel plus Herceptin (ACATH).

Study 4 regimens: doxorubicin and cyclophosphamide followed by docetaxel (ACAT) or docetaxel plus Herceptin (ACATH); docetaxel and carboplatin plus Herceptin (TCH).

Figure 1 Studies 1 and 2: Cumulative Incidence of Time to First LVEF Decline of *10 Percentage Points from Baseline and to Below 50% with Death as a Competing Risk Event

Table 5 Study 7: Per Patient Incidence of Adverse Reactions of All Grades (Incidence * 5% between Arms) or Grade 3 /4 (Incidence >1% between Arms) and Higher Incidence in Herceptin Arm Herceptin +FC (N = 294) N (%) Body System/ Adverse Event Investigations Neutropenia Hypokalemia Anemia Thrombocytopenia Blood And Lymphatic System Disorders Febrile Neutropenia Gastrointestinal Disorders Diarrhea Stomatitis Dysphagia Body as a Whole Fatigue Fever Mucosal Inflammation Chills Metabolism And Nutrition Disorders Weight Decrease Infections And Infestations Upper Respiratory Tract Infections Nasopharyngitis Renal And Urinary Disorders Renal Failure and Impairment Nervous System Disorders Dysgeusia

centages of

tin

ACb

3 n = 135

18%

4% 2%

9%

Grades 3/4

All Grades Grades 3/ 4

230 (78) 83 (28) 81 (28) 47 (16)

101 (34) 28 (10) 36 (12) 14 (5)

212 (73) 83 (29) 69 (24) 16 (6) 61 (21) 30 (10) 33 (11) 8 (3)

_

15 (5)

_

8 (3)

109 (37) 72 (24) 19 (6)

27 (9) 2 (1) 7 (2)

80 (28) 43 (15) 10 ( 3)

11 (4) 6 (2) 1 ()1)

Time 0 is the date of randomization.

102 (35) 54 (18)

12 (4) 3 (1)

82 (28) 36 (12)

7 (2) 0 (0)

Figure 3 Study 4: Cumulative Incidence of Time to First LVEF Decline of * 10 Percentage Points from Baseline and to Below 50% with Death as a Competing Risk Event

37 (13) 23 (8)

6 (2) 1 ()1)

18 (6) 0 (0)

2 (1) 0 (0)

69 (23)

6 (2)

40 (14)

7 (2)

56 (19) 37 (13)

0 (0) 0 (0)

29 (10) 17 (6)

0 (0) 0 (0)

53 (18)

8 (3)

42 (15)

5 (2)

28 (10)

0 (0)

14 (5)

0 (0)

LVEF *10% *16% <50% decrease decrease

2%

29%

9%

7% 4 studies, a

and

Figure 2 Study 3: Cumulative Incidence of Time to First LVEF Decline of * 10 Percentage Points from Baseline and to Below 50% with Death as a Competing Risk Event

Time 0 is the date of randomization.

LVEF <50% and Absolute Decrease from Baseline

Studies 1 & 2b ACATH 22.8% (366) (n=1606)

Time 0 is initiation of paclitaxel or Herceptin + paclitaxel therapy.

All Grades

The following subsections provide additional detail regarding adverse reactions observed in clinical trials of adjuvant breast, metastatic breast cancer, metastatic gastric cancer, or postmarketing experience. Cardiomyopathy Serial measurement of cardiac function (LVEF) was obtained in clinical trials in the adjuvant treatment of breast cancer. In Study 3, the median duration of follow-up was 12.6 months (12.4 months in the observation arm; 12.6 months in the 1-year Herceptin arm); and in Studies 1 and 2, 23 months in the AC-T arm, 24 months in the AC-TH arm. In Studies 1 and 2, 6% of patients were not permitted to initiate Herceptin following completion of AC chemotherapy due to cardiac dysfunction (LVEF < 50% or * 15 point decline in LVEF from baseline to end of AC).

Following initiation of Herceptin therapy, the incidence of new-onset dose-limiting myocardial dysfunction was higher among patients receiving Herceptin and paclitaxel as compared to those receiving paclitaxel alone in Studies 1 and 2, and in patients receiving Herceptin monotherapy compared to observation in Study 3 (see Table 6, Figures 1 and 2).

Table 6a Per-patient Incidence of New Onset Myocardial Dysfunction (by LVEF) Studies 1, 2, 3 and 4

17%

icin)

FC (N = 290) N (%)

Absolute LVEF Decrease <20% and *10% *20%

18.3% (294)

11.7% (188)

33.4% (536)

9.2% (148)

ACAT (n=1488)

9.1% (136)

5.4% (81)

2.2% (33)

18.3% (272)

2.4% (36)

Study 3 Herceptin (n=1678)

8.6% (144)

7.0% (118)

3.8% (64)

22.4% (376)

3.5% (59)

Observation (n=1708)

2.7% (46)

2.0% (35)

1.2% (20)

11.9% (204)

1.2% (21)

Study 4c TCH (n=1056)

8.5% (90)

5.9% (62)

3.3% (35)

34.5% (364)

6.3% (67)

ACATH (n=1068)

17% (182)

13.3% (142)

9.8% (105)

44.3% (473)

13.2% (141)

ACAT (n=1050)

9.5% (100)

6.6% (69)

3.3% (35)

34% (357)

5.5% (58)

For Studies 1, 2 and 3, events are counted from the beginning of Herceptin treatment. For Study 4, events are counted from the date of randomization.

The incidence of treatment emergent congestive heart failure among patients in the metastatic breast cancer trials was classified for severity using the New York Heart Association classification system (I−IV, where IV is the most severe level of cardiac failure) (see Table 2). In the metastatic breast cancer trials the probability of cardiac dysfunction was highest in patients who received Herceptin concurrently with anthracyclines. In Study 7, 5.0% of patients in the Herceptin plus chemotherapy arm compared to 1.1% of patients in the chemotherapy alone arm had LVEF value below 50% with a * 10% absolute decrease in LVEF from pretreatment values.

Infusion Reactions During the first infusion with Herceptin, the symptoms most commonly reported were chills and fever, occurring in approximately 40% of patients in clinical trials. Symptoms were treated with acetaminophen, diphenhydramine, and meperidine (with or without reduction in the rate of Herceptin infusion); permanent discontinuation of Herceptin for infusional toxicity was required in <1% of patients. Other signs and/or symptoms may include nausea, vomiting, pain (in some cases at tumor sites), rigors, headache, dizziness, dyspnea, hypotension, elevated blood pressure, rash, and asthenia. Infusional toxicity occurred in 21% and 35% of patients, and was severe in 1.4% and 9% of patients, on second or subsequent Herceptin infusions administered as monotherapy or in combination with chemotherapy, respectively. In the post-marketing setting, severe infusion reactions, including hypersensitivity, anaphylaxis, and angioedema have been reported. Anemia In randomized controlled clinical trials, the overall incidence of anemia (30% vs. 21% [Study 5]), of selected NCI-CTC Grade 2-5 anemia (12.5% vs. 6.6% [Study 1]), and of anemia requiring transfusions (0.1% vs. 0 patients [Study 2]) were increased in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. Following the administration of Herceptin as a single agent (Study 6), the incidence of NCI-CTC Grade 3 anemia was < 1%. In Study 7 (metastatic gastric cancer) on the Herceptin containing arm as compared to the chemotherapy alone arm the overall incidence of anemia was 28% compared 21% and of NCI CTC Grade 3/4 anemia was 12.2% compared to 10.3%. Neutropenia In randomized controlled clinical trials in the adjuvant setting, the incidence of selected NCI-CTC Grade 4−5 neutropenia (2% vs. 0.7% [Study 2]) and of selected Grade 2−5 neutropenia (7.1% vs. 4.5% [Study 1]) were increased in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. In a randomized, controlled trial in patients with metastatic breast cancer, the incidences of NCI-CTC Grade 3/4 neutropenia (32% vs. 22%) and of febrile neutropenia (23% vs. 17%) were also increased in patients randomized to Herceptin in combination with myelosuppressive chemotherapy as compared to chemotherapy alone. In Study 7 (metastatic gastric cancer) on the Herceptin containing arm as compared to the chemotherapy alone arm, the incidence of NCI CTC Grade 3/4 neutropenia was 36.8% compared to 28.9%; febrile neutropenia 5.1% compared to 2.8%. Infection The overall incidences of infection (46% vs. 30% [Study 5]), of selected NCI-CTC Grade 2−5 infection/febrile neutropenia

(22% vs. 14% [Study 1]) and of selected Grade 3−5 infection/ febrile neutropenia (3.3% vs. 1.4%) [Study 2]), were higher in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. The most common site of infections in the adjuvant setting involved the upper respiratory tract, skin, and urinary tract. In Study 4, the overall incidence of infection was higher with the addition of Herceptin to AC-T but not to TCH [44% (AC-TH), 37% (TCH), 38% (AC-T)]. The incidences of NCI-CTC Grade 3−4 infection were similar [25% (AC-TH), 21% (TCH), 23% (AC-T)] across the three arms. In a randomized, controlled trial in treatment of metastatic breast cancer, the reported incidence of febrile neutropenia was higher (23% vs. 17%) in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to chemotherapy alone. Pulmonary Toxicity Adjuvant Breast Cancer Among women receiving adjuvant therapy for breast cancer, the incidence of selected NCI-CTC Grade 2−5 pulmonary toxicity (14% vs. 5% [Study 1]) and of selected NCI-CTC Grade 3−5 pulmonary toxicity and spontaneous reported Grade 2 dyspnea (3.4% vs. 1% [Study 2]) was higher in patients receiving Herceptin and chemotherapy compared with chemotherapy alone. The most common pulmonary toxicity was dyspnea (NCI-CTC Grade 2−5: 12% vs.

4% [Study 1]; NCI-CTC Grade 2−5: 2.5% vs. 0.1% [Study 2]).

Pneumonitis/pulmonary infiltrates occurred in 0.7% of patients receiving Herceptin compared with 0.3% of those receiving chemotherapy alone. Fatal respiratory failure occurred in 3 patients receiving Herceptin, one as a component of multiorgan system failure, as compared to 1 patient receiving chemotherapy alone. In Study 3, there were 4 cases of interstitial pneumonitis in Herceptin-treated patients compared to none in the control arm. Metastatic Breast Cancer Among women receiving Herceptin for treatment of metastatic breast cancer, the incidence of pulmonary toxicity was also increased. Pulmonary adverse events have been reported in the post-marketing experience as part of the symptom complex of infusion reactions. Pulmonary events include bronchospasm, hypoxia, dyspnea, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, and acute respiratory distress syndrome. For a detailed description, see Warnings and Precautions.

Thrombosis/Embolism In 4 randomized, controlled clinical trials, the incidence of thrombotic adverse events was higher in patients receiving Herceptin and chemotherapy compared to chemotherapy alone in three studies (3.0% vs. 1.3% [Study 1], 2.5% and 3.7% vs. 2.2% [Study 4] and 2.1% vs. 0% [Study 5]).

Diarrhea Among women receiving adjuvant therapy for breast cancer, the incidence of NCI-CTC Grade 2−5 diarrhea (6.2% vs.

4.8% [Study 1]) and of NCI-CTC Grade 3−5 diarrhea (1.6% vs.

0% [Study 2]), and of Grade 1−4 diarrhea (7% vs. 1% [Study 3]) were higher in patients receiving Herceptin as compared to controls. In Study 4, the incidence of Grade 3−4 diarrhea was higher [5.7% AC-TH, 5.5% TCH vs. 3.0% AC-T] and of Grade 1−4 was higher [51% AC-TH, 63% TCH vs. 43% AC-T] among women receiving Herceptin. Of patients receiving Herceptin as a single agent for the treatment of metastatic breast cancer, 25% experienced diarrhea. An increased incidence of diarrhea was observed in patients receiving Herceptin in combination with chemotherapy for treatment of metastatic breast cancer. Renal Toxicity In Study 7 (metastatic gastric cancer) on the Herceptin-containing arm as compared to the chemotherapy alone arm the incidence of renal impairment was 18% compared to 14.5%. Severe (Grade 3/4) renal failure was 2.7% on the Herceptin-containing arm compared to 1.7% on the chemotherapy only arm. Treatment discontinuation for renal insufficiency/failure was 2% on the Herceptin-containing arm and 0.3% on the chemotherapy only arm. In the postmarketing setting, rare cases of nephrotic syndrome with pathologic evidence of glomerulopathy have been reported.

The time to onset ranged from 4 months to approximately 18 months from initiation of Herceptin therapy. Pathologic findings included membranous glomerulonephritis, focal glomerulosclerosis, and fibrillary glomerulonephritis.

Complications included volume overload and congestive heart failure. Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. Among 903 women with metastatic breast cancer, human anti-human antibody (HAHA) to Herceptin was detected in one patient using an enzymelinked immunosorbent assay (ELISA). This patient did not experience an allergic reaction. Samples for assessment of HAHA were not collected in studies of adjuvant breast cancer.

The incidence of antibody formation is highly dependent on the sensitivity and the specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Herceptin with the incidence of antibodies to other products may be misleading. Post-Marketing Experience The following adverse reactions have been identified during post approval use of Herceptin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. • Infusion reaction [see Warnings and Precautions] • Oligohydramnios or oligohydramnios sequence, including pulmonary hypoplasia, skeletal abnormalities, and neonatal death [see Warnings and Precautions] • Glomerulopathy [see Adverse Reactions] DRUG INTERACTIONS In Study 5, the mean serum trough concentration of trastuzumab was consistently elevated approximately 1.5-fold, when administered in combination with paclitaxel as compared to trough concentrations of trastuzumab when administered in combination with an anthracycline and cyclophosphamide.

In other pharmacokinetic studies, where Herceptin was administered in combination with paclitaxel, docetaxel or doxorubicin, Herceptin did not alter the plasma concentrations of these chemotherapeutic agents, or the metabolites that were analyzed. In a drug interaction substudy conducted in patients in Study 7, the pharmacokinetics of cisplatin,

capecitabine and their metabolites were not altered when administered in combination with Herceptin. USE IN SPECIFIC POPULATIONS Pregnancy: Category D [see Warnings and Precautions, Nonclinical Toxicology] Herceptin can cause fetal harm when administered to a pregnant woman. In postmarketing reports use of Herceptin during pregnancy resulted in cases of oligohydramnios and of oligohydramnios sequence, manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. These case reports described oligohydramnios in pregnant women who received Herceptin either alone or in combination with chemotherapy. In some case reports, amniotic fluid index increased after Herceptin was stopped. In one case, Herceptin therapy resumed after the amniotic fluid index improved, and oligohydramnios recurred. Monitor women exposed to Herceptin during pregnancy for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care.

The efficacy of IV hydration in management of oligohydramnios due to Herceptin exposure is not known. Advise women of the potential hazard to the fetus resulting from Herceptin exposure during pregnancy. Encourage pregnant women with breast cancer who are using Herceptin to enroll in MotHER-the Herceptin Pregnancy Registry: phone 1-800-690-6720. [see Patient Counseling Information]. No teratogenic effects were observed in offspring from reproduction studies in cynomolgus monkeys at doses up to 25 times the recommended weekly human dose of 2 mg/kg trastuzumab. In mutant mice lacking HER2, embryos died in early gestation. Trastuzumab exposure was reported at delivery in offspring of cynomolgus monkeys treated during the early (Days 20-50 of gestation) or late (Days 120-150 of gestation) fetal development periods, at levels of 15 to 28% of the maternal blood levels. Nursing Mothers It is not known whether Herceptin is excreted in human milk, but human IgG is excreted in human milk. Published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Trastuzumab was present in the breast milk of lactating cynomolgus monkeys given 12.5 times the recommended weekly human dose of 2 mg/kg of Herceptin. Infant monkeys with detectable serum levels of trastuzumab did not have any adverse effects on growth or development from birth to 3 months of age; however, trastuzumab levels in animal breast milk may not accurately reflect human breast milk levels. Because many drugs are secreted in human milk and because of the potential for serious adverse reactions in nursing infants from Herceptin, a decision should be made whether to discontinue nursing, or discontinue drug, taking into account the elimination half-life of trastuzumab and the importance of the drug to the mother.

Pediatric Use The safety and effectiveness of Herceptin in pediatric patients has not been established. Geriatric Use Herceptin has been administered to 386 patients who were 65 years of age or over (253 in the adjuvant treatment and 133 in metastatic breast cancer treatment settings). The risk of cardiac dysfunction was increased in geriatric patients as compared to younger patients in both those receiving treatment for metastatic disease in Studies 5 and 6, or adjuvant therapy in Studies 1 and 2. Limitations in data collection and differences in study design of the 4 studies of Herceptin in adjuvant treatment of breast cancer preclude a determination of whether the toxicity profile of Herceptin in older patients is different from younger patients. The reported clinical experience is not adequate to determine whether the efficacy improvements (ORR, TTP, OS, DFS) of Herceptin treatment in older patients is different from that observed in patients <65 years of age for metastatic disease and adjuvant treatment. In Study 7 (metastatic gastric cancer), of the 294 patients treated with Herceptin 108 (37%) were 65 years of age or older, while 13 (4.4%) were 75 and over. No overall differences in safety or effectiveness were observed.

OVERDOSAGE There is no experience with overdosage in human clinical trials. Single doses higher than 8 mg/kg have not been tested. PATIENT COUNSELING INFORMATION • Advise patients to contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness [see Boxed Warning Cardiomyopathy]. • Advise pregnant women and women of childbearing potential that Herceptin exposure can result in fetal harm [see Warnings and Precautions and Use in Specific Populations]. • Advise women of childbearing potential to use effective contraceptive methods during treatment and for a minimum of six months following Herceptin [see Warnings and Precautions]. • Advise nursing mothers treated with Herceptin to discontinue nursing or discontinue Herceptin, taking into account the importance of the drug to the mother [see Use in Specific Populations]. • Encourage women who are exposed to Herceptin during pregnancy to enroll in MotHER- the Herceptin Pregnancy Registry (1-800-690-6720) [see Warnings and Precautions and Use in Specific Populations].

HERCEPTIN® [trastuzumab] Manufactured by: Genentech, Inc. A Member of the Roche Group 1 DNA Way South San Francisco, CA 94080-4990 Initial US Approval: September 1998 Revision Date: October 29, 2010 Herceptin® is a registered trademark of Genentech, Inc. HER0000111000 © 2010 Genentech, Inc.

TON_December 2010_FINAL_v2_TON 12/8/10 11:48 AM Page 4

Editorial Board EDITOR-IN-CHIEF

Sharon S. Gentry,

Kena C. Miller,

Rita Wickham,

Beth Faiman,

RN, MSN, AOCN

RN, MSN, FNP

OCN, PhD, RN

RN, MSN, APRN, BC, AOCN

Derrick L. Davis Forsyth Regional Cancer Center Winston-Salem, NC

Roswell Park Cancer Institute Buffalo, NY

Rush University College of Nursing Rush-PresbyterianSt. Luke’s Medical Center Chicago, IL

Cassandra J. Hammond, RN,

Patricia Molinelli,

Karla Wilson, RN,

Cleveland Clinic Taussig Cancer Institute Cleveland, OH

Elizabeth Bilotti, RN, MSN, APRN, BC, OCN

MS, RN, APN-C, AOCNS

MSN, FNP-C, CPON

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Avid Education Partners, LLC Sharpsburg, MD

Somerset Medical Center Somerville, NJ

City of Hope National Medical Center Duarte, CA

Catherine S. Bishop, DNP, NP,

Shannon Hazen,

Dolores “Jeff” Nordquist, RN, MS,

Pharmacy John F. Aforismo,

AOCNP

Novant Health Presbyterian Cancer Center Charlotte, NC

CS, FNP

BSc Pharm, RPh, FASCP

Deena Damsky Dell, RN, MSN,

Patricia Irouer Hughes, RN, MSN,

Melinda Oberleitner, RN,

Nutrition Karen Connelly,

Vienna, VA

MSN, CRNP

RN, BSN, OCN

Mayo Clinic Rochester, MN

R. J. Health Systems International, LLC Wethersfield, CT

AOCN, BC

BSN, OCN

DNS, APRN, CNS

RD, CSO

Fox Chase Cancer Center Philadelphia, PA

Piedmount Healthcare Rex, GA

College of Nursing and Allied Health Professions University of Louisiana Lafayette, LA

Somerset Medical Center Somerville, NJ

Wendy DiSalvo,

Taline Khoukaz,

Gary Shelton,

DNP, APRN, AOCN

NP, MSN, ACNP-C

Genentech New London, NH

University of Southern California Norris Cancer Center & Hospital Los Angeles, CA

MSN, ARNP, AOCN

Patient Advocate Peg Ford

Denice Economou, RN,

Sandra E. Kurtin,

Lori Stover, RN,

RN, MS, AOCN, ANP-C

BSN

MN, CNS, AOCN City of Hope National Medical Center Duarte, CA

Arizona Cancer Center Tucson, AZ

Constance Engelking, RN,

Elizabeth Lima,

MS, CNS, OCN

Cleveland Clinic Taussig Cancer Institute Cleveland, OH

The CHE Consulting Group, Inc. Mt. Kisco, NY

PA-C

Coronado, CA

NYU Cancer Institute New York, NY

Social Work Carolyn Messner,

Western Pennsylvania Cancer Institute Pittsburgh, PA

DSW, MSW, LCSW-R, BCD

Pamela Hallquist Viale, RN, MS,

Managed Care and Pharmaceutical Management Burt Zweigenhaft,

CS, ANP, AOCN Saratoga, CA

CancerCare New York, NY

BS BioPharma Partners LLC New York, NY

Amy Ford, RN,

Ann McNeill,

Connie Visovsky,

Isabell Castellano, RN

BSN, OCN

MSN, RN, NP-C, OCN

RN, PhD, APRN

Bristol-Myers Squibb Children’s Hospital Robert Wood Johnson University Hospital New Brunswick, NJ

Innovex Dallas, TX

The Cancer Center at Hackensack University Medical Center Hackensack, NJ

University of Nebraska College of Nursing Omaha, NE

Jeanne Westphal, RN Meeker County Memorial Hospital Litchfield, MN

4

December 2010 I VOL 3, NO 8

www.TheOncologyNurse.com

TON_December 2010_FINAL_TON 12/6/10 11:19 AM Page 5

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TON_December 2010_FINAL_v2_TON 12/8/10 11:47 AM Page 6

FROM THE EDITOR PUBLISHING STAFF Publisher Philip Pawelko phil@greenhillhc.com

T

wo new reports call for changes in education to ensure that healthcare professionals have the competencies necessary to work in an increasingly complex healthcare system. Since oncology is one of the most complex and rapidly advancing areas of medicine, their recommendations have implications for oncology nurses Beth Faiman, RN, and our colleagues.

In a report by the Lancet ComMSN, APRN, mission (Frenk J, et al. Lancet. Nov BC, AOCN 26, 2010. Epub ahead of print), the Editor-in-Chief authors propose a number of instructional and institutional reforms, including “team-based education to break down professional silos.”

A report by the Institute of Medicine specifically addresses nursing education and practice (The Future of Nursing: Leading Change, Advancing Health; 2010). “Nurses’ roles, responsibilities, and education should change significantly

Editorial Director Karen Rosenberg karen@greenhillhc.com Associate Editor Dawn Lagrosa dawn@greenhillhc.com Director, Client Services John W. Hennessy john@greenhillhc.com Production Manager Stephanie Laudien Business Manager Blanche Marchitto blanche@greenhillhc.com Executive Administrator Andrea Boylston Circulation Department circulation@greenhillhc.com Editorial Contact: Telephone: 732-992-1891 Fax: 732-656-7938

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Readers are encouraged to contact the manufacturer with questions about the features or limitations of the products mentioned. Neither the Editorial Board nor the Publisher assumes any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this periodical. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosage, the method and duration of administration, or contraindications. It is the responsibility of the treating physician or other healthcare professional, relying on independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Every effort has been made to check generic and trade names, and to verify dosages. The ultimate responsibility, however, lies with the prescribing physician.

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6

December 2010 I VOL 3, NO 8

to meet the increased demand for care that will be created by health care reform and to advance improvements in America’s increasingly complex health system,” the report states. Among the changes they recommend are removing scope of practice barriers and improving the education system to include the creation of a residency program. The report also calls for nursing associations, schools, and other organizations to “provide nurses greater opportunities to gain leadership skills and put them into practice.”

In many ways, oncology nurses are ahead of the curve on these issues and are already putting some of these ideas into practice. Many of us have advanced education and credentials; we work closely with our colleagues in multidisciplinary teams; and we play an active role in patient and nursing education throughout the continuum of cancer care. Oncology nurses are well positioned to take a leadership role in advancing the profession and ensuring that patients receive the highest-quality care.

The Oncology Nurse will continue to provide reports on the latest advances in nursing practice and cancer care to help our readers meet the challenges of practice in a changing healthcare environment. ●

CONFERENCE NEWS: ONS APN/IOL

8 Faces at the conference 9 Prophylactic minocycline keeps cetuximab-induced rash at bay 10 Collaborative program trains oncology specialist nurses 26 Telephone support increases adherence to IV chemotherapy for recurrent ovarian cancer 28 Survey shows gaps in oncology nurses’ knowledge about cardiotoxicity of cancer drugs

December 2010 • VOL 3, NO 8 45 PARP inhibitor improves survival in triple-negative breast cancer

DEPARTMENTS

24 36 46 49

International News Oncology Drug Codes Nursing Life Meetings

Journal of Oncology

CANCER COMPLICATIONS

16 Prompt pain relief for vertebral compression fractures with balloon kyphoplasty

NAVIGATION & SURVIVORSHIP

™

The Official Journal of the Academy of Oncology Nurse Navigators ®

Between pages 34 and 35 CARE COORDINATION

LUNG CANCER

20 Stereotactic radiation may be as effective as surgery for some non–small-cell lung cancers

25 Fast neutron radiotherapy may be safe and effective for lung cancer patients 32 Low-dose CT screening found to reduce lung cancer deaths in large study

CONTINUING EDUCATION

30 Maintenance therapy in patients with advanced non–small-cell lung cancer

BREAST CANCER

44 Prolonging chemotherapy in metastatic breast cancer improves survival

44 Tamoxifen may confer a limited benefit in older women with early-stage breast cancer

1 City-wide patient navigation network coordinates Washington, DC, cancer care

NAVIGATION TRAINING

1 Center provides platform for discussion of cancer survivorship, navigation, and policy

PSYCHOSOCIAL ISSUES

3 Most oncology nurses unfamiliar with IOM report on caring for the whole patient

4 Integrative psychooncology services: how the Cleveland Clinic did it

BREAST CANCER

2 Patient navigation improves mammography rates in the inner city

SURVIVORSHIP

4 Survivors often dissatisfied with breast-conserving treatment results www.TheOncologyNurse.com

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Conference News

Faces at the Conference ONCOLOGY NURSING SOCIETY’S 11TH ANNUAL ADVANCED PRACTICE NURSING CONFERENCE/INSTITUTES OF LEARNING

Orlando, Florida, November 11-14, 2010.

Congratulations to Tanya Laudick of Greeley, Colorado, winner of our iPad giveaway.

Millie Toth celebrates breast cancer awareness with pink gloves.

Bobbie Piccolo checks out a contemporary infusion chair.

Michelle Blanca and Sylvia Robertson point out what they are learning.

Judy Sigmon catches up on the latest in mastectomy bras and prostheses.

Karen Stephenson stops by to chat with The Oncology Nurse-APN/PA Editor-in-Chief Beth Faiman.

Magda Ostos-Germain and Ali Khan pose for our camera.

Maureen Berry, Michael Rehbein, and Pamela Grant-Navarro take time out for coffee.

Ami Rowe tests state-of-the-art technology.

Photos by Mark Losh • For more photos go to www.TheOncologyNurse.com 8

December 2010 I VOL 3, NO 8

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Conference News ONS APN/IOL

Prophylactic Minocycline Keeps Cetuximab-induced Rash at Bay

By Fran Lowry

ORLANDO—Breakthrough pain in cancer patients can be managed easily and effectively with fentanyl pectin nasal spray, according to new data.

Minocycline, given before the start of treatment with cetuximab and chemoradiotherapy, plus topical pimecrolimus as needed, can reduce the severity of cetuximab-induced skin toxicity in patients with non–small-cell lung cancer (NSCLC), according to researchers from The Netherlands.

Cetuximab, a chimeric monoclonal antibody that binds to the extracellular domain of the epidermal growth

patients received cetuximab once weekly for 6 weeks along with daily cisplatin and radiotherapy. The 12 patients in group 1 were treated on demand after the appearance of an

acneiform rash. The 14 patients in group 2 received prophylactic oral minocycline, 100 mg/day for 45 days, and, if necessary, topical pimecrolimus, 1%, twice daily.

Toxicity was scored according to the Common Toxicity Criteria for Adverse Events, version 3.0.

In the first group, 11 of 12 patients Continued on page 10

Help reduce the risk of infection in patients receiving moderate-risk* chemotherapy regimens

Act before febrile neutropenia strikes Potential consequences of febrile neutropenia may be serious and can impact patient care First- and every-cycle Neulasta® achieved: ■ 94% reduction in febrile neutropenia (17% placebo vs 1% Neulasta®; P < 0.001).1,2 ■ 93% reduction in febrile neutropenia– related hospitalization (14% placebo vs 1% Neulasta®; P < 0.001).1,2

“If we give minocycline prophylactically and do not wait for the rash to appear, we manage to reduce the skin toxicity to a maximum of grade 2.”

—Wilma Uyterlinde, MANP

■ 80% reduction in febrile neutropenia– related IV anti-infective use (10% placebo vs 2% Neulasta®; P < 0.001).1,2 Neulasta® (pegfilgrastim) is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Neulasta® is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Important Safety Information factor receptor, has shown activity in patients with metastatic colorectal cancer, in addition to patients with NSCLC, but its potential for severe skin toxicity may cause some patients to abandon their treatment, said Wilma Uyterlinde, MANP, a nurse practitioner at the Netherlands Cancer Institute in Amsterdam.

In 2008, oncologists at the institute began to test the feasibility of combining cetuximab with concurrent chemoradiation in their patients with locally advanced NSCLC. “We added cetuximab to our treatment because of the promising effects it was shown to have in colorectal cancer patients, and when we did so, we saw a lot of grade 3 skin toxicity, so we conferred with a dermatologist and an oncologist and we came up with a new protocol to see if we could reduce it,” said Uyterlinde, who specializes in thoracic oncology.

