AUGUST Vol 2 No 5

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AUGUST 2011

www.TheOncologyNurse.com

VOL 4, NO 5

BREAST CANCER

CANCER CENTER PROFILE

Baptist Memorial HospitalMemphis Surgical Oncology Nurses Care for Patients’ Complex Needs By Dawn Lagrosa

Differences and Similarities Among Ixabepilone and the Taxanes in Metastatic Breast Cancer By Teresa Davis, RN, OCN Clinical Trials Coordinator, Jackson Oncology Associates, PLLC, Jackson, Mississippi

P

aclitaxel and docetaxel are among the most active chemotherapy options for metastatic breast cancer.1,2 Use of these agents continues to evolve, as evidenced by their increasing use in early breast cancer and the emergence of a Cremophor EL–free formula-

tion of paclitaxel (nanoparticle albuminbound paclitaxel), which exhibits improved efficacy and tolerability profiles. Use of taxanes, however, almost always leads to taxane resistance at some point, which limits their clinical efficacy and application. Continued on page 18

CONFERENCE NEWS: ONS

Managing Hyperglycemia in Patients Receiving Steroid Treatment Proactive Patient Education Is Key Lisa Douglass cares for a patient on the surgical oncology unit at Baptist Memorial Hospital-Memphis.

t Baptist Memorial Hospital-Memphis, nurses man a 19-bed surgical oncology unit, taking care of a full range of surgical oncology patients “who have had complex surgery, for example, Whipple procedures, colon procedures, advanced gynecologic, ovarian debulking, as well as some of the newer procedures, which are the robotic hysterectomies and robotic prostatectomies,” says Betsy Brooks, manager of the surgical oncology unit.

A

Continued on page 29

By Christin Melton

BOSTON—Recognizing steroid-induced hyperglycemia early and addressing it promptly can prevent significant adverse effects associated with this complication. Educating patients on the importance of and methods for maintaining good blood glucose control helps mitigate damage to the vascular system and kidneys from hyperglycemia. It also lessens

susceptibility to infection, a complication of hyperglycemia that is of serious concern in immunocompromised patients. For oncology nurses, this imperative is a key concern for their patients with cancer whose treatment plan includes glucocorticoid medications, such as dexamethasone, prednisone, or methylprednisolone, and other steroidal therapies have an elevated Continued on page 15

INSIDE

HEMATOLOGIC CANCERS

Nursing Care of a Patient with B-Cell Acute Lymphoblastic Leukemia

COMPLIMENTARY CE

By Jayshree Shah, NP John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey

CONFERENCE NEWS

O

ncology nurses have an array of skills in and knowledge of cancer. As oncology nurse practitioners, it is vital that we help patients understand their cancer diagnosis.

Often people think of solid cancers and liquid tumors as the same tumor type, which they are not. The problem for patients with liquid tumors is that their disease is not visible or palpable. When Continued on page 14

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Cancer Burden in the HIV-Infected Population in the United States

Annual Congress of the Oncology Nursing Society

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American Society of Clinical Oncology . . . . . . . . . . . . . . . 30 GENETIC COUNSELING

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Is the Term “Genetic Counselor” Being Used Appropriately in Your Community?

©2011 Green Hill Healthcare Communications, LLC

THE WHOLE PATIENT . . . . . . . . . .

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When Hair Is Not “Just Hair”

Nutri ion

Ne Featuw re

Karen

with

The Healthy Benefits of Tomatoes Page 39

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Your inspiration, You guide your HER2+ breast cancer patients through their course of treatment with care and support. The HER Connection program can provide some extra help, including:

Text tips and email tailored to HER journey Live outreach call program Live 24/7 support line

Boxed WARNINGS and Additional Important Safety Information s 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 trial, one patient who developed CHF died of cardiomyopathy

s Exposure to Herceptin during pregnancy can result in oligohydramnios, in some cases complicated by pulmonary hypoplasia and neonatal death

s Evaluate cardiac function prior to and during treatment. For adjuvant therapy, also evaluate cardiac function after completion of Herceptin. Discontinue Herceptin for cardiomyopathy

s Detection of HER2 protein overexpression is necessary for selection of patients appropriate for Herceptin therapy

s Exacerbation of chemotherapy-induced neutropenia has also occurred

s Herceptin can result in serious and fatal infusion reactions and pulmonary toxicity. Discontinue Herceptin for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome

Š2011 Genentech USA, Inc.

6391928 Onc Nurse Jrnl Ad AUG M01 indd 1-2

s The most common adverse reactions associated with Herceptin use were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia

So. San Francisco, CA

All rights reserved.

HER0000422100

6/11

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HER commitment

Adjuvant indications Herceptin is indicated for adjuvant treatment of HER2-overexpressing node-positive or nodenegative (ER/PR-negative or with one high-risk feature*) breast cancer:

s As part of a treatment regimen containing doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel s With docetaxel and carboplatin s As a single agent following multi-modality anthracycline-based therapy *High-risk is defined as ER/PR positive with one of the following features: tumor size >2 cm, age <35 years, or tumor grade 2 or 3.

Please see brief summary of full Prescribing Information, including Boxed WARNINGS and additional important safety information, on the following pages.

8/3/11 3:02 PM

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HERCEPTINÂŽ (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 s AS PART OF A TREATMENT REGIMEN consisting of doxorubicin, cyclophosphamide, and either PACLITAXEL OR DOCETAXEL s WITH DOCETAXEL AND CARBOPLATIN s AS A SINGLE AGENT FOLLOWING MULTI MODALITY ANTHRACYCLINE based therapy. Metastatic Breast Cancer Herceptin is INDICATED s )N COMBINATION WITH PACLITAXEL FOR lRST LINE TREATMENT OF (%2 OVEREXPRESSING METASTATIC BREAST CANCER s !S A SINGLE AGENT FOR TREATMENT OF (%2 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 mUOROURACIL 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 ,6%& 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 (ERCEPTIN INDUCED LEFT VENTRICULAR CARDIAC DYSFUNCTION has not been studied. Cardiac Monitoring Conduct thorough cardiac assessment, including history, physical examination, AND DETERMINATION OF ,6%& BY ECHOCARDIOGRAM OR -5'! SCAN 4HE FOLLOWING SCHEDULE IS RECOMMENDED s "ASELINE LVEF measurement immediately prior to initiation of Herceptin s ,6%& MEASUREMENTS EVERY MONTHS DURING AND UPON COMPLETION OF (ERCEPTIN s 2EPEAT ,6%& MEASUREMENT AT WEEK INTERVALS IF (ERCEPTIN IS WITHHELD FOR SIGNIlCANT LEFT VENTRICULAR cardiac dysfunction [see Dosage and Administration= s ,6%& measurements every 6 months for at least 2 years following completion of Herceptin as a component of adjuvant therapy. )N 3TUDY OF PATIENTS DISCONTINUED (ERCEPTIN due to clinical evidence of myocardial dysfunction or SIGNIlCANT DECLINE IN ,6%& )N 3TUDY THE NUMBER OF PATIENTS who discontinued Herceptin due to cardiac toxicity was 2.6% )N 3TUDY A TOTAL OF PATIENTS IN THE TCH arm (1.5% during the chemotherapy phase and 1.4% DURING THE MONOTHERAPY PHASE AND PATIENTS IN THE !# 4( ARM DURING THE CHEMOTHERAPY PHASE AND 4.2% during the monotherapy phase) discontinued Herceptin DUE TO CARDIAC TOXICITY !MONG 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 !PPROXIMATELY HALF OF THE SURVIVING PATIENTS HAD RECOVERY TO A NORMAL ,6%& DElNED AS ≼ 50%) on continuing MEDICAL MANAGEMENT AT THE TIME OF LAST FOLLOW UP )NCIDENCE of congestive heart failure is presented in Table 1. The safety of continuation or resumption of Herceptin in patients with (ERCEPTIN INDUCED LEFT VENTRICULAR CARDIAC DYSFUNCTION HAS not been studied. Table 1 )NCIDENCE OF #ONGESTIVE (EART &AILURE IN !DJUVANT "REAST #ANCER 3TUDIES Study 1 & 2a 4 a

Regimen !#b→Paclitaxel+ (ERCEPTIN #HEMO→(ERCEPTIN !#b→Docetaxel+ (ERCEPTIN Docetaxel+Carbo+ (ERCEPTIN

Incidence of CHF Herceptin Control

Includes 1 patient with fatal cardiomyopathy. !NTHRACYCLINE DOXORUBICIN AND CYCLOPHOSPHAMIDE

b

Table 2 Incidence of Cardiac Dysfunctiona in Metastatic "REAST #ANCER 3TUDIES Study 5 !# b 5 (paclitaxel) 6

Incidence .9(! )–)6 .9(! )))–)6 Herceptin Control Herceptin Control

Event Cardiac $YSFUNCTION Cardiac Dysfunction 11% 1% 4% 1% Cardiac c Dysfunction . ! . ! a #ONGESTIVE HEART FAILURE OR SIGNIlCANT ASYMPTOMATIC decrease in LVEF. b !NTHRACYCLINE DOXORUBICIN OR EPIRUBICIN AND cyclophosphamide. c Includes 1 patient with fatal cardiomyopathy. )N 3TUDY THE INCIDENCE OF .#) #4# 'RADE CARDIAC ischemia/infarction was higher in the Herceptin containing REGIMENS !# 4( AND 4#( AS COMPARED TO NONE IN !# 4 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 SIGNIlCANT 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 IDENTIlCATION 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 (ERCEPTIN DURING PREGNANCY resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal ABNORMALITIES AND NEONATAL DEATH !DVISE 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 INlLTRATES PLEURAL EFFUSIONS NON CARDIOGENIC PULMONARY EDEMA PULMONARY INSUFlCIENCY and hypoxia, acute respiratory distress syndrome, and PULMONARY lBROSIS 3UCH 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 .#) #4# 'RADE – 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 BENElT HAS BEEN SHOWN $UE TO DIFFERENCES IN TUMOR HISTOPATHOLOGY USE &$! APPROVED TESTS FOR THE SPECIlC TUMOR TYPE BREAST OR GASTRIC gastroesophageal adenocarcinoma) to assess HER2 protein OVEREXPRESSION AND (%2 GENE AMPLIlCATION 4ESTS SHOULD BE PERFORMED BY LABORATORIES WITH DEMONSTRATED PROlCIENCY IN THE SPECIlC TECHNOLOGY BEING UTILIZED )MPROPER ASSAY PERFORMANCE INCLUDING USE OF SUBOPTIMALLY lXED TISSUE FAILURE TO UTILIZE SPECIlED REAGENTS DEVIATION FROM SPECIlC assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results. Several &$! APPROVED COMMERCIAL ASSAYS ARE AVAILABLE TO AID IN THE selection of breast cancer and metastatic gastric cancer patients for Herceptin therapy. Users should refer to the PACKAGE INSERTS OF SPECIlC ASSAY KITS FOR INFORMATION ON THE Intended Use, and the validation and performance of each assay. Limitations in assay precision make it inadvisable to RELY ON A SINGLE METHOD TO RULE OUT POTENTIAL (ERCEPTIN BENElT Treatment outcomes for adjuvant breast cancer (Studies AND AND FOR METASTATIC BREAST CANCER 3TUDY AS A FUNCTION OF )(# AND &)3( TESTING ARE PROVIDED IN 4ABLES AND !SSESSMENT OF (%2 PROTEIN OVEREXPRESSION AND (%2 GENE AMPLIlCATION IN METASTATIC GASTRIC CANCER SHOULD BE PERFORMED USING &$! APPROVED TESTS SPECIlCALLY 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. 3TUDY DEMONSTRATED THAT GENE AMPLIlCATION AND PROTEIN overexpression were not as well correlated as with breast cancer. Treatment outcomes for metastatic gastric cancer 3TUDY BASED ON (%2 GENE AMPLIlCATION &)3( 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 s #ARDIOMYOPATHY ;see Warnings and Precautions= s )NFUSION REACTIONS ;see Warnings and

Precautions= s %MBRYO FETAL 4OXICITY ;see Warnings and Precautions= s 0ULMONARY TOXICITY ;see Warnings and Precautions= s %XACERBATION 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 !DVERSE REACTIONS REQUIRING interruption or discontinuation of Herceptin treatment include #(& SIGNIlCANT 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 INmAMMATION NASOPHARYNGITIS AND DYSGEUSIA 4HE MOST common adverse reactions which resulted in discontinuation OF TREATMENT ON THE (ERCEPTIN CONTAINING ARM IN THE ABSENCE of disease progression were infection, diarrhea, and febrile neutropenia. Clinical Trials Experience "ECAUSE 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 REmECT THE RATES OBSERVED in practice. Adjuvant Breast Cancer Studies The data below REmECT EXPOSURE TO (ERCEPTIN ACROSS THREE RANDOMIZED OPEN LABEL STUDIES 3TUDIES AND WITH N OR WITHOUT N TRASTUZUMAB IN THE ADJUVANT TREATMENT OF BREAST CANCER 4HE DATA SUMMARIZED IN 4ABLE BELOW FROM 3TUDY REmECT EXPOSURE TO (ERCEPTIN IN PATIENTS THE median treatment duration was 51 weeks and median number OF INFUSIONS WAS !MONG THE PATIENTS ENROLLED IN 3TUDY THE MEDIAN AGE WAS YEARS RANGE TO YEARS OF PATIENTS WERE #AUCASIAN AND WERE !SIAN Table 3 !DVERSE 2EACTIONS FOR 3TUDY !LL 'RADESa :

!DVERSE 2EACTION

1 Year Herceptin Observation N N

Cardiac (YPERTENSION $IZZINESS %JECTION &RACTION $ECREASED 0ALPITATIONS #ARDIAC !RRHYTHMIASb #ARDIAC &AILURE #ONGESTIVE #ARDIAC &AILURE #ARDIAC $ISORDER Ventricular Dysfunction 4 (0.2%) Respiratory Thoracic Mediastinal Disorders #OUGH )NmUENZA $YSPNEA 52) 2HINITIS 0HARYNGOLARYNGEAL 0AIN 3INUSITIS Epistaxis 25 (2%) Pulmonary Hypertension 4 (0.2%) Interstitial Pneumonitis 4 (0.2%) Gastrointestinal Disorders $IARRHEA .AUSEA 6OMITING #ONSTIPATION $YSPEPSIA 5PPER !BDOMINAL 0AIN Musculoskeletal & Connective Tissue Disorders !RTHRALGIA "ACK 0AIN -YALGIA "ONE 0AIN -USCLE 3PASM Nervous System Disorders (EADACHE 0ARAESTHESIA Skin & Subcutaneous Tissue Disorders Rash 70 (4%) .AIL $ISORDERS Pruritis 40 (2%) General Disorders Pyrexia 100 (6%) %DEMA 0ERIPHERAL #HILLS !ESTHENIA )NmUENZA LIKE )LLNESS Sudden Death 1 (0.06%) Infections .ASOPHARYNGITIS 54) Immune System Disorders Hypersensitivity 10 (0.6%) !UTOIMMUNE 4HYROIDITIS

0 (0%) 1 (0.06%) 0 (0%) 0 (0%) 10 (0.6%) 10 (0.6%) 6 (0.4%) 0 (0%) 1 (0.06%)

4HE INCIDENCE OF 'RADE ADVERSE REACTIONS WAS IN both arms for each listed term. b Higher level grouping term. 4HE DATA FROM 3TUDIES AND WERE OBTAINED FROM PATIENTS OF WHOM RECEIVED (ERCEPTIN THE MEDIAN treatment duration was 50 weeks. The median age was YEARS RANGE – OF PATIENTS WERE 7HITE "LACK (ISPANIC AND !SIAN )N 3TUDY ONLY 'RADE – ADVERSE EVENTS TREATMENT RELATED 'RADE EVENTS AND 'RADE – DYSPNEA WERE COLLECTED DURING AND FOR UP TO MONTHS FOLLOWING PROTOCOL SPECIlED TREATMENT 4HE FOLLOWING NON CARDIAC ADVERSE REACTIONS OF 'RADE – OCCURRED AT AN incidence of at least 2% greater among patients randomized to Herceptin plus chemotherapy as compared to chemotherapy ALONE ARTHRALGIA VS FATIGUE VS INFECTION VS HOT mASHES VS ANEMIA VS 7%), dyspnea (12% vs. 4%), rash/desquamation (11% vs. 7%), neutropenia (7% vs. 5%), headache (6% vs. 4%), and insomnia VS 4HE MAJORITY OF THESE EVENTS WERE 'RADE a

2 in severity. In Study 2, data collection was limited to the FOLLOWING INVESTIGATOR ATTRIBUTED TREATMENT RELATED ADVERSE REACTIONS .#) #4# 'RADE AND HEMATOLOGIC TOXICITIES 'RADE – NON HEMATOLOGIC TOXICITIES SELECTED 'RADE – toxicities associated with taxanes (myalgia, arthralgias, nail changes, motor neuropathy, sensory neuropathy) and Grade 1−5 cardiac toxicities occurring during chemotherapy and/ OR (ERCEPTIN TREATMENT 4HE 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 VS MYALGIA VS NAIL CHANGES VS AND DYSPNEA VS 4HE MAJORITY OF THESE events were Grade 2 in severity. Safety data from Study 4 REmECT EXPOSURE TO (ERCEPTIN AS PART OF AN ADJUVANT TREATMENT regimen from 2124 patients receiving at least one dose of STUDY TREATMENT ;!# 4( N 4#( N = 4HE OVERALL MEDIAN TREATMENT DURATION WAS WEEKS IN BOTH THE !# 4( and TCH arms. The median number of infusions was 26 in the !# 4( ARM AND IN THE 4#( ARM INCLUDING WEEKLY INFUSIONS during the chemotherapy phase and every three week dosing IN THE MONOTHERAPY PERIOD !MONG THESE PATIENTS THE MEDIAN AGE WAS YEARS RANGE TO YEARS )N 3TUDY THE TOXICITY PROlLE WAS SIMILAR TO THAT REPORTED IN 3TUDIES AND WITH the exception of a low incidence of CHF in the TCH arm. Metastatic Breast Cancer Studies 4HE DATA BELOW REmECT EXPOSURE TO (ERCEPTIN IN ONE RANDOMIZED OPEN LABEL STUDY 3TUDY OF CHEMOTHERAPY WITH N OR WITHOUT N trastuzumab in patients with metastatic breast cancer, and one SINGLE ARM STUDY 3TUDY N IN PATIENTS WITH METASTATIC breast cancer. Data in Table 4 are based on Studies 5 and 6. !MONG THE PATIENTS TREATED IN 3TUDY THE MEDIAN AGE WAS YEARS RANGE – YEARS %IGHTY NINE PERCENT WERE 7HITE "LACK !SIAN AND OTHER RACIAL ETHNIC GROUPS !LL PATIENTS RECEIVED MG KG INITIAL DOSE OF (ERCEPTIN FOLLOWED by 2 mg/kg weekly. The percentages of patients who received Herceptin treatment for ≼ 6 months and ≼ 12 months were AND RESPECTIVELY !MONG THE PATIENTS TREATED IN SINGLE AGENT STUDIES PATIENTS FROM 3TUDY THE MEDIAN AGE WAS YEARS RANGE – YEARS WERE 7HITE WERE "LACK WERE !SIAN AND 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 ≼ MONTHS WERE AND RESPECTIVELY Table 4 0ER 0ATIENT )NCIDENCE OF !DVERSE 2EACTIONS /CCURRING in ≼ 5% of Patients in Uncontrolled Studies or at Increased )NCIDENCE IN THE (ERCEPTIN !RM 3TUDIES AND