To test their protocol, the researchers divided patients into two groups. All

Do not administer Neulasta® to patients with a history of serious allergic reactions to pegfilgrastim or filgrastim.

Splenic rupture, including fatal cases, can occur following the administration of Neulasta®. Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving Neulasta®.

Acute respiratory distress syndrome (ARDS) can occur in patients receiving Neulasta®. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving Neulasta® for ARDS. Discontinue Neulasta® in patients with ARDS. Serious allergic reactions, including anaphylaxis, can occur in patients receiving Neulasta®. The majority of reported events occurred upon initial exposure. Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue Neulasta® in patients with serious allergic reactions.

Severe sickle cell crises can occur in patients with sickle cell disorders receiving Neulasta®. Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim, the parent compound of pegfilgrastim.

The granulocyte colony-stimulating factor (G-CSF) receptor, through which pegfilgrastim and filgrastim act, has been found on tumor cell lines. The possibility that pegfilgrastim acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim is not approved, cannot be excluded.

Bone pain and pain in extremity occurred at a higher incidence in Neulasta®-treated patients as compared with placebo-treated patients.

Please see brief summary of Neulasta® Prescribing Information on the adjacent page. *Regimens associated with 17% risk of febrile neutropenia.

References: 1. Vogel C, et al. J Clin Oncol. 2005;23:1178-1184. 2. Neulasta® (pegfilgrastim) Prescribing Information. Thousand Oaks, Calif: Amgen. © 2010 Amgen. All rights reserved.

MC49047-A-1

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Conference News Prophylactic Minocycline Keeps Cetuximab-induced... Continued from page 9 developed grade 2 or 3 acneiform rash, and one patient discontinued treatment because of the rash. In the second group, three of 14 patients developed grade 2 rash, and none of the patients developed grade 3 rash. This represents a significant difference between the groups (P = .001), Uyterlinde said.

BRIEF SUMMARY OF PRESCRIBING INFORMATION Neulasta® (pegfilgrastim) injection, for subcutaneous use INDICATIONS AND USAGE Neulasta is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Neulasta is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

CONTRAINDICATIONS Do not administer Neulasta to patients with a history of serious allergic reactions to pegfilgrastim or filgrastim.

WARNINGS AND PRECAUTIONS Splenic Rupture Splenic rupture, including fatal cases, can occur following the administration of Neulasta. Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving Neulasta.

Acute Respiratory Distress Syndrome Acute respiratory distress syndrome (ARDS) can occur in patients receiving Neulasta. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving Neulasta, for ARDS. Discontinue Neulasta in patients with ARDS. Serious Allergic Reactions Serious allergic reactions, including anaphylaxis, can occur in patients receiving Neulasta. The majority of reported events occurred upon initial exposure. Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue Neulasta in patients with serious allergic reactions. Do not administer Neulasta to patients with a history of serious allergic reactions to pegfilgrastim or filgrastim.

Use in Patients With Sickle Cell Disorders Severe sickle cell crises can occur in patients with sickle cell disorders receiving Neulasta. Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim, the parent compound of pegfilgrastim.

Potential for Tumor Growth Stimulatory Effects on Malignant Cells The granulocyte-colony stimulating factor (G-CSF) receptor through which pegfilgrastim and filgrastim act has been found on tumor cell lines. The possibility that pegfilgrastim acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim is not approved, cannot be excluded.

ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the Brief Summary: s 3PLENIC 2UPTURE ;3EE Warnings and Precautions] s !CUTE 2ESPIRATORY $ISTRESS 3YNDROME ;3EE Warnings and Precautions] s 3ERIOUS !LLERGIC 2EACTIONS ;3EE Warnings and Precautions] s 5SE IN 0ATIENTS WITH 3ICKLE #ELL $ISORDERS ;3EE Warnings and Precautions] s 0OTENTIAL FOR 4UMOR 'ROWTH 3TIMULATORY %FFECTS ON -ALIGNANT #ELLS ;3EE Warnings and Precautions] The most common adverse reactions occurring in r 5% of patients and with a between-group difference of r 5% higher in the pegfilgrastim arm in placebo controlled clinical trials are bone pain and pain in extremity.

Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Neulasta clinical trials safety data are based upon 932 patients receiving Neulasta in seven randomized clinical trials. The population was 21 to 88 years of age and 92% female. The ethnicity was 75% Caucasian, 18% Hispanic, 5% Black, and 1% Asian. Patients with breast (n = 823), lung and thoracic tumors (n = 53) and lymphoma (n = 56) received Neulasta after nonmyeloablative cytotoxic chemotherapy. Most patients received a single 100 mcg/kg (n = 259) or a single 6 mg (n = 546) dose per chemotherapy cycle over 4 cycles.

The following adverse reaction data in Table 1 are from a randomized, double-blind, placebo-controlled study in patients with metastatic or non-metastatic breast cancer

“In the cohort that did not get prophylactic treatment, we sometimes had to send patients to a specialized hospital for their skin toxicity because it was so bad, and we had to stop treatment with cetuximab because of the rash,” Uyterlinde noted. “If we give minocycline prophylactically and do not wait for the rash to receiving docetaxel 100 mg/m2 every 21 days. (Study 3).

A total of 928 patients were randomized to receive either 6 mg Neulasta (n = 467) or placebo (n = 461). The patients were 21 to 88 years of age and 99% female. The ethnicity was 66% Caucasian, 31% Hispanic, 2% Black, and <1% Asian, Native American or other.

Bone pain and pain in extremity occurred at a higher incidence in Neulasta-treated patients as compared with placebo-treated patients.

Table 1. Adverse Reactions With ≥ 5% Higher Incidence in Neulasta Patients Compared to Placebo in Study 3 System Organ Class Preferred Term

Placebo (N = 461)

Neulasta 6 mg SC on Day 2 (N = 467)

Musculoskeletal and connective tissue disorders Bone pain

26%

31%

Pain in extremity

4%

9%

Leukocytosis In clinical studies, leukocytosis (WBC counts > 100 x 109/L) was observed in less than 1% of 932 patients with nonmyeloid malignancies receiving Neulasta. No complications attributable to leukocytosis were reported in clinical studies.

Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. Binding antibodies to pegfilgrastim were detected using a BIAcore assay. The approximate limit of detection for this assay is 500 ng/mL. Pre-existing binding antibodies were detected in approximately 6% (51/849) of patients with metastatic breast cancer. Four of 521 pegfilgrastim-treated subjects who were negative at baseline developed binding antibodies to pegfilgrastim following treatment. None of these 4 patients had evidence of neutralizing antibodies detected using a cell-based bioassay.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, and the observed incidence of antibody positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Neulasta with the incidence of antibodies to other products may be misleading.

Postmarketing Experience The following adverse reactions have been identified during post approval use of Neulasta. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) reported frequency of the reaction, or (3) strength of causal relationship to Neulasta.

Gastro-intestinal disorders: 3PLENIC RUPTURE ;SEE Warnings and Precautions] Blood and lymphatic system disorder: Sickle cell crisis ;SEE Warnings and Precautions] Respiratory, thoracic, and mediastinal disorder: ARDS ;SEE Warnings and Precautions] General disorders and administration site conditions: Injection site reactions Skin and subcutaneous tissue disorders: Allergic reactions/ hypersensitivity, including anaphylaxis, skin rash, and urticaria, Sweet’s syndrome, generalized erythema and FLUSHING ;SEE Warnings and Precautions] DRUG INTERACTIONS No formal drug interaction studies between Neulasta and other drugs have been performed. Increased hematopoietic activity of the bone marrow in response to growth factor therapy may result in transiently positive bone-imaging changes. Consider these findings when interpreting boneimaging results.

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. Pegfilgrastim was embryotoxic and increased pregnancy loss in pregnant rabbits that received cumulative doses approximately 4 times the recommended human dose (based on body surface area). Signs of maternal toxicity occurred at these doses. Neulasta should be used during

appear, we manage to reduce the skin toxicity to a maximum of grade 2.”

She noted that controlling the acneiform rash did not compromise the effectiveness of cetuximab.

“It has not been proven that developing a rash means that cetuximab is working,” she said. “This is what they pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

In animal reproduction studies, when pregnant rabbits received pegfilgrastim at cumulative doses approximately 4 times the recommended human dose (based on body surface area), increased embryolethality and spontaneous abortions occurred. Signs of maternal toxicity (reductions in body weight gain/food consumption) and decreased fetal weights occurred at maternal doses approximately equivalent to the recommended human dose (based on body surface area). There were no structural anomalies observed in rabbit offspring at any dose tested. No evidence of reproductive/ developmental toxicity occurred in the offspring of pregnant rats that received cumulative doses of pegfilgrastim approximately 10 times the recommended human dose (based on body surface area).

Women who become pregnant during Neulasta treatment are encouraged to enroll in Amgen’s Pregnancy Surveillance Program.

Patients or their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll.

say, but it has never really been proven.

That is a hypothesis. Controlling the rash works by a different mechanism and does not prevent the cetuximab from working on the tumor.”

The protocol has now become the institute’s standard for use in patients with other types of cancer undergoing treatment with cetuximab, she said. ●

Collaborative Program Trains Oncology Specialist Nurses

By Karen Rosenberg

Nursing Mothers It is not known whether pegfilgrastim is secreted in human milk.

Other recombinant G-CSF products are poorly secreted in breast milk and G-CSF is not orally absorbed by neonates. Caution should be exercised when administered to a nursing woman.

ORLANDO—Despite the need for nurses with specialized oncology knowledge to care for the growing population of cancer patients and survivors, few graduate oncology nursing programs currently exist. A collaboration between The Ohio State University Comprehensive Cancer Center–The James Cancer Hospital (OSUCCC-James) and the university’s College of Nursing (CON) has been established to help fulfill the need for nurses with specialized oncology education.

The collaboration between the cancer center and the college, described in a poster presented by Deborah Hanes, RN, CNS, and her colleagues, has re sulted in a graduate oncology nursing program and an oncology clinical nurse specialist internship. The graduate nursing program will provide curriculum and clinical practicum sites by the CON and OSUCCC-James. The internship will train registered nurses with at least 3 years of experience as a registered nurse to become oncology clinical nurse specialists. Interns will be full-time employees of OSUCCC-James and will pursue part-time study following the CON curriculum; program participants will receive tuition reimbursement.

The framework for all educational experiences will be the cancer continuum, with emphasis on survivorship.

Both the graduate program and the internship are based on adult learning theory. Students’ success rates on the Advanced Oncology Clinical Nurse Specialist examination will be one measure of the program’s success.

The developers of the program anticipate that it will boost oncology recruitment and retention, and that patients will benefit from care based on graduate-level oncology nursing education. ●

Pediatric Use Safety and effectiveness of Neulasta in pediatric patients have not been established. The adverse reaction profile and pharmacokinetics of pegfilgrastim were studied in 37 pediatric patients with sarcoma. The mean (± standard DEVIATION ;3$= SYSTEMIC EXPOSURE !5#0-inf) of pegfilgrastim after subcutaneous administration at 100 mcg/kg was 22.0 (± 13.1) mcg·hr/mL in the 6 to 11 years age group (n = 10), 29.3 (± 23.2) mcg·hr/mL in the 12 to 21 years age group (n = 13), and 47.9 (± 22.5) mcg·hr/mL in the youngest age group (0 to 5 years, n = 11). The terminal elimination half-lives of the corresponding age groups were 20.2 (± 11.3) hours, 21.2 (± 16.0) hours, and 30.1 (± 38.2) hours, respectively.

The most common adverse reaction was bone pain.

Geriatric Use Of the 932 patients with cancer who received Neulasta in clinical studies, 139 (15%) were age 65 and over, and 18 (2%) were age 75 and over. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients.

Renal Impairment In a study of 30 subjects with varying degrees of renal dysfunction, including end stage renal disease, renal dysfunction had no effect on the pharmacokinetics of pegfilgrastim. Therefore, pegfilgrastim dose adjustment in patients with renal dysfunction is not necessary.

DOSAGE AND ADMINISTRATION The recommended dosage of Neulasta is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle in adults. Do not administer Neulasta between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer Neulasta if discoloration or particulates are observed.

NOTE: The needle cover on the single-use prefilled syringe contains dry natural rubber (latex); persons with latex allergies should not administer this product.

This product, its production, and/or its use may be covered by one or more US Patents, including US Patent Nos. 5,824,784; 5,582,823; 5,580,755, as well as other patents or patents pending.

Neulasta® (pegfilgrastim) Manufactured by: Amgen Inc. One Amgen Center Drive Thousand Oaks, California 91320-1799 © 2010 Amgen Inc. All rights reserved. www.neulasta.com 1-800-77-AMGEN (1-800-772-6436) v 11.0

Conference News continued on page 26

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“After my balloon kyphoplasty, I’m walking pain-free again.”

Tom Callaghan experienced debilitating pain due to spinal fractures caused by multiple myeloma. He underwent a minimally invasive procedure, Balloon Kyphoplasty, to treat the spinal fractures.

KYPHON® Balloon Kyphoplasty

To learn more about Balloon Kyphoplasty, visit our website at www.kyphon.com.

The complication rate with KYPHON® Balloon Kyphoplasty has been demonstrated to be low. As with all surgical procedures, there are risks associated with the procedure, including serious complications, and though rare, some of which can be fatal. For complete information regarding indications for use, contraindications, warnings, precautions, adverse events, and methods of use, please reference the devices’ Instructions for Use included with the product. © 2009 Medtronic Spine LLC. All Rights Reserved. 16003611_001 rev 1

TON_December 2010_FINAL_TON 12/6/10 11:19 AM Page 12

Genetic Testing

Multigene Signature Scores and Breast Cancer... demonstrated a consistent statistical link to distant breast cancer recurrence (Figure 1)2 as well as to the degree of response to chemotherapy (Figure 2).3 An algorithm is used to calculate a “recurrence score” (RS) from the expression results for each of 16 cancerrelated genes. The RS ranges from zero to 100. Cutoff points for RS risk groups are defined: low risk, <18; intermediate risk, 18 to 30; and high risk, ≥31. The RS provides information that is independent from age, size, and grade of the tumor.2 This information helps tailor treatment for the individual patient. In addition, the RS is a more significant predictor of distant recurrence-free survival independent of age and tumor size.2 Assigning Individualized Options for Treatment (Rx), a multi-institutional trial known as TAILORx, aims to determine, more specifically, how predictive the assay is for the intermediate-risk RS group.4 The manufacturer has Clinical Laboratory Improvement Amendments certification, and strictly

adheres to College of American Pathology standards.

The 21-gene assay is for use in patients with stage I or II, node-negative, ER-positive breast cancer who will be treated with hormone therapy. In 2007, the assay was included in the 2007 American Society of Clinical Oncology clinical guidelines on the use of tumor markers in breast cancer.5 In 2008, the National Comprehensive Cancer Network incorporated the assay into its breast cancer clinical practice guidelines.6 These inclusions reinforce the significance of molecular diagnostics in breast cancer treatment planning and, in particular, the potential value of the individualized information provided.

After the assay became available to clinicians, the manufacturer discovered that 4% to 6% of specimens sent for testing that were ER-positive on immunohistochemistry (IHC) staining were not ER-positive by RT-PCR. In addition, 9% to 20% of specimens that were ER-negative by IHC were ER-pos-

IntermediateRisk Group

Distant Recurrence at 10 Years

Low-Risk Group

High-Risk Group

Source: Reference 2.

Reprinted with permission from Genomic Health.

Recurrence Score

Figure 1. Statistical link between recurrence score and distant breast cancer recurrence

n = 353 Low, RS <18

n = 134

n = 164 High, RS ≥31

0

10%

20%

30%

Absolute Increase (%) in DRFS at 10 Years (mean ± SE) from Chemotherapy

40% Source: Reference 3.

Reprinted with permission from Genomic Health.

DRFS indicates distant recurrence-free survival; RS, recurrence score; SE, standard error.

Figure 2. Statistical link between RS and the degree of response to chemotherapy

12

December 2010 I VOL 3, NO 8

Continued from cover

The researchers suggested that patients with a low RS might be candidates for a shorter course of chemotherapy. itive by RT-PCR. This raised concern: Are there women who could benefit from hormone therapy who are not being identified? To answer this question, the company started including individual quantitative ER, PR, and HER2 scores as part of its reports in 2008. It now offers an ER qualifier program to guide decisions on testing specimens, based on medical necessity as determined by the referring physician, if the ER status by IHC is in question.

Recently presented information suggests increased applications for the 21gene assay. Three studies have shown that it is also informative for women with node-positive, hormone receptor (HR)-positive, invasive breast cancer.

Goldstein and colleagues looked at the prognostic ability of the assay in HRpositive operable breast cancer with one to three positive nodes. They found that a low RS is predictive of an excellent outcome at 5 years, and that a low RS is a common finding in these patients (49%).7 The researchers suggested that patients with a low RS might be candidates for a shorter course of chemotherapy, plus hormonal therapy; and that a high score may be used to select patients who need more aggressive chemotherapy or who would be candidates for clinical trials evaluating novel agents.7 Dowsett and colleagues, on behalf of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group, presented a follow-up study referred to as transATAC at the San Antonio Breast Cancer Symposium in 2008.8 They looked at the risk of distant recurrence using the 21-gene assay in postmenopausal breast cancer patients with and without positive nodes who were treated with either tamoxifen or anastrozole, an aromatase inhibitor. Pre viously, the RS score had only been validated in patients treated with tamoxifen; in the present day, an aromatase inhibitor is usually the endocrine treatment of choice in postmenopausal women. The researchers evaluated 302 node-positive women and 872 node-negative women. They concluded that the RS for women treated with tamoxifen may be applied for those treated with anastrozole with adjustment for the lower risk of recurrence seen with aromatase inhibitors.

They further concluded that the RS is an independent predictor of disease recurrence in node-positive as well as

node-negative HR-positive patients (Figure 3, page 14).8 Albain and colleagues, on behalf of the Breast Cancer Intergroup of North America, presented results of a retrospective analysis of a randomized study (SWOG 8814) of the prognostic and predictive value of the RS in postmenopausal women with node-positive, ERpositive breast cancer.9 They investigated specifically whether the RS was prognostic in women treated with tamoxifen alone and whether it identified women who could possibly avoid anthracyclinebased chemotherapy (cyclophosphamide/doxorubicin/fluorouracil [CAF]) despite higher risk of recurrence. This chemotherapy regimen is more “modern” than the regimen of cyclophosphamide/methotrexate/fluor ouracil used in earlier adjuvant studies. The researchers determined the RS for 367 specimens and found that the RS was prognostic for the group treated with tamoxifen alone. They also determined that CAF therapy had no benefit in patients with a low RS, but that there was an improvement in disease-free survival (DFS) for women with a high RS after adjustment for the number of positive nodes. An improvement in breast cancer–specific survival (BCSS) was also observed for women with a high RS treated with chemotherapy. The 10-year BCSS was 73% compared with 54% for the tamoxifen alone group in the high RS group. The predictive benefit of the RS was significant in the first 5 years only (P = .029); there was no additional prediction beyond this time (P = .58), although there was a cumulative benefit at 10 years (P = .053). The researchers concluded that a low RS identifies women who, despite positive nodes, might not benefit from CAF.9 Based on these results, the Centers for Medicare & Medicaid Services (CMS) extended coverage for Oncotype DX to ER-positive patients with micrometastases and one to three positive nodes.10 An editorial in Lancet Oncology states, “…the consistency across studies suggests that there is little risk of falsely concluding that there is no chemotherapy benefit in patients with low recurrence scores.”11 Small studies have been conducted to determine whether the 21-gene assay may help predict response to neoadjuvant therapy. Anderson and colleagues

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Genetic Testing compared RS, ER, PR, and HER2 scores from core biopsies to surgical specimens on more than 11,000 samples. They had a 92% correlative success rate.12 With the confidence that core biopsies provide accurate information, three small studies examined RS and response to neoadjuvant therapy.13-15 Two studies used chemotherapy; one used hormonal therapy. No patients with a low RS had a pathologic complete response (pCR) in the chemotherapy studies; however, these patients had a much better clinical response in the hormonal therapy group.

Therefore, assay results may help physicians and patients assess the benefit of neoadjuvant therapy options.

Finally, the usefulness of the 21-gene assay for both physicians and patients has been confirmed in several studies. Based on assay results in node-negative patients, physicians have reported changing their treatment recommendations 20% to 31.5% of the time. The most frequent change is to omit chemotherapy.16-18 At one comprehensive cancer center, the number of patients getting chemotherapy decreased from 55% to 25%.19 More than 80% of patients stated that the results influenced their decisions, and more than 90% were glad they took the test.

Patients reported less anxiety and situational conflict.20 Oratz and colleagues polled more than 1000 physicians who ordered the assay for node-positive patients and found that there was a change in chemotherapy recommendation 42% of the time.21 70-gene prognostic signature Available in Europe since 2004, MammaPrint received US Food and Drug Administration (FDA) approval in February 2007. It was the first clearance issued by the FDA for a breast cancer recurrence test based on data that showed that the gene signature adds independent prognostic information to clinicopathologic risk assessment. The test was validated for use in patients less than 61 years of age with stage I or II, node-negative, ER-positive or ER-negative tumors. MammaPrint was developed in an untreated, heterogeneous patient population.22 In June 2007, Agendia also obtained FDA clearance for use of its tissue preservative (RNARetain). It should be noted that there is a difference in FDA approval and FDA clearance. Clearance provides marketing permission for a test that is considered to pose a low risk to public health and that has been shown to be substantially equivalent to another test. Formal approval provides marketing permission for a test that is new or may be of higher risk to the user; studies are evaluated that show the test does what it claims. This 70-gene prognostic signature became commercially available in the United States in 2008.

Using a process called microarray

www.TheOncologyNurse.com

gene chip technology, the test identified 70 genes linked to the genomic pathways associated with breast cancer recurrence. An algorithm was used to establish two gene signatures (Figure 4, page 14). The test uses fresh-frozen tissue or tissue that must be put into a DNA preservative within an hour and then mailed to the manufacturer. It does not provide an individual RS, but rather

binary results. A “low-risk signature” or “good prognosis” means a woman has a 95% chance of DFS at 5 years, a 90% chance at 10 years, and a 99% BCSS rate at 5 years. A “high-risk signature” or “poor prognosis” means a woman has a 78% chance of DFS at 5 years, a 71% chance at 10 years, and an 80% BCSS rate at 5 years.22-24 The 70-gene prognostic signature has

been found to be of benefit in deciding prognosis in women with node-positive disease. In 2007, Mook and colleagues presented the results from 106 patients with one to three positive lymph nodes.25 They found that the 70-gene signature outperformed clinicopathologic prognostic factors. In patients with a good prognostic score, at 10 years, overall survival Continued on page 14

with dedicated Amgen Reimbursement Counselors There is A place you can go for user-friendly online tools and reimbursement forms… …where your coverage questions can be Answered …where online Access to forms is simple …where you can talk to A single Amgen Reimbursement Counselor for all your reimbursement activity

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Amgen Assist™ and Amgen Inc. do not guarantee success in obtaining reimbursement. Third party payment for medical products and services is affected by numerous factors, not all of which can be anticipated or resolved by our Amgen Assist™ staff. ©Amgen. All rights reserved. MC48319-B 06/10

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Genetic Testing

Multigene Signature Scores and Breast Cancer...

(OS) was 99.7% and DFS was 94%. In patients with a poor prognostic score, OS was 66% and DFS was 62%. Based on these results, patients with one to three positive nodes were incorporated into the Microarray in Node Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy (MINDACT) trial to obtain prospective validation.25 MINDACT is a prospective, randomized trial being conducted by an international breast group (TRANSBIG) comparing the 70-gene signature with the common clinicopathologic criteria in selecting breast cancer patients with zero to three positive nodes for adjuvant chemotherapy.26 In addition, in 2009, Saghatchian and colleagues reported an analysis of frozen tumor samples from 519 node-positive patients followed for 10 years. They found the 70-gene signature to be a strong prognostic marker of disease recurrence and BCSS. Patients with a high genomic risk and elevated number of positive lymph nodes (more than three) have a very poor prognosis; therefore, the researchers suggested that these patients may want to consider more aggressive treatment.27 Based on these

results, CMS provides coverage for the 70-gene prognostic signature for all patients with stage I and II breast cancer, including those with one to three positive nodes.10 CMS coverage for the 70-gene signature has also been expanded to include all age groups. Bedard and colleagues looked at 204 women aged 65 years and older (median, 70 years). They found that the 70-gene signature remained an independent prognostic indicator in this group.28 Data were confirmed in a group of patients between 55 and 70 years of age.29 Finally, studies have been reported showing the predictive value of the 70gene signature. Although there has been no prospective analysis of the predictive value of this test in randomized, controlled, phase 3 trials, Knauer and colleagues presented data at the 2009 St. Gallen Breast Cancer Conference on a meta-analysis of 1637 tumor samples of women who received adjuvant chemotherapy plus hormonal therapy or hormonal therapy alone for T1-3, N0-1, M0 breast cancers. This was a heterogeneous group of women: ER-positive, ER-negative, HER2-positive, and HER2-nega-

4+ positive nodes

CI

Continued from page 13

tive. Median follow-up was 7.1 years.

Data on 167 neoadjuvant chemotherapy patients were also reviewed. The researchers found that the 70-gene prognostic signature was predictive of neoadjuvant and adjuvant therapy. For low-risk patients, chemotherapy plus hormonal therapy did not demonstrate a significant benefit compared with hormonal therapy alone; however, there was a clear benefit in high-risk patients. In patients who received neoadjuvant therapy, there was no pCR in low-risk patients, but there was a 20% pCR in high-risk patients.24,30,31 Agendia can also provide geneexpression levels of the ER, PR, and HER2 in freshly preserved tumor biopsies using a high-density microchip assay called TargetPrint. TargetPrint has been validated against FDA-approved IHC assays. It can be ordered with or without ordering MammaPrint.

Conclusion The additional information about the clinical behavior of a patient’s cancer provided by these assays should help the clinician in personalizing a therapeutic program for patients. Hopefully, fewer patients who will not benefit from chemotherapy will be exposed to the toxicity of these agents. ● Disclosure Ms Dell is a member of Genomic Health’s speakers’ bureau.

References

1-3 positive nodes Node negative

Source: Reference 8.

Reprinted with permission from Genomic Health.

Figure 3. Risk of distant recurrence increases with the number of positive nodes for all recurrence scores

Source: Reference 23.

Reprinted with permission from Agendia.

Threshold set with 10% false negatives (91% sensitivity, 73% specificity)

Figure 4. 70-gene prognostic signature, supervised analysis

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December 2010 I VOL 3, NO 8

1. Edge S, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Handbook. 7th ed. New York, NY: Springer; 2010.

2. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817-2826.

3. Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol.

2006;24:3726-3734.

4. Sparano JA. The TAILORx trial: individualized options for treatment. Commun Oncol. 2006;3:494-496.

5. Harris L, Fritsche H, Mennel R, et al; for the American Society of Clinical Oncology. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287-5312.

6. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Breast Cancer. V.2.2010. www.nccn.org/professionals/physician_gls/PDF/breast. pdf. Accessed March 26, 2010.

7. Goldstein LJ, Gray R, Childset BH, et al. Prognostic utility of 21-gene assay in hormone receptor (HR) positive operable breast cancer and 0-3 positive axillary nodes treated with adjuvant chemohormonal therapy (CHT): an analysis of Intergroup Trial E2197. J Clin Oncol. 2007;25(18S):Abstract 526.

8. Dowsett M, Allred C, Knox J, et al. Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial. J Clin Oncol. 2008;26:1059-1065.

9. Albain KS, Barlow WE, Shak S, et al; for the Breast Cancer Intergroup of North America. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogenreceptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol.

2010; 11:55-65.

10. Medicare Coverage Database. Baltimore, MD: Centers for Medicare & Medicaid Services; 2009.

11. Andre F, Delalage S. First generation genomic tests for breast cancer treatment. Lancet Oncol. 2010;11:6-7.

12. Anderson JM, Shak S, Millward C, et al; for Genomic Health Inc. Molecular characterization of breast cancer core biopsy specimens by gene expression analysis using standarized quantitative RT-PCR. San Antonio Breast Cancer Symposium. 2009:Abstract 6021.

13. Akashi-Tanaka S. Predicting responses to chemotherapy in breast cancer: from bench to bedside. Breast Cancer.

September 30, 2009. Epub ahead of print.

14. Gianni L, Zambetti M, Clark K, et al. Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol. 2005;23:7265-7277.

15. Chang JC, Makris A, Gutierrez MC, et al. Gene expression patterns in formalin-fixed paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients. Breast Cancer Res Treat. 2008; 108:233-240.

16. Liang H, et al. A retrospective analysis of the impact of Oncotype DX low recurrence score results on treatment decisons in a single academic breast cancer center. San Antonio Breast Cancer Symposium.

2007:Abstract 2061.

17. Lo SS, Norton J, Mumby PB, et al. Prospective multicenter study of the impact of the 21 gene recurrence score (RS) assay on medical oncologist (MO) and patient (pt) adjuvant breast cancer (BC) treatment selection. J Clin Oncol. 2007;25(18S):Abstract 577.

18. Kamal AH, Loprinzi CL, Reynolds C, et al. How well do standard prognostic criteria predict Oncotype DX (ODX) scores? J Clin Oncol. 2007;25(18S): Abstract 576.

19. Erb C, Fox KR, Patel M, et al. Evaluation of practice patterns in the treatment of node-negative, hormonereceptor positive breast cancer patients with the use of the assay at the University of Pennsylvania. San Antonio Breast Cancer Symposium. 2007:Abstract 3082.

20. Mumby PB, Lo SS, Norton J, et al. Prospective multi-center study of the impact of the 21-gene recurrence score assay on patient satisfaction, anxiety and decisional conflict for adjuvant breast cancer treatment selection. San Antonio Breast Cancer Symposium.

2007:Abstract 1092.

21. Oratz R, Chao C, Skrzypczak S, et al; for Genomic Health Inc. Effect of 21-gene recurrence score results on treatment recommendations in patients with lymph node-positive, estrogen receptor-positive breast cancer.

San Antonio Breast Cancer Symposium. 2009: Abstract 2031.

22. Buyse M, Loi S, van’t Veer L, et al; for the TRANSBIG Consortium. Validation and clinical utility of a 70gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst. 2006;98:1183-1192.

23. van’t Veer LJ, Dai H, van de Vijver MJ, He YD, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530-536.

24. Straver M, Glas AM, Hannemann J, et al. The 70gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat.

2010;119:551-558.