Herceptin 3INGLE 0ACLITAXEL (ERCEPTIN !#b a !GENT 0ACLITAXEL !LONE !#b !LONE N N N N N

"ODY AS A 7HOLE Pain 47% 61% 62% 57% 42% !STHENIA &EVER #HILLS (EADACHE !BDOMINAL PAIN "ACK PAIN )NFECTION Flu syndrome 10% 12% 5% 12% 6% !CCIDENTAL INJURY !LLERGIC REACTION Cardiovascular Tachycardia 5% 12% 4% 10% 5% #ONGESTIVE heart failure Digestive .AUSEA $IARRHEA 6OMITING Nausea and VOMITING !NOREXIA Heme & Lymphatic !NEMIA ,EUKOPENIA Metabolic Peripheral edema 10% 22% 20% 20% 17% %DEMA Musculoskeletal "ONE PAIN !RTHRALGIA Nervous )NSOMNIA $IZZINESS 0ARESTHESIA $EPRESSION Peripheral NEURITIS .EUROPATHY Respiratory Cough INCREASED Dyspnea 22% 27% 26% 42% 25% Rhinitis 14% 22% 5% 22% 16% 0HARYNGITIS 3INUSITIS Skin 2ASH Herpes SIMPLEX !CNE Urogenital Urinary tract INFECTION a Data for Herceptin single agent were from 4 studies, INCLUDING PATIENTS FROM 3TUDY b !NTHRACYCLINE DOXORUBICIN OR EPIRUBICIN AND cyclophosphamide.

M

I

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Metastatic Gastric Cancer The data below are based on THE EXPOSURE OF PATIENTS TO (ERCEPTIN IN COMBINATION WITH A mUOROPYRIMIDINE CAPECITABINE OR &5 AND CISPLATIN (Study 7). In the Herceptin plus chemotherapy arm, the initial DOSE OF (ERCEPTIN MG KG WAS ADMINISTERED ON $AY PRIOR to chemotherapy) followed by 6 mg/kg every 21 days until DISEASE PROGRESSION #ISPLATIN WAS ADMINISTERED AT MG M2 ON $AY AND THE mUOROPYRIMIDINE WAS ADMINISTERED AS EITHER capecitabine 1000 mg/m2 ORALLY TWICE A DAY ON $AYS OR mUOROURACIL MG M2/day as a continuous intravenous infusion Days 1 through 5. Chemotherapy was administered for SIX DAY CYCLES -EDIAN DURATION OF (ERCEPTIN TREATMENT WAS WEEKS MEDIAN NUMBER OF (ERCEPTIN INFUSIONS ADMINISTERED was eight.

"ODY 3YSTEM !DVERSE %VENT

Grades

FC . N (%) !LL Grades Grades ?

17%

Time 0 is the date of randomization.

Figure 3 Study 4: Cumulative Incidence of Time to First LVEF Decline of ≼ 0ERCENTAGE 0OINTS FROM "ASELINE AND TO "ELOW 50% with Death as a Competing Risk Event

0 (0)

0 (0)

Time 0 is the date of randomization.

,6%& AND !BSOLUTE $ECREASE FROM "ASELINE

!BSOLUTE ,6%& $ECREASE

LVEF ≼10% ≼ DECREASE DECREASE

AND ≼10% ≼20%

!#→4 N

Study 3 (ERCEPTIN N

/BSERVATION N

Study 4c 4#( N

!#→4( N

!#→4 N

&OR 3TUDIES AND EVENTS ARE COUNTED FROM THE BEGINNING of Herceptin treatment. For Study 4, events are counted from the date of randomization.

a

Figure 2 3TUDY #UMULATIVE )NCIDENCE OF 4IME TO &IRST ,6%& Decline of ≼ 0ERCENTAGE 0OINTS FROM "ASELINE AND TO "ELOW WITH $EATH AS A #OMPETING 2ISK %VENT

≤1)

Studies 1 & 2b !#→4( N

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

The following subsections provide additional detail regarding adverse reactions observed in clinical trials of adjuvant breast, METASTATIC BREAST CANCER METASTATIC GASTRIC CANCER OR POST marketing experience. Cardiomyopathy Serial measurement of cardiac function (LVEF) was obtained in clinical trials in the ADJUVANT TREATMENT OF BREAST CANCER )N 3TUDY THE MEDIAN DURATION OF FOLLOW UP WAS MONTHS MONTHS IN THE OBSERVATION ARM MONTHS IN THE YEAR (ERCEPTIN ARM AND IN 3TUDIES AND MONTHS IN THE !# 4 ARM MONTHS IN THE !# 4( ARM )N 3TUDIES AND OF PATIENTS WERE NOT PERMITTED TO INITIATE (ERCEPTIN FOLLOWING COMPLETION OF !# CHEMOTHERAPY DUE TO CARDIAC DYSFUNCTION ,6%& OR ≼ POINT DECLINE IN ,6%& FROM BASELINE TO END OF !# 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 3TUDY SEE 4ABLE &IGURES AND Table 6a 0ER PATIENT )NCIDENCE OF .EW /NSET -YOCARDIAL $YSFUNCTION BY ,6%& 3TUDIES AND

6%

!LL Grades

Investigations .EUTROPENIA (YPOKALEMIA !NEMIA 4HROMBOCYTOPENIA "LOOD !ND ,YMPHATIC System Disorders &EBRILE .EUTROPENIA ? Gastrointestinal Disorders $IARRHEA 3TOMATITIS $YSPHAGIA "ODY AS A 7HOLE &ATIGUE &EVER Mucosal )NmAMMATION #HILLS ≤1) -ETABOLISM !ND Nutrition Disorders 7EIGHT $ECREASE )NFECTIONS !ND Infestations Upper Respiratory 4RACT )NFECTIONS .ASOPHARYNGITIS 2ENAL !ND 5RINARY Disorders Renal Failure and )MPAIRMENT Nervous System Disorders $YSGEUSIA

Herceptin +FC . N (%)

Figure 1 Studies 1 and 2: Cumulative Incidence of Time to First LVEF Decline of ≼ 0ERCENTAGE 0OINTS FROM "ASELINE AND TO "ELOW WITH $EATH AS A #OMPETING 2ISK %VENT

Table 5 3TUDY 0ER 0ATIENT )NCIDENCE OF !DVERSE 2EACTIONS OF !LL 'RADES )NCIDENCE ≼ BETWEEN !RMS OR 'RADE )NCIDENCE BETWEEN !RMS AND (IGHER )NCIDENCE IN (ERCEPTIN !RM

3 TUDIES AND REGIMENS DOXORUBICIN AND CYCLO PHOSPHAMIDE FOLLOWED BY PACLITAXEL !#→T) or paclitaxel PLUS (ERCEPTIN !#→TH). c Study 4 regimens: doxorubicin and cyclophosphamide FOLLOWED BY DOCETAXEL !#→T) or docetaxel plus Herceptin !#→4( DOCETAXEL AND CARBOPLATIN PLUS (ERCEPTIN 4#( b

The incidence of treatment emergent congestive heart failure among patients in the metastatic breast cancer trials was CLASSIlED FOR SEVERITY USING THE .EW 9ORK (EART !SSOCIATION CLASSIlCATION SYSTEM )–)6 WHERE )6 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 $URING THE lRST INFUSION WITH (ERCEPTIN 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 (ERCEPTIN INFUSION PERMANENT DISCONTINUATION OF (ERCEPTIN FOR INFUSIONAL TOXICITY WAS REQUIRED IN 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 OF PATIENTS AND WAS SEVERE IN AND of patients, on second or subsequent Herceptin infusions administered as monotherapy or in combination with CHEMOTHERAPY RESPECTIVELY )N 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 VS ;3TUDY = OF SELECTED .#) #4# 'RADE 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 .#) #4# 'RADE ANEMIA WAS )N 3TUDY (metastatic gastric cancer) on the Herceptin containing arm as compared to the chemotherapy alone arm the overall INCIDENCE OF ANEMIA WAS COMPARED AND OF .#) #4# 'RADE ANEMIA WAS COMPARED TO Neutropenia In randomized controlled clinical trials in the adjuvant setting, THE INCIDENCE OF SELECTED .#) #4# 'RADE – NEUTROPENIA 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 .#) #4# 'RADE NEUTROPENIA VS AND OF FEBRILE NEUTROPENIA VS 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 .#) #4# 'RADE NEUTROPENIA WAS COMPARED TO FEBRILE NEUTROPENIA COMPARED TO Infection The OVERALL INCIDENCES OF INFECTION VS ;3TUDY = OF SELECTED .#) #4# 'RADE – INFECTION FEBRILE NEUTROPENIA

VS ;3TUDY = AND OF SELECTED 'RADE – INFECTION FEBRILE NEUTROPENIA VS ;3TUDY = 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 (ERCEPTIN TO !# 4 BUT NOT TO 4#( ; !# 4( 4#( !# 4 = 4HE INCIDENCES OF .#) #4# 'RADE – INFECTION WERE SIMILAR ; !# 4( 4#( !# 4 = ACROSS THE three arms. In a randomized, controlled trial in treatment of metastatic breast cancer, the reported incidence of febrile NEUTROPENIA WAS HIGHER VS IN PATIENTS RECEIVING (ERCEPTIN IN COMBINATION WITH MYELO SUPPRESSIVE CHEMO therapy as compared to chemotherapy alone. Pulmonary Toxicity !DJUVANT "REAST #ANCER !MONG WOMEN RECEIVING adjuvant therapy for breast cancer, the incidence of selected .#) #4# 'RADE – PULMONARY TOXICITY VS ;3TUDY = AND OF SELECTED .#) #4# 'RADE – PULMONARY TOXICITY AND SPONTANEOUS REPORTED 'RADE DYSPNEA VS ;3TUDY = was higher in patients receiving Herceptin and chemotherapy compared with chemotherapy alone. The most common PULMONARY TOXICITY WAS DYSPNEA .#) #4# 'RADE – VS ;3TUDY = .#) #4# 'RADE – VS ;3TUDY = 0NEUMONITIS PULMONARY INlLTRATES OCCURRED IN OF PATIENTS RECEIVING (ERCEPTIN COMPARED WITH OF THOSE RECEIVING CHEMOTHERAPY ALONE &ATAL RESPIRATORY FAILURE OCCURRED IN PATIENTS RECEIVING (ERCEPTIN ONE AS A COMPONENT OF MULTI organ system failure, as compared to 1 patient receiving CHEMOTHERAPY ALONE )N 3TUDY THERE WERE CASES OF INTERSTITIAL PNEUMONITIS IN (ERCEPTIN TREATED PATIENTS COMPARED TO NONE IN THE CONTROL ARM -ETASTATIC "REAST #ANCER !MONG WOMEN RECEIVING (ERCEPTIN 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 INlLTRATES 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 VS ;3TUDY = AND VS ;3TUDY = AND VS ;3TUDY = Diarrhea !MONG WOMEN RECEIVING ADJUVANT THERAPY FOR BREAST CANCER THE INCIDENCE OF .#) #4# 'RADE – DIARRHEA VS ;3TUDY = AND OF .#) #4# 'RADE – DIARRHEA VS ;3TUDY = AND OF 'RADE – DIARRHEA VS ;3TUDY = were higher in patients receiving Herceptin as compared to CONTROLS )N 3TUDY THE INCIDENCE OF 'RADE – DIARRHEA WAS HIGHER ; !# 4( 4#( VS !# 4= AND OF 'RADE – WAS HIGHER ; !# 4( 4#( VS !# 4= AMONG women receiving Herceptin. Of patients receiving Herceptin as a single agent for the treatment of metastatic breast cancer, EXPERIENCED DIARRHEA !N 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 (ERCEPTIN CONTAINING ARM AS COMPARED TO THE chemotherapy alone arm the incidence of renal impairment WAS COMPARED TO 3EVERE 'RADE RENAL FAILURE WAS ON THE (ERCEPTIN CONTAINING ARM COMPARED TO on the chemotherapy only arm. Treatment discontinuation for RENAL INSUFlCIENCY FAILURE WAS ON THE (ERCEPTIN CONTAINING ARM AND ON THE CHEMOTHERAPY ONLY ARM )N 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 MONTHS FROM INITIATION OF (ERCEPTIN THERAPY 0ATHOLOGIC lNDINGS INCLUDED MEMBRANOUS GLOMERULONEPHRITIS FOCAL GLOMERULOSCLEROSIS AND lBRILLARY GLOMERULONEPHRITIS Complications included volume overload and congestive heart failure. Immunogenicity !S WITH ALL THERAPEUTIC PROTEINS THERE IS A POTENTIAL FOR IMMUNOGENICITY !MONG WOMEN WITH METASTATIC BREAST CANCER HUMAN ANTI HUMAN ANTIBODY (!(! TO (ERCEPTIN WAS DETECTED IN ONE PATIENT USING AN ENZYME LINKED IMMUNOSORBENT ASSAY %,)3! 4HIS PATIENT DID NOT experience an allergic reaction. Samples for assessment of (!(! WERE NOT COLLECTED IN STUDIES OF ADJUVANT BREAST CANCER The incidence of antibody formation is highly dependent on THE SENSITIVITY AND THE SPECIlCITY OF THE ASSAY !DDITIONALLY THE observed incidence of antibody (including neutralizing ANTIBODY POSITIVITY IN AN ASSAY MAY BE INmUENCED 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 IDENTIlED DURING POST APPROVAL USE OF (ERCEPTIN "ECAUSE 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 s )NFUSION REACTION ;see Warnings and Precautions] s /LIGOHYDRAMNIOS OR OLIGOHYDRAMNIOS SEQUENCE INCLUDING pulmonary hypoplasia, skeletal abnormalities, and neonatal death [see Warnings and Precautions= s 'LOMERULOPATHY ;see Adverse Reactions] DRUG INTERACTIONS In Study 5, the mean serum trough concentration of trastuzumab WAS CONSISTENTLY ELEVATED APPROXIMATELY 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 )N POST marketing 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 mUID INDEX INCREASED AFTER (ERCEPTIN was stopped. In one case, Herceptin therapy resumed after THE AMNIOTIC mUID 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. 4HE EFlCACY OF )6 HYDRATION IN MANAGEMENT OF OLIGOHYDRAMNIOS DUE TO (ERCEPTIN EXPOSURE IS NOT KNOWN !DVISE WOMEN OF THE potential hazard to the fetus resulting from Herceptin exposure during pregnancy. Encourage pregnant women with breast CANCER WHO ARE USING (ERCEPTIN TO ENROLL IN -OT(%2 THE (ERCEPTIN 0REGNANCY 2EGISTRY PHONE ;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 $AYS OF GESTATION OR LATE $AYS OF GESTATION FETAL DEVELOPMENT PERIODS AT LEVELS OF TO 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 MONTHS OF AGE HOWEVER trastuzumab levels in animal breast milk may not accurately REmECT HUMAN BREAST MILK LEVELS "ECAUSE 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 (ERCEPTIN HAS BEEN ADMINISTERED TO PATIENTS WHO WERE YEARS OF AGE OR OVER IN THE ADJUVANT TREATMENT AND 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 PROlLE OF (ERCEPTIN IN OLDER PATIENTS IS different from younger patients. The reported clinical EXPERIENCE IS NOT ADEQUATE TO DETERMINE WHETHER THE EFlCACY improvements (ORR, TTP, OS, DFS) of Herceptin treatment in older patients is different from that observed in patients YEARS OF AGE FOR METASTATIC DISEASE AND ADJUVANT TREATMENT )N 3TUDY METASTATIC GASTRIC CANCER OF THE PATIENTS TREATED WITH (ERCEPTIN WERE YEARS OF AGE OR OLDER WHILE WERE AND OVER .O OVERALL differences in safety or effectiveness were observed. OVERDOSAGE There is no experience with overdosage in HUMAN CLINICAL TRIALS 3INGLE DOSES HIGHER THAN MG KG HAVE not been tested. PATIENT COUNSELING INFORMATION s !DVISE 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= s !DVISE PREGNANT WOMEN and women of childbearing potential that Herceptin exposure can result in fetal harm [see Warnings and Precautions and Use in Specific Populations= s !DVISE WOMEN OF CHILDBEARING potential to use effective contraceptive methods during treatment and for a minimum of six months following Herceptin [see Warnings and Precautions= s !DVISE 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= s %NCOURAGE women who are exposed to Herceptin during pregnancy to ENROLL IN -OT(%2 THE (ERCEPTIN 0REGNANCY 2EGISTRY ;see Warnings and Precautions and Use in Specific Populations]. HERCEPTINŽ [trastuzumab] Manufactured by: Genentech, Inc. A Member of the Roche Group $.! 7AY 3OUTH 3AN &RANCISCO #! )NITIAL 53 !PPROVAL 3EPTEMBER 2EVISION $ATE /CTOBER HerceptinŽ is a registered trademark of Genentech, Inc. HER0000111000 Š 2010 Genentech, Inc.