25. Mook S, Rutgers EJT, Peterse JL, et al. The Amsterdam 70-gene signature predicts outcome in breast cancer patients with 1-3 positive lymph nodes. San Antonio Breast Cancer Symposium. 2007:Abstract 1064.

26. EORTC Trial 10041 (BIG 3-04)—MINDACT. October 14, 2009. www.eortc.be/services/unit/mindact/ MINDACT_websiteii.asp. Accessed January 19, 2010.

27. Saghatchian M, Mook S, Pruneri G, et al.

Combining genomic profiling (70 gene-MamaPrint) with nodal status allows to classify patients with primary breast cancer and positive lymph nodes (1-9) into very distinct prognostic subgroups that could help tailor treatment. San Antonio Breast Cancer Symposium. 2009: Abstract 102.

28. Bedard PL, Mook S, Knauer M, et al. The 70-gene profile (MammaPrint) is an independent predictor of breast cancer specific survival for women 65 years of age or older. San Antonio Breast Cancer Symposium.

2009:Abstract 4049.

29. Mook S, Schmidt MK, Weigelt B, et al. The 70-gene prognosis signature predicts early metastasis in breast cancer patients between 55 and 70 years of age. Ann Oncol. October 13, 2009. Epub ahead of print.

30. Knauer M, Staver M, Rutgers E, et al. The 70-gene MammaPrint signature is predictive for chemotherapy benefit in early breast cancer. Breast. 2009;18(suppl 1):36. Abstract 73.

31. Albain K, Paik S, van’t Veer L. Prediction of adjuvant chemotherapy benefit in endocrine responsive, early breast cancer using multigene assays. Breast.

2009;18(S3):S141-S145.

www.TheOncologyNurse.com

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In the fight against asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer...

Extends Survival PROVENGE® is the first FDA-approved autologous cellular immunotherapy—activating a patient’s own antigen-presenting cells to stimulate an immune response against prostate cancer.

• Extended median survival beyond 2 years—25.8 months compared with 21.7 months for patients in the control group (P=.032) • Reduction in risk of death—22.5% (HR=0.775, 95% CI: 0.614, 0.979) • Most common adverse events—Chills, fatigue, fever, back pain, nausea, joint ache, and headache • Therapy complete in 3 cycles—3 infusions, at approximately 2-week intervals* *Each infusion is preceded by a standard leukapheresis procedure. The dosing interval ranged from 1 to 15 weeks in controlled clinical trials.

Now Available—To learn more about getting access to PROVENGE, call Dendreon ON Call at 1-877-336-3736.

INDICATION: PROVENGE® (sipuleucel-T) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.

IMPORTANT SAFETY INFORMATION: PROVENGE is intended solely for autologous use and is not routinely tested for transmissible infectious diseases.

In controlled clinical trials, serious adverse events reported in the PROVENGE group include acute infusion reactions (occurring within 1 day of infusion) and cerebrovascular events. Severe (Grade 3) acute infusion reactions were reported in 3.5% of patients in the PROVENGE group. Reactions included chills, fever, fatigue, asthenia, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting. No Grade 4 or 5 acute infusion reactions were reported in patients in the PROVENGE group.

The most common adverse events (incidence ≥15%) reported in the PROVENGE group are chills, fatigue, fever, back pain, nausea, joint ache, and headache.

Please see Brief Summary of full Prescribing Information on the next page.

©2010 Dendreon Corporation.

All rights reserved. November 2010. Printed in the U.S.A. Dendreon, the Dendreon logo, and PROVENGE are registered trademarks of Dendreon Corporation.

P-A-11.10-072.00

www.PROVENGE.com

TON_December 2010_FINAL_TON 12/6/10 11:19 AM Page 16

Cancer Complications

Prompt Pain Relief for Vertebral Compression Fractures with Balloon Kyphoplasty

By Caroline Helwick

MILAN—Painful vertebral compression fractures can be promptly and effectively treated with balloon kyphoplasty, according to an international

study presented at the 35th European Society for Medical Oncology Congress.

The Cancer Patient Fracture Evaluation (CAFE) study was the first to ran-

domize cancer patients with vertebral compression fractures to balloon kyphoplasty or standard nonsurgical treatment (controls). The results were reported by

PROVENGE® (sipuleucel-T) Suspension for Intravenous Infusion

Rx Only

BRIEF SUMMARY — See full Prescribing Information for complete product information INDICATIONS AND USAGE: PROVENGE® (sipuleucel-T) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.

DOSAGE AND ADMINISTRATION • For Autologous Use Only.

• The recommended course of therapy for PROVENGE is 3 complete doses, given at approximately 2-week intervals.

• Premedicate patients with oral acetaminophen and an antihistamine such as diphenhydramine.

• Before infusion, confirm that the patient’s identity matches the patient identifiers on the infusion bag.

• Do Not Initiate Infusion of Expired Product.

• Infuse PROVENGE intravenously over a period of approximately 60 minutes.

Do Not Use a Cell Filter.

• Interrupt or slow infusion as necessary for acute infusion reactions, depending on the severity of the reaction.

(See Dosage and Administration [2] of full Prescribing Information.)

CONTRAINDICATIONS: None.

WARNINGS AND PRECAUTIONS • PROVENGE is intended solely for autologous use.

• Acute infusion reactions (reported within 1 day of infusion) included, but were not limited to, fever, chills, respiratory events (dyspnea, hypoxia, and bronchospasm), nausea, vomiting, fatigue, hypertension, and tachycardia. In controlled clinical trials, 71.2% of patients in the PROVENGE group developed an acute infusion reaction.

In controlled clinical trials, severe (Grade 3) acute infusion reactions were reported in 3.5% of patients in the PROVENGE group. Reactions included chills, fever, fatigue, asthenia, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting. The incidence of severe events was greater following the second infusion (2.1% vs 0.8% following the first infusion), and decreased to 1.3% following the third infusion. Some (1.2%) patients in the PROVENGE group were hospitalized within 1 day of infusion for management of acute infusion reactions. No Grade 4 or 5 acute infusion reactions were reported in patients in the PROVENGE group.

Closely monitor patients with cardiac or pulmonary conditions. In the event of an acute infusion reaction, the infusion rate may be decreased, or the infusion stopped, depending on the severity of the reaction. Appropriate medical therapy should be administered as needed.

• Handling Precautions for Control of Infectious Disease. PROVENGE is not routinely tested for transmissible infectious diseases. Therefore, patient leukapheresis material and PROVENGE may carry the risk of transmitting infectious diseases to health care professionals handling the product. Universal precautions should be followed.

• Concomitant Chemotherapy or Immunosuppressive Therapy. Use of either chemotherapy or immunosuppressive agents (such as systemic corticosteroids) given concurrently with the leukapheresis procedure or PROVENGE has not been studied.

PROVENGE is designed to stimulate the immune system, and concurrent use of immunosuppressive agents may alter the efficacy and/or safety of PROVENGE. Therefore, patients should be carefully evaluated to determine whether it is medically appropriate to reduce or discontinue immunosuppressive agents prior to treatment with PROVENGE. • Product Safety Testing. PROVENGE is released for infusion based on the microbial and sterility results from several tests: microbial contamination determination by Gram stain, endotoxin content, and in-process sterility with a 2-day incubation to determine absence of microbial growth. The final (7-day incubation) sterility test results are not available at the time of infusion. If the sterility results become positive for microbial contamination after PROVENGE has been approved for infusion, Dendreon will notify the treating physician. Dendreon will attempt to identify the microorganism, perform antibiotic sensitivity testing on recovered microorganisms, and communicate the results to the treating physician. Dendreon may request additional information from the physician in order to determine the source of contamination.

(See Warnings and Precautions [5] of full Prescribing Information.)

ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety evaluation of PROVENGE is based on 601 prostate cancer patients in the PROVENGE group who underwent at least 1 leukapheresis procedure in four

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December 2010 I VOL 3, NO 8

Leonard Bastian, MD, of the Klinikum Leverkusen in Leverkusen, Germany.

“We found that we can reduce pain immediately in these patients,” Bastian

randomized, controlled clinical trials. The control was non-activated autologous peripheral blood mononuclear cells.

The most common adverse events, reported in patients in the PROVENGE group at a rate ≥15%, were chills, fatigue, fever, back pain, nausea, joint ache, and headache. Severe (Grade 3) and life-threatening (Grade 4) adverse events were reported in 23.6% and 4.0% of patients in the PROVENGE group compared with 25.1% and 3.3% of patients in the control group. Fatal (Grade 5) adverse events were reported in 3.3% of patients in the PROVENGE group compared with 3.6% of patients in the control group.

Serious adverse events were reported in 24.0% of patients in the PROVENGE group and 25.1% of patients in the control group. Serious adverse events in the PROVENGE group included acute infusion reactions (see Warnings and Precautions), cerebrovascular events, and single case reports of eosinophilia, rhabdomyolysis, myasthenia gravis, myositis, and tumor flare.

PROVENGE was discontinued in 1.5% of patients in Study 1 (PROVENGE group n=341; Control group n=171) due to adverse events. Some patients who required central venous catheters for treatment with PROVENGE developed infections, including sepsis. A small number of these patients discontinued treatment as a result. Monitoring for infectious sequelae in patients with central venous catheters is recommended.

Each dose of PROVENGE requires a standard leukapheresis procedure approximately 3 days prior to the infusion. Adverse events that were reported ≤1 day following a leukapheresis procedure in ≥5% of patients in controlled clinical trials included citrate toxicity (14.2%), oral paresthesia (12.6%), paresthesia (11.4%), and fatigue (8.3%).

Table 1 provides the frequency and severity of adverse events reported in ≥5% of patients in the PROVENGE group of randomized, controlled trials of men with prostate cancer.

The population included 485 patients with metastatic castrate resistant prostate cancer and 116 patients with non-metastatic androgen dependent prostate cancer who were scheduled to receive 3 infusions of PROVENGE at approximately 2-week intervals. The population was age 40 to 91 years (median 70 years), and 90.6% of patients were Caucasian.

Table 1 Incidence of Adverse Events Occurring in ≥5% of Patients Randomized to PROVENGE PROVENGE (N = 601)

Any Adverse Event Chills Fatigue Fever Back pain Nausea Joint ache Headache Citrate toxicity Paresthesia Vomiting Anemia Constipation Pain Paresthesia oral Pain in extremity Dizziness Muscle ache Asthenia Diarrhea Influenza-like illness Musculoskeletal pain Dyspnea Edema peripheral Hot flush Hematuria Muscle spasms

Control* (N = 303)

All Grades n (%)

Grade 3-5 n (%)

All Grades n (%)

591 (98.3) 319 (53.1) 247 (41.1) 188 (31.3) 178 (29.6) 129 (21.5) 118 (19.6) 109 (18.1) 89 (14.8) 85 (14.1) 80 (13.3) 75 (12.5) 74 (12.3) 74 (12.3) 74 (12.3) 73 (12.1) 71 (11.8) 71 (11.8) 65 (10.8) 60 (10.0) 58 (9.7) 54 (9.0) 52 (8.7) 50 (8.3) 49 (8.2) 46 (7.7) 46 (7.7)

186 (30.9) 13 (2.2) 6 (1.0) 6 (1.0) 18 (3.0) 3 (0.5) 11 (1.8) 4 (0.7) 0 (0.0) 1 (0.2) 2 (0.3) 11 (1.8) 1 (0.2) 7 (1.2) 0 (0.0) 5 (0.8) 2 (0.3) 3 (0.5) 6 (1.0) 1 (0.2) 0 (0.0) 3 (0.5) 11 (1.8) 1 (0.2) 2 (0.3) 6 (1.0) 2 (0.3)

291 (96.0) 33 (10.9) 105 (34.7) 29 (9.6) 87 (28.7) 45 (14.9) 62 (20.5) 20 (6.6) 43 (14.2) 43 (14.2) 23 (7.6) 34 (11.2) 40 (13.2) 20 (6.6) 43 (14.2) 40 (13.2) 34 (11.2) 17 (5.6) 20 (6.6) 34 (11.2) 11 (3.6) 31 (10.2) 14 (4.6) 31 (10.2) 29 (9.6) 18 (5.9) 17 (5.6)

Grade 3-5 n (%) 97 (32.0) 0 (0.0) 4 (1.3) 3 (1.0) 9 (3.0) 0 (0.0) 5 (1.7) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 7 (2.3) 3 (1.0) 3 (1.0) 0 (0.0) 1 (0.3) 0 (0.0) 0 (0.0) 2 (0.7) 3 (1.0) 0 (0.0) 3 (1.0) 3 (1.0) 1 (0.3) 1 (0.3) 3 (1.0) 0 (0.0)

(Table 1 continued on next page.)

www.TheOncologyNurse.com

TON_December 2010_FINAL_TON 12/6/10 11:19 AM Page 17

Cancer Complications said at a press conference. “Cancer patients with vertebral compression fractures having balloon kyphoplasty have a superior outcome.”

Balloon kyphoplasty involves a 1-cm incision into the fractured vertebra through which a balloon is inserted and inflated to restore the shape and height of the vertebra. The balloon is then

deflated and removed, and quick-setting bone cement is injected into the vertebral body to maintain the shape.

The study population included 134 patients with three or fewer vertebral compression fractures who were randomized to kyphoplasty (n = 70) or nonsurgical management (n = 64), mainly physical therapy, analgesics,

and sometimes braces and bed rest.

Patients were followed for 1 year.

After 1 month, the Roland-Morris Disability Questionnaire score dropped by 8.3 points in the kyphoplasty group but increased slightly by 0.1 point in the nonsurgical group. After just 1 week, the kyphoplasty group reported significant improvements in back pain,

Table 1 Incidence of Adverse Events Occurring in ≥5% of Patients Randomized to PROVENGE PROVENGE (N = 601)

Hypertension Anorexia Bone pain Upper respiratory tract infection Insomnia Musculoskeletal chest pain Cough Neck pain Weight decreased Urinary tract infection Rash Sweating Tremor

Control* (N = 303)

All Grades n (%)

Grade 3-5 n (%)

All Grades n (%)

Grade 3-5 n (%)

45 (7.5) 39 (6.5) 38 (6.3) 38 (6.3)

3 (0.5) 1 (0.2) 4 (0.7) 0 (0.0)

14 (4.6) 33 (10.9) 22 (7.3) 18 (5.9)

0 (0.0) 3 (1.0) 3 (1.0) 0 (0.0)

37 (6.2) 36 (6.0)

0 (0.0) 2 (0.3)

22 (7.3) 23 (7.6)

1 (0.3) 2 (0.7)

35 (5.8) 34 (5.7) 34 (5.7) 33 (5.5) 31 (5.2) 30 (5.0) 30 (5.0)

0 (0.0) 3 (0.5) 2 (0.3) 1 (0.2) 0 (0.0) 1 (0.2) 0 (0.0)

17 (5.6) 14 (4.6) 24 (7.9) 18 (5.9) 10 (3.3) 3 (1.0) 9 (3.0)

0 (0.0) 2 (0.7) 1 (0.3) 2 (0.7) 0 (0.0) 0 (0.0) 0 (0.0)

*Control was non-activated autologous peripheral blood mononuclear cells.

Cerebrovascular Events. In controlled clinical trials, cerebrovascular events, including hemorrhagic and ischemic strokes, were reported in 3.5% of patients in the PROVENGE group compared with 2.6% of patients in the control group.

Recent FDA Approval

(See Adverse Reactions [6] of full Prescribing Information.)

To report SUSPECTED ADVERSE REACTIONS, contact Dendreon Corporation at 1-877-336-3736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Trastuzumab for HER2-positive Metastatic Stomach Cancer The US Food and Drug Administration (FDA) has approved trastuzumab (Herceptin, Roche) in combination with chemotherapy (cisplatin plus either capecitabine or 5-fluorouracil) for human epidermal growth factor receptor type 2 (HER2)-positive metastatic cancer of the stomach or gastroesophageal junction in patients who have not received prior medicines for their metastatic disease.

Approval was based on results of a phase 3 study (ToGA), which showed that patients who received trastuzumab plus chemotherapy had improved overall survival (HR, 0.73; 95% CI, 0.60-0.91; P = .0038). Median overall survival was 13.5 months for patients on combination therapy compared with 11 months for those on chemotherapy alone. An analysis based on an additional year of follow-up showed the numbers to be slightly lower (HR, 0.80; 95% CI, 0.67-0.97; P = .02; median overall survival, 13.1 vs 11.7 months).

Dendreon Corporation 3005 First Avenue Seattle, Washington 98121

©2010 Dendreon Corporation.

All rights reserved. November 2010. Printed in the U.S.A. Dendreon, the Dendreon logo, and PROVENGE are registered trademarks of Dendreon Corporation.

P-A-11.10-073.00

www.TheOncologyNurse.com

with a change in the numerical rating scale of -3.8 points, compared with virtually no change in the control group, and they used less analgesia.

The difference between the groups in the two pain measurements was highly significant (P <.0001), Bastian noted.

Patients receiving balloon kyphoplasty reported significantly fewer days with limited activity—6.2 days fewer per 2 weeks (P <.0001)—and greater improvements in quality of life as measured by an eight-point advantage in the SF-36 score (P <.0001).

Crossover to kyphoplasty was allowed after 1 month, and the 38 patients who did so experienced similar benefits with regard to back pain relief, activity level, and quality of life.

“All the balloon kyphoplasty patients reported sustained improvements throughout the 12-month period of the study,” Bastian said.

Adverse events were similar except for the occurrence of one intraoperative non–Q-wave myocardial infarction that resolved in the kyphoplasty group and a cement leakage to the disc and adjacent fracture 1 day later in another patient.

The indication for this procedure is virtually any painful vertebral compression fracture or multiple fractures.

Bones that have been highly compromised due to metastases, however, may not be amenable to kyphoplasty. ●

December 2010 I VOL 3, NO 8

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Cancer Center Profile Geisinger Medical Center’s Cancer Institute Joins the NCCCP Continued from cover

Thanjavur Ravikumar, MD, FACS, performs surgery in Geisinger’s Center for Surgical Innovation.

Geisinger’s Cancer Institute, believes that serving this mix of patients marries well with the NCCCP’s mission of reducing cancer healthcare disparities.

NCCCP cancer centers are directed to increase programs to reach the underserved in their communities more effectively, thus improving access to cancer screening, treatment, and research.

Community outreach The centerpiece at Geisinger is value-based healthcare delivery, a philosophy evident in its advanced patientcentered medical home program, known as ProvenHealth Navigator. At Geisinger, medical homes are caregivers, such as primary care physicians or nurse case managers, who provide service excellence beyond just seeing patients in an acute-care setting. Their proactive approach to chronic diseases is recognized by the National Committee for Quality Assurance—all 40 facilities distributed throughout Geisinger’s community have been recognized as Level 3, the highest level awarded for the medical home model.

This philosophy of managing patients through a disease continuum that is continued into wellness programs—a philosophy that is also practiced by Geisinger’s cancer specialists—parallels the NCCCP’s vision of cancer as a disease continuum, according to Ravikumar.

NCCCP cancer centers are tasked with improving the quality of care at community hospitals by promoting datadriven, evidence-based, and coordinated cancer care. In addition, NCCCP cancer centers are working to enhance their cancer survivorship and palliative care services.

With a $1.7-million award from the NCCCP, Geisinger hopes to reach these goals. To do so, Geisinger will use its

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December 2010 I VOL 3, NO 8

medical home model to reach patients and physicians who are not members of the Geisinger system. “We need to provide the same services to both Geisinger patients and non-Geisinger patients in the 11 counties that surround us,” said Ravikumar in an interview with The Oncology Nurse. “Our plan through the NCCCP, our obligation, is to all patients in the counties that we serve.”

The centerpiece at Geisinger is value-based healthcare delivery, a philosophy evident in its advanced patientcentered medical home program.

According to Ravikumar, Geisinger plans to reach out to area physicians who are not participants in the Geisinger system through the Keystone Health Information Exchange (KeyHIE) initiative. This initiative aims to provide healthcare professionals with the timely information they need to provide the best care possible for their patients.

Through the initiative’s master patient list, patients’ charts and all medical information that reside at any participating hospital can be accessed through a secure web-based browser.

Information technology GMC’s Cancer Institute also has “significant strength in information technology,” noted Ravikumar. This is another area that marries well with the NCCCP’s mission. NCCCP cancer centers are charged with exploring what is needed to adapt or adopt the tools of the National Cancer Institute’s (NCI)

cancer Bioinformatics Grid (caBIG) as well as to enhance their electronic health record (EHR) networks to support and link cancer patients and researchers nationwide. “What the NCCCP wants to do is connect all the cancer centers in the country through a grid called caBIG. They are trying to bring everyone up to speed. We are already advanced in that area, so perhaps the NCCCP thought that it would be a good thing for centers like ours to lead the way,” said Ravikumar.

For the past 8 years, Geisinger has been recognized as one of the nation’s “100 Most Wired Hospitals and Health Systems” by Hospitals & Health Networks (H&HN), the journal of the American Hospital Association. As one of the most digitally advanced healthcare providers in the nation, Geisinger uses information technology to address safety and quality, customer service, business processes, workforce, and public health.

Research In addition, Geisinger already has a very robust biospecimen initiative through MyCode. Currently, MyCode has 20,000 DNA samples from patients throughout Geisinger. Patients at all levels of health are asked to participate, provide a blood sample, and give consent for its use in research. “If any studies need to be done across the cancer research at the community level, we are well positioned to carry out the mission of the NCCCP,” explained Ravikumar. To help the NCCCP reach its goal of applying NCI Best Practices for Biospecimen Resources to enable all community cancer centers to contribute to the national biobank, Geisinger is expanding its specimen collection beyond Geisinger-affiliated cancer centers by “helping them retrieve the specimen when they operate on cancer patients,” Ravikumar said.

As a member of the Community Clinical Oncology Program (CCOP), Geisinger already has 11 of the 15 NCCCP clinical trials open at its cancer centers. According to Ravikumar, Geisinger plans to expand those 11 trials and open the additional four trials to patients in its community. Because of its rural patient base, Geisinger will offer trials at multiple sites so, as Ravikumar explains, the patients “do not have to come to us in our main center.” In addition, Geisinger accrues to trials through other oncology groups including the Eastern Cooperative Oncology Group and the North Central Cancer Treatment Group. “Using the NCCCP mechanism, we are going to make these trials available to people in the community through outreach and navigators and transportation service,” explained

Ravikumar. “In addition, for clinical trials, we are going to enlist oncologists, radiation doctors, surgeons, and primary care physicians who are not Geisinger physicians and make sure that they have access to NCCCP clinical trials.”

Quality care All of this, of course, is about the quality of care delivered. “We have some ideas of how we will use our EHR and our model of ProvenHealth to improve the quality of patient care, so every patient gets the same level of care,” said Ravikumar, a surgeon by profession. This care will continue through the disease continuum and include survivorship and palliative care. This past year, Geisinger has launched the Geisinger accelerated performance program (GAPP) initiative. “One of the central focuses of the GAPP initiative is palliative care, making sure that the patients that we cannot cure we offer palliation as a focus and that we keep their quality of life central to our mission.”

GMC’s Cancer Institute will not be resting on its laurels. By becoming an NCCCP cancer center, Geisinger hopes to improve on its delivery of innovation and discovery and to enhance its diffusion of research and technology to positively influence cancer care today and tomorrow. Ravikumar looks forward to working with the other physician directors at the other sites.

“We belong to the club. We may have one model. Others may other models.

We will basically learn from each other,” Ravikumar said. ●

Recent FDA Approval Dasatinib for Ph+ CP-CML The US Food and Drug Administration (FDA) has approved a new indication for dasatinib (Sprycel, Bristol-Myers Squibb)—treatment of Philadelphia chromosome–positive chronic phase chronic myeloid leukemia (Ph+ CP-CML). This indication expands on the drug’s original approval in 2006 to treat adults with CP-CML with resistant disease or who were intolerant of prior therapies.

An oral kinase inhibitor, dasatinib’s side effects can include de creased bone marrow activity, fluid retention, diarrhea, headache, muscle and bone pain, and rash.

Because it was approved under the FDA’s accelerated approval program, the manufacturer is required to collect additional long-term efficacy and safety data.

www.TheOncologyNurse.com

TON_December 2010_FINAL_TON 12/6/10 11:20 AM Page 19

ALOXI provides powerful CINV prevention that canâ&#x20AC;&#x2122;t be ignored. ÂŽ

Help support your patientsâ&#x20AC;&#x2122; chemotherapy treatment goals s Powerful CINV prevention in the first 24 hours and up to 5 days following moderately emetogenic chemotherapy1,2 s Lasts long against nausea following moderately emetogenic chemotherapy s Powerful acute CINV prevention following highly emetogenic chemotherapy 4 s %ISAI OFFERS A VARIETY OF SUPPORT PROGRAMS AND RESOURCES

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

Important Safety Information s !,/8) IS CONTRAINDICATED IN PATIENTS KNOWN TO HAVE HYPERSENSITIVITY TO THE DRUG OR ANY of its components s -OST COMMONLY REPORTED ADVERSE REACTIONS IN CHEMOTHERAPY INDUCED NAUSEA AND VOMITING include headache (9%) and constipation (5%) Please see the brief summary of the Full Prescribing Information on the adjacent page.

References: 1. Gralla R, Lichinitser M, Van der Vegt S, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol. 2003;14:1570-1577. 2. Eisenberg P, Figueroa-Vadillo J, Zamora R, et al. Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer. 2003;98:2473-2482. 3. Data on file. Eisai Inc., Woodcliff Lake, NJ. 4. Aapro MS, Grunberg SM, Manikhas GM, et al. A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol.

2006;17:1441-1449.

STARTS STRONG. LASTS LONG.

ALOXIÂŽ IS A REGISTERED TRADEMARK OF (ELSINN (EALTHCARE 3!

3WITZERLAND USED UNDER LICENSE $ISTRIBUTED AND MARKETED BY %ISAI )NC ÂĽ %ISAI )NC !LL RIGHTS RESERVED 0RINTED IN 53! !,/ "

TON_December 2010_FINAL_TON 12/6/10 11:20 AM Page 20

Lung Cancer

Stereotactic Radiation May Be as Effective as Surgery for Some Nonâ&#x20AC;&#x201C;small-cell Lung Cancers See also pages 25 & 32.

By John Schieszer

SAN DIEGOâ&#x20AC;&#x201D;Stereotactic radiation appears to be highly effective and safe for treatment of patients with operable,

ALOXIÂŽ (palonosetron HCl) injection BRIEF SUMMARY OF PRESCRIBING INFORMATION INDICATIONS AND USAGE Chemotherapy-Induced Nausea and Vomiting ALOXI is indicated for: L =23@/B3:G 3;3B=53<71 1/<13@ 163;=B63@/>G K >@3D3<B7=< =4 /1CB3 /<2 23:/G32 </CA3/ /<2

D=;7B7<5 /AA=17/B32 E7B6 7<7B7/: /<2 @3>3/B 1=C@A3A L 756:G 3;3B=53<71 1/<13@ 163;=B63@/>G K >@3D3<B7=< =4 /1CB3 </CA3/ /<2 D=;7B7<5 /AA=17/B32 E7B6 7<7B7/: /<2 @3>3/B 1=C@A3A DOSAGE AND ADMINISTRATION Recommended Dosing Chemotherapy-Induced Nausea and Vomiting =A/53 4=@ 2C:BA / A7<5:3 ;5 ) 2=A3 /2;7<7AB3@32 =D3@ A31=<2A =A7<5 A6=C:2 =11C@ />>@=F7;/B3:G ;7<CB3A 034=@3 B63 AB/@B =4 163;=B63@/>G Instructions for I.V. Administration "+ 7A AC>>:732 @3/2G 4=@ 7<B@/D3<=CA 7<831B7=< "+ A6=C:2 <=B 03 ;7F32 E7B6 =B63@ 2@C5A :CA6 B63 7<4CA7=< :7<3 E7B6 <=@;/: A/:7<3 034=@3 /<2 /4B3@ /2;7<7AB@/B7=< =4 "+ #/@3<B3@/: 2@C5 >@=2C1BA A6=C:2 03 7<A>31B32 D7AC/::G 4=@ >/@B71C:/B3 ;/BB3@ /<2 27A1=:=@/B7=< 034=@3 /2;7<7AB@/B7=< E63<3D3@ A=:CB7=< /<2 1=<B/7<3@ >3@;7B CONTRAINDICATIONS "+ 7A 1=<B@/7<271/B32 7< >/B73<BA 9<=E< B= 6/D3 6G>3@A3<A7B7D7BG B= B63 2@C5 =@ /<G =4 7BA 1=;>=<3<BA [see Adverse Reactions (6) 7< 4C:: >@3A1@707<5 7<4=@;/B7=< ] WARNINGS AND PRECAUTIONS Hypersensitivity G>3@A3<A7B7D7BG @3/1B7=<A ;/G =11C@ 7< >/B73<BA E6= 6/D3 3F6707B32 6G>3@A3<A7B7D7BG B= =B63@ '

@313>B=@ /<B/5=<7ABA ADVERSE REACTIONS 31/CA3 1:7<71/: B@7/:A /@3 1=<2C1B32 C<23@ E723:G D/@G7<5 1=<27B7=<A /2D3@A3 @3/1B7=< @/B3A =0A3@D32 7< B63 1:7<71/: B@7/:A =4 / 2@C5 1/<<=B 03 27@31B:G 1=;>/@32 B= @/B3A 7< B63 1:7<71/: B@7/:A =4 /<=B63@ 2@C5 /<2 ;/G <=B @3J 31B B63 @/B3A @3>=@B32 7< >@/1B713 < 1:7<71/: B@7/:A 4=@ B63 >@3D3<B7=< =4 </CA3/ /<2 D=;7B7<5 7<2C132 0G ;=23@/B3:G =@ 6756:G 3;3B=53<71 163;=B63@/>G

/2C:B >/B73<BA @3137D32 >/:=<=A3B@=< 2D3@A3 @3/1B7=<A E3@3 A7;7:/@ 7< 4@3?C3<1G /<2 A3D3@7BG E7B6 "+ /<2 =<2/<A3B@=< =@ 2=:/A3B@=< =::=E7<5 7A / :7AB7<5 =4 /:: /2D3@A3 @3/1B7=<A @3>=@B32 0G â&#x2030;Ľ =4 >/B73<BA 7< B63A3 B@7/:A '/0:3

Table 1: Adverse Reactions from ChemotherapyInduced Nausea and Vomiting Studies â&#x2030;Ľ 2% in any Treatment Group ALOXI Ondansetron Dolasetron Event 0.25 mg 32 mg I.V. 100 mg I.V. (N=410) (N=194) (N=633) 3/2/163

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20

December 2010 I VOL 3, NO 8

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in fewer side effects, according to a new Japanese study presented at the 52nd annual meeting of the American

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Society for Radiation Oncology.