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Editorial Board EDITOR-IN-CHIEF

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

Cassandra J. Hammond, RN,

Dolores “Jeff” Nordquist, RN, MS,

Rita Wickham,

MSN, CRNP

CS, FNP

Avid Education Partners, LLC Sharpsburg, MD

Mayo Clinic Rochester, MN

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

Elizabeth Bilotti,

Shannon Hazen,

RN, MSN, APRN, BC, OCN

RN, BSN, OCN

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Catherine Bishop, DNP, NP, AOCNP Virginia Cancer Care Lansdowne, VA

Novant Health Presbyterian Cancer Center Charlotte, NC

MSN, FNP-C, CPON

Pharmacy John F. Aforismo, BSc Pharm, RPh, FASCP R. J. Health Systems International, LLC Wethersfield, CT

NP, MSN, ACNP-C

Sandra E. Kurtin,

DNP, APRN, AOCN

RN, MS, AOCN, ANP-C Arizona Cancer Center Tucson, AZ

Denice Economou, RN,

Elizabeth Lima,

MN, CNS, AOCN

Cleveland Clinic Taussig Cancer Institute Cleveland, OH

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

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

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Wendy DiSalvo,

MS, CNS, OCN

City of Hope National Medical Center Duarte, CA

Jayshree Shah, NP,

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

Constance Engelking, RN,

DNS, APRN, CNS

Piedmount Healthcare Rex, GA

AOCN, BC

City of Hope National Medical Center Duarte, CA

Karla Wilson, RN,

BSN, OCN

Taline Khoukaz,

Genentech New London, NH

Melinda Oberleitner, RN,

Patricia Irouer Hughes, RN, MSN,

Deena Damsky Dell, RN, MSN, Fox Chase Cancer Center Philadelphia, PA

OCN, PhD, RN

Gary Shelton, MSN, ARNP, AOCN

Nutrition Karen Connelly, RD, CSO

NYU Cancer Institute New York, NY

Somerset Medical Center Somerville, NJ

Lori Stover, RN, BSN

Patient Advocate Peg Ford

Western Pennsylvania Cancer Institute Pittsburgh, PA

Ovarian Cancer Advocacy Alliance Coronado, CA

Joseph D. Tariman, PhD,

Social Work Carolyn Messner,

APRN,BC

DSW, MSW, LCSW-R, BCD

PA-C

Ann McNeill, MSN, RN, NP-C, OCN John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Amy Ford, RN,

Kena C. Miller,

BSN, OCN

RN, MSN, FNP

Innovex Dallas, TX

Roswell Park Cancer Institute Buffalo, NY

Northwestern University Myeloma Program Chicago, IL

Pamela Hallquist Viale, RN, MS, CS, ANP, AOCN Saratoga, CA

CancerCare New York, NY

Managed Care and Pharmaceutical Management Burt Zweigenhaft, BS BioPharma Partners LLC New York, NY

Isabell Castellano, RN Sharon S. Gentry,

Patricia Molinelli,

Connie Visovsky,

RN, MSN, AOCN

MS, RN, APN-C, AOCNS

RN, PhD, APRN

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

6

AugusT 2011 I VOL 4, NO 5

Somerset Medical Center Somerville, NJ

University of South Florida College of Nursing Tampa, FL

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

Jeanne Westphal, RN Meeker County Memorial Hospital Litchfield, MN

www.TheOncologyNurse.com

TON_August2011_FINAL_TON 8/19/11 12:20 PM Page 7

TON_August2011_11_TON 8/18/11 12:29 PM Page 8

From the Editor

E

ach summer, we take time to relax; maybe vacation with family or travel to far-away lands. For those of us with young children, relaxation may not describe the season accurately. But for all of us, this time comes to an end and, often, we appreciate returning to work and to our patients. We hope that some of the Beth Faiman, RN, MSN, newer nursing interventions disAPRN, BC, AOCN Editor-in-Chief cussed in this issue will better the care you provide and the quality of life of your patients. With everything from updated screening guidelines to education on genotyping, we complete our coverage from the Oncology Nursing Society Annual Congress. We also share information from the American Society of Clinical Oncology Annual Meeting, highlighting how nurses can use the plethora of new data to enhance their practice. For those who treat patients with leukemia, Ms Shah details our important contributions to patient care. For

PUBLISHING STAFF Senior Vice President, Sales & Marketing Philip Pawelko phil@greenhillhc.com Publisher John W. Hennessy john@greenhillhc.com Editorial Director Kristin Siyahian kristin@greenhillhc.com Associate Editor Dawn Lagrosa dawn@greenhillhc.com Quality Control Director Barbara Marino 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

those who treat patients with breast cancer, Ms Davis brings clarity to the pros and cons of the epothilones and the taxanes. And for all of us, Dr Shiels discusses how ever-changing population demographics affect our delivery of care. It is through our awareness of our patients as a “whole patient” that we can best care for them, a sentiment echoed in Ms Beausang’s understanding of how a patient’s appearance affects their well-being. For those of you who navigate patients or help them across the continuum through survivorship, don’t forget to check out the Second Annual Oncology Navigation and Survivorship Conference this September or its coverage in the November issue of the Journal of Oncology Navigation & Survivorship. And to finish the summer off in style, we offer you nutritional information to celebrate the season, complete with recipes—Spicy Gazpacho with Cucumber Cilantro Granita, Pico De Gallo, Pasta Fagioli, and Garden Fresh Tomato Sauce. Stay tuned for more recipes in each issue. As always, I hope this issue of The Oncology NurseAPN/PA benefits your practice. We look forward to your feedback. ●

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Do you recognize these patients? Before Cycle 1, identify your patients’ individual risk factors for CINV s In addition to the emetogenic potential of a chemotherapy regimen, consider a patient’s additional risk factors for emesis.1 — Female, age <50 years, history of low alcohol intake (<1.5 oz/day), history of morning or motion sickness, and preexisting anxiety or nausea1,2 s Because with every additional risk factor, the risk of emesis increases.1,2. s Because a 5-HT3 antagonist and a corticosteroid alone may not be enough to prevent CINV for 5 days. Motion sickness Younger than age 50 ✔ Anxiety ✔

Female ✔ Light drinker ✔

✔

An antiemetic regimen with a 5-HT3 antagonist, a corticosteroid, and

EMEND—Helps provide superior CINV prevention for 5 days. References: 1. Navari RM. Pathogenesis-based treatment of chemotherapy-induced nausea and vomiting—two new agents. J Support Oncol. 2003;1(2):89–103. 2. Osoba D, Zee B, Pater J, et al; for Quality of Life and Symptom Control Committees of the National Cancer Institute of Canada Clinical Trials Group. Determinants of postchemotherapy nausea and vomiting in patients with cancer. J Clin Oncol. 1997;15(1):116–123.

EMEND, in combination with other antiemetic agents, is indicated in adults for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin; and for prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

Selected Important Safety Information (continued)

EMEND has not been studied for treatment of established nausea and vomiting. Chronic continuous administration of EMEND is not recommended.

Chronic continuous use of EMEND for prevention of nausea and vomiting is not recommended because it has not been studied and because the drug interaction profile may change during chronic continuous use.

Selected Important Safety Information EMEND is contraindicated in patients who are hypersensitive to any component of the product. EMEND is a dose-dependent inhibitor of cytochrome P450 isoenzyme 3A4 (CYP3A4). EMEND should not be used concurrently with pimozide, terfenadine, astemizole, or cisapride. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions. EMEND should be used with caution in patients receiving concomitant medications, including chemotherapy agents, that are primarily metabolized through CYP3A4. Inhibition of CYP3A4 by EMEND could result in elevated plasma concentrations of these concomitant medications. Conversely, when EMEND is used concomitantly with another CYP3A4 inhibitor, aprepitant plasma concentrations could be elevated. When EMEND is used concomitantly with medications that induce CYP3A4 activity, aprepitant plasma concentrations could be reduced, and this may result in decreased efficacy of aprepitant. Chemotherapy agents that are known to be metabolized by CYP3A4 include docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, and vincristine. In clinical studies, EMEND was administered commonly with etoposide, vinorelbine, or paclitaxel. The doses of these agents were not adjusted to account for potential drug interactions. In separate pharmacokinetic studies, EMEND did not influence the pharmacokinetics of docetaxel or vinorelbine. Because a small number of patients in clinical studies received the CYP3A4 substrates vinblastine, vincristine, or ifosfamide, particular caution and careful monitoring are advised in patients receiving these agents or other chemotherapy agents metabolized primarily by CYP3A4 that were not studied. Coadministration of EMEND with warfarin (a CYP2C9 substrate) may result in a clinically significant decrease in international normalized ratio (INR) of prothrombin time. In patients on chronic warfarin therapy, the INR should be closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of EMEND with each chemotherapy cycle.

Merck Oncology Copyright © 2011 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. All rights reserved. ONCO-1001721-0004 emend.com

The efficacy of hormonal contraceptives may be reduced during coadministration with and for 28 days after the last dose of EMEND. Alternative or backup methods of contraception should be used during treatment with and for 1 month after the last dose of EMEND.

In clinical trials of EMEND in patients receiving highly emetogenic chemotherapy, the most common adverse events reported at a frequency greater than with standard therapy, and at an incidence greater than 10% were asthenia/fatigue (17.8% EMEND vs 11.8% standard therapy), nausea (12.7% vs 11.8%), hiccups (10.8% vs 5.6%), diarrhea (10.3% vs 7.5%), and anorexia (10.1% vs 9.5%). In clinical trials of EMEND in patients receiving moderately emetogenic chemotherapy, the most common adverse events reported at a frequency greater than with standard therapy were alopecia (12.4% EMEND vs 11.9% standard therapy), dyspepsia (5.8% vs 3.8%), nausea (5.8% vs 5.1%), neutropenia (5.8% vs 5.6%), asthenia (4.7% vs 4.6%), and stomatitis (3.1% vs 2.7%). In clinical trials, EMEND increased the AUC of dexamethasone, a CYP3A4 substrate, by approximately 2-fold; therefore, the oral dose of dexamethasone administered in the regimen with EMEND should be reduced by approximately 50% to achieve exposures of dexamethasone similar to those obtained without EMEND. EMEND increased the AUC of methylprednisolone by 1.34-fold and 2.5-fold on Days 1 and 3, respectively. The intravenous dose of methylprednisolone should be reduced by approximately 25% and the oral dose by 50% when coadministered with EMEND. Please see Brief Summary of Prescribing Information on the following pages. For copies of the Prescribing Information, call 800-672-6372, visit emend.com, or contact your Merck representative. CINV=chemotherapy-induced nausea and vomiting. Persons depicted are for illustrative purposes only and are not actual patients.

An antiemetic regimen including

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Brief Summary of the Prescribing Information for

INDICATIONS AND USAGE Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV): EMEND, in combination with other antiemetic agents, is indicated for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC), including high-dose cisplatin; and for prevention of nausea and vomiting associated with initial and repeat courses CAPSULES of moderately emetogenic cancer chemotherapy (MEC). Prevention of Postoperative Nausea and Vomiting (PONV): EMEND is indicated for prevention of postoperative nausea and vomiting. Limitations of Use: EMEND has not been studied for treatment of established nausea and vomiting. Chronic continuous administration is not recommended. CONTRAINDICATIONS EMEND is contraindicated in patients who are hypersensitive to any component of the product. EMEND is a dose-dependent inhibitor of cytochrome P450 isoenzyme 3A4 (CYP3A4). EMEND should not be used concurrently with pimozide, terfenadine, astemizole, or cisapride. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions [see Drug Interactions]. WARNINGS AND PRECAUTIONS CYP3A4 Interactions: EMEND, a dose-dependent inhibitor of CYP3A4, should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4. Moderate inhibition of CYP3A4 by aprepitant, 125-mg/80-mg regimen, could result in elevated plasma concentrations of these concomitant medications. Weak inhibition of CYP3A4 by a single 40-mg dose of aprepitant is not expected to alter the plasma concentrations of concomitant medications that are primarily metabolized through CYP3A4 to a clinically significant degree. When aprepitant is used concomitantly with another CYP3A4 inhibitor, aprepitant plasma concentrations could be elevated. When EMEND is used concomitantly with medications that induce CYP3A4 activity, aprepitant plasma concentrations could be reduced and this may result in decreased efficacy of EMEND [see Drug Interactions]. Chemotherapy agents that are known to be metabolized by CYP3A4 include docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, and vincristine. In clinical studies, EMEND (125-mg/80-mg regimen) was administered commonly with etoposide, vinorelbine, or paclitaxel. The doses of these agents were not adjusted to account for potential drug interactions. In separate pharmacokinetic studies no clinically significant change in docetaxel or vinorelbine pharmacokinetics was observed when EMEND (125-mg/80-mg regimen) was coadministered. Due to the small number of patients in clinical studies who received the CYP3A4 substrates vinblastine, vincristine, or ifosfamide, particular caution and careful monitoring are advised in patients receiving these agents or other chemotherapy agents metabolized primarily by CYP3A4 that were not studied [see Drug Interactions]. Coadministration With Warfarin (a CYP2C9 substrate): Coadministration of EMEND with warfarin may result in a clinically significant decrease in international normalized ratio (INR) of prothrombin time. In patients on chronic warfarin therapy, the INR should be closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day regimen of EMEND with each chemotherapy cycle, or following administration of a single 40-mg dose of EMEND for prevention of postoperative nausea and vomiting [see Drug Interactions]. Coadministration With Hormonal Contraceptives: Upon coadministration with EMEND, the efficacy of hormonal contraceptives during and for 28 days following the last dose of EMEND may be reduced. Alternative or backup methods of contraception should be used during treatment with EMEND and for 1 month following the last dose of EMEND [see Drug Interactions]. Patients With Severe Hepatic Impairment: There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (ChildPugh score >9). Therefore, caution should be exercised when EMEND is administered in these patients. Chronic Continuous Use: Chronic continuous use of EMEND for prevention of nausea and vomiting is not recommended because it has not been studied and because the drug interaction profile may change during chronic continuous use. ADVERSE REACTIONS The overall safety of aprepitant was evaluated in approximately 5300 individuals. 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 clinical practice. Clinical Trials Experience: Chemotherapy-Induced Nausea and Vomiting: Highly Emetogenic Chemotherapy: In 2 well-controlled clinical trials in patients receiving highly emetogenic cancer chemotherapy, 544 patients were treated with aprepitant during Cycle 1 of chemotherapy and 413 of these patients continued into the Multiple-Cycle extension for up to 6 cycles of chemotherapy. EMEND was given in combination with ondansetron and dexamethasone. In Cycle 1, clinical adverse experiences were reported in approximately 69% of patients treated with the aprepitant regimen compared with approximately 68% of patients treated with standard therapy. Following are the percentage of patients receiving highly emetogenic chemotherapy in Cycle 1 with clinical adverse experiences reported at an incidence of ≥3% for the aprepitant regimen (n=544) and standard therapy (n=550), respectively: Body as a whole/Site unspecified: asthenia/fatigue: 17.8, 11.8; dizziness: 6.6, 4.4; dehydration: 5.9, 5.1; abdominal pain: 4.6, 3.3; fever: 2.9, 3.5; mucous membrane disorder: 2.6, 3.1 Digestive system: nausea: 12.7, 11.8; constipation: 10.3, 12.2; diarrhea: 10.3, 7.5; vomiting: 7.5, 7.6; heartburn: 5.3, 4.9; gastritis: 4.2, 3.1; epigastric discomfort: 4.0, 3.1 Eyes, ears, nose, and throat: tinnitus: 3.7, 3.8 Hemic and lymphatic system: neutropenia: 3.1, 2.9 Metabolism and nutrition: anorexia: 10.1, 9.5 Nervous system: headache: 8.5, 8.7; insomnia: 2.9, 3.1 Respiratory system: hiccups: 10.8, 5.6 In addition, isolated cases of serious adverse experiences, regardless of causality, of bradycardia, disorientation, and perforating duodenal ulcer were reported in highly emetogenic CINV clinical studies. Moderately Emetogenic Chemotherapy: During Cycle 1 of 2 moderately emetogenic chemotherapy studies, 868 patients were treated with the aprepitant regimen and 686 of these patients continued into extensions for up to 4 cycles of chemotherapy. In the combined analysis of Cycle 1 data for these 2 studies, adverse experiences were reported in approximately 69% of patients treated with the aprepitant regimen compared with approximately 72% of patients treated with standard therapy. In the combined analysis of Cycle 1 data for these 2 studies, the adverse-experience profile in both moderately emetogenic chemotherapy studies was generally comparable to the highly emetogenic chemotherapy studies. Following are the percentage of patients receiving moderately emetogenic chemotherapy in Cycle 1 with clinical adverse experiences reported at an incidence of ≥3% for the aprepitant regimen (n=868) and standard therapy (n=846), respectively: Blood and lymphatic system disorders: neutropenia: 5.8, 5.6 Metabolism and nutrition disorders: anorexia: 6.2, 7.2 Psychiatric disorders: insomnia: 2.6, 3.7 Nervous system disorders: headache: 13.2, 14.3; dizziness: 2.8, 3.4 Gastrointestinal disorders: constipation: 10.3, 15.5; diarrhea: 7.6, 8.7; dyspepsia: 5.8, 3.8; nausea: 5.8, 5.1; stomatitis: 3.1, 2.7 Skin and subcutaneous tissue disorders: alopecia: 12.4, 11.9 General disorders and general administration site conditions: fatigue: 15.4, 15.6; asthenia: 4.7, 4.6 In a combined analysis of these 2 studies, isolated cases of serious adverse experiences were similar in the 2 treatment groups. Highly and Moderately Emetogenic Chemotherapy: The following additional clinical adverse experiences (incidence >0.5% and greater than standard therapy), regardless of causality, were reported in patients treated with the aprepitant regimen in either HEC or MEC studies: Infections and infestations: candidiasis, herpes simplex, lower respiratory infection, oral candidiasis, pharyngitis, septic shock, upper respiratory infection, urinary tract infection Neoplasms benign, malignant, and unspecified (including cysts and polyps): malignant neoplasm, non–small-cell lung carcinoma Blood and lymphatic system disorders: anemia, febrile neutropenia, thrombocytopenia Metabolism and nutrition disorders: appetite decreased, diabetes mellitus, hypokalemia Psychiatric disorders: anxiety disorder, confusion, depression Nervous system: peripheral neuropathy, sensory neuropathy, taste disturbance, tremor Eye disorders: conjunctivitis Cardiac disorders: myocardial infarction, palpitations, tachycardia Vascular disorders: deep venous thrombosis, flushing, hot flush, hypertension, hypotension Respiratory, thoracic, and mediastinal disorders: cough, dyspnea, nasal secretion, pharyngolaryngeal pain, pneumonitis, pulmonary embolism, respiratory insufficiency, vocal disturbance Gastrointestinal disorders: abdominal pain upper, acid reflux, deglutition disorder, dry mouth, dysgeusia, dysphagia, eructation, flatulence, obstipation, salivation increased Skin and subcutaneous tissue disorders: acne, diaphoresis, pruritus, rash Musculoskeletal and connective tissue disorders: arthralgia, back pain, muscular weakness, musculoskeletal pain, myalgia Renal and urinary disorders: dysuria, renal insufficiency Reproductive system and breast disorders: pelvic pain General disorders and administrative site conditions: edema, malaise, pain, rigors Investigations: weight loss Stevens-Johnson syndrome was reported as a serious adverse experience in a patient receiving aprepitant with cancer chemotherapy in another CINV study. Laboratory Adverse Experiences: Following are the percentage of patients receiving highly emetogenic chemotherapy in Cycle 1 with laboratory adverse experiences reported at an incidence of ≥3% for the aprepitant regimen (n=544) and standard therapy (n=550), respectively: Proteinuria: 6.8, 5.3 ALT increased: 6.0, 4.3 Blood urea nitrogen increased: 4.7, 3.5 Serum creatinine increased: 3.7, 4.3