Stereotactic body radiation therapy (SBRT) is an increasingly popular treatment and has been shown to be effective in medically inoperable stage I NSCLC patients. This trial, however, was the first to examine its use in stage I lung cancer patients who are eligible for surgery. â&#x20AC;&#x153;We can now confirm with more confidence that SBRT is an effective treatment alternative for [older] aged patients with nonâ&#x20AC;&#x201C;small-cell lung cancer,â&#x20AC;? said Yasushi Nagata, MD, a professor of radiation oncology at Hiroshima University, Japan. â&#x20AC;&#x153;In the future, there is a possibility that radiation will be a substitute for surgery in selected patients with stage I NSCLC. I encourage patients with early lung cancer to talk to their doctor to understand all their treatment options.â&#x20AC;?

In this study, patients underwent four radiation treatments over the course of 4 to 8 days. SBRT, sometimes called radiosurgery, refers to a single or several highly targeted radiation treatments.

From July 2004 to January 2007, 65 patients from 15 institutions were followed for a median of 45 months posttreatment. Researchers sought to determine the effectiveness and safety of stereotactic radiation treatments by determining the patient groupâ&#x20AC;&#x2122;s overall survival at 3 years after treatment (76%).

The mean age of the patients was 79 years (range, 50-91 years), and 45 of 65 patients were men. The median tumor size was 21 mm (range, 10-30 mm).

To date, a total of 25 progressions have been observed, and the 3-year progression-free survival rate is 54.5%. The local progression-free survival rate at 3 years is 68.5%, and the event-free survival rate is 51.4%. No grade 4 or 5 toxicities have been observed. Grade 3 adverse events included chest pain in 1.5%, dyspnea in 3.1%, hypoxia in 1.5%, and pneumonitis in 3.1%. â&#x20AC;&#x153;This would be a lot less painful than surgery,â&#x20AC;? said Nagata in an interview with The Oncology Nurse. â&#x20AC;&#x153;There is also a big cost savings. The cost could be half of surgery. This is something that American cancer specialists may want to think about. It is important for the oncology nurse to know about this too.

This could be a substitute for surgery, and patients need to know this.â&#x20AC;?

He said this study is particularly important because it included so many older-aged patients. Nagata said that in the United States this approach for these patients is only now starting to become part of clinical practice. â&#x2014;?

www.TheOncologyNurse.com

TON_December 2010_FINAL_TON 12/6/10 11:20 AM Page 21

Who Will Be the ONE? The Oncology Nurse Excellence Award Winner The Oncology Nurse-APN/PA is pleased to announce the inaugural Nurse Excellence Award. The award will recognize an oncology nurse nominated by his/her peers for an outstanding contribution to oncology nursing practice, patient care, research, or education in 2010.

The four leading nominees will be profiled in the February issue of The Oncology Nurse-APN/PA. Readers will have an opportunity to vote for the winner online at www.TheOncologyNurse.com/award or by visiting The Oncology Nurse-APN/PA booth at the 2011 ONS Congress. The winner will be announced in the June issue of The Oncology Nurse-APN/PA .

Nominate a Nurse online at

www.TheOncologyNurse.com/award

TON_December 2010_FINAL_TON 12/6/10 11:20 AM Page 22

Clinical challenge: Treatment selection for patients with lower-risk MDS* Supportive care: The most common initial MDS treatment 90% of patients with newly diagnosed myelodysplastic syndromes (MDS) present with anemia, and most patients eventually become red blood cell (RBC) transfusion dependent.1 For years, MDS was treated with best supportive care—RBC or platelet transfusions and antibiotics.2 With the advent of hematopoietic growth factor therapy, supportive care expanded to include erythropoiesis-stimulating agents (ESAs), with or without G-CSF,† which were used to reduce the need for transfusions.3,4

Survival decreases with increasing transfusion requirements5 Therefore, it is critical to achieve transfusion independence in patients with transfusiondependent MDS. While ESAs can effectively relieve the symptoms of anemia, they may not be sufficient to provide RBC transfusion independence in all MDS patients.6-9 Some of your patients with lower-risk MDS may need treatment other than growth factors (GFs).

Use baseline serum erythropoietin (sEPO) levels to guide treatment decisions Because the response to ESAs declines with increasing baseline sEPO levels, it is critical to measure endogenous levels of erythropoietin before initiating treatment with ESAs. As many as 85% of patients with MDS have elevated baseline sEPO levels,10 making them less likely to respond to growth factors. Patients with high sEPO levels (>500 U/L) and high transfusion needs (≥2 RBC units/month) have a low chance of response to erythropoietin.3 Current treatment guidelines recommend that the determination of baseline sEPO levels should be a required part of the initial evaluation of patients with cytopenias.11 *MDS, myelodysplastic syndromes; lower-risk MDS, Low- and Intermediate-1–risk MDS per International Prognostic Scoring System (IPSS). † G-CSF, granulocyte colony-stimulating factor. Growth factor therapy includes ESA ± G-CSF or granulocyte/macrophage (GM)-CSF.3

©2010 Celgene Corporation

07/10

CELG10174T

TON_December 2010_FINAL_TON 12/6/10 11:20 AM Page 23

Two variables can be used to help predict response to growth factor therapy: Baseline sEPO levels and RBC transfusion burden 9

INTERMEDIATE

GOOD Transfusion Requirement sEPO Level

Chance of responding to ESAs‡

POOR

Low (<2 units/month)

High (≥2 units/month)

Low (<2 units/month)

High (≥2 units/month)

Low (≤500 U/L)

Low (≤500 U/L)

High (>500 U/L)

High (>500 U/L)

74%

23%

7%

Adapted from Hellström-Lindberg et al (2003).9

Consider baseline sEPO levels and transfusion burden when determining treatment options for your RBC transfusion-dependent patients with lower-risk MDS. It is also important to continually evaluate these patients.

If your patients have a predicted intermediate or poor response to ESAs, it may be appropriate to consider non-growth factor therapies.3

‡

The Hellström-Lindberg study defined complete erythroid response as an increase in hemoglobin (HgB) to ≥11.5 g/dL. Partial response was defined as an increase in HgB of ≥1.5 g/dL in patients with anemia who are not transfusion dependent, and for RBC transfusion-dependent patients, a stable HgB level for ≥4 weeks and transfusion independence.9

References: 1. Italian Cooperative Study Group For rHuEpo in Myelodysplastic Syndromes. A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes. Br J Haematol. 1998;103:1070-1074. 2. Nimer SD. ASH 50th anniversary review: Myelodysplastic syndromes. Blood.

2008;111(10):4841-4851. 3. Sekeres MA, Fu AZ, Maciejewski JP, Golshayan A-R, Kalaycio ME, Kattan MW. A decision analysis to determine the appropriate treatment for low-risk myelodysplastic syndromes. Cancer. 2007;109(6):1125-1132. 4. Fenaux P, Kelaidi C. Treatment of the 5q- syndrome. American Society of Hematology Education Program–Myelodysplastic Syndromes. Hematology. 2006;192-198. 5. Malcovati L, Della Porta MG, Cazzola M. Predicting survival and leukemic evolution in patients with myelodysplastic syndrome. Haematologica.

2006;91(12):1588-1590. 6. Jädersten M, Montgomery SM, Dybedal I, Porwit-MacDonald A, Hellström-Lindberg E. Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood. 2005;106(3):803-811. 7. Miller KB, Kim HT, Greenberg P, et al. Phase III prospective randomized trial of EPO with or without G-CSF versus supportive therapy alone in the treatment of myelodysplastic syndromes (MDS): results of the ECOG-CLSG trial (E1996). Blood. 2004;104(11):24a. Abstract 70. 8. Musto P, Lanza F, Balleari E, et al. Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes. Br J Haematol. 2004;128(2):204-209. 9. Hellström-Lindberg E, Gulbrandsen N, Lindberg G, et al.

A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life.

Br J Haematol. 2003;120(6):1037-1046. 10. Hofmann W-K, Koeffler HP. Myelodysplastic syndrome. Annu Rev Med. 2005;56:1-16. 11. National Comprehensive Cancer Network®.

Myelodysplastic Syndromes. V.2.2010. NCCN Clinical Practice Guidelines in Oncology ™.

TON_December 2010_FINAL_TON 12/6/10 11:20 AM Page 24

International News

Reports from the European Association for the Study of Diabetes, the International Thyroid Congress, and the University of Melbourne

By Jill Stein

Increased Cancer Risk in Insulin Users Decreases Over Time STOCKHOLM—New data undermine the widely held notion that the greater likelihood of cancer seen in diabetic patients on insulin therapy increases with longer insulin use.

In fact, the findings, reported at the 46th European Association for the Study of Diabetes meeting, show that the increased cancer risk in diabetes drops substantially with long-term insulin use.

Daniel Witte, MD, PhD, research group leader at the Steno Diabetes Center in Gentofte, Denmark, and colleagues tracked the entire Danish population of 5.5 million people over 13 years to assess the association between length of insulin use and cancer incidence. The Steno Diabetes Center is owned by Novo Nordisk.

Over the past several decades, numerous studies have found elevated rates of cancer of the liver, kidney,

CARTOON

24

December 2010 I VOL 3, NO 8

female breast, and corpus uteri in diabetic patients.

The new study confirmed that there is an excess cancer risk in patients with diabetes and also that insulinusing diabetics have a higher cancer risk than diabetics not using insulin.

For example, 20.9% of nondiabetic Danish men 65 years of age and older are likely to develop cancer over the next 10 years compared with 22.3% of diabetic men not using insulin and 23.7% of diabetic men using insulin.

The corresponding figures for women are 15.4%, 16.1%, and 19.5%.

For all cancer types combined, the effect of insulin use was highest immediately after the start of treatment and decreased to a stable level 3 to 4 years after the first insulin prescription. This pattern was also seen for the duration of diabetes, with the risk being highest in the period just after diagnosis and decreasing to a point where the patient had no excess risk after 3 years.

The investigators say that theirs is the largest registry linkage study to date to focus on diabetes.

The investigators noted that their results suggest that it may not be duration or insulin that carries the risk. Instead the risk may be partly due to causes common to cancer and diabetes/insulin treatment, such as obesity.

Thyroid Cancer Patients Embrace Unconventional Treatments PARIS—Most patients with thyroid cancer report that they used some form of complementary and alternative medicine (CAM) over the past 12 months, researchers reported at the 14th International Thyroid Congress.

Jennifer E. Rosen, MD, assistant professor of surgery at Boston University School of Medicine, Massachusetts, and colleagues analyzed responses to an online questionnaire on CAM use that was completed by 1324 patients who belonged to a thyroid cancer survivors’ organization.

The survey found that 80% of patients said they had used some form of CAM therapy during the past 12 months and that only 6.6% of respondents said that they did not use any form of CAM. The two most commonly used CAM therapies were prayer (35.3%) and multivitamins (41.8%). When prayer and multivitamins were excluded from the analysis, 67.5% of patients used some form of CAM therapy during the past 12 months.

After prayer and multivitamins, the five most commonly used CAM practice therapies were massage therapy, chiropractic therapy, yoga, meditation, and acupuncture. The five most commonly used CAM biologic therapies were herbal tea, special diets, herbal supplements, homeopathy, and ginger.

CAM therapies were most often used for the treatment of symptoms (69.1%), but a high percentage of patients used CAM as part of their thyroid cancer treatment (30.9%).

More than half of patients (54.2%) said that they had used CAM more than 10 times in the past 12 months.

About two thirds of patients believed that CAM treatments were helpful, and about one third believed that they had no effect. Nearly 20% of respondents reported that their physician did not know that they were using CAM therapies and had not inquired about CAM use.

Overall, the results demonstrate that the rate of CAM use in thyroid cancer patients is twice that reported from national surveys of the general US population.

Interactive Presentation Helps Inform Patients Awaiting Cancer Surgery MELBOURNE—Investigators at the University of Melbourne are reporting favorable results using an interactive multimedia presentation (IMP) to teach prostate cancer patients scheduled for a radical prostatectomy (RP) about their procedure and potential complications.

In fact, preliminary findings show that patients who watched an IMP scored better on a knowledge test than patients who underwent the conventional surgery consent process.

For the study, 40 men wait-listed for open RP were randomized to either the standard surgery consent process or IMP. With the standard consent process, patients received detailed information about the procedure from physicians and nurses.

Patients assigned to the IMP group watched 51 slides that described basic anatomy, how the prostate works, and how the operation is performed and also provided information on potential complications and postoperative care.

About half of the slides included interactive questions that had to be answered correctly before the patient could view the next slide.

Results showed that patients in the IMP group answered 36% more questions about the procedure correctly than patients in the standard consent group.

In addition to improving patient knowledge, the IMP can help medical staff obtain informed consent and also reduce patient anxiety and potential dissatisfaction as well as the possibility of a lawsuit if the surgery is not as successful as anticipated.

Study investigator Nathan Lawrentschuk, MBBS, FRACS, a urologic oncologist, and his colleagues pointed out that although the IMP evaluated in the study was developed for prostate cancer surgery, the tool can potentially be adapted for use in patients awaiting other surgical procedures.

The investigators reported their results in the October 2010 issue of the British Journal of Urology International. ●

www.TheOncologyNurse.com

TON_December 2010_FINAL_TON 12/6/10 11:58 AM Page 25

Lung Cancer

Fast Neutron Radiotherapy May Be Safe and Effective for Lung Cancer Patients See also pages 20 & 32.

By John Schieszer

SAN DIEGO—Two studies presented at the 52nd annual meeting of the American Society for Radiation Oncology have found that the use of fast neutron radiotherapy (FNRT), a form of radiation that is about three times more powerful than typical photon radiotherapy, is highly effective and safe for patients with non–small-cell lung cancer (NSCLC).

Researchers analyzed results for NSCLC patients who were treated at a single institution from 1993 to 2006.

Treatments included a combination of fast neutron and photon radiotherapy.

FNRT lost favor in the medical community in the past because, in some cancer patients, delivering FNRT resulted in higher toxicities.

biological effectiveness for neutron radiotherapy was found to be three times greater than photon radiotherapy in the normal lung tissue and four times more

effective for targeted tumors. In the study group, there were no grade 3 or 4 toxicities. All treatment-related toxicities, such as radiation pneumonitis,

“There are only five centers in the world that are using fast neutron therapy,” said study investigator Andre Konski, MD, MBA, who is professor and chair of the Department of Radiation Oncology at Wayne State University School of Medicine, Detroit, Michigan.

“It is able to treat tumors that are resistant to photon radiotherapy.”

Konski said 20% to 30% of lung cancer patients do not respond to photon radiotherapy and still have significant symptoms. “They still need to have their symptoms palliated, and we are able to palliate their symptoms,” he said in an interview with The Oncology Nurse. “Our findings are good news, and we were happy that we did not have similar toxicities as have been seen in treating similar patients.”

Although FNRT can help with many types of cancer, it reportedly works best on lung cancer, sarcomas, glioblastomas, prostate cancer, and head and neck cancers. In the FNRT study for salvage therapy, Konski and his colleagues studied the outcomes of 20 patients with NSCLC who had failed primary treatment with chemotherapy and/or radiotherapy. The estimated clinical relative

www.TheOncologyNurse.com

Continued on page 46

Before the research is published…

DECEMB ER 2010 www.TheOn cologyNurs e.com VOL 3, NO 8

Before

CANCER

the guideline is issued…

The estimated clinical relative biological effectiveness for neutron radiotherapy was found to be three times greater than photon radiotherapy in the normal lung tissue.

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CARE COORDINATION

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VOL 1, NO

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Leadership

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Renton, Washington NavicaSNP grew collaboration and Policy (caSNP), out of • Navigation a of Jay R. Swanson, Cancer Institutethe George Washington that there is “overlapthe understanding training is designed navigators, Saint Elizabeth RN, BSN, OCN for versity’s School (GWCI) and the uni- navigation, survivorship,between patient including nurses, Cancer Institute workers, and of Public Lincoln, Nebraska and policy both of social Health

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Carol Lewis, RN, Memorial HermannBSN, OCN, CRNI The Woodlands, Texas

AONN Staff Sean T. Walsh Executive Director sean@AONNonline.org

and Services DepartmentHealth and national these intersect with local and Policy, was healthcare of Health established support from in 2009 with Steven Patierno, PhD,policy,” explained executive director Pfizer and Foundation. the Pfizer of the GWCI. “We wanted The platform to create a advance patient center’s goals are to vivorshipto talk about navigation navigation survivorship and surin the context efforts both and cancer united of policy in program.” nationally locally and a through training, The center research, offers training three levels: programs at

lay from institutions persons. Trainees try learn about across the countheir patients, barriers that affect are trained launch or improve programs, to gain tools for implementing and tutional change. insti• Executive level training is designed for chief executive officers, chief financial officers, hospital adminis-

GUIDE OUR Start a Local, PATH State, or Regional Join a Committee

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between pa ges 34 and 35

You read it first in

www.TheOncologyNurse.com December 2010 I VOL 3, NO 8

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Conference News ONS APN/IOL

Telephone Support Increases Adherence to IV Chemotherapy for Recurrent Ovarian Cancer

By Fran Lowry

ORLANDO—Women who are on intravenous (IV) chemotherapy regimens for recurrent ovarian carcinoma are at risk for nonadherence or nonpersistence with their treatment. But telephone support by an advanced practice nurse (APN) can lower this risk and even boost compliance, a new, nonrandomized study suggests.

“Nonadherence is not just an issue with oral chemotherapy,” said Susan Moore, RN, MSN, ANP, AOCN, of MCG Oncology, Chicago, Illinois, at her poster presentation. “Patients who are on IV regimens can also be nonadherent with their treatment. We think they are adherent because they show up, but often they are nonpersistent, meaning that they stop before the end of a planned regimen. Telephone support is just another way for APNs to do their outreach to patients.”

just don’t come back.”

This study evaluated the efficacy of an APN-staffed telephone patient-sup-

port program in increasing adherence to IV chemotherapy in this setting.

Participants in the program received a

Important Safety Information WARNINGS AND PRECAUTIONS: • Due to the risk of QT prolongation, ensure that potassium and magnesium are within the normal range before administration • Treatment with ISTODAX® has been associated with thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; therefore, monitor these hematological parameters during treatment with ISTODAX and modify the dose as necessary • Electrocardiographic (ECG) changes have been observed with ISTODAX

“Telephone support is just another way for APNs to do their outreach to patients.”

—Susan Moore, RN, MSN, ANP, AOCN

APNs are challenged to develop programs that support patient adherence and persistence to prescribed cancer therapies, especially therapies for advanced disease. Ovarian cancer is a particularly difficult cancer to treat, Moore noted.

“Patients who are on liposomal doxorubicin may not be completing their full six cycles. Many drop out because of side effects that are not well managed. Patients who are on this drug have usually been on other chemotherapies before, so they already know the drill,” she said. “They’re not having a very good quality of life. Sometimes patients are afraid or embarrassed to call their nurse or their doctor to tell them they want to quit. Instead, they

26

December 2010 I VOL 3, NO 8

• In patients with congenital long QT syndrome, a history of significant cardiovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation, appropriate cardiovascular monitoring precautions should be considered, such as monitoring electrolytes and ECGs at baseline and periodically during treatment • Based on its mechanism of action, ISTODAX may cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential hazard to the fetus (Pregnancy Category D) • ISTODAX binds to estrogen receptors. Advise women of childbearing potential that ISTODAX may reduce the effectiveness of estrogencontaining contraceptives

ADVERSE REACTIONS: The most common Grade 3/4 adverse reactions (>5%) regardless of causality reported in Study 1 (n=102) were infections (11%) and asthenia/fatigue (8%) and in Study 2 (n=83) were lymphopenia

Please see following pages for Brief Summary of full Prescribing Information.

telephone call from an oncology APN before and after each chemotherapy infusion for up to six cycles to reinforce

(37%), infections (33%), neutropenia (27%), leukopenia (22%), anemia (16%), asthenia/fatigue (14%), thrombocytopenia (14%), hypophosphatemia (10%), vomiting (10%), dermatitis/exfoliative dermatitis (8%), hypermagnesemia (8%), hyperuricemia (8%), hypocalcemia (6%), nausea (6%), and pruritus (6%).

The most common adverse reactions regardless of causality in Study 1 (n=102) were nausea (56%), asthenia/fatigue (53%), infections (46%), vomiting (34%), and anorexia (23%), and in Study 2 (n=83) were nausea (86%), asthenia/fatigue (77%), anemia (72%), thrombocytopenia (65%), ECG ST-T wave changes (63%), neutropenia (57%), and lymphopenia (57%).

DRUG INTERACTIONS: • ISTODAX is metabolized by CYP3A4. Avoid concomitant use with strong CYP3A4 inhibitors and potent CYP3A4 inducers if possible • Caution should also be exercised with concomitant use of moderate CYP3A4 inhibitors and P-glycoprotein (P-gp, ABCB1) inhibitors • Physicians should carefully monitor prothrombin time (PT) and International Normalized Ratio (INR) in patients concurrently administered ISTODAX and warfarin sodium derivatives

USE IN SPECIFIC POPULATIONS: • Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ISTODAX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother • Patients with moderate and severe hepatic impairment and/or patients with end-stage renal disease should be treated with caution

ISTODAX® is a registered trademark of Astellas Pharma, Inc. ©2010 Celgene Corporation 10/10 IST10074

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Conference News patient education on adverse effects to chemotherapy and the importance of reporting serious adverse effects. The APN also stressed the importance of completing the chemotherapy regimen as prescribed.

“The advanced practice nurse would do outbound calls to the patients to see how they were doing,” Moore explained. “They did not manage the

patient, because that was up to the practice. Instead, they provided additional information and let the patient know that there was somebody else out there that they could come to with their questions.”

Patients could make as many inbound calls as they wanted, she added. “They were called once per cycle, but they could call into the call center every day,

twice a day, five times a day if they needed some help or support. Some of it was psychosocial support, but most was about things like ‘I don’t feel well today and I don’t know what to do.’ The nurses would listen and give them general advice about what they could do to help themselves feel better, and then directed the women back to their physician and the nurse in the practice office.”

Pharmaceutical records were used to provide information on adherence in a group of patients undergoing similar IV chemotherapy without APN telephone support, who served as controls.

A total of 617 patients consecutively enrolled in the APN support program from January 2006 to March 2010. ● Conference News continued on page 28

ISTODAX® is indicated for treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy

Please see Important Safety Information on adjacent page.

Please see following pages for Brief Summary of full Prescribing Information.

www.TheOncologyNurse.com

December 2010 I VOL 3, NO 8

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Conference News

Survey Shows Gaps in Oncology Nurses’ Knowledge about Cardiotoxicity of Cancer Drugs

By Karen Rosenberg

ORLANDO—More education about assessment and management of cardiotoxicity would strengthen the quality

of nursing care of cancer patients, according to a new study.

The study by Wendy Vogel, MSN,

FNP, AOCONP, of Kingsport Hematology Oncology Associates, Kingsport, Tennessee, and Marilyn Haas, PhD,

ANP-BC, CNS, of CarePartners, Asheville, North Carolina, showed a gap in knowledge among oncology nurses,

Rx Only

ISTODAX® (romidepsin) for injection For intravenous infusion only The following is a brief summary only; see full prescribing information for complete product information.

1 INDICATIONS AND USAGE ISTODAX is indicated for treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.

2 DOSAGE AND ADMINISTRATION 2.1 Dosing Information The recommended dose of romidepsin is 14 mg/m2 administered intravenously over a 4-hour period on days 1, 8 and 15 of a 28-day cycle. Cycles should be repeated every 28 days provided that the patient continues to benefit from and tolerates the therapy.

2.2 Dose Modification Nonhematologic toxicities except alopecia • Grade 2 or 3 toxicity: Treatment with romidepsin should be delayed until toxicity returns to ≤Grade 1 or baseline, then therapy may be restarted at 14 mg/m2. If Grade 3 toxicity recurs, treatment with romidepsin should be delayed until toxicity returns to ≤Grade 1 or baseline and the dose should be permanently reduced to 10 mg/m2.

• Grade 4 toxicity: Treatment with romidepsin should be delayed until toxicity returns to ≤Grade 1 or baseline, then the dose should be permanently reduced to 10 mg/m2.

• Romidepsin should be discontinued if Grade 3 or 4 toxicities recur after dose reduction.

Hematologic toxicities • Grade 3 or 4 neutropenia or thrombocytopenia: Treatment with romidepsin should be delayed until the specific cytopenia returns to ANC ≥1.5×109/L and/or platelet count ≥75×109/L or baseline, then therapy may be restarted at 14 mg/m2.

• Grade 4 febrile (≥38.5ºC) neutropenia or thrombocytopenia that requires platelet transfusion: Treatment with romidepsin should be delayed until the specific cytopenia returns to ≤Grade 1 or baseline, and then the dose should be permanently reduced to 10 mg/m2.

2.3 Instructions for Preparation and Intravenous Administration ISTODAX should be handled in a manner consistent with recommended safe procedures for handling cytotoxic drugs.

4 CONTRAINDICATIONS None.

5 WARNINGS AND PRECAUTIONS 5.1 Monitoring: Laboratory Tests Due to the risk of QT prolongation, potassium and magnesium should be within the normal range before administration of ISTODAX [See Warnings and Precautions (5.3) and Adverse Reactions (6)].

5.2 Hematologic Treatment with ISTODAX can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; therefore, these hematological parameters should be monitored during treatment with ISTODAX, and the dose should be modified, as necessary [See Dosage and Administration (2.2) and Adverse Reactions (6)].

5.3 Electrocardiographic Changes Several treatment-emergent morphological changes in ECGs (including T-wave and STsegment changes) have been reported in clinical studies. The clinical significance of these changes is unknown [See Adverse Reactions (6)].

In patients with congenital long QT syndrome, patients with a history of significant cardiovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.

5.4 Use in Pregnancy There are no adequate and well-controlled studies of ISTODAX in pregnant women.

However, based on its mechanism of action, ISTODAX may cause fetal harm when administered to a pregnant woman. A study in rats did not expose pregnant animals to enough romidepsin to fully evaluate adverse outcomes.

If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential hazard to the fetus [See Use in Specific Populations (8.1)].

5.5 Use in Women of Childbearing Potential Advise women of childbearing potential that ISTODAX may reduce the effectiveness of estrogen-containing contraceptives. An in vitro binding assay determined that romidepsin competes with β-estradiol for binding to estrogen receptors [See Nonclinical Toxicology (13.1)].

6 ADVERSE REACTIONS 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the

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December 2010 I VOL 3, NO 8

clinical trials of another drug and may not reflect the rates observed in practice.

The safety of ISTODAX was evaluated in 185 patients with CTCL in 2 single arm clinical studies in which patents received a starting dose of 14 mg/m2. The mean duration of treatment in these studies was 5.6 months (range: <1 to 83.4 months).

Common Adverse Reactions Table 1 summarizes the most frequent adverse reactions (>20%) regardless of causality using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCICTCAE, Version 3.0). Due to methodological differences between the studies, the AE data are presented separately for Study 1 and Study 2. Adverse reactions are ranked by their incidence in Study 1. Laboratory abnormalities commonly reported (>20%) as adverse reactions are included in Table 1.

Table 1. Adverse Reactions Occurring in >20% of Patients in Either CTCL Study (N=185) Study 1 (n=102) Adverse Reactions n (%) Any adverse reaction Nausea Asthenia/fatigue Infections Vomiting Anorexia Hypomagnesemia Diarrhea Pyrexia Anemia Thrombocytopenia Dysgeusia Constipation Neutropenia Hypotension Pruritus Hypokalemia Dermatitis/Exfoliative dermatitis Hypocalcemia Leukopenia Lymphopenia Alanine aminotransferase increased Aspartate aminotransferase increased Hypoalbuminemia Electrocardiogram ST-T wave changes Hyperglycemia Hyponatremia Hypermagnesemia Hypophosphatemia Hyperuricemia

Study 2 (n=83)

All

Grade 3 or 4

All

Grade 3 or 4

99 (97) 57 (56) 54 (53) 47 (46) 35 (34) 23 (23) 22 (22) 20 (20) 20 (20) 19 (19) 17 (17) 15 (15) 12 (12) 11 (11) 7 (7) 7 (7) 6 (6) 4 (4) 4 (4) 4 (4) 4 (4) 3 (3) 3 (3) 3 (3) 2 (2) 2 (2) 1 (<1) 0 0 0

36 (35) 3 (3) 8 (8) 11 (11) 1 (<1) 1 (<1) 1 (<1) 1 (<1) 4 (4) 3 (3) 0 0 2 (2) 4 (4) 3 (3) 0 0 1 (<1) 0 0 0 0 0 1 (<1) 0 2 (2) 1 (<1) 0 0 0

83 (100) 71 (86) 64 (77) 45 (54) 43 (52) 45 (54) 23 (28) 22 (7) 19 (23) 60 (72) 54 (65) 33 (40) 32 (39) 47 (57) 19 (23) 26 (31) 17 (20) 22 (27) 43 (52) 38 (46) 47 (57) 18 (22) 23 (28) 40 (48) 52 (63) 42 (51) 17 (20) 22 (27) 22 (27) 27 (33)

68 (82) 5 (6) 12 (14) 27 (33) 8 (10) 3 (4) 0 1 (1) 1 (1) 13 (16) 12 (14) 0 1 (1) 22 (27) 3 (4) 5 (6) 2 (2) 7 (8) 5 (6) 18 (22) 31 (37) 2 (2) 3 (4) 3 (4) 0 1 (1) 2 (2) 7 (8) 8 (10) 7 (8)

Serious Adverse Reactions Serious adverse reactions reported in > 2% of patients in Study 1 were infection, sepsis, and pyrexia. In Study 2, serious adverse reactions in > 2% of patients were infection, supraventricular arrhythmia, neutropenia, fatigue, edema, central line infection, ventricular arrhythmia, nausea, pyrexia, leukopenia, and thrombocytopenia.

Most deaths were due to disease progression. In Study 1, there were two deaths due to cardiopulmonary failure and acute renal failure. In Study 2, there were six deaths due to infection (4), myocardial ischemia, and acute respiratory distress syndrome.

Discontinuations Discontinuation due to an adverse event occurred in 21% of patients in Study 1 and 11% in Study 2. Discontinuations occurring in at least 2% of patients in either study included infection, fatigue, QT prolongation, and dyspnea.

7 DRUG INTERACTIONS 7.1 Coumadin or Coumadin Derivatives Prolongation of PT and elevation of INR were observed in a patient receiving ISTODAX concomitantly with warfarin. Although the interaction potential between ISTODAX and Coumadin or Coumadin derivatives has not been formally studied, physicians should carefully monitor PT and INR in patients concurrently administered ISTODAX and Coumadin or Coumadin derivatives [See Clinical Pharmacology (12.3)].

7.2 Drugs that Inhibit or Induce Cytochrome P450 3A4 Enzymes Romidepsin is metabolized by CYP3A4. Although there are no formal drug interaction studies for ISTODAX, strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) may increase concentrations of romidepsin. Therefore, co-administration with strong CYP3A4 inhibitors should be avoided if possible. Caution should be exercised with concomitant use of moderate CYP3A4 inhibitors.

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Conference News including advanced practice nurses (APNs), treating women with breast cancer. “This is a wide-open field for oncology nursing research,” said Vogel, who presented the findings.

To evaluate oncology nurses’ knowledge and practice patterns regarding cardiotoxicity in women with earlystage breast cancer treated with human epidermal growth factor receptor 2

inhibitors/vascular endothelial growth factor inhibitors, the researchers developed a 24-item survey. Surveys were distributed before and after the 2009 Advanced Practice Nursing Conference/Institutes of Learning. Of the 248 nurses who responded to the survey, 88% of respondents worked in medical oncology settings; 26% identified themselves as APNs, 49% as

Co-administration of potent CYP3A4 inducers (e.g., dexamethasone, carbamazepine, phenytoin, rifampin, rifabutin, rifapentine, phenobarbital) may decrease concentrations of romidepsin and should be avoided if possible. Patients should also refrain from taking St. John’s Wort.

7.3 Drugs that Inhibit Drug Transport Systems Romidepsin is a substrate of the efflux transporter P-glycoprotein (P-gp, ABCB1). If ISTODAX is administered with drugs that inhibit P-gp, increased concentrations of romidepsin are likely, and caution should be exercised.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category D [See ‘Warnings and Precautions’ section].

There are no adequate and well-controlled studies of ISTODAX in pregnant women.

However, based on its mechanism of action, ISTODAX may cause fetal harm when administered to a pregnant woman. A study in rats did not expose pregnant animals to enough romidepsin to fully evaluate adverse developmental outcomes. If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential harm to the fetus.

In an animal reproductive study, pregnant rats received daily intravenous romidepsin during the period of organogenesis up to a dose of 0.06 mg/kg/day (0.36 mg/m2/day). This dose in rats is approximately equivalent to 18% the estimated human daily dose based on body surface area and resulted in 5% reduction in fetal weight. Embryofetal toxicities associated with the use of ISTODAX were not adequately assessed in this study.

8.3 Nursing Mothers It is not known whether romidepsin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ISTODAX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use The safety and effectiveness of ISTODAX in pediatric patients has not been established.

8.5 Geriatric Use Of the 167 patients with CTCL in trials, 23% were >65 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects; however, greater sensitivity of some older individuals cannot be ruled out.

8.6 Hepatic Impairment No dedicated hepatic impairment study for ISTODAX has been conducted. Mild hepatic impairment does not alter pharmacokinetics of romidepsin based on a population pharmacokinetic analysis. Patients with moderate and severe hepatic impairment should be treated with caution [See Clinical Pharmacology (12.3)].

8.7 Renal Impairment No dedicated renal impairment study for ISTODAX has been conducted. Based upon the population pharmacokinetic analysis, renal impairment is not expected to significantly influence drug exposure. The effect of end-stage renal disease on romidepsin pharmacokinetics has not been studied. Thus, patients with end-stage renal disease should be treated with caution [See Clinical Pharmacology (12.3)].

10 OVERDOSAGE No specific information is available on the treatment of overdosage of ISTODAX. Toxicities in a single-dose study in rats or dogs, at intravenous romidepsin doses up to 2.2 fold the recommended human dose based on the body surface area, included irregular respiration, irregular heart beat, staggering gait, tremor, and tonic convulsions.

In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., clinical monitoring and supportive therapy, if required. There is no known antidote for ISTODAX and it is not known if ISTODAX is dialyzable.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been performed with romidepsin. Romidepsin was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Romidepsin was not clastogenic in an in vivo rat bone marrow micronucleus assay when tested to the maximum tolerated dose (MTD) of 1 mg/kg in males and 3 mg/kg in females (6 and 18 mg/m2 in males and females, respectively). These doses were up to 1.3-fold the recommended human dose, based on body surface area.

Based on non-clinical findings, male and female fertility may be compromised by treatment with ISTODAX. In a 26-week toxicology study, romidepsin administration resulted in testicular degeneration in rats at 0.33 mg/kg/dose (2 mg/m2/dose) following the clinical dosing schedule. This dose resulted in AUC0-inf. values that were approximately 2% the exposure level in patients receiving the recommended dose of 14 mg/m2/dose. A similar effect was seen in mice after 4 weeks of drug administration at higher doses. Seminal vesicle and prostate organ weights were decreased in a separate study in rats after 4 weeks of daily drug administration at 0.1 mg/kg/day (0.6 mg/m2/day), approximately 30% the estimated human daily dose based on body surface area. Romidepsin showed high affinity for binding to estrogen receptors in pharmacology studies. In a 26-week toxicology study in rats, atrophy was seen in the ovary, uterus, vagina and mammary gland of females administered doses as low as 0.1 mg/kg/dose (0.6 mg/m2/dose) following the clinical dosing schedule. This dose resulted in AUC0-inf. values that were 0.3% of those in patients receiving the recommended dose of 14 mg/m2/dose. Maturation arrest of ovarian follicles and decreased weight of ovaries were observed in a separate study in rats after four weeks of daily drug administration at 0.1 mg/kg/day (0.6 mg/m2/day). This dose is approximately 30% the estimated human daily dose based on body surface area.

www.TheOncologyNurse.com

staff nurses, and 25% as other. Fiftyeight percent worked in the community outpatient setting, and 56% reported spending at least 1 to 2 hours per week educating breast cancer patients about cardiotoxicity.

Only 12% of the survey respondents said they felt very comfortable about assessing cardiotoxicity, and 25% reported feeling less than comfortable.

16 HOW SUPPLIED/STORAGE AND HANDLING Keep out of reach of children.

Procedures for proper handling and disposal of anticancer drugs should be considered.

Several guidelines on this subject have been published [See References (15)].

17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling.

17.1 Instructions • Patients should be instructed to report excessive nausea or vomiting, abnormal heartbeat, chest pain, or shortness of breath to their physician. Patients receiving ISTODAX should seek immediate medical attention if unusual bleeding occurs.

• ISTODAX binds to estrogen receptors. Advise women of childbearing potential that ISTODAX may reduce the effectiveness of estrogen-containing contraceptives [See Warnings and Precautions (5.5)].

• Patients should be instructed to read the patient insert carefully.

More than 10% of respondents were uncertain which breast cancer drugs can cause cardiotoxicity, and more than 20% were unsure whether chemotherapeutic agents were discontinued or dose-reduced because of cardiotoxicity in their practice.

Respondents reported that their primary resource used for managing breast cancer was textbooks (34%) followed by pharmaceutical representatives (18%), national guidelines (18%), and the Internet (17%). This was concerning, Vogel said, because textbooks do not provide the most up-to-date information, and guidelines prepared by the American Heart Association and American College of Cardiology are not specific for cancer patients.

Only 12% of the survey respondents said they felt very comfortable about assessing cardiotoxicity, and 25% reported feeling less than comfortable.

Evidence-based guidelines on assessment and management of cardiotoxicity in patients with cancer are needed, Vogel said. This is becoming increasingly important, she explained, because “we’re seeing patients age with cancer.”

Better communication is needed between oncologists and cardiologists, she added, and “that’s where oncology nurses can make a difference—coordination of care.” ●

For more ONS APN/IOL news and pictures, see the February 2011 issue of The Oncology Nurse-APN/PA.

Recent FDA Approval

Manufactured for: Celgene Corporation Summit, NJ 07901 Manufactured by: Ben Venue Laboratories, Inc. Bedford, OH 44146 ISTODAX® is a registered trademark of Astellas Pharma, Inc. U.S. Patents: 4,977,138; 7,608,280; 7,611,724 ISTBVPI.001/PPI.001

03/10

Revised: March 2010

Eribulin for Late-stage Refractory Breast Cancer The US Food and Drug Admin istration (FDA) has approved eribulin mesylate (Halaven, Eisai) to treat patients with metastatic breast cancer who have received at least two previous chemotherapy regimens for late-stage disease.

Approval was based on a single study of 762 patients who were randomized to either treatment with eribulin or another singleagent therapy chosen by their oncologist.

December 2010 I VOL 3, NO 8

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CONTINUING EDUCATION PROGRAM CE5 • RELEASE DATE: DECEMBER 15, 2010 • EXPIRATION DATE: DECEMBER 15, 2011 ESTIMATED TIME TO COMPLETE: 1.0 HOUR

Maintenance Therapy in Patients with Advanced Non–small-cell Lung Cancer

By Federico Cappuzzo, MD Professor and Director, Department of Medical Oncology, Ospedale Riuniti, Livorno, Italy

STATEMENT OF NEED

Non–small-cell lung cancer (NSCLC) is frequently diagnosed at an advanced stage. Firstline treatment of advanced disease typically includes platinum-doublet chemotherapy; however, after initial clinical benefit most patients develop progressive disease within 2 to 3 months of their final cycle of chemotherapy. In addition, a large percentage of patients do not have the opportunity to receive effective therapy following first-line treatment, making active maintenance an attractive option.

Erlotinib, an oral epidermal growth factor receptor tyrosine-kinase inhibitor, is an established second-line treatment for advanced NSCLC. The agent’s proven efficacy coupled with its oral administration and acceptable tolerability provide a strong rationale for investigation of its potential role as maintenance therapy. Although we do not yet know whether using an agent like erlotinib as fist-line maintenance is better than using the same agent only at disease progression, the likelihood of rapid progression after first-line chemotherapy coupled with a lack of means of predicting who will have the opportunity to receive second-line therapy strongly supports the use of maintenance therapy.

TARGET AUDIENCE

Advanced practice nurses, registered nurses, and other interested healthcare professionals, especially those caring for cancer patients LEARNING OBJECTIVE

After completing this activity, the reader should be able to: • Discuss maintenance therapy in patients with nonprogressive NSCLC following firstline platinum-doublet chemotherapy.

N

on–small-cell lung cancer (NSCLC) is the most common type of lung cancer and is frequently diagnosed at an advanced stage, when effective therapeutic options are limited. First-line treatment of advanced disease typically includes platinum-doublet chemotherapy, which is associated with a median overall survival (OS) of 8 to 11 months.1 Approximately 70% to 80% of patients receiving first-line chemotherapy will show clinical benefit,2-5 but most patients will develop progressive disease within 2 to 3 months of their final cycle of chemotherapy.3,6,7 Unfortunately, clinical trials of long-duration platinumbased chemotherapy as first-line treatment have consistently shown increased toxicity with little or no survival improvement.8-13

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December 2010 I VOL 3, NO 8

Second-line treatments are indicated after disease progression; however, between one third and one half of patients do not receive second-line therapy.3,6,7,9-11,14-17 Patients may be ineligible for second-line therapy because of rapid disease progression, worsening performance status, or increased symptom burden.7 As a result, a large percentage of patients do not have the

Approximately 70% to 80% of patients receiving first-line chemotherapy will show clinical benefit, but most patients will develop progressive disease within 2 to 3 months of their final cycle of chemotherapy.

opportunity to receive effective therapy following first-line treatment. Active maintenance therapy (ie, treatment given after initial chemotherapy in the absence of disease progression) should, in theory, improve survival because it allows clinicians not only to provide access to more lines of effective treatment but also to treat a larger number of patients, including those who might otherwise be ineligible for additional lines of therapy.

Trials of maintenance therapy Several previous phase 3 trials have shown an improvement in OS with maintenance therapy with chemotherapeutic agents compared with initiation of second-line therapy at the time of disease progression.18 Fidias and associates compared immediate with delayed docetaxel after frontline therapy with gemcitabine plus carboplatin in 309 patients with advanced NSCLC.7 They found a statistically significant improvement in progression-free survival (PFS) and a nonstatistically significant increase in OS with immediate versus delayed docetaxel without increased toxicity or decreased quality of life.

Ciuleanu and colleagues compared maintenance therapy with pemetrexed with placebo after four cycles of plat-

inum-based chemotherapy in 663 patients with advanced NSCLC.6 Pemetrexed therapy was well tolerated and improved both PFS and OS. Pemetrexed was the first chemotherapy approved by the US Food and Drug Administration as maintenance therapy for nonsquamous NSCLC (Eli Lilly press release. July 6, 2009).

The SATURN trial Erlotinib, an oral epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor, is an established second-line treatment for advanced NSCLC. The agent’s proven efficacy coupled with its oral administration and acceptable tolerability provide a strong rationale for investigation of its potential role as maintenance therapy.19-24 The Sequential Tarceva in Unresectable NSCLC (SATURN) trial was designed to examine the effect of erlotinib as maintenance therapy on PFS in patients with nonprogressive disease following first-line platinum-doublet chemotherapy.25 The randomized, CONTINUING NURSING EDUCATION ACCREDITATION AND CONTACT HOURS STATEMENT

Science Care is approved by the California Board of Registered Nursing, Provider number 15559, for 1.0 Contact hour.

METHOD OF PARTICIPATION

1. Read the article in its entirety 2. Go to www.TheOncologyNurse.com 3. Select “Continuing Education” 4. Click on this article’s title from the list shown 5. Select “Click here to complete the posttest and obtain a CE certificate online” 6. Complete and submit the CE posttest and CE Activity Evaluation 7. Print your Certificate of Credit This activity is provided free of charge to participants.

placebo-controlled, phase 3 trial was conducted at 110 sites in 26 countries.

Study population and protocol The trial included 889 patients who had completed four cycles of standard platinum-doublet chemotherapy without disease progression and unacceptable toxicity. Patients were randomized to receive erlotinib, 150 mg/day, or placebo until progression or unacceptable toxicity or death. Patients were stratified by EGFR immunohistochemistry status, disease stage, Eastern Cooperative Oncology Group (ECOG) performance status, chemotherapy regimen, smoking history, and region.

The coprimary end points were PFS in all analyzable patients regardless of EGFR status, and PFS in patients with EGFR immunohistochemistry–positive tumors.

Results Overall, 437 patients in the erlotinib group and 447 patients in the placebo group were evaluable for PFS. Disclosures are as follows: • Frederico Cappuzzo, MD, has nothing to disclose.

• Dawn Lagrosa has nothing to disclose.

• Tara L. Rich, MSN, RN, CNP, has nothing to disclose.

• Karen Rosenberg has nothing to disclose.

• Jill Stein has nothing to disclose.

The staff of Science Care have nothing to disclose.

DISCLAIMER

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EDITORIAL BOARD

Frederico Cappuzzo, MD Professor and Director Department of Medical Oncology Ospedale Riuniti 57124 Leghorn 0586 223111 Italy Tara L. Rich, MSN, RN, CNP Taussig Cancer Institute Cleveland Clinic 9500 Euclid Avenue Cleveland, OH 44195

www.TheOncologyNurse.com

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www.TheOncologyNurse.com After a median follow-up of 11.4 months in the erlotinib group and 11.5 months in the placebo group, median PFS was significantly longer with erlotinib than with placebo in all evaluable patients irrespective of EFGR status: 12.3 weeks for the erlotinib group versus 11.1 weeks for the placebo group (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.62-0.2; P <.0001). PFS was also significantly prolonged in erlotinibtreated patients with EGFR immunohistochemistry–positive tumors (median PFS, 12.3 vs 11.1 weeks; HR, 0.69; 95% CI, 0.58-0.82; P <.0001). An improvement in PFS was observed in all patient subgroups regardless of gender, ethnic origin, histology, or smoking status.

Erlotinib was also superior to placebo in PFS for both EGFR mutation–positive and EGFR wild-type subgroups, with the greatest benefit shown in patients with EGFR mutation–positive tumors.

OS, a secondary end point, was significantly prolonged with erlotinib versus placebo in the intention-to-treat population (median 12.0 vs 11.0 months; HR, 0.81; 95% CI, 0.70-0.95; P = .0088).

Safety and quality of life Erlotinib was well tolerated in the maintenance setting, the incidence and severity of side effects being slightly lower than those noted in an earlier phase 3 study of second-line and third-

Erlotinib was also superior to placebo in PFS for both EGFR mutation–positive and EGFR wild-type subgroups, with the greatest benefit shown in patients with EGFR mutation–positive tumors. line erlotinib.21 The most common adverse events were skin rash and diarrhea, which were usually mild to moderate. Skin rash occurred in 37 (9%) of 443 erlotinib-treated patients versus none of 445 placebo-treated patients, and diarrhea occurred in seven (2%) erlotinib patients versus no placebo patients. Serious adverse events were documented in 47 (11%) patients ran-

domized to erlotinib versus 34 (8%) patients assigned to placebo. The most frequently reported serious event was pneumonia, occurring in seven (2%) patients receiving erlotinib and four (<1%) patients receiving placebo. Most patients on erlotinib did not need dose reductions or interruptions.

Quality-of-life measures, which were Continued on page 32

COMMENTARY

Using the Results of the SATURN Study

By Tara L. Rich, MSN, RN, CNP Taussig Cancer Institute Cleveland Clinic, Ohio

I

recently attended a presentation on the emerging concept of clinical pathways in the context of healthcare reform. The concept caused me to think about the role of the oncology practitioner as it parallels that of an artist. It is the concepts of interpretation, patient individuality, and creativity that drive our medical decisions when we care for patients. In the past 2 years, the emerging data on the treatment of advanced non–small-cell lung cancer (NSCLC) have both increased our ability to be creative in our decision making and caused confusion in doing so.

Standard first-line treatment of advanced stage NSCLC is platinumdoublet chemotherapy, which has been proven by multiple trials, with a median overall survival (OS) of 8 to 11 months.1,2 Until recently, the standard of care was to implement second-line therapy only after disease progression.3,4 For many reasons, such as poor performance status and rapid progression of disease for example, some patients are not able to proceed with secondline therapy. In 2009, maintenance pemetrexed was proved to be superior to best supportive care after four cycles of platinum-doublet chemotherapy, with a statistically significant increase in both progression-free survival (PFS) and OS.5 In another study, Fidias and associates compared immediate versus delayed second-line docetaxel (75 mg/m2, 21-day cycle) after four cycles of first-line gemcitabine (days 1, 8)/carboplatin (day 1) in a phase 3 clinical trial, demonstrating a statistically significant difference in PFS, although no significant difference in OS, with the

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immediate-docetaxel arm.6 The Sequential Tarceva in Unresectable NSCLC (SATURN) trial, a randomized, placebo-controlled phase 3 study, compared maintenance erlotinib (150 mg/day) with placebo, following four cycles of platinum-based chemotherapy.7 PFS was analyzable in 884 patients, which is, in my opinion, a significant sample size considering the target population of advanced NSCLC patients who were able to receive four cycles of platinum-doublet chemotherapy without disease progression and maintain an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. The coprimary end points were PFS in all patients and PFS in patients with tumors that demonstrated epidermal growth factor receptor (EGFR) protein overexpression by immunohistochemistry (IHC) status.

The results demonstrated improvement in PFS in the erlotinib arm in all analyzable patients, a median time of 12.3 versus 11.1 weeks (hazard ratio [HR], 0.71; P <.0001). The median time of PFS was exactly the same for the patients with tumors that were EGFRpositive by IHC (HR, 0.69; P <.0001).

Of more interest, the proportion of patients with PFS at 6 months was 25% in the erlotinib arm compared with 15% in those receiving placebo. The subgroup analysis of PFS was interesting, demonstrating a benefit with erlotinib compared with placebo, irrespective of histology. Of most importance, OS was significantly prolonged with erlotinib versus placebo in the intention-to-treat population (median, 12.0 vs 11.0 months; HR, 0.81; P = .0088) in addition to the EGFR-positive-by-IHC pop-

ulation (HR, 0.77; P = .0063), as well as those without activating EGFR mutations (HR, 0.77; P = .0234). We are awaiting the subgroup analysis results of the OS data for the EGFR-positive-by IHC population, including those who received second-line erlotinib after disease progression. The SATURN study is the first to look at tyrosine-kinase inhibitor targeted therapy in the maintenance setting after first-line platinumdoublet chemotherapy. Its results have led to a new indication for erlotinib and open the door to further studies of targeted therapies for maintenance.

Another study, ECOG 4599, introduced the use of bevacizumab, a monoclonal antibody against the vascular endothelial growth factor, in conjunction with the standard doublet of paclitaxel/carboplatin, which was maintained until disease progression.

Based on the statistically significant results, it is now standard of care to assess bevacizumab eligibility in patients beginning first-line platinumdoublet chemotherapy. Typically, clinicians continue bevacizumab until disease progression, because that was the study’s design. An as yet unopened ECOG trial, NCT01107626, will investigate the use of maintenance bevacizumab versus maintenance pemetrexed. Patients with advanced stage NSCLC will receive four cycles of paclitaxel/carboplatin/bevacizumab, followed by randomization to one of three maintenance arms: pemetrexed alone, bevacizumab alone, or a pemetrexed/bevacizumab combination.8 Although this study is not yet open for accrual, it should be very interesting to follow its outcomes.

Even with recent trials validating the efficacy of immediate second-line docetaxel, maintenance pemetrexed, and maintenance erlotinib, questions remain unanswered. Future studies, including NCT01107626, will help us better select the appropriate maintenance treatment for individual patients.

Continued studies in combination with clinical judgment will further assist us in determining the value of immediate or maintenance therapy versus treatment breaks until disease progression. ● References 1. Ramalingam S, Belani CP. Systemic chemotherapy for advanced non-small cell lung cancer: recent advances and future directions. Oncologist. 2008; 13(suppl 1):5-13.

2. Schiller JH, Harrington D, Belani CP, et al; for the Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-smallcell lung cancer. N Engl J Med. 2002;346:92-98.

3. 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.

4. Socinski MA, Schell MJ, Peterman A, et al. Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced stage IIIB/IV non-small-cell lung cancer. J Clin Oncol. 2002;20:1335-1343.

5. Ciuleanu T, Brodowicz T, Zielinski C, et al.

Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study.

Lancet. 2009;374:1432-1440.

6. Fidias PM, Dakhil SR, Lyss AP, et al. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J Clin Oncol.

2009;27:591-598.

7. Cappuzzo F, Ciuleanu T, Stelmakh L, et al; for the SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010;11:521-529.

8. Bevacizumab or pemetrexed disodium alone or in combination after induction therapy in treating patients with advanced non-squamous non-small cell lung cancer. Clinicaltrials.gov identifier NCT01107626. www. clinicaltrials.gov. Accessed August 8, 2010.

December 2010 I VOL 3, NO 8

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CONTINUING EDUCATION Continued from page 31

Maintenance Therapy in Patients with Advanced Non–small-cell Lung Cancer evaluated using the widely validated Functional Assessment of Cancer Therapy-Lung questionnaire, were similar in the erlotinib and placebo groups. Notably, erlotinib-treated patients had a longer time to pain onset and the need for analgesics.

The SATURN study is, to our knowledge, the first to demonstrate that maintenance therapy with a targeted agent after a conventional firstline platinum-based chemotherapy regimen can significantly prolong PFS and OS in advanced NSCLC. Based on the results of the study, the US Food and Drug Administration approved erlotinib for maintenance therapy of NSCLC. Conclusions • A molecularly targeted therapy, given as maintenance immediately after a standard first-line platinumbased chemotherapy regimen, can significantly improve the outcome of metastatic NSCLC. • Erlotinib significantly improves PFS in patients who have completed four cycles of standard platinumdoublet chemotherapy without disease progression and unacceptable toxicity, irrespective of EGFR status.

• Maintenance erlotinib significantly improves PFS in patients with EGFR immunohistochemistry–positive tumors.

• The superiority of erlotinib as maintenance therapy over placebo in

PFS prolongation is not influenced by patient gender, ethnic origin, histology, or smoking status.

• Erlotinib is well tolerated when used as maintenance therapy.

It has not yet been determined, however, whether using an agent as firstline maintenance yields better results than using the same agent at disease progression.

Clinical recommendations Although we do not yet know whether using an agent like erlotinib as first-line maintenance is better than using the same agent only at disease progression, the likelihood of rapid progression after first-line chemotherapy coupled with a lack of means of predicting who will have the opportunity to receive second-line therapy strongly supports the use of maintenance therapy. The use of treatment immediately after first-line chemotherapy increases the number of patients who might benefit from active therapy by postponing disease progression and lengthening survival. ● References 1. Ramalingam S, Belani CP. Systemic chemotherapy for advanced non-small cell lung cancer: recent advances and future directions. Oncologist. 2008;13(suppl 1):5-13.

2. Reck M, von Pawel J, Zatloukal P, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-smalllung cancer (AVAiL). J Clin Oncol. 2009;27:1227-1234.

3. Brodowicz T, Krzakowski M, Zwitter M, et al; for the Central European Cooperative Oncology Group CECOG. Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial. Lung Cancer. 2006;52:155-163.

4. Leighl NB, Paz-Ares L, Doullard JY, et al. Randomied phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell-lung cancer.

National Cancer Institute of Canada-Clinical Trials Group Study BR.18. J Clin Oncol. 2005;23:2831-2839.

5. Williamson SK, Crowley JJ, Lara PN Jr, et al. Phase III trial of paclitaxel plus carboplatin with or without tirapazamine in advanced non-small-cell lung cancer: Southwest Oncology Group Trial S0003. J Clin Oncol.

2005;23:9097-9104.

6. Ciuleanu T, Brodowicz T, Zielinski C, et al.

Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study.

Lancet. 2009;374:1432-1440.

7. Fidias PM, Dakhil SR, Lyss AP, et al. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J Clin Oncol.

2009;27:591-598.

8. Socinski MA, Schell MJ, Peterman A, et al. Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced stage IIIB/IV non-small-cell lung cancer.

J Clin Oncol. 2002;20:1335-1343.

9. von Plessen C, Bergman B, Andresen O, et al.

Palliative chemotherapy beyond three courses conveys no survival or consistent quality-of-life benefits in advanced non-small-cell lung cancer. Br J Cancer.

2006;95:966-973.

10. Barata FJ, Parente B, Teixeira E, et al. Optimal duration of chemotherapy in non-small-cell lung cancer: multicenter, randomized, prospective clinical trial comparing 4 vs 6 cycles of carboplatin and gemcitabine [abstract]. J Thoracic Oncol. 2007;2(suppl 4):S666.

11. Park JO, Kim SW, Ahn JS, et al. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non-small-cell lung cancer. J Clin Oncol. 2007;25:5233-5239.

12. Smith IE, O’Brien MER, Talbot DC, et al. Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol. 2001; 19:1336-1343.

13. Pfister DG, Johnson DH, Azzoli CG, et al; for the American Society of Clinical Oncology. American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003.

J Clin Oncol. 2004;22:330-353.

14. Belani CP, Barstis J, Perry MC, et al. Multicenter, randomized trial for stage IIIB or IV non-small-cell lung cancer using weekly paclitaxel and carboplatin followed by maintenance weekly paclitaxel or observation. J Clin Oncol. 2003;21:2933-2939.

15. Pirker R, Pereira JR, Szczesna A, et al; for the FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009; 373:1525-1531.

16. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naïve patients with advanced-stage non-small-cell-lung cancers. J Clin Oncol. 2008;26:3543-3551.

17. Stinchcombe TE, Socinski MA. Treatment paradigms for advanced stage non-small-cell lung cancer in the era of multiple lines of therapy. J Thoracic Oncol.

2009;4:243-250.

18. Stinchcombe TE, Evans T. Role of maintenance therapy in advanced non-small-cell lung cancer. In: American Society of Clinical Oncology. 2010 Educational Book. Alexandria, VA: American Society of Clinical Oncology; 2010:297-302.

19. Azzoli CG, Baker S Jr, Temin S, et al; for the American Society of Clinical Oncology. American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV nonsmall-cell lung cancer. J Clin Oncol. 2009;27:6251-6266.

20. D’Addario G, Felip E; for the ESMO Guidelines Working Group. Non-small-cell lung cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009;20(suppl 4):68-70.

21. Shepherd FA, Pereira JR, Ciuleanu T, et al; for the National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123-132.

22. Bezjak A, Tu D, Seymour L, et al. Symptom improvement in lung cancer patients treated with erlotinib: quality of life analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21.

J Clin Oncol. 2006;24:3831-3837.

23. Ramalingam S, Sandler AB. Salvage therapy for advanced non-small cell lung cancer: factors influencing treatment selection. Oncologist. 2006;11:655-665.

24. Gatzemeier U, Pluzanska A, Szczesna A, et al. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol. 2007;25:1545-1552.

25. Cappuzzo F, Ciuleanu T, Stelmakh L, et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomized, placebo-controlled phase 3 study. Lancet Oncol. 2010;11:521-529.

Jill Stein contributed to the preparation of this article.

LUNG CANCER

Low-dose CT Screening Found to Reduce Lung Cancer Deaths in Large Study See also pages 20 & 25.

By Karen Rosenberg

A

large National Cancer Institute (NCI)-sponsored study has shown for the first time that a screening method can reduce deaths from lung cancer by detecting cancers at relatively early stages.

The National Lung Screening Trial (NLST), a randomized national trial involving more than 53,000 current and former heavy smokers aged 55 to 74 years, compared the effects of two screening methods for lung cancer— low-dose helical computed tomography (CT) and standard chest radiography—on lung cancer mortality. Results showed a highly significant 20% reduction in lung cancer deaths among trial participants screened with low-dose helical CT. “A validated approach that can re -

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duce lung cancer mortality by even 20% has the potential to spare very significant numbers of people from the ravages of this disease,” said NCI Director Harold Varmus, MD. NLST participants were required to have a smoking history of at least 30 pack-years and were either current or former smokers without signs, symptoms, or history of lung cancer at enrollment. Participants were randomly assigned to receive three annual screens with either low-dose helical CT (often referred to as spiral CT) or standard chest radiography. Screening was done at enrollment and at the end of their first and second years on the trial, and participants were then followed for up to another 5 years.