EMEND® (aprepitant) capsules AST increased: 3.0, 1.3 The following additional laboratory adverse experiences (incidence >0.5% and greater than standard therapy), regardless of causality, were reported in patients treated with the aprepitant regimen: alkaline phosphatase increased, hyperglycemia, hyponatremia, leukocytes increased, erythrocyturia, leukocyturia. The adverse-experience profiles in the Multiple-Cycle extensions of HEC and MEC studies for up to 6 cycles of chemotherapy were generally similar to that observed in Cycle 1. Postoperative Nausea and Vomiting: In well-controlled clinical studies in patients receiving general anesthesia, 564 patients were administered 40-mg aprepitant orally and 538 patients were administered 4-mg ondansetron IV. Clinical adverse experiences were reported in approximately 60% of patients treated with 40-mg aprepitant compared with approximately 64% of patients treated with 4-mg ondansetron IV. Following are the percentage of patients receiving general anesthesia with clinical adverse experiences reported at an incidence of ≥3% in the combined studies for aprepitant 40 mg (n=564) and ondansetron (n=538), respectively: Infections and infestations: urinary tract infection: 2.3, 3.2 Blood and lymphatic system disorders: anemia: 3.0, 4.3 Psychiatric disorders: insomnia: 2.1, 3.3 Nervous system disorders: headache: 5.0, 6.5 Cardiac disorders: bradycardia: 4.4, 3.9 Vascular disorders: hypotension: 5.7, 4.6; hypertension: 2.1, 3.2 Gastrointestinal disorders: nausea: 8.5, 8.6; constipation: 8.5, 7.6; flatulence: 4.1, 5.8; vomiting 2.5, 3.9 Skin and subcutaneous tissue disorders: pruritus: 7.6, 8.4 General disorders and general administration site conditions: pyrexia: 5.9, 10.6 The following additional clinical adverse experiences (incidence >0.5% and greater than ondansetron), regardless of causality, were reported in patients treated with aprepitant: Infections and infestations: postoperative infection Metabolism and nutrition disorders: hypokalemia, hypovolemia Nervous system disorders: dizziness, hypoesthesia, syncope Vascular disorders: hematoma Respiratory, thoracic, and mediastinal disorders: dyspnea, hypoxia, respiratory depression Gastrointestinal disorders: abdominal pain, abdominal pain upper, dry mouth, dyspepsia Skin and subcutaneous tissue disorders: urticaria General disorders and administrative site conditions: hypothermia, pain Investigations: blood pressure decreased Injury, poisoning, and procedural complications: operative hemorrhage, wound dehiscence Other adverse experiences (incidence ≤0.5%) reported in patients treated with aprepitant 40 mg for postoperative nausea and vomiting included: Nervous system disorders: dysarthria, sensory disturbance Eye disorders: miosis, visual acuity reduced Respiratory, thoracic, and mediastinal disorders: wheezing Gastrointestinal disorders: bowel sounds abnormal, stomach discomfort There were no serious adverse drug-related experiences reported in the postoperative nausea and vomiting clinical studies in patients taking 40-mg aprepitant. Laboratory Adverse Experiences: One laboratory adverse experience, hemoglobin decreased (40-mg aprepitant 3.8%, ondansetron 4.2%), was reported at an incidence ≥3% in a patient receiving general anesthesia. The following additional laboratory adverse experiences (incidence >0.5% and greater than ondansetron), regardless of causality, were reported in patients treated with aprepitant 40 mg: blood albumin decreased, blood bilirubin increased, blood glucose increased, blood potassium decreased, glucose urine present. The adverse experience of increased ALT occurred with similar incidence in patients treated with aprepitant 40 mg (1.1%) as in patients treated with ondansetron 4 mg (1.0%). Other Studies: In addition, 2 serious adverse experiences were reported in postoperative nausea and vomiting (PONV) clinical studies in patients taking a higher dose of aprepitant: 1 case of constipation, and 1 case of subileus. Angioedema and urticaria were reported as serious adverse experiences in a patient receiving aprepitant in a non-CINV/non-PONV study. Postmarketing Experience: The following adverse reactions have been identified during postmarketing use of aprepitant. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to the drug. Skin and subcutaneous tissue disorders: pruritus, rash, urticaria Immune system disorders: hypersensitivity reactions including anaphylactic reactions DRUG INTERACTIONS Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9. Effect of Aprepitant on the Pharmacokinetics of Other Agents: CYP3A4 substrates: Weak inhibition of CYP3A4 by a single 40-mg dose of aprepitant is not expected to alter the plasma concentrations of concomitant medications that are primarily metabolized through CYP3A4 to a clinically significant degree. However, higher aprepitant doses or repeated dosing at any aprepitant dose may have a clinically significant effect. As a moderate inhibitor of CYP3A4 at a dose of 125 mg/80 mg, aprepitant can increase plasma concentrations of concomitantly administered oral medications that are metabolized through CYP3A4 [see Contraindications]. The use of fosaprepitant may increase CYP3A4 substrate plasma concentrations to a lesser degree than the use of oral aprepitant (125 mg). 5-HT3 antagonists: In clinical drug interaction studies, aprepitant did not have clinically important effects on the pharmacokinetics of ondansetron, granisetron, or hydrodolasetron (the active metabolite of dolasetron). Corticosteroids: Dexamethasone: EMEND, when given as a regimen of 125 mg with dexamethasone coadministered orally as 20 mg on Day 1, and EMEND when given as 80 mg/day with dexamethasone coadministered orally as 8 mg on Days 2 through 5, increased the AUC of dexamethasone, a CYP3A4 substrate, by 2.2-fold on Days 1 and 5. The oral dexamethasone doses should be reduced by approximately 50% when coadministered with EMEND (125-mg/80-mg regimen), to achieve exposures of dexamethasone similar to those obtained when it is given without EMEND. The daily dose of dexamethasone administered in clinical chemotherapy-induced nausea and vomiting studies with EMEND reflects an approximate 50% reduction of the dose of dexamethasone. A single dose of EMEND (40 mg) when coadministered with a single oral dose of dexamethasone 20 mg, increased the AUC of dexamethasone by 1.45-fold. Therefore, no dose adjustment is recommended. Methylprednisolone: EMEND, when given as a regimen of 125 mg on Day 1 and 80 mg/day on Days 2 and 3, increased the AUC of methylprednisolone, a CYP3A4 substrate, by 1.34-fold on Day 1 and by 2.5-fold on Day 3, when methylprednisolone was coadministered intravenously as 125 mg on Day 1 and orally as 40 mg on Days 2 and 3. The IV methylprednisolone dose should be reduced by approximately 25% and the oral methylprednisolone dose should be reduced by approximately 50% when coadministered with EMEND (125-mg/80-mg regimen) to achieve exposures of methylprednisolone similar to those obtained when it is given without EMEND. Although the concomitant administration of methylprednisolone with the single 40-mg dose of aprepitant has not been studied, a single 40-mg dose of EMEND produces a weak inhibition of CYP3A4 (based on midazolam interaction study) and it is not expected to alter the plasma concentrations of methylprednisolone to a clinically significant degree. Therefore, no dose adjustment is recommended. Chemotherapeutic agents: [see Warnings and Precautions] Docetaxel: In a pharmacokinetic study, EMEND (125-mg/80-mg regimen) did not influence the pharmacokinetics of docetaxel. Vinorelbine: In a pharmacokinetic study, EMEND (125-mg/80-mg regimen) did not influence the pharmacokinetics of vinorelbine to a clinically significant degree. CYP2C9 substrates (warfarin, tolbutamide): Aprepitant has been shown to induce the metabolism of S(–) warfarin and tolbutamide, which are metabolized through CYP2C9. Coadministration of EMEND with these drugs or other drugs that are known to be metabolized by CYP2C9, such as phenytoin, may result in lower plasma concentrations of these drugs. Warfarin: A single 125-mg dose of EMEND was administered on Day 1 and 80 mg/day on Days 2 and 3 to healthy subjects who were stabilized on chronic warfarin therapy. Although there was no effect of EMEND on the plasma AUC of R(+) or S(–) warfarin determined on Day 3, there was a 34% decrease in S(–) warfarin (a CYP2C9 substrate) trough concentration accompanied by a 14% decrease in the prothrombin time (reported as international normalized ratio or INR) 5 days after completion of dosing with EMEND. In patients on chronic warfarin therapy, the prothrombin time (INR) should be closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day regimen of EMEND with each chemotherapy cycle, or following administration of a single 40-mg dose of EMEND for prevention of postoperative nausea and vomiting. Tolbutamide: EMEND, when given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, decreased the AUC of tolbutamide (a CYP2C9 substrate) by 23% on Day 4, 28% on Day 8, and 15% on Day 15, when a single dose of tolbutamide 500 mg was administered orally prior to the administration of the 3-day regimen of EMEND and on Days 4, 8, and 15. EMEND, when given as a 40-mg single oral dose on Day 1, decreased the AUC of tolbutamide (a CYP2C9 substrate) by 8% on Day 2, 16% on Day 4, 15% on Day 8, and 10% on Day 15, when a single dose of tolbutamide 500 mg was administered orally prior to the administration of EMEND 40 mg and on Days 2, 4, 8, and 15. This effect was not considered clinically important. Oral contraceptives: Aprepitant, when given once daily for 14 days as a 100-mg capsule with an oral contraceptive containing 35 mcg of ethinyl estradiol and 1 mg of norethindrone, decreased the AUC of ethinyl estradiol by 43%, and decreased the AUC of norethindrone by 8%. In another study, a daily dose of an oral contraceptive containing ethinyl estradiol and norethindrone was administered on Days 1 through 21, and EMEND was given as a 3-day regimen of 125 mg on Day 8 and 80 mg/day on Days 9 and 10 with ondansetron 32 mg IV on Day 8 and oral dexamethasone given as 12 mg on Day 8 and 8 mg/day on Days 9, 10, and 11. In the study, the AUC of ethinyl estradiol decreased by 19% on Day 10 and there was as much as a 64% decrease in ethinyl estradiol trough concentrations during Days 9 through 21. While there was no effect of EMEND on the AUC of norethindrone on Day 10, there was as much as a 60% decrease in norethindrone trough concentrations during Days 9 through 21. In another study, a daily dose of an oral contraceptive containing ethinyl estradiol and norgestimate (which is converted to norelgestromin) was administered on Days 1 through 21, and EMEND 40 mg was given on Day 8. In the study, the AUC of ethinyl estradiol decreased by 4% and 29% on Day 8 and Day 12, respectively, while the AUC of norelgestromin increased by 18% on Day 8 and decreased by 10% on Day 12. In