As of October 20, 2010, 354 partici-

pants in the CT arm of the study had died of lung cancer compared with 442 of those in the chest radiography group.

The Data and Safety Monitoring Board concluded that this 20.3% reduction in lung cancer mortality met the standard for statistical significance.

“The fact that low-dose helical CT provides a decided benefit is a result that will have implications for the screening and management of lung cancer for many years to come,” said Christine Berg, MD, NLST, project officer for the Lung Screening Study at NCI. An ancillary finding was that all-cause mortality was 7% lower in participants screened with low-dose helical CT than in those screened with chest radiography.

Further analysis will be required to fully elucidate the reason for this difference.

The investigators do not recommend helical CT screening for all smokers, pointing out that it has several possible disadvantages, including the cumulative effects of radiation from multiple CT scans; false-positive results leading to further tests and procedures with possible complications; and costs and anxiety related to the screening process itself. They note too that the population enrolled in this study was a highly motivated and primarily urban group that was screened at major medical centers, and the results may not accurately predict the effects of recommending low-dose helical CT scanning for other populations.

Further information about the NLST can be found at www.cancer.gov/news center/qa/2002/nlstqaQA. ●

www.TheOncologyNurse.com

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Chronic Lymphocytic Leukemia The Essentials of Patient Care LOG ON TODAY TO PARTICIPATE www.coexm.com/ace02.asp Release Date: April 29, 2010 Expiration Date: April 28, 2011

TARGET AUDIENCE This activity is intended for hematologists, oncologists and others who are involved with the care of patients with Chronic Lymphocytic Leukemia (CLL).

STATEMENT OF NEED CLL is the most common type of leukemia in the United States, with over 15,000 new cases per year, characterized by the accumulation of monoclonal B cells in the bone marrow, peripheral blood, and lymphoid tissue. Primarily a disease of the elderly, the median survival for CLL varies substantially: many patients survive more than 10 years after diagnosis, but a subset of symptomatic patients have shorter life expectancies—in the range of 1.5 to 6 years. The clinical/research body of knowledge in CLL is rapidly changing and represents a challenge for the whole treatment team.

FACULTY Neil E. Kay, MD Professor Department of Medicine Mayo Clinic Rochester, Minnesota

Michael Keating, MD Course Chair Professor of Medicine Deputy Department Chairman Department of Leukemia M.D. Anderson Cancer Center Houston, Texas

EDUCATIONAL OBJECTIVES On completion of this activity, participants should be able to: • List the essential steps in diagnosis and treatment planning of the CLL patient • Select CLL treatment regimens based on patient characteristics • Define data supporting the benefit/risk ratio of upfront, relapsed, and refractory CLL setting • Define strategies to manage fludarabine-resistant CLL • Describe emerging therapies in CLL

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

This activity has been approved for 1.5 AMA PRA Category 1 Credits™.

For further information and to participate, please go to: www.coexm.com/ace02.asp

In collaboration with

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Journal of Oncology

NAVIGATION & SURVIVORSHIP

™

The Official Journal of the Academy of Oncology Nurse Navigators ® DECEMBER 2010

www.AONNonline.org

VOL 1, NO 7

CARE COORDINATION

City-wide Patient Navigation Network Coordinates Washington, DC, Cancer Care

By Karen Rosenberg

Leadership Council Lillie Shockney, RN, BS, MAS Johns Hopkins Breast Center Johns Hopkins University School of Medicine Baltimore, Maryland Sharon Gentry, RN, MSN, AOCN, CBCN Derrick L. Davis Forsyth Regional Cancer Center Winston-Salem, North Carolina Nicole Messier, RN Vermont Cancer Center Burlington, Vermont Pamela Matten, RN, BSN, OCN St. Joseph Hospital Orange, California Elaine Sein, RN, BSN, OCN, CBCN Fox Chase Cancer Center Partners Rockledge, Pennsylvania Tricia Strusowski, MS, RN Helen F. Graham Cancer Center Christiana Care Health System Newark, Delaware

T

he George Washington Cancer Institute (GWCI) recently received a $2.4-million grant from the DC Cancer Consortium to establish and coordinate a City-wide Patient Navigation Network (CPNN) in Washington, DC. The CPNN will create a seamless, cohesive framework for coordination of cancer care throughout the city to ensure that all city residents get appropriate cancer screening and treatment regardless of their ability to pay. The network will also help patients identify support services throughout the cancer continuum, including posttreatment survivorship.

Twenty-five separate institutions, including hospitals, cancer centers, and community organizations in the Washington, DC, area are members of

the network, and patient navigators are embedded at every site, said Steven Patierno, PhD, executive director of the GWCI.

and a secure Internet-based data collection process, which allows the navigators to upload their navigation logs and their patient interactions in real time.

“The CPNN will create a seamless, cohesive framework for coordination of cancer care throughout the city.”

—Steven Patierno, PhD

The program, he explained, provides training once a month to every navigator and every navigator’s supervisor. It also provides a central communications portal

He gave an example of how coordination of care works. “If a patient is seen at a community advocacy group that does Continued on page 2

NAVIGATION TRAINING

Center Provides Platform for Discussion of Cancer Survivorship, Navigation, and Policy

By Karen Rosenberg

Linda Fleisher, MPH, PhD(c) Fox Chase Cancer Center Cheltenham, Pennsylvania Susan M. Gardner, RN, CBEC, CBCN Valley Medical Center Renton, Washington Jay R. Swanson, RN, BSN, OCN Saint Elizabeth Cancer Institute Lincoln, Nebraska Carol Lewis, RN, BSN, OCN, CRNI Memorial Hermann The Woodlands, Texas

T

he Center for the Advancement of Cancer Survivorship, Navigation, and Policy (caSNP), a collaboration of the George Washington Cancer Institute (GWCI) and the university’s School of Public Health and Health Services Department of Health Policy, was established in 2009 with support from Pfizer and the Pfizer Foundation. The center’s goals are to advance patient navigation and cancer survivorship efforts both locally and nationally through training, research,

policy analysis, and education. caSNP grew out of the understanding that there is “overlap between patient navigation, survivorship, and policy and both of these intersect with local and national healthcare policy,” explained Steven Patierno, PhD, executive director of the GWCI. “We wanted to create a platform to talk about navigation and survivorship in the context of policy in a united program.”

The center offers training programs at three levels:

• Navigation training is designed for navigators, including nurses, social workers, and lay persons. Trainees from institutions across the country learn about barriers that affect their patients, are trained to launch or improve programs, and gain tools for implementing institutional change.

• Executive-level training is designed for chief executive officers, chief financial officers, hospital

AONN Staff Sean T. Walsh Executive Director sean@AONNonline.org

GUIDE OUR PATH Start a Chapter/Affiliate Join a Committee

www.AONNonline.org ©2010 Green Hill Healthcare Communications, LLC

Continued on page 2

TON_December 2010_FINAL_TON 12/6/10 12:05 PM Page B2

City-wide Patient Navigation Network... Continued from cover

Chelsea Phelps, American Cancer Society/ George Washington Cancer Institute navigator speaks with a patient in the waiting area of the George Washington University/Medical Faculty Associates Katzen Cancer Center.

entering what he or she did to navigate the patient. If the patient has a suspicious finding and needs a biopsy at a comprehensive medical center, the screening navigator connects the patient to a navigator embedded in one of the medical centers, who also has access to the patient’s de-identified data and can continue the process. We continue that all the way through until the survivorship period. It’s an absolutely remarkable program; it’s unprecedented anywhere else.”

Patient Navigation Research Program The CPNN is an outgrowth of the Patient Navigation Research Program (PNRP), a 5-year national study on the effectiveness of patient navigation funded by the National Cancer Institute and the American Cancer Society. GWCI is one of nine sites throughout the country participating in the program. Data are being collected to answer two key questions: (1) Does patient navigation narrow the window between a suspicious finding and diagnostic resolution? And (2) Does it narrow the window between diagnosis and the onset of treatment?

Center Provides Platform for Discussion... Continued from cover administrators and other mid-level supervisors. “We give them business models, we give them tools for follow-up, everything they need to launch a program, maintain a program, and build a sustainable program,” Patierno said.

• The policy scholars program for physicians, nurses, and research scientists addresses health policy and its impact on cancer care, throughout the continuum of cancer care.

In addition to these training programs,

caSNP engages in health policy analysis.

Patierno and his caSNP colleagues have contributed a chapter on survivorship and healthcare with, which will be included in a book to be published in January (Feverstein M, Ganz P, eds.

Quality Health Care for Caner Survivors.

Sprirger). And the GWCI in collaboration with the American Cancer Society has received a grant from the Centers from Disease Control and Prevention to launch a virtual national cancer survivorship resource center. ●

caSNP staff at the First Annual Survivorship Symposium. Left to right: Melekte Truneh, MBA; Mandi Pratt Chapman, MA; Becky Beauregard; and Amina Gilyard, MEd.

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December 2010 I VOL 1, NO 7

The DC PNRP was launched in 2005 and two major concepts have emerged, said Patierno. “The first is what we call longitudinal navigation because we began to understand that the barriers that affect access to care during treatment also extend to screening and posttreatment into survivorship. So we started talking about longitudinal navigation,” he explained. “We started propagating a model whereby patient navigation could be extended into the outreach arm of the continuum of healthcare. Not that the navigators would become outreach specialists but they would be coupled with outreach workers to help people overcome barriers to accessing screening. Then we started using navigators during the transition from active care into the posttreatment survivorship period, whom we call survivorship navigators.”

The other unique aspect of the program, is network navigation, which Patierno says “is completely unique to Washington, DC” although other cities are looking into it. “We were able to unite through PNRP, five otherwise unaffiliated, competing medical centers, and four community advocacy organizations to all work together in this partic-

ular area. We created a seamless network where patients could actually be navigated within and between otherwise unaffiliated medical centers in Washington, DC.” Patierno has worked closely with Harold Freeman, who developed the concept of navigation to help patients in underserved communities overcome barriers to healthcare and reduce disparities in the care received. “Regardless of where patients are in the care continuum, there are barriers and the role of the navigator is to overcome those barriers,” he notes. “That’s the critical issue. That means that patient navigation should be available to all patients regardless of their race or socioeconomic status, but it also means that the patients who will benefit the most from patient navigation will be the underserved and those who do not have the resources that others do.”

The concept of patient navigation is “very powerful,” he says. “You would have to look very long and very hard to find a new concept in healthcare that integrated itself into the healthcare consciousness faster than patient navigation.

It has not just rolled across the country; it has steamrolled across the country. We just need to steer it a little bit.” ●

BREAST CANCER

Patient Navigation Improves Mammography Rates in the Inner City

By Dawn Lagrosa

P

atient navigation in the primary care setting can improve adherence to biennial mammograms among inner-city, low-income, minority populations, based on the results of a study by researchers at Boston University School of Medicine. The study also demonstrates the feasibility of adopting patient navigation to similar urban safety-net settings across the country.

At the primary care level, 3895 women aged 51 to 70 years who were patients of record at internal medicine practices located at an academic safety-net hospital were randomized to either navigation intervention or usual care (controls). For the intervention group, patients who underwent their last mammogram more than 18 months previously received telephone calls and reminder letters.

Participants consisted of 71% racial/ ethnic minorities and 23% nonEnglish speakers; 63% had public or no health insurance. Mammography adherence rates rose in the interven-

©iStockphoto.com/art-4-art

not provide clinical services, the navigator at the advocacy group can put the patient’s information into the secure log and navigate that patient to a screening site, let’s say a mammography center.

The navigator at the mammography center has access to that same patient code, opens up the log and continues

tion group, from 78% at baseline to 87% after intervention. For the control group, rates remained somewhat stable, dropping slightly from 78% at baseline to 76% after the intervention period. Hispanic women showed high rates of mammography compliance in both the intervention (85%) and control (83%) groups.

This study was published online October 8 in the Journal of General Internal Medicine. ● www.AONNonline.org

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PSYCHOSOCIAL ISSUES

Most Oncology Nurses Unfamiliar with IOM Report on Caring for the Whole Patient

By Caroline Helwick

A

2007 report by the Institute of Medicine (IOM) concluded that psychosocial issues created or exacerbated by cancer are “palpable, important, and potentially crippling” but can be effectively addressed by services and interventions. The report, Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs, also acknowledged that appropriate psychosocial care is the “exception rather than the rule in cancer care today,” and a study by the Oncology Nursing Society (ONS) bore this out.

The ONS research, presented at the annual meeting of the American Psychosocial Oncology Society, found that almost two thirds of oncology nurses were unfamiliar with the IOM report and its recommendations (Table 1), according to Tracy Gosselin, RN, MSN, AOCN, director of oncology services at Duke University Hospital, Durham, North Carolina.

“Although nurses may assess patients’ needs, multiple barriers pertaining to individuals and institutions still exist related to communication, knowledge of IOM recommendations, and resources,” Gosselin said. “These barriers may impair their ability to provide the necessary psychosocial care to patients and their families.”

The web-based survey was developed by the ONS Psychosocial Project and the ONS Research Team. Questions were aligned with recommendations from the IOM report. The 34-item survey was pilot-tested on 76 ONS members, more than half of whom had a master’s degree in nursing and were advanced practice nurses.

The pool of candidates has since been expanded to 400 nurses, but the presentation was based on the 76 in the pilot study.

Institute of Medicine’s Table 1 Standard of Care for Meeting Psychosocial Health Needs All cancer care should ensure the provision of appropriate psychosocial health services by: • Facilitating effective communication between patients and care providers • Identifying each patient’s psychosocial health needs • Designing and implementing a plan that links the patient with needed psychosocial services, coordinates biomedical and psychosocial care, and engages and supports patients in managing their illness and health • Systematically following up on, reevaluating, and adjusting plans

www.AONNonline.org

Seventy-one percent were aged 45 to 59 years, 97% worked with adults, 56% worked in the outpatient setting, 31% worked in the inpatient setting, and 74% worked in frontline patient care.

Regarding their knowledge of the IOM report, 64% were “not at all” or “not very” familiar with the report, whereas only 34% were “somewhat” or “very” familiar with it, she reported.

It is important to note that only 12% reported that someone in their work setting had communicated or taken action based on the IOM recommendations. Forty-two percent had not taken action, and 41% were unsure if any action had been taken.

The responsibility for the provision of psychosocial health services typically fell to a social worker (43%), followed by a nurse (17%), an advanced practice nurse (17%), a behavioral health professional (9%), a physician (3%), a pastor or spiritual care counselor (3%), or another individual (7%).

The nurses used a variety of methods for assessing and identifying the psychosocial issues and needs of their patients, but discussion with the patient was by far the most common (Table 2). Thirty-six percent said they applied evidence-based resources for psychosocial care to their practices.

Table 2 Tools and Methods Used to Assess Psychosocial Needs (n = 76) Method Interview and discussion Numeric, Likert, or visual analog scale Activities of daily living scale No specific instrument National Comprehensive Cancer Network Distress Thermometer Depression scale Anxiety scale Social support scale Acculturation scale Caregiver strain index Other

having time to assess and provide these services, to lack of insurance coverage, and to access to suitable providers,” she noted. “We know that the bulk of cancer patients are not treated in academic medical centers like ours. If you are a rural healthcare provider, do you have someone to refer these patients to? This is another important issue.”

Only 20% cited a lack of experience

N (%) 59 (78) 20 (26) 15 (20) 15 (20) 10 (13) 9 (12) 3 (4) 3 (4) 2 (3) 2 (3) 6 (8)

in assessment or screening tools for distress as a barrier to the delivery of psychosocial care.

These results were incorporated into a 3-year plan that has been submitted to the ONS, which includes recommendations for advocacy, education, and research related to the integration of evidence-based practices into psychosocial care delivery. ●

Journal of Oncology

NAVIGATION & SURVIVORSHIP

™

The Official Journal of the Academy of Oncology Nurse Navigators ®

Almost two thirds of oncology nurses were unfamiliar with the IOM report and its recommendations.

“They used a variety of assessments, but the best evidence for this is from the NCCN [National Comprehensive Cancer Network], which developed the Distress Thermometer. This incorporates symptomatology, spirituality, economics, transportation, and other elements of stress and coping. Only 13% were using this,” Gosselin pointed out.

Perhaps some of the insufficiency in psychosocial service can be attributed to the multiple barriers faced by healthcare providers, including lack of time at work (49%), lack of patient and family access to providers (41%), lack of insurance coverage or high cost of services (41%), and lack of community resources (29%), she added.

“The key barriers were related to

Submit a Manuscript Today!

The ONLY journal focused on patient navigation and survivorship care in oncology patients.

Academy of Oncology Nurse Navigators (AONN) is pleased to announce the extension of its official publication into 2011.

If you have ever wanted to be a published author or have simply been looking for the right journal to publish your work, regarding these two specific topic areas, the wait is over.

Please submit manuscripts online at www.AONNonline.org/manuscripts Want to get more involved?

Submit your CV/Bio to be considered for expert advisory board positions to editorial@greenhillhc.com.

If you have any questions about AONN or the Journal of Oncology Navigation & Survivorship, please contact Sean T. Walsh, Executive Director of AONN, at sean@AONNonline.org.

December 2010 I VOL 1, NO 7

3

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PSYCHOSOCIAL ISSUES

Integrative Psychooncology Services: How the Cleveland Clinic Did It

By Caroline Helwick

A

2007 report by the Institute of Medicine emphasized that psychosocial support is an integral part of caring for cancer patients but is the exception, not the rule, in most cancer centers. Not so at the Cleveland Clinic’s Taussig Cancer Institute, which answered this need by embedding an interdisciplinary psychosocial oncology program into its cancer care system.

Isabel Schuermeyer, MD, psychiatrist and director of the program, described the rationale for the psychooncology program and how it has improved cancer care at the Taussig Cancer Institute, which sees approximately 1400 new patients a year and 250 per day.

“Historically, the way things worked at our institution, and probably at most institutions, was for our psychosocial oncology services to function as independent practitioners in their own silos, with little collaboration with each other,” she said. “Psychiatry referrals for cancer patients were made directly to the Department of Psychiatry, with a wait time up to 3 months.”

Developing the program “What we have done is to develop a collaborative way of bringing a number of

services together,” she said. These services include not only counseling but also disparities outreach, spiritual care, support groups, and other auxiliary services.

The first step was to expand the existing services to include the provision of first-line mental health services and psychotherapy. The program now employs one psychiatrist (Schuermeyer), eight social workers, and a support staff that includes nutrition counseling, spiritual care, disparities outreach, and a “4th Angel Mentoring Program.”

This cut the wait time for a mental health referral to 1 week, although this has recently crept back up to 1 month, she acknowledged. Schuermeyer personally has more than 700 patient-visits a year for a variety of conditions, mostly related to the cancer diagnosis.

There is now a clear protocol for psychiatry referrals and a more formal structure for psychotherapy and for triage. There is also a user-friendly referral process for medical staff, and patients can self-refer themselves as well, through a call center.

Social workers offer supportive counseling and assistance with community resources. They also perform the clinical assessments of patients, referring non-

The first steps were to develop strong interdepartmental collaboration, reallocate social workers within the cancer center, and add a psychiatrist, with the goal of building a strong interdisciplinary service. emergency cases for oncology social work intervention and emergency cases to the psychiatrist for prompt intervention.

The psychosocial services are noted in the patients’ electronic medical record so that oncologists remain informed. Efforts are made to maintain confidentiality in dialogue, she added.

Psychotherapy is provided free of charge to patients who are in cancer treatment if their psychiatric diagnosis is believed to be secondary to their cancer diagnosis (ie, difficulty coping, etc), she said. One person is in charge of maintaining the schedule of referrals and ensuring that the proper protocol is followed.

Administration was onboard from the start “The administration was supportive from the beginning,” Schuermeyer said.

“Dr. Derek Raghavan, the institute’s chair, is dedicated to the psychosocial oncology concept.”

The first steps were to develop strong interdepartmental collaboration, reallocate social workers within the cancer center, and add a psychiatrist, with the goal of building a strong interdisciplinary service. Next, the electronic medical record was modified to include a schedule for psychooncology services, and standard operating procedures were developed.

Protocols for handling emergencies were also developed. The program stays on track through monthly staff meetings.

“The result of this is that our providers now work together to better manage patients and to optimize their psychosocial care, all within one cancer center,” she said. ●

SURVIVORSHIP

Survivors Often Dissatisfied with Breast-conserving Treatment Results

By John Schieszer

SAN DIEGO—One third of breast cancer survivors who received breastconserving treatments (lumpectomy and radiation) rate the appearance of their posttreatment breast as “fair” or “poor” in comparison with their untreated breast, according to a study presented at the 52nd annual meeting of the American Society for Radiation Oncology.

In addition, one fifth of patients reported complications, including chronic pain in their breast or arm, and loss of arm or shoulder flexibility following treatment.

The study is the first to examine patients’ impressions of the cosmetic appearance of their breast following treatment. These findings differ dramatically from those of previous studies, in which clinicians were more likely to label posttreatment breasts as “good” or “excellent” in appearance. The authors of this study say that these findings shed light on how patients’ treatment expectations may differ from their physicians’

4

december 2010 I VOL 1, NO 7

and reveal a need for additional patient education about potential outcomes.

“Most patients are ultimately happy they were able to preserve their breast, but our study shows that often how they feel about the way they look after treatment is not as good as doctors would

As cure rates for breast and other cancers continue to improve, attention to survivorship issues is more important than ever before. have predicted,” said lead study author Christine Hill-Kayser, MD, assistant professor of radiation oncology at the University of Pennsylvania School of Medicine, Philadelphia.

Among the 503 patients surveyed who had a lumpectomy followed by

radiotherapy, 16% rated cosmesis as “excellent”; 52%, “good”; 30%, “fair”; and 2%, “poor.” Interestingly, 43% of women reported chronic skin or soft-tissue changes, 22% chronic pain in the breast or arm, 21% a loss of arm or shoulder flexibility, and 8% chronic swelling.

The study data were collected from patients who voluntarily created an online survivorship care plan using the LIVESTRONG Care Plan, which provides users with an easy-to-follow road map for managing their health as they finish treatment and transition to life as a cancer survivor.

“It’s very important that cancer survivors be empowered by information.

They should be aware not only of the possible complications associated with their treatment, but also that there are things that they can do about many of them,” said Hill-Kayser.

Currently, more than 50% of women with stage I or II breast cancer undergo

both lumpectomy and radiation. These patients commonly report scarring, skin puckering, changes in color or texture of skin, size or shape asymmetry between the treated and untreated breast, and nipple distortion. Although it may not be possible to correct all of these problems, Hill-Kayser says a variety of therapies are available for women with treatment complications, including physical therapy and weight training regimens for patients who experience the painful arm-swelling condition called lymphedema and shoulder pain and/or stiffening.

The findings from this study may be of particular interest to oncology nurses.

“As cure rates for breast and other cancers continue to improve, attention to survivorship issues is more important than ever before,” said Hill-Kayser.

“Understanding more about the way that survivors feel after their treatment is one step toward helping patients live as well as possible after cancer.” ● www.AONNonline.org

TON_December 2010_FINAL_TON 12/6/10 11:22 AM Page 35

CONTINUING EDUCATION CREDITS

Current activities at www.COEXM.com include:

TON_December 2010_FINAL_TON 12/6/10 11:22 AM Page 36

ONCOLOGY DRUG CODES Supplied by: RJ Health Systems

Medications Used for the Treatment of Hematologic Cancers The following sections will assist healthcare professionals and payers by providing appropriate coding, billing, and reimbursement information associated with the management of multiple myeloma or myelodysplastic syndromes.

Multiple Myeloma Multiple myeloma is a type of cancer that begins in plasma cells (white blood cells that produce antibodies).

The following sections include: • Associated ICD-9-CM codes used for the classification of multiple myeloma or myelodysplastic syndromes • Drugs that have been FDA-approved in the treatment of multiple myeloma or myelodysplastic syndromes • Drugs that are Compendia listed for off-label use for breast cancer based on clinical studies that suggest beneficial use in some cases.

Please note: if a check mark appears in the FDA column it will NOT appear in the compendia off-label use column • Corresponding HCPCS/CPT® codes and code descriptions • Current Code Price (AWP-based pricing) • Most recent ASP plus 6% (Medicare allowable), if applicable • Possible CPT® Administration Codes for each medication

generic (Brand) name arsenic trioxide (Trisenox) betamethasone (Celestone)

HCPCS code: code description J9017: injection, arsenic trioxide, 1 mg J8499b: prescription drug, oral, non-chemotherapeutic, not otherwise specified betamethasone J0702: injection, acetate and betamethasone acetate betamethasone 3 mg, and sodium phosphate betamethasone sodium (Celestone Soluspan) phosphate 3 mg bortezomib J9041: injection, (Velcade) bortezomib, 0.1 mg carmustine J9050: injection, (BiCNU) carmustine, 100 mg cisplatin J9060: cisplatin, powder (Platinol AQ) or solution, per 10 mg cisplatin J9062: cisplatin, (Platinol AQ) 50 mg cortisone acetate J8499b: prescription drug, (Cortone) oral, non-chemotherapeutic, not otherwise specified cyclophosphamide J8530: cyclophosphamide, (Cytoxan) oral, 25 mg cyclophosphamide J9070: cyclophosphamide, (Cytoxan) 100 mg (all 100-mg NDCs inactive; 500-mg NDCs used to calculate code price)

36

December 2010 I VOL 3, NO 8

Associated ICD-9-CM Codes Used for Multiple Myeloma 203 Multiple myeloma and immunoproliferative neoplasms The following fifth-digit subclassification is for use with category 203: 0 without mention of having achieved remission >Failed remission< 1 in remission 2 in relapse 203.0 Multiple myeloma Kahler’s disease Myelomatosis excludes: solitary myeloma (238.6) 203.1 Plasma cell leukemia Plasmacytic leukemia 203.8 Other immunoproliferative neoplasms

FDAapproved for multiple myeloma

Compendia listed off-label use for multiple myelomaa ✓

Current code price (AWP-based pricing), effective 11/1/10 $47.51

Medicare allowable (ASP + 6%), effective 10/1/10-12/31/10 $37.25

CPT ® administration codes 96413, 96415

NDC level pricing $8.00

NDC level pricing $6.24

✓

$46.66

$39.29

✓

$205.69

$175.88

✓

$4.33

$1.50

96409, 96413, 96415

✓

$21.66

$7.49

96409, 96413, 96415

✓

✓

NDC level pricing $2.09

NDC level pricing $0.83

✓

$10.57

$5.96

✓

✓

N/A

11900, 11901, 20600, 20605, 20610, 96372

96409 96413, 96415

N/A

N/A 96409, 96413, 96415

www.TheOncologyNurse.com

TON_December 2010_FINAL_TON 12/6/10 11:22 AM Page 37

ONCOLOGY DRUG CODES Supplied by: RJ Health Systems

FDAapproved for multiple myeloma

generic (Brand) name cyclophosphamide (Cytoxan)

HCPCS code: code description J9080: cyclophosphamide, ✓ 200 mg (all 100-mg NDCs inactive; 500-mg NDCs used to calculate code price) ✓ cyclophosphamide J9090: cyclophosphamide, (Cytoxan) 500 mg ✓ cyclophosphamide J9091: cyclophosphamide, (Cytoxan) 1 gram ✓ cyclophosphamide J9092: cyclophosphamide, (Cytoxan) 2 grams daunorubicin J9151: injection, (DaunoXome) daunorubicin citrate, liposomal formulation, 10 mg dexamethasone J8540: dexamethasone, (Decadron) oral, 0.25 mg dexamethasone J1100: injection, (Decadron) dexamethasone sodium phosphate, 1 mg doxorubicin J9000: injection, (Adriamycin) doxorubicin hydrochloride, 10 mg ✓ doxorubicin liposomal J9001: injection, (Doxil) doxorubicin hydrochloride, all lipid formulations, 10 mg epirubicin J9178: injection, (Ellence) epirubicin HCl, 2 mg etoposide J8560: etoposide, oral, (Vepesid) 50 mg etoposide J9181: injection, (Etopophos, Toposar) etoposide, 10 mg hydrocortisone J8499b: prescription drug, (Cortef) oral, non-chemotherapeutic, not otherwise specified hydrocortisone J1720: injection, (Solu-Cortef) hydrocortisone sodium succinate, up to 100 mg ifosfamide J9208: injection, (Ifex) ifosfamide, 1 gram interferon alfa-2b J9214: injection, interferon, (Intron-A) alfa-2b, recombinant, 1 million units interferon alfa-n3 J9215: injection, interferon, (Alferon-N) alfa-n3, (human leukocyte derived), 250,000 international units lomustine J8999b: prescription drug, (CeeNU) oral, chemotherapeutic, not otherwise specified lomustine S0178: lomustine, (CeeNU) oral, 10 mg melphalan (Alkeran) melphalan (Alkeran)

J8600: melphalan, oral, 2 mg J9245: injection, melphalan hydrochloride, 50 mg

Compendia listed off-label use for multiple myelomaa

Current code price (AWP-based pricing), effective 11/1/10 $21.15

Medicare allowable (ASP + 6%), effective 10/1/10-12/31/10 $11.92

CPT ® administration codes 96409, 96413, 96415

$52.87

$29.79

96409, 96413, 96415

$95.21

$59.59

96409, 96413, 96415

$171.35

$119.18

96409, 96413, 96415

✓

$68.00

$57.66

96413

✓

$0.09

$0.37

N/A

✓

$0.15

$0.09

✓

$13.20

$3.04

$613.03

$486.80

✓

$5.38

$1.80

✓

$57.33

$28.48

✓

$0.53

$0.55

✓

✓

NDC level pricing $2.33

NDC level pricing $3.42

✓

$42.00

$34.15

96413, 96415

✓

$21.90

$16.06

96372, 96401

✓

$25.09

None reported

11900, 11901

✓

NDC level pricing $10.59

NDC level pricing S0178 not payable by Medicare $4.80

✓

✓

$5.68

✓

$1,922.50

$1,401.83

11900, 11901, 20600, 20605, 20610, 96372, 96374 96409 96413

96409, 96413 N/A 96413, 96415 N/A

96365, 96366, 96372, 96374

N/A

N/A

N/A 96409, 96413 Continued on page 38

www.TheOncologyNurse.com

December 2010 I VOL 3, NO 8

37

TON_December 2010_FINAL_TON 12/6/10 11:22 AM Page 38

ONCOLOGY DRUG CODES Supplied by: RJ Health Systems Continued from page 37

generic (Brand) name methylprednisolone (Depo-Medrol) methylprednisolone (Depo-Medrol) methylprednisolone (Depo-Medrol) methylprednisolone (Solu-Medrol) methylprednisolone (Solu-Medrol) paclitaxel (Onxol, Taxol) peginterferon alfa-2b (Peg-Intron)

HCPCS code: code description J1020: injection, methylprednisolone acetate, 20 mg J1030: injection, methylprednisolone acetate, 40 mg J1040: injection, methylprednisolone acetate, 80 mg J2920: injection, methylprednisolone sodium succinate, up to 40 mg J2930: injection, methylprednisolone sodium succinate, up to 125 mg J9265: injection, paclitaxel, 30 mg J3590b: unclassified biologics

FDAapproved for multiple myeloma

Compendia listed off-label use for multiple myelomaa ✓

Current code price (AWP-based pricing), effective 11/1/10 $3.78

Medicare allowable (ASP + 6%), effective 10/1/10-12/31/10 $2.48

CPT ® administration codes 11900, 11901, 20600, 20605, 20610, 96372

✓

$5.22

$4.72

11900, 11901, 20600, 20605, 20610, 96372

✓

$9.52

$8.59

11900, 11901, 20600, 20605, 20610, 96372

✓

$2.36

$1.81

96365, 96366, 96372, 96374

✓

$4.15

$2.54

96365, 96366, 96372, 96374

✓

$15.54

$7.45

96413, 96415

✓

S0148: injection, pegylated interferon alfa-2b, 10 micrograms prednisolone J7510: prednisolone, (Prelone, Millipred) oral, per 5 mg prednisone J7506: prednisone, (Orasone, Deltasone) oral, per 5 mg procarbazine J8999b: prescription drug, (Matulane) oral, chemotherapeutic, not otherwise specified procarbazine S0182: procarbazine HCl, (Matulane) oral, 50 mg

✓

NDC level pricing $116.77

✓

$0.59

NDC level pricing S0148 not payable by Medicare $0.02

✓

$0.04

$0.04

N/A

✓

teniposide (Vumon) thalidomide (Thalomid)

✓

$376.55

NDC level pricing S0182 not payable by Medicare $323.66

N/A

✓

NDC level pricing $55.68

✓

NDC level pricing $1,348.55

NDC level pricing $1,090.84

96413

✓

$5.83

$3.98

96409

✓

$11.66

$7.96

96409

✓

$29.15

$19.90

96409

$263.39

$223.10

peginterferon alfa-2b (Peg-Intron)

topotecan (Hycamtin) vinCRIStine (Vincasar PFS) vinCRIStine (Vincasar PFS) vinCRIStine (Vincasar PFS) zoledronic acid (Zometa)

Q2017: injection, teniposide, 50 mg J8999b: prescription drug, oral, chemotherapeutic, not otherwise specified J9350: injection, topotecan, 4 mg J9370: vincristine sulfate, 1 mg J9375: vincristine sulfate, 2 mg J9380: vincristine sulfate, 5 mg J3487: injection, zoledronic acid (Zometa), 1 mg

✓

✓

96372

96372

N/A

N/A

96413, 96415 N/A

96365, 96374

Continued on page 40

38

December 2010 I VOL 3, NO 8

www.TheOncologyNurse.com

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ONCOLOGY DRUG CODES Supplied by: RJ Health Systems Continued from page 38

Associated ICD-9-CM Codes Used for Myelodysplastic Syndromes

Myelodysplastic Syndromes Myelodysplastic syndromes are a group of diseases in which the bone marrow does not make enough healthy blood cells.

generic (Brand) name amifostine (Ethyol) arsenic trioxide (Trisenox) azacitidine (Vidaza) clofarabine (Clolar) cytarabine (Cytosar-U) cytarabine (Cytosar-U) darbepoetin alfa (Aranesp) darbepoetin alfa (Aranesp) decitabine (Dacogen) epoetin alfa (Procrit, Epogen) epoetin alfa (Procrit, Epogen)

epoetin alfa (Procrit, Epogen)

40

HCPCS code: code description J0207: injection, amifostine, 500 mg J9017: injection, arsenic trioxide, 1 mg J9025: injection, azacitidine, 1 mg J9027: injection, clofarabine, 1 mg J9100: injection, cytarabine, 100 mg J9110: injection, cytarabine, 500 mg J0881: injection, darbepoetin alfa, 1 microgram (non-ESRD use) J0882: injection, darbepoetin alfa, 1 microgram (for ESRD on dialysis) J0894: injection, decitabine, 1 mg J0885: injection, epoetin alfa (for non-ESRD use), 1000 units J0886: injection, epoetin alfa 1000 units (for ESRD on dialysis; renal dialysis facilities and hospitals must use code Q4081, effective 1/1/07) Q4081: injection, epoetin alfa, 100 units (for ESRD on dialysis; for renal dialysis facilities and hospital use)

December 2010 I VOL 3, NO 8

238 Neoplasm of uncertain behavior of other and unspecified sites and tissues 238.7 Other lymphatic and hematopoietic tissues excludes: acute myelogenous leukemia (205.0) chronic myelomonocytic leukemia (205.1) myelosclerosis, not otherwise specified (289.89) myelosis: not otherwise specified (205.9) megakaryocytic (207.2) 238.72 Low-grade myelodysplastic syndrome lesions Refractory anemia (RA) Refractory anemia with ringed sideroblasts (RARS) Refractory cytopenia with multilineage dysplasia (RCMD) Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS) 238.73 High-grade myelodysplastic syndrome lesions Refractory anemia with excess blasts-1 (RAEB-1) Refractory anemia with excess blasts-2 (RAEB-2) 238.74 Myelodysplastic syndrome with 5q deletion 5q minus syndrome, not otherwise specified excludes: constitutional 5q deletion (758.39) high-grade myelodysplastic syndrome with 5q deletion (238.73) 238.75 Myelodysplastic syndrome, unspecified

FDAapproved for myelodysplastic syndromes

Compendia listed off-label use for myelodysplastic syndromesa ✓

Current code price (AWP-based pricing), effective 11/1/10 $564.95

Medicare allowable (ASP + 6%), effective 10/1/10-12/31/10 $318.66

CPT ® administration codes 96374

$47.51

$37.25

$6.03

$5.13

✓

$135.00

$115.41

✓

$1.25

$1.98

✓

$10.20

$3.67

✓

$6.44

$2.90

96409, 96413, 96415, 96450 96409, 96413, 96415, 96450 96372, 96374

✓

$6.44

$2.90

96372, 96374

$35.50

$30.74

96413, 96415

✓

$15.34

$9.68

96372, 96374

✓

$15.34

$9.68

96372, 96374

✓

$1.53

$0.97

96372, 96374

✓

✓

✓

96413, 96415 96401, 96409, 96413 96413, 96415

www.TheOncologyNurse.com

TON_December 2010_FINAL_TON 12/6/10 11:22 AM Page 41

ONCOLOGY DRUG CODES Supplied by: RJ Health Systems

generic (Brand) name

HCPCS code: code description

etoposide (Vepesid) etoposide (Toposar, Etopophos) filgrastim (Neupogen) filgrastim (Neupogen) fludarabine (Fludara) imatinib (Gleevec)

J8560: etoposide, oral, 50 mg J9181: injection, etoposide, 10 mg J1440: injection, filgrastim (G-CSF), 300 micrograms J1441: injection, filgrastim (G-CSF), 480 micrograms J9185: injection, fludarabine phosphate, 50 mg J8999b: prescription drug, oral, chemotherapeutic, not otherwise specified S0088: imatinib, 100 mg

imatinib (Gleevec) lenalidomide (Revlimid) lymphocyte immune globulin (Atagam) lymphocyte immune globulin (Thymoglobulin) sargramostim (Leukine) thalidomide (Thalomid) topotecan (Hycamtin)

FDAapproved for myelodysplastic syndromes

J8999b: prescription drug, oral, chemotherapeutic, not otherwise specified J7504: lymphocyte immune globulin, antithymocyte globulin, equine, parenteral, 250 mg J7511: lymphocyte immune globulin, antithymocyte globulin, rabbit, parenteral, 25 mg J2820: injection, sargramostim (GM-CSF), 50 micrograms J8999b: prescription drug, oral, chemotherapeutic, not otherwise specified J9350: injection, topotecan, 4 mg

Compendia listed off-label use for myelodysplastic syndromesa

Current code price (AWP-based pricing), effective 11/1/10

Medicare allowable (ASP + 6%), effective 10/1/10-12/31/10

✓

$57.33

$28.48

✓

$0.53

$0.55

✓

$283.02

$233.43

✓

$450.66

$366.81

✓

$285.16

$139.57

NDC level pricing $48.56

CPT ® administration codes N/A 96413, 96415 96365, 96366, 96369, 96370, 96372, 96374 96365, 96366, 96369, 96370, 96372, 96374 96413

✓

NDC level pricing $643.21

NDC level pricing S0088: not payable by Medicare NDC level pricing $496.95

96365, 96366

✓

$636.48

$417.51

96365, 96366

✓

$44.64

$23.88

✓

NDC level pricing $1,348.55

NDC level pricing $1,090.84

✓

✓

✓

✓

N/A

N/A

N/A

96365, 96366, 96372 N/A

96413

a

Compendia references available upon request.

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

b

References HCPCS Level II Expert, 2010 • Current Procedural Terminology (CPT®), 2010 (CPT® copyright © 2010 American Medical Association. All rights reserved. CPT® is a registered trademark of the American Medical Association) • ICD-9-CM for Professionals Volumes 1 & 2, 2010 • The Drug Reimbursement Coding and Pricing Guide by RJ Health Systems International, LLC, Volume 7, Number 4, 4th Quarter 2010 • FDA-approved indication (from product’s prescribing information) • National Cancer Institute® • www.ReimbursementCodes.com powered by RJ Health Systems International, LLC, Wethersfield, Connecticut • CMS (Centers for Medicare & Medicaid Services), Medicare Allowable 4th Quarter 2010 (effective dates: 10/1/10-12/31/10).

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

ASP indicates average sales price; AWP, average wholesale price; CMS, Centers for Medicare & Medicaid Services; CPT, Current Procedural Terminology; FDA, US Food and Drug Administration; ESRD, end-stage renal disease; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; HCPCS, Healthcare Common Procedure Coding System; NDC, National Drug Code.

This information was supplied by:

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

www.TheOncologyNurse.com

December 2010 I VOL 3, NO 8

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YOU INFUSE ANTHRACYCLINES, BUT ARE YOU PREPARED FOR AN EXTRAVASATION? TWO PRICE OPTIONS AVAILABLE

Totect® Kit (dexrazoxane) for injection is for intravenous infusion only. Totect is indicated for the treatment of extravasation resulting from intravenous anthracycline chemotherapy.

First and only FDA approved treatment for anthracycline extravasation.

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

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

Cited in nursing guidelines.3,4 Extravasation management is now a chemotherapy administration safety standard.5

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

ASD Healthcare Cardinal Specialty McKesson/OTN Oncology Supply US Oncology (800) 746-6273 (866) 677-4844 (800) 482-6700 (800) 633-7555 (888) 987-6679 1

Mouridsen HT et al. Treatment of anthracycline extravasation with savene (dexrazoxane).

Results from two prospective clinical multicentre studies. Ann Oncol 2007; 18:546-550.

2 Totect® package insert.

3 Polovich M, White JM, Olsen, M (eds.). Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (ed 3). Pittsburgh, PA, Oncology Nursing Society, 2009.

4 Alexander M, Corrigan A, Gorski L, Hankins J, Perucca R. (eds). Infusion Nurses Society Infusion Nursing an Evidence-Based Approach (ed 3). Boston, MA, Infusion Nurses Society, 2009.

5 Jacobsen J., et al. American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards. Oncology Nursing Forum, 2009; 36:651-658. © 2010 Topotarget USA. All rights reserved. TOT0112/7-10 Totect and its logo mark are registered trademarks of Topotarget A/S

TON_December 2010_FINAL_TON 12/6/10 11:22 AM Page 43

Totect® – Brief prescribing information Please refer to the package insert for full prescribing information. Each Totect carton contains 10 vials of Totect® (dexrazoxane for injection) 500 mg and 10 vials of 50 mL diluent. Indication: Treatment of extravasation resulting from IV anthracycline chemotherapy. Dosage and administration: Totect is a cytotoxic drug. Vial contents must be mixed and diluted before use. Totect should not be mixed or administered with any other drug during the infusion. Administration of Totect should begin as soon as possible and within 6 hours following the anthracycline extravasation. Totect should be given as an intravenous (IV) infusion once daily for 3 consecutive days. The dose of Totect is based on the patient’s body surface area: day one, 1000 mg/m2; day two, 1000 mg/m2; day three, 500 mg/m2. For patients with a body surface area of > 2 m2, a dose of 2000 mg should be given on days 1 and 2, and a dose of 1000 mg should be given on day 3. Treatment on Day 2 and Day 3 should start at the same hour (+/- 3 hours) as on the first day. The Totect dose should be reduced 50% for patients with creatinine clearance values of <40 mL/minute. Cooling procedures such as ice packs should be removed from the affected area at least 15 minutes prior to Totect administration. Totect (dexrazoxane for injection) must be reconstituted with diluent supplied in the carton. The patient’s Totect dose is diluted in 0.9% 1000 mL NaCl prior to administration. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.3-5 Direct contact of Totect® with the skin or mucous membranes prior to and following reconstitution should be avoided. If contact occurs, wash immediately and thoroughly with water. Contraindications: None.

Warnings and Precautions: Myelosuppression: treatment with Totect is associated with leukopenia, neutropenia, and thrombocytopenia. Hematological monitoring should be performed. Use in Pregnancy: Pregnancy Category D. Totect can cause fetal harm when administered to a pregnant woman. There is no adequate information about the use of Totect in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Adverse reactions: The most common adverse reactions (≥ 16%) are nausea, pyrexia, injection site pain and vomiting.

www.totect.com

Rx only

Totect® is a registered trademark of Topotarget A/S US Patent No. 6,727,253B2 NDC 38423-110-01

TOT0112/7-10 © 2010 Topotarget USA

Drug Interactions: No drug interactions have been identified. Based on anecdotal reports concurrent use of topical dimethyl sulfoxide (DMSO) at the site of tissue injury may reduce the benefit of Totect. Additionally, nonclinical studies using a mouse model that simulates extravasation of anthracyclines has shown that concomitant treatment with topical DMSO decreases the efficacy of systemic dexrazoxane. Use in Specific Populations: Nursing Mothers: Discontinue drug or nursing, taking into consideration the importance of drug to the mother. Renal Impairment: Reduce the Totect dose by 50% In patients with creatinine clearance values <40 mL/min. Pediatric Use: The safety and effectiveness of Totect in pediatric patients have not been established.

Geriatric Use: This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Overdosage: There are no data on overdosage. There is no known antidote for dexrazoxane.

Carcinogenesis, Mutagenesis, Impairment of Fertility: The carcinogenic potential of dexrazoxane has not been investigated. Nevertheless, a study by the National Cancer Institute has reported that long term dosing with razoxane (the racemic mixture of dexrazoxane, ICRF-187, and its enantiomer ICRF-186) is associated with the development of malignancies in rats and possibly in mice. Dexrazoxane was not mutagenic to bacteria in vitro (Ames assay), but caused significant chromosomal aberrations in mammalian cells in vitro. It also increased the formation of micronucleated polychromatic erythrocytes in mice. Thus, dexrazoxane is mutagenic and clastogenic. The possible adverse effects of Totect on the fertility of humans and experimental animals, male or female, have not been adequately studied. Testicular atrophy was seen with dexrazoxane administration at doses as low as 30 mg/kg weekly for 6 weeks in rats (about 1/5 the human dose on a mg/m2 basis) and as low as 20 mg/kg weekly for 13 weeks in dogs (about half the human dose on a mg/m2 basis).

Manufactured by: Ben Venue Laboratories, Inc. Bedford, OH 44146 Hameln Pharmaceuticals GmbH 31789 Hameln Germany

Manufactured for: Topotarget A/S Fruebjergvej 3 DK-2100 Copenhagen Denmark

TON_December 2010_FINAL_TON 12/6/10 11:22 AM Page 44

Breast Cancer

Prolonging Chemotherapy in Metastatic Breast Cancer Improves Survival

By Caroline Helwick

MILAN—Prolonging chemotherapy until disease progression improves progression-free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer (MBC), according to a systematic analysis presented at the 35th European Society for Medical Oncology Congress.

The findings address an important debate in oncology, said Alessandra Gennari, MD, of Ospedali Galliera in Genova. “In metastatic breast cancer there is substantial controversy over how long chemotherapy should be continued in the absence of significant toxicity, after the achievement of disease control,” said Gennari.

Typically, the number of cycles tends to be based on the response to treatment, symptomatic improvement, patient tolerability and, “most importantly,” physician preference, she said. “We asked whether prolonging chemotherapy after patients respond or stabilize would be associated with longer survival and time to progression.”

The investigators searched for randomized trials in the first-line MBC set-

ting comparing longer and shorter durations of chemotherapy. Data were obtained from literature databases and meeting abstracts and through contact with individual authors of studies. Trials

“These results provide support to the clinical approach of prolonging first-line chemotherapy in the absence of significant toxicity and disease progression.”

—Alessandra Gennari, MD

comparing different types of chemotherapy or including high-dose chemotherapy were excluded.

Subgroup analyses were performed according to time of randomization, type of maintenance chemotherapy, number of cycles in the shorter arm, and

whether patients received concomitant endocrine treatment.

The investigators found 11 studies involving 2269 patients to be eligible for analysis.

Longer chemotherapy was better Patients receiving chemotherapy of longer duration had a 36% reduction in the risk of progression and a 9% reduction in the risk of death. “These results are more than clinically meaningful— they are statistically significant,” Gennari said at a press briefing. “The results justify why we must tell patients that they should continue chemotherapy.”

Assuming that the median OS in MBC after first-line chemotherapy is 24 months, longer chemotherapy was associated with absolute improvements of about 3 months in PFS and 2 months in OS. In the regression analysis, the magnitude of this effect was remarkably similar across groups of trials, and the effect of longer chemotherapy was independent of any of the factors in the subgroup analysis.

“These results provide support to the clinical approach of prolonging firstline chemotherapy in the absence of significant toxicity and disease progression,” she commented.

Questions remain as to the optimal maintenance chemotherapy, such as: Should the same drug or a different one be used? Should sequences be planned?

What is the role of low-dose maintenance therapies? Would targeted agents be optimal?

“Do more prolonged side effects justify a gain of 3 months in PFS and 2 months of OS?” asked Miguel Martin, MD, of the Hospital Universitario Gregorio Marañón in Madrid, who discussed the paper at the meeting. “I guess that most patients would accept that deal.”

He said there were many caveats to the analysis, including potential literature bias. Many negative trials are never published, he noted.

“Even considering the caveats of the analysis,” he concluded, “this Italian study provides support for the administration of chemotherapy until disease progression.” ●

Tamoxifen May Confer a Limited Benefit in Older Women with Early-stage Breast Cancer

By John Schieszer

SAN DIEGO—Omitting adjuvant tamoxifen may not put women aged older than 65 years with early-stage breast cancer at increased risk for local or distant disease recurrence, according to a large, retrospective study presented at the 52nd annual meeting of the American Society for Radiation Oncology.

Researchers from the Cancer Institute of New Jersey and Yale University reported that women aged 65 years and older treated with conservative surgery and radiation therapy (CS + RT), who did not receive adjuvant tamoxifen, did not appear to have worse outcomes. Use of tamoxifen in this cohort did not confer any systemic benefit, in terms of contralateral breast cancer rates, systemic failure rates, and survival rates, according to the investigators.

Currently, adjuvant tamoxifen is recommended for all women with estrogen receptor–positive breast carcinoma regardless of age. It has been unclear, however, whether CS + RT is as effective as CS + RT plus tamoxifen in older women with small, nodenegative breast cancer.

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December 2010 I VOL 3, NO 8

“Perhaps, if these women don’t benefit from this drug, they may not need it and they may do well enough with adjuvant radiation therapy.”

—Rahul Parikh, MD

The researchers reviewed a singleinstitution database of 2478 patients and selected 224 patients aged 65 or older who had pathologic T1 N0 M0

breast cancer treated with CS + RT between 1979 and 2003. The median follow-up time was 62.6 months. Of the 224 women, 102 (45.5%) received tamoxifen and 122 (54.5%) did not.

The researchers found that there were four local relapses and 15 distant metastases during the study. The 10year local relapse-free survival was 98% in both the tamoxifen group and the no tamoxifen group. The 10-year distant metastasis-free survival was 83% in the tamoxifen group, and 89% in the no tamoxifen group. Ten-year cause-specific and overall survival were also statistically similar in the two groups.

“We found that tamoxifen did not offer a benefit at almost every end point we looked at, including local control, distant control of the disease, breast cancer–specific survival as well as overall survival,” said study investigator Rahul Parikh, MD, resident in radiation oncology at Robert Wood Johnson Medical School, New Brunswick, New Jersey.

“These findings held up in multivariate analyses, and this is an expensive drug and it is not without side effects.”

Parikh said if these findings are confirmed in other studies, it may be time to rethink how breast cancer patients 65 and older are managed. “The side effects of tamoxifen can include hot flashes, endometrial hyperplasia, which can in a small number of women lead to endometrial cancer,” he said. “So perhaps, if these women don’t benefit from this drug, they may not need it and they may do well enough with adjuvant radiation therapy.” ●

21st Annual National Interdisciplinary Breast Center Conference This year’s conference offers three certifications: • Breast Patient Navigators • Clinical Breast Examiners • Breast Self-Examination Trainers, who will be certified to teach educator leaders who, in turn, will become certified to teach patients how to perform breast self-examination.

www.breastcare.org

www.TheOncologyNurse.com

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Breast Cancer

PARP Inhibitor Improves Survival in Triple-negative Breast Cancer

By Caroline Helwick

MILAN—The investigative poly (ADPribose) polymerase (PARP) inhibitor iniparib (BSI-021) improved not only progression-free survival (PFS) but also overall survival (OS) in the final analysis of a randomized phase 2 study, presented at the 35th European Society for Medical Oncology Congress by Joyce O’Shaughnessy, MD, of US Oncology and Baylor Sammons Cancer Center, Houston.

Co-investigator John E. Pippen, MD, of Texas Oncology, Dallas, said in a press briefing, “These tumors are very troublesome, as they are associated with high rates of symptomatic visceral and brain metastases. Progressionfree survival is short, and median survival is only about 13 months. There are limited treatment options.”

One emerging option seems to be agents that inhibit PARP, a key enzyme in cell proliferation and DNA repair that is upregulated in triplenegative tumors. Iniparib and olaparib are the first two agents in this class and “may prove valuable in triplenegative breast cancer as well as other types of cancers,” Pippen said.

The open-label study included 123 patients who received iniparib (5.6 mg/kg) plus gemcitabine (1000 mg/m2) and carboplatin (AUC = 2) every 3 weeks, or gemcitabine/carboplatin alone.

Patients in the iniparib arm not only had a longer time to progression but also a longer survival time than patients receiving only standard chemotherapy.

Median OS was 12.2 months with the combination, compared with 7.7 months without iniparib, which was a 43% reduction in risk (P = .014).

Median PFS was 5.9 versus 3.6 months (P = .012), respectively. Objective responses were observed in 52.5% of those in the combination arm compared with 32.3% of those receiving standard chemotherapy (P = .023), and the clinical benefit rate was 55.7% compared with 33.9% (P = .015), respectively, O’Shaughnessy reported.

“The magnitude of survival advantage is unusual in breast cancer and in metastatic tumors in general,” she offered. “This may be the first therapy available specifically for these patients with few options.”

Most patients had three metastatic sites of disease, and 60% had received no prior treatment for them.

Adverse events were similar between the arms. Grade 3/4 toxicities, which were primarily hematologic, were seen in 81% of patients receiving the combination versus 86% of those receiving

www.TheOncologyNurse.com

standard chemotherapy. Serious events occurred in 29% and 28% of patients, respectively. Fewer patients discontinued treatment because of toxicity in the iniparib arm.

Commenting on the findings, Angelo Di Leo, MD, head of Sandro

Pitigliani Medical Oncology Unit at the Hospital of Prato, Italy, said, “Triple-negative breast cancer ac counts for about 15% of all breast cancers, and there is a desperate need to identify effective agents for these patients. This trial suggests a clear

superiority of combining chemotherapy with iniparib over chemotherapy alone. Such a clear superiority is not usually observed in a trial where only 123 patients have been recruited.

This suggests that the drug might be very active.” ●

A Friday Satellite Symposium preceding the 52nd ASH Annual Meeting

Challenging Cases in Multiple Myeloma A Dialogue Between Community and Academic Clinicians to Improve Patient Care and Outcomes December 3, 2010 Rosen Centre Hotel Ballrooms A & B, Orlando, Florida Register online today at www.myelomacases.com/register PROGRAM DESCRIPTION

PROGRAM AGENDA

This continuing medical education symposium will serve as a forum for discussion of current questions and concerns regarding the treatment and management of patients through the multiple myeloma (MM) life cycle. A panel of domestic and international myeloma experts will be joined by representatives from community cancer care facilities and private oncology practices. By thoroughly engaging participants with interactive cases and physician point-counterpoint-style discussions, this symposium will provide evidence-based treatment and management recommendations and address new treatment regimens and management strategies based on recent clinical trials and emerging data. In addition to considering differences in domestic and international care, barriers and/or limitations faced by community cancer centers and private-practice oncologists will be debated.

12:30 -

1:00 PM

Registration and Lunch Service

1:00 -

1:10 PM

Welcome and Introduction Sundar Jagannath, MD - Chair

CASE PRESENTATIONS Each case will be presented by an expert faculty member and discussed by the international and community panel.

1:10 – 1:40 PM

Case 1: Difficult diagnosis G. David Roodman, MD, PhD

1:40 – 2:10 PM

Case 2: Newly diagnosed, stem cell transplant eligible patient Sundar Jagannath, MD

2:10 – 2:40 PM

Case 3: First-line therapy in a non-SCT eligible patient Stefan Knop, MD

2:40 – 3:10 PM

Case 4: Multiple risk factors Jonathan L. Kaufman, MD

3:10 – 3:40 PM

Case 5: Treatment of MM across the life cycle Noopur Raje, MD

3:40 -

3:50 PM

Question & Answer Session

3:50 -

4:00 PM

Closing Remarks Sundar Jagannath, MD

LEARNING OBJECTIVES At the end of this activity participants will be able to: • Apply early management strategies that consider new diagnostic and staging criteria for SMM, MGUS, and MM and new imaging studies in order to improve prognosis for your patients.

• Evaluate novel therapeutic regimens as induction therapy for your patients considering an SCT in order to provide the most rapid response and allow the largest amount of stem cell collection, while maintaining safety and tolerance.

• Integrate novel agent-based regimens that provide optimal outcomes and a survival benefit into your management strategy for patients ineligible for SCT after appraising emerging data from clinical trials.

• Identify patient- and disease-associated factors that impact choice of therapeutic agent and formulate management strategies using a risk-adapted approach to treatment of MM. • Construct optimal treatment regimens based on novel combinations and make informed treatment decisions in order to improve the long-term outlook for myeloma patients across the life cycle of the disease.

TARGET AUDIENCE This activity has been developed for hematologists and medical oncologists, as well as nurses, pharmacists, and other allied health professionals who are interested in meeting the challenges faced when treating patients with multiple myeloma in academic and community settings.

ACCREDITATION INFORMATION Physician Accreditation The University of Cincinnati designates this activity for a maximum of 3 AMA PRA Category 1 Credits ™. The University of Cincinnati is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Physicians should only claim credit commensurate with the extent of their participation in the activity.

Registered Nurse Designation Medical Learning Institute, Inc. (MLI) Provider approved by the California Board of Registered Nursing, Provider Number 15106, for 3.0 contact hours.

Registered Pharmacy Designation Medical Learning Institute is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. Completion of this activity provides for 3.0 contact hours (0.3 CEUs) of continuing education credit.

The universal activity number for this activity is 0468-9999-10-058-L01-P.

FACULTY CHAIR: Sundar Jagannath, MD Professor, Hematology and Medical Oncology Mount Sinai School of Medicine’s Tisch Cancer Institute Director of the Multiple Myeloma Program, The Mount Sinai Medical Center New York, NY Stefan Knop, MD University Hospital Würzburg Würzburg, Germany

Leon Dragon, MD, FACP Medical Director Kellogg Cancer Center Northshore University HealthSystem Highland Park, IL Charles M. Farber, MD, PhD Section Chief of Hematology and Oncology Department of Medicine Carol G. Simon Cancer Center, Morristown, NJ Shoba Kankipati, MD Associate Physician EPIC Care East Bay Partners in Cancer Care San Francisco Bay Area, CA Jonathan L. Kaufman, MD Assistant Professor Blood and Marrow Transplantation Department of Hematology and Medical Oncology Emory University School of Medicine Member, Winship Cancer Institute Emory University, Atlanta, GA

Noopur Raje, MD Associate Professor of Medicine Harvard Medical School Director, Center for Multiple Myeloma Massachusetts General Hospital Boston, MA G. David Roodman, MD, PhD Professor of Medicine Vice Chair for Research Department of Medicine Director, Myeloma Program Director, Bone Biology Center University of Pittsburgh Medical Center Pittsburgh, PA Ari Umutyan, MD Redwood Regional Medical Group Hematology and Medical Oncology Napa, CA

ACKNOWLEDGMENT This activity is supported by an educational grant from Millennium Pharmaceuticals, Inc.

This activity is jointly sponsored by the University of Cincinnati, Medical Learning Institute, Inc., a nonprofit medical accreditation company, and Center of Excellence Media, LLC.

December 2010 I VOL 3, NO 8

45

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Nursing Life ©iStockphoto.com/DNY59

RECIPE

California Nurse Receives 2010 ASTRO Nurse Excellence Award for Patient, Nurse Education

By John Schieszer

Roasted Salmon with Pumpkin Salsa

E

ating healthy can be challenging during the holiday season.

However, there is no reason why a healthy meal cannot also be tempting and delicious. This recipe features pumpkin salsa, a winter version of this popular summertime food that is so versatile it can be used as a main dish or a dessert. Pumpkin provides an excellent source of betacarotene, blood pressure–lowering potassium, immune-boosting zinc, and cholesterol-reducing fiber. Pumpkin salsa can also be used as a dessert.

Top a bowl of low-fat vanilla ice cream with this sweet and savory salsa and make a delicious antioxidantrich sweet treat. For even more variety, replace the pumpkin with butternut squash.

Ingredients 1 pound pumpkin, small diced 2 cups water 1 cup brown sugar ½ cup cider vinegar ½ cup toasted walnuts ½ cup dried cranberries 1 teaspoon cinnamon

SAN DIEGO—Elizabeth Brunton, RN, MSN, OCN, started in the nursing field in 1973. More than 35 years later, she is the recipient of the American Society for Radiation Oncology (ASTRO) Nurse Excellence Award. This award is presented annually to a registered nurse who goes above and beyond the normal standards of nursing practice.

“I really like taking care of patients.

I like being a patient advocate, and I enjoy the teaching aspect of it,” said Burton in an interview with The Oncology Nurse. Brunton likes to help patients through the whole treatment process and knowing that she can make a difference in their life.

She also enjoys educating nurses and is a regular speaker at ASTRO nurse meetings as well as local Oncology Nursing Society events. For her presentation on mucositis at ASTRO’s annual meeting in 2005, Brunton received the highest evaluation ratings within ASTRO for that year.

Brunton received her Bachelor of Science degree in nursing from the University of California, Los Angeles, and her Master of Science degree in nursing from Case Western Reserve University in Cleveland, Ohio. She is the lead nurse and primary nurse in the radiation oncology department at Scripps Clinic and Scripps Green Hospital in La Jolla, California, where

“I really like taking care of patients. I like being a patient advocate, and I enjoy the teaching aspect of it.”

—Elizabeth Brunton, RN, MSN, OCN

she has worked since 1986.

In her daily role at her hospital, Brunton is responsible for assessing the physical, nutritional, and emotional needs of radiation therapy patients and assuring their optimal care. She also makes education a major part of her career. She worked across departments at Scripps to develop patient education materials on radiation therapy to help patients and their families better understand the life-saving treatment. In 2009, she also created a patient education orientation program for new patients. The course educates patients and their families about all aspects of radiation therapy, including physics, nursing, therapy, and simulation. Participants are asked to evaluate the course afterward, and the results are reported as part of Scripps’ quality improvement process.

Brunton also assists cancer patients during the transition from being in active treatment to survivorship. She ini-

tiated a procedure in the radiation oncology department to ensure that all patients receive information regarding their stage, pertinent test results, and specific information regarding their disease.

“The nice thing about radiation therapy is that there is a variety, because we treat everything from head to toe. We treat some patients for cure, and we treat some patients for palliation. We get to see them in follow-up over time, so it is very rewarding,” said Brunton.

“You really get a chance to know the patients and their families. In a lot of specialties, you may see the patient once or twice, but in our specialty, we really get to know the patient.”

Part of the key to her success has been that she always tries to find the things at her job that she enjoys. These are the things she stays focused on when she has days when her job is very difficult. “I always try to step out of my box and try to learn new things,” she says. ●

1 teaspoon allspice 1 tablespoon orange zest Four 4-ounce portions of wild salmon

Directions • Coat salmon with nonstick cooking spray and salt-free seasoning.

• Roast salmon in the oven at 400° for about 10 minutes.

• Bring water and brown sugar to a boil in a medium saucepan. Add pumpkin, and simmer for 10 minutes or until tender. In the final minute, add cranberries.

• Strain and toss with remaining ingredients.

LUNG CANCER

Fast Neutron Radiotherapy May Be Safe... Continued from page 25 Among the 12 patients who had longer than a 1-month follow-up, six patients had no evidence of local cancer progression. The median local

completed. The 1-year survival rate was 20%, and 1-year disease-free survival was 10%.

For the study of FNRT for advanced

“Our findings are good news, and we were happy that we did not have similar toxicities as have been seen in treating similar patients.”

Serves 8: 2 ounces sauce; 4 ounces salmon

—Andre Konski, MD, MBA

Nutritional Information Each serving provides: 320 calories, 12 g protein, 1.5 g saturated fat, 60 mg cholesterol, 60 mg sodium, 28 g total carbohydrate, 2 g dietary fiber, 23 g sugars, 25 g protein

46

December 2010 I VOL 3, NO 8

control of the other six patients was 3 months. Nine of 14 symptomatic patients had successful palliation within 1 month after treatment was

stage NSCLC, the researchers looked at the results in 23 patients who received a combination of FNRT and photon radiotherapy between March

1993 and December 2006. The median follow-up was 5 months. No grade 4 toxicities were recorded; however, three patients developed grade 3 radiation pneumonitis. A total of 12 patients developed grade 1 or 2 esophagitis and nine patients developed grade 1 radiation dermatitis. One patient had grade 3 radiation dermatitis.

Among the 20 patients who had longer than 1-month follow-up, 16 had no evidence of local progression, and the median local control of the other four who did have recurrence was 3 months. The median overall survival was 7 months, and the median disease-free survival was almost 3 months. One-year overall survival was 32.4%, and 1-year disease-free survival was 5.3%. ●

www.TheOncologyNurse.com

TON_December 2010_FINAL_TON 12/6/10 11:22 AM Page 47

Presents the Third Annual Curriculum for

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

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

★ Earn Continuing Education Credits ★ 8-part newsletter series

CASE STUDY DISCUSSIONS: • Front-line Therapy

• Non-Transplant Patients

• Maintenance Settings

• Cytogenetics

• Transplant Settings

• Side Effect Management

• Retreatment Settings

• Bone Health

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

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

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

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

These activities are jointly sponsored by

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

TON_December 2010_FINAL_TON 12/6/10 11:23 AM Page 48

www.AONNonline.org JOIN TODAY $39.95

First Year Membership

Member Benefits Include: â&#x20AC;˘ â&#x20AC;˘ â&#x20AC;˘ â&#x20AC;˘ â&#x20AC;˘

Best Practices Continuing Education Networking Community Resources Publications

BLOGS

Experts from various disciplines will be featured in blog segments over the course of the year, allowing members to interact with their colleagues on multiple subject areas.

RESOURCES

Informational/educational resources to help you and your patients navigate their cancer treatment and improve their quality of life.

PUBLICATIONS

Members receive subscriptions to the Journal of Oncology Navigation & Survivorship, The Oncology Nurse-APN/PA, and the bimonthly Journal of Multidisciplinary Cancer Care (a more than $150 value).

TON_December 2010_FINAL_TON 12/6/10 11:23 AM Page 49

Meetings MARCH 2011

©iStockphoto.com/Sam Valtenbergs

JANUARY 2011

20-22 SAN FRANCISCO, CA Gastrointestinal Cancers Symposium www.gicasymposium.org

FEBRUARY 2011

10-12 LOS ANGELES, CA 11th National Conference on Cancer Nursing Research www.ons.org

17-19

ORLANDO, FL Genitourinary Cancers Symposium www.gucasymposium.org

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MARCH 2011

2-5 SAN ANTONIO, TX

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Society of Surgical Oncology Annual Cancer Symposium www.surgonc.org

9-13 HOLLYWOOD, FL National Comprehensive Cancer Network 16th Annual Conference: Clinical Practice Guidelines & Quality Cancer Care www.nccn.org

www.TheOncologyNurse.com

APRIL 2011

12-16

17-19

Apr 28-May 1

LAS VEGAS, NV National Interdisciplinary Breast Center Conference www.breastcare.org

WASHINGTON, DC Association of Community Cancer Centers Annual National Meeting www.accc-cancer.org

BOSTON, MA 36th Oncology Nursing Society Annual Congress www.ons.org

RITUXAN® (Rituximab) Brief summary—Please consult full prescribing information. counts prior to each Rituxan course. During treatment with Rituxan and chemotherapy, obtain CBC and platelet counts at weekly to monthly intervals and more frequently in WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), patients who develop cytopenias. [See Adverse Reactions]. s The duration of cytopenias SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL caused by Rituxan can extend months beyond the treatment period. ADVERSE LEUKOENCEPHALOPATHY (PML) REACTIONS The most common adverse reactions of Rituxan (incidence ≥25%) Infusion Reactions: Rituxan administration can result in serious, including observed in clinical trials of patients with NHL were infusion reactions, fever, fatal infusion reactions. Deaths within 24 hours of Rituxan infusion have lymphopenia, chills, infection, and asthenia. The most common adverse reactions of occurred. Approximately 80% of fatal infusion reactions occurred in Rituxan (incidence ≥25%) observed in clinical trials of patients with CLL were: infusion association with the first infusion. Carefully monitor patients during reactions and neutropenia. Clinical Trials Experience in Lymphoid Malignancies infusions. Discontinue Rituxan infusion and provide medical treatment for Because clinical trials are conducted under widely varying conditions, adverse reaction Grade 3 or 4 infusion reactions [see Warnings and Precautions, Adverse rates observed in the clinical trials of a drug cannot be directly compared to rates in the Reactions]. s Tumor Lysis Syndrome (TLS): Acute renal failure requiring clinical trials of another drug and may not reflect the rates observed in practice. The data dialysis with instances of fatal outcome can occur in the setting of TLS described below reflect exposure to Rituxan in 2282 patients, with exposures ranging from a single infusion up to 6–8 months. Rituxan was studied in both single-agent and following treatment of non-Hodgkin’s lymphoma (NHL) patients with Rituxan active-controlled trials (n = 356 and n = 1926). The population included 679 patients [see Warnings and Precautions, Adverse Reactions]. s Severe Mucocutaneous with low-grade follicular lymphoma, 927 patients with DLBCL, and 676 patients with Reactions: Severe, including fatal, mucocutaneous reactions can occur in CLL. Most NHL patients received Rituxan as infusion of 375 mg/m2 per infusion, given as patients receiving Rituxan [see Warnings and Precautions, Adverse a single agent weekly for up to 8 doses, in combination with chemotherapy for up to 8 Reactions]. s Progressive Multifocal Leukoencephalopathy (PML): JC virus doses, or following chemotherapy for up to 16 doses. CLL patients received Rituxan 375 infection resulting in PML and death can occur in patients receiving Rituxan mg/m2 as an initial infusion followed by 500 mg/m2 for up to 5 doses, in combination with [see Warnings and Precautions, Adverse Reactions]. s fludarabine and cyclophosphamide. Seventy-one percent of CLL patients received 6 cycles and 90% received at least 3 cycles of Rituxan-based therapy. Infusion ® INDICATIONS AND USAGE Non-Hodgkin’s Lymphoma (NHL) Rituxan (rituximab) is Reactionss In the majority of patients with NHL, infusion reactions consisting of fever, indicated for the treatment of patients with: Relapsed or refractory, low-grade or chills/rigors, nausea, pruritus, angioedema, hypotension, headache, bronchospasm, follicular, CD20-positive, B-cell NHL as a single agent; Previously untreated follicular, urticaria, rash, vomiting, myalgia, dizziness, or hypertension occurred during the first CD20-positive, B-cell NHL in combination with CVP chemotherapy; Non-progressing Rituxan infusion. Infusion reactions typically occurred within 30 to 120 minutes of (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after beginning the first infusion and resolved with slowing or interruption of the Rituxan first-line CVP chemotherapy; Previously untreated diffuse large B-cell, CD20-positive infusion and with supportive care (diphenhydramine, acetaminophen, and intravenous NHL in combination with CHOP or other anthracycline-based chemotherapy regimens. saline). The incidence of infusion reactions was highest during the first infusion (77%) Chronic Lymphocytic Leukemia (CLL) Rituxan® (rituximab) is indicated, in and decreased with each subsequent infusion. [See Boxed Warning, Warnings and combination with fludarabine and cyclophosphamide (FC), for the treatment of patients Precautions.] Infections Serious infections (NCI CTCAE Grade 3 or 4), including sepsis, with previously untreated and previously treated CD20-positive CLL. Limitations of use occurred in less than 5% of patients with NHL in the single-arm studies. The overall Rituxan is not recommended for use in patients with severe, active infections. incidence of infections was 31% (bacterial 19%, viral 10%, unknown 6%, and fungal WARNINGS AND PRECAUTIONS Infusion Reactions Rituxan can cause severe, 1%). [See Warnings and Precautions.] In randomized, controlled studies where Rituxan including fatal, infusion reactions. Severe reactions typically occurred during the first was administered following chemotherapy for the treatment of follicular or low-grade infusion with time to onset of 30–120 minutes. Rituxan-induced infusion reactions and NHL, the rate of infection was higher among patients who received Rituxan. In diffuse sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, large B-cell lymphoma patients, viral infections occurred more frequently in those who pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, received Rituxan. Cytopenias and hypogammaglobulinemiaa In patients with NHL ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death. Premedicate receiving rituximab monotherapy, NCI-CTC Grade 3 and 4 cytopenias were reported in patients with an antihistamine and acetaminophen prior to dosing. Institute medical 48% of patients. These included lymphopenia (40%), neutropenia (6%), leukopenia management (e.g. glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion (4%), anemia (3%), and thrombocytopenia (2%). The median duration of lymphopenia reactions as needed. Depending on the severity of the infusion reaction and the required was 14 days (range, 1–588 days) and of neutropenia was 13 days (range, 2–116 days). interventions, temporarily or permanently discontinue Rituxan. Resume infusion at a A single occurrence of transient aplastic anemia (pure red cell aplasia) and two minimum 50% reduction in rate after symptoms have resolved. Closely monitor the occurrences of hemolytic anemia following Rituxan therapy occurred during the singlefollowing patients: those with pre-existing cardiac or pulmonary conditions, those who arm studies. In studies of monotherapy, Rituxan-induced B-cell depletion occurred in experienced prior cardiopulmonary adverse reactions, and those with high numbers of 70% to 80% of patients with NHL. Decreased IgM and IgG serum levels occurred in 14% circulating malignant cells (≥25,000/mm3). [See Boxed Warning, Warnings and of these patients. Relapsed or Refractory, Low-Grade NHL Adverse reactions in Table 1 Precautions, Adverse Reactions.] Tumor Lysis Syndrome (TLS) Acute renal failure, occurred in 356 patients with relapsed or refractory, low-grade or follicular, CD20-positive, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, B-cell NHL treated in single-arm studies of Rituxan administered as a single agent. [See some fatal, can occur within 12–24 hours after the first infusion of Rituxan in patients Clinical Studies.] Most patients received Rituxan 375 mg/m2 weekly for 4 doses. with NHL. A high number of circulating malignant cells (≥25,000/mm3) or high tumor burden Table 1 confers a greater risk of TLS. Administer aggressive intravenous hydration and anti- Incidence of Adverse Reactions in ≥5% of Patients with Relapsed or Refractory, Lowhyperuricemic therapy in patients at high risk for TLS. Correct electrolyte abnormalities, Grade or Follicular NHL, Receiving Single-agent Rituxan (N = 356)a,b monitor renal function and fluid balance, and administer supportive care, including dialysis as All Grades (%) Grade 3 and 4 (%) All Grades (%) Grade 3 and 4 (%) indicated. [See Boxed Warning.] Severe Mucocutaneous Reactions Mucocutaneous Any Adverse Events 99 57 Respiratory p y System y 38 4 reactions, some with fatal outcome, can occur in patients treated with Rituxan. These Bodyy as a Whole 86 10 Increased Cough 13 1 Fever 53 1 Rhinitis 12 1 reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid Chills 33 3 Bronchospasm 8 1 dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of these Infection 31 4 Dyspnea 7 1 Sinusitis 6 0 Asthenia 26 1 reactions has varied from 1–13 weeks following Rituxan exposure. Discontinue Rituxan Headache 19 1 Metabolic and Nutritional in patients who experience a severe mucocutaneous reaction. The safety of Abdominal Pain 14 1 Disorders 38 3 Pain 12 1 Angioedema 11 1 readministration of Rituxan to patients with severe mucocutaneous reactions has not Back Pain 10 1 Hyperglycemia 9 1 been determined. [See Boxed Warning, Adverse Reactions.] Progressive Multifocal Throat Irritation 9 0 Peripheral Edema 8 0 5 0 LDH Increase 7 0 Leukoencephalopathy (PML) JC virus infection resulting in PML and death can occur HemeFlushing and Lymphatic y p System y 67 48 Digestive g System y 37 2 in Rituxan-treated patients with hematologic malignancies or with autoimmune diseases.

Lymphopenia 48 40 Nausea 23 1 Leukopenia 14 4 Diarrhea 10 1 The majority of patients with hematologic malignancies diagnosed with PML received Neutropenia 14 6 Vomiting 10 1 Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell Thrombocytopenia 12 2 Nervous System y 32 1 Anemia 8 3 Dizziness 10 1 transplant. The patients with autoimmune diseases had prior or concurrent Skin and Appendages Anxiety 5 1 pp g 44 2 immunosuppressive therapy. Most cases of PML were diagnosed within 12 months of Night Sweats 15 1 Musculoskeletal System y 26 3 Rash 15 1 Myalgia 10 1 their last infusion of Rituxan. Consider the diagnosis of PML in any patient presenting Pruritus 14 1 10 1 Arthralgia with new-onset neurologic manifestations. Evaluation of PML includes, but is not limited Urticaria 8 1 Cardiovascular System y 25 3 Hypotension 10 1 to, consultation with a neurologist, brain MRI, and lumbar puncture. Discontinue Rituxan Hypertension 6 1 and consider discontinuation or reduction of any concomitant chemotherapy or a b immunosuppressive therapy in patients who develop PML. [See Boxed Warning, Adverse Adverse reactions observed up to 12 months following Rituxan. Adverse reactions graded for severity Reactions.] Hepatitis B Virus (HBV) Reactivation Hepatitis B virus (HBV) reactivation by NCI-CTC criteria. with fulminant hepatitis, hepatic failure, and death can occur in patients with hematologic In these single-arm Rituxan studies, bronchiolitis obliterans occurred during and up to malignancies treated with Rituxan. The median time to the diagnosis of hepatitis was 6 months after Rituxan infusion. Previously Untreated Low-Grade NHL In Study 4, approximately 4 months after the initiation of Rituxan and approximately one month after patients in the R-CVP arm experienced a higher incidence of infusional toxicity and the last dose. Screen patients at high risk of HBV infection before initiation of Rituxan. neutropenia compared to patients in the CVP arm. The following adverse reactions Closely monitor carriers of hepatitis B for clinical and laboratory signs of active HBV occurred more frequently (≥5%) in patients receiving R-CVP compared to CVP alone: infection for several months following Rituxan therapy. Discontinue Rituxan and any rash (17% vs. 5%), cough (15% vs. 6%), flushing (14% vs. 3%), rigors (10% vs. 2%), concomitant chemotherapy in patients who develop viral hepatitis, and institute pruritus (10% vs. 1%), neutropenia (8% vs. 3%), and chest tightness (7% vs. 1%). In appropriate treatment including antiviral therapy. Insufficient data exist regarding the Study 5, the following adverse reactions were reported more frequently (≥5%) in safety of resuming Rituxan in patients who develop hepatitis subsequent to HBV patients receiving Rituxan following CVP compared to patients who received no further reactivation. [See Adverse Reactions.] Infections Serious, including fatal, bacterial, therapy: fatigue (39% vs. 14%), anemia (35% vs. 20%), peripheral sensory fungal, and new or reactivated viral infections can occur during and up to one year neuropathy (30% vs. 18%), infections (19% vs. 9%), pulmonary toxicity (18% vs. following the completion of Rituxan-based therapy. New or reactivated viral infections 10%), hepato-biliary toxicity (17% vs. 7%), rash and/or pruritus (17% vs. 5%), included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, arthralgia (12% vs. 3%), and weight gain (11% vs. 4%). Neutropenia was the only West Nile virus, and hepatitis B and C. Discontinue Rituxan for serious infections and Grade 3 or 4 adverse reaction that occurred more frequently (≥2%) in the Rituxan arm institute appropriate anti-infective therapy. [See Adverse Reactions.] Cardiovascular Discontinue infusions for serious or life-threatening cardiac arrhythmias. Perform compared with those who received no further therapy (4% vs. 1%). [See Clinical s the following adverse reactions, cardiac monitoring during and after all infusions of Rituxan for patients who develop Studies.] DLBCLL In Studies 6 and 7, [see Clinical Studies] clinically significant arrhythmias, or who have a history of arrhythmia or angina. [See regardless of severity, were reported more frequently (≥5%) in patients age ≥60 years receiving R-CHOP as compared to CHOP alone: pyrexia (56% vs. 46%), lung disorder Adverse Reactions.] Renal Severe, including fatal, renal toxicity can occur after Rituxan administration in patients with NHL. Renal toxicity has occurred in patients who (31% vs. 24%), cardiac disorder (29% vs. 21%), and chills (13% vs. 4%). Detailed experience tumor lysis syndrome and in patients with NHL administered concomitant safety data collection in these studies was primarily limited to Grade 3 and 4 adverse cisplatin therapy during clinical trials. The combination of cisplatin and Rituxan is not an reactions and serious adverse reactions. In Study 7, a review of cardiac toxicity approved treatment regimen. Monitor closely for signs of renal failure and discontinue determined that supraventricular arrhythmias or tachycardia accounted for most of Rituxan in patients with a rising serum creatinine or oliguria. Bowel Obstruction and the difference in cardiac disorders (4.5% for R-CHOP vs. 1.0% for CHOP). The Perforation Abdominal pain, bowel obstruction and perforation, in some cases leading following Grade 3 or 4 adverse reactions occurred more frequently among patients in to death, can occur in patients receiving Rituxan in combination with chemotherapy. In the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs. postmarketing reports, the mean time to documented gastrointestinal perforation was 6 7%) and lung disorder (6% vs. 3%). Other Grade 3 or 4 adverse reactions occurring (range 1–77) days in patients with NHL. Perform a thorough diagnostic evaluation and more frequently among patients receiving R-CHOP were viral infection (Study 7), institute appropriate treatment for complaints of abdominal pain. [See Adverse neutropenia (Studies 7 and 8), and anemia (Study 8). CLL The data below reflect Reactions.] Immunization The safety of immunization with live viral vaccines following exposure to Rituxan in combination with fludarabine and cyclophosphamide in 676 s The age range was Rituxan therapy has not been studied and vaccination with live virus vaccines is not patients with CLL in Study 9 or Study 10 [see Clinical Studies]. recommended. Laboratory Monitoring In patients with lymphoid malignancies, during 30–83 years and 71% were men. Detailed safety data collection in Study 9 was limited treatment with Rituxan monotherapy, obtain complete blood counts (CBC) and platelet to Grade 3 and 4 adverse reactions and serious adverse reactions. Infusion-related

adverse reactions were defined by any of the following adverse events occurring during or within 24 hours of the start of infusion: nausea, pyrexia, chills, hypotension, vomiting, and dyspnea. In Study 9, the following Grade 3 and 4 adverse reactions occurred more frequently in R-FC–treated patients compared to FC-treated patients: infusion reactions (9% in R-FC arm), neutropenia (30% vs. 19%), febrile neutropenia (9% vs. 6%), leukopenia (23% vs. 12%), and pancytopenia (3% vs. 1%). In Study 10, the following Grade 3 or 4 adverse reactions occurred more frequently in R-FC–treated patients compared to FC-treated patients: infusion reactions (7% in R-FC arm), neutropenia (49% vs. 44%), febrile neutropenia (15% vs. 12%), thrombocytopenia (11% vs. 9%), hypotension (2% vs. 0%), and hepatitis B (2% vs. <1%). Fifty-nine percent of R-FC–treated patients experienced an infusion reaction of any severity. Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Rituxan with the incidence of antibodies to other products may be misleading. Using an ELISA assay, anti-human antichimeric antibody (HACA) was detected in 4 of 356 (1.1%) patients with low-grade or follicular NHL receiving single-agent Rituxan. Three of the four patients had an objective clinical response. The clinical relevance of HACA formation in Rituxan-treated patients is unclear. Postmarketing Experience The following adverse reactions have been identified during post-approval use of Rituxan in hematologic malignancies. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to Rituxan. Hematologic: prolonged pancytopenia, marrow hypoplasia, and late-onset neutropenia, hyperviscosity syndrome in Waldenstrom’s macroglobulinemia. Cardiac:: fatal cardiac failure. Immune/ Autoimmune Events: uveitis, optic neuritis, systemic vasculitis, pleuritis, lupus-like syndrome, serum sickness, polyarticular arthritis, and vasculitis with rash. Infection: viral infections, including progressive multifocal leukoencephalopathy (PML), increase in fatal infections in HIV-associated lymphoma, and a reported increased incidence of Grade 3 and 4 infections in patients with previously treated lymphoma without known HIV infection. Neoplasia: disease progression of Kaposi’s sarcoma. Skin: severe mucocutaneous reactions. Gastrointestinal: bowel obstruction and perforation. Pulmonary: fatal bronchiolitis obliterans and pneumonitis (including interstitial pneumonitis). DRUG INTERACTIONS Formal drug interaction studies have not been performed with Rituxan. In patients with CLL, Rituxan did not alter systemic exposure to fludarabine or cyclophosphamide. USE IN SPECIFIC POPULATIONS Pregnancy Category C: There are no adequate and well-controlled studies of rituximab in pregnant women.

Postmarketing data indicate that B-cell lymphocytopenia generally lasting less than six months can occur in infants exposed to rituximab in-utero. Rituximab was detected postnatally in the serum of infants exposed in-utero. Non-Hodgkin’s lymphoma is a serious condition that requires treatment. Rituximab should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

Reproduction studies in cynomolgus monkeys at maternal exposures similar to human therapeutic exposures showed no evidence of teratogenic effects. However, B-cell lymphoid tissue was reduced in the offspring of treated dams. The B-cell counts returned to normal levels, and immunologic function was restored within 6 months of birth.

Nursing Mothers It is not known whether Rituxan is secreted into human milk.

However, Rituxan is secreted in the milk of lactating cynomolgus monkeys, and IgG is excreted in human milk. Published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts. The unknown risks to the infant from oral ingestion of Rituxan should be weighed against the known benefits of breast-feeding. Pediatric Use The safety and effectiveness of Rituxan in pediatric patients have not been established. Geriatric Use Diffuse Large B-Cell NHLL 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 or greater. No overall differences in effectiveness were observed between these patients and younger patients. Cardiac adverse reactions, mostly supraventricular arrhythmias, occurred more frequently among elderly patients.

Serious pulmonary adverse reactions were also more common among the elderly, including pneumonia and pneumonitis. Low-Grade or Follicular Non-Hodgkin’s Lymphoma Clinical studies of Rituxan in low-grade or follicular, CD20-positive, B-cell NHL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. Chronic Lymphocytic Leukemia Among patients with CLL evaluated in two randomized active-controlled trials, 243 of 676 Rituxan-treated patients (36%) were 65 years of age or older; of these, 100 Rituxan-treated patients (15%) were 70 years of age or older. In exploratory analyses defined by age, there was no observed benefit from the addition of Rituxan to fludarabine and cyclophosphamide among patients 70 years of age or older in Study 9 or in Study 10; there was also no observed benefit from the addition of Rituxan to fludarabine and cyclophosphamide among patients 65 years of age or older in Study 10 [see Clinical Studies]. s Patients 70 years or older received lower dose intensity of fludarabine and cyclophosphamide compared to younger patients, regardless of the addition of Rituxan.

In Study 9, the dose intensity of Rituxan was similar in older and younger patients, however in Study 10 older patients received a lower dose intensity of Rituxan. The incidence of Grade 3 and 4 adverse reactions was higher among patients receiving R-FC who were 70 years or older compared to younger patients for neutropenia [44% vs. 31% (Study 9); 56% vs. 39% (Study 10)], febrile neutropenia [16% vs. 6% (Study 9)], anemia [5% vs. 2% (Study 9); 21% vs. 10% (Study 10)], thrombocytopenia [19% vs. 8% (Study 10)], pancytopenia [7% vs. 2% (Study 9); 7% vs. 2% (Study 10)] and infections [30% vs.

14% (Study 10)]. OVERDOSAGE There has been no experience with overdosage in human clinical trials. Single doses of up to 500 mg/m2 have been administered in clinical trials. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term animal studies have been performed to establish the carcinogenic or mutagenic potential of Rituxan or to determine potential effects on fertility in males or females. PATIENT COUNSELING INFORMATION Patients should be provided the Rituxan Medication Guide and provided an opportunity to read prior to each treatment session. It is important that the patient’s overall health be assessed at each visit and the risks of Rituxan therapy and any questions resulting from the patient’s reading of the Medication Guide be discussed. Rituxan is detectable in serum for up to six months following completion of therapy. Individuals of childbearing potential should use effective contraception during treatment and for 12 months after Rituxan therapy.

Revised 02/2010 (4851501) Jointly Marketed by: Biogen Idec Inc. 5200 Research Place San Diego, CA 92122 Genentech USA, Inc. 1 DNA Way South San Francisco, CA 94080-4990 ©2010 Biogen Idec Inc. and Genentech, Inc. 7140919 February 2010

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ACROSS APPROVED CLL AND NHL INDICATIONS

DRIVING PATIENT OUTCOMES Supporting your central role in patient care

Resources to support pp yyour p patients with NHL and CLL Patients can talk to a nurse educator about RITUXAN, CLL, and NHL 24 hours a day, 7 days a week. Call the RITUXAN Support Center at (888) 455-2220.

You, your patients, and their caregivers can turn to RITUXAN.com for additional resources and materials.

RITUXAN Access Solutions is committed to connecting your patients to RITUXAN, regardless of their ability to pay; for more information, please visit www.RituxanAccessSolutions.com.

Indications

Warnings and Precautions

RITUXAN® (Rituximab) is indicated for the treatment of patients with: Previously untreated and previously treated CD20positive CLL in combination with fludarabine and cyclophosphamide (FC) Relapsed or refractory, low-grade or follicular, CD20positive, B-cell NHL as a single agent Weekly ×4

Weekly ×8

Bulky disease

Retreatment

Previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after firstline CVP chemotherapy Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracyclinebased chemotherapy regimens RITUXAN is not recommended for use in patients with severe, active infections.

BOXED WARNINGS RITUXAN administration can result in serious, including fatal, adverse reactions. These include infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (PML)

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

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

Additional Important Safety Information The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with NHL were infusion reactions, fever, lymphopenia, chills, infection, and asthenia. The most frequent Grade 3 or 4 adverse reactions observed in NHL were cytopenias, including lymphopenia The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with CLL were infusion reactions and neutropenia. Most patients treated with R-FC experienced at least one Grade 3 or 4 adverse reaction.

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

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

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