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EMENDŽ (aprepitant) capsules addition, the trough concentrations of ethinyl estradiol and norelgestromin on Days 8 through 21 were generally lower following coadministration of the oral contraceptive with EMEND 40 mg on Day 8 compared to the trough levels following administration of the oral contraceptive alone. The coadministration of EMEND may reduce the efficacy of hormonal contraceptives (these can include birth control pills, skin patches, implants, and certain IUDs) during and for 28 days after administration of the last dose of EMEND. Alternative or backup methods of contraception should be used during treatment with EMEND and for 1 month following the last dose of EMEND. Midazolam: EMEND increased the AUC of midazolam, a sensitive CYP3A4 substrate, by 2.3-fold on Day 1 and 3.3-fold on Day 5, when a single oral dose of midazolam 2 mg was coadministered on Day 1 and Day 5 of a regimen of EMEND 125 mg on Day 1 and 80 mg/day on Days 2 through 5. The potential effects of increased plasma concentrations of midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) should be considered when coadministering these agents with EMEND (125 mg/80 mg). A single dose of EMEND (40 mg) increased the AUC of midazolam by 1.2-fold on Day 1, when a single oral dose of midazolam 2 mg was coadministered on Day 1 with EMEND 40 mg; this effect was not considered clinically important. In another study with intravenous administration of midazolam, EMEND was given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, and midazolam 2 mg IV was given prior to the administration of the 3-day regimen of EMEND and on Days 4, 8, and 15. EMEND increased the AUC of midazolam by 25% on Day 4 and decreased the AUC of midazolam by 19% on Day 8 relative to the dosing of EMEND on Days 1 through 3. These effects were not considered clinically important. The AUC of midazolam on Day 15 was similar to that observed at baseline. An additional study was completed with intravenous administration of midazolam and EMEND. Intravenous midazolam 2 mg was given 1 hour after oral administration of a single dose of EMEND 125 mg. The plasma AUC of midazolam was increased by 1.5-fold. Depending on clinical situations (eg, elderly patients) and degree of monitoring available, dosage adjustment for intravenous midazolam may be necessary when it is coadministered with EMEND for the chemotherapy-induced nausea and vomiting indication (125 mg on Day 1 followed by 80 mg on Days 2 and 3). Effect of Other Agents on the Pharmacokinetics of Aprepitant: Aprepitant is a substrate for CYP3A4; therefore, coadministration of EMEND with drugs that inhibit CYP3A4 activity may result in increased plasma concentrations of aprepitant. Consequently, concomitant administration of EMEND with strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir) should be approached with caution. Because moderate CYP3A4 inhibitors (eg, diltiazem) result in a 2-fold increase in plasma concentrations of aprepitant, concomitant administration should also be approached with caution. Aprepitant is a substrate for CYP3A4; therefore, coadministration of EMEND with drugs that strongly induce CYP3A4 activity (eg, rifampin, carbamazepine, phenytoin) may result in reduced plasma concentrations of aprepitant that may result in decreased efficacy of EMEND. Ketoconazole: When a single 125-mg dose of EMEND was administered on Day 5 of a 10-day regimen of 400 mg/day of ketoconazole, a strong CYP3A4 inhibitor, the AUC of aprepitant increased approximately 5-fold and the mean terminal half-life of aprepitant increased approximately 3-fold. Concomitant administration of EMEND with strong CYP3A4 inhibitors should be approached cautiously. Rifampin: When a single 375-mg dose of EMEND was administered on Day 9 of a 14-day regimen of 600 mg/day of rifampin, a strong CYP3A4 inducer, the AUC of aprepitant decreased approximately 11-fold and the mean terminal half-life decreased approximately 3-fold. Coadministration of EMEND with drugs that induce CYP3A4 activity may result in reduced plasma concentrations and decreased efficacy of EMEND. Additional Interactions: EMEND is unlikely to interact with drugs that are substrates for the P-glycoprotein transporter, as demonstrated by the lack of interaction of EMEND with digoxin in a clinical drug interaction study. Diltiazem: In patients with mild to moderate hypertension, administration of aprepitant once daily, as a tablet formulation comparable to 230 mg of the capsule formulation, with diltiazem 120 mg 3 times daily for 5 days, resulted in a 2-fold increase of aprepitant AUC and a simultaneous 1.7-fold increase of diltiazem AUC. These pharmacokinetic effects did not result in clinically meaningful changes in ECG, heart rate, or blood pressure beyond those changes induced by diltiazem alone. Paroxetine: Coadministration of once-daily doses of aprepitant, as a tablet formulation comparable to 85 mg or 170 mg of the capsule formulation, with paroxetine 20 mg once daily, resulted in a decrease in AUC by approximately 25% and C max by approximately 20% of both aprepitant and paroxetine. USE IN SPECIFIC POPULATIONS Pregnancy: Teratogenic effects: Pregnancy Category B: Reproduction studies have been performed in rats at oral doses up to 1000 mg/kg twice daily (plasma AUC 0–24hr >5 <26M7A <$ 01>DC C8<4B C74 7D<0= 4G?>BDA4 0C C74 A42><<4=343 3>B4 0=3 8= A0118CB 0C >A0; 3>B4B up to 25 mg/kg/day (plasma AUC 0–24hr >5 <26M7A <$ 01>DC C8<4B C74 7D<0= 4G?>BDA4 0C C74 A42><<4=343 3>B4 0=3 70E4 A4E40;43 no evidence of impaired fertility or harm to the fetus due to aprepitant. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing Mothers: Aprepitant is excreted in the milk of rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for possible serious adverse reactions in nursing infants from aprepitant and because of the potential for tumorigenicity shown for aprepitant in rodent carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use: Safety and effectiveness of EMEND in pediatric patients have not been established. Geriatric Use: In 2 well-controlled chemotherapy-induced nausea and vomiting clinical studies, of the total number of patients (N=544) treated with EMEND, 31% were 65 and over, while 5% were 75 and over. In well-controlled postoperative nausea and vomiting clinical studies, of the total number of patients (N=1120) treated with EMEND, 7% were 65 and over, while 2% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Greater sensitivity of some older individuals cannot be ruled out. Dosage adjustment in the elderly is not necessary. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenicity studies were conducted in Sprague-Dawley rats and in CD-1 mice for 2 years. In the rat carcinogenicity studies, animals were treated with oral doses ranging from 0.05 to 1000 mg/kg twice daily. The highest dose produced a systemic exposure to aprepitant (plasma AUC 0–24hr ) of 0.7 to 1.6 times the human exposure (AUC 0–24hr <26M7A <$ 0C the recommended dose of 125 mg/day. Treatment with aprepitant at doses of 5 to 1000 mg/kg twice daily caused an increase in the incidences of thyroid follicular cell adenomas and carcinomas in male rats. In female rats, it produced hepatocellular adenomas at 5 to 1000 mg/kg twice daily and hepatocellular carcinomas and thyroid follicular cell adenomas at 125 to 1000 mg/kg twice daily. In the mouse carcinogenicity studies, the animals were treated with oral doses ranging from 2.5 to 2000 mg/kg/day. The highest dose produced a systemic exposure of about 2.8 to 3.6 times the human exposure at the recommended dose. Treatment with aprepitant produced skin fibrosarcomas at 125 and 500 mg/kg/day doses in male mice. Aprepitant was not genotoxic in the Ames test, the human lymphoblastoid cell (TK6) mutagenesis test, the rat hepatocyte DNA strand break test, the Chinese hamster ovary (CHO) cell chromosome aberration test, and the mouse micronucleus test. Aprepitant did not affect the fertility or general reproductive performance of male or female rats at doses up to the maximum feasible dose of 1000 mg/kg twice daily (providing exposure in male rats lower than the exposure at the recommended human dose and exposure in female rats at about 1.6 times the human exposure). PATIENT COUNSELING INFORMATION [See FDA-Approved Patient Labeling.] Instructions: Physicians should instruct their patients to read the patient package insert before starting therapy with EMEND and to reread it each time the prescription is renewed. Patients should be instructed to take EMEND only as prescribed. For prevention of chemotherapy-induced nausea and vomiting (CINV), patients should be advised to take their first dose (125 mg) of EMEND 1 hour prior to chemotherapy treatment. For prevention of postoperative nausea and vomiting (PONV), patients should receive their medication (40-mg capsule of EMEND) within 3 hours prior to induction of anesthesia. Allergic reactions, which may be serious, and may include hives, rash, and itching, and cause difficulty in breathing or swallowing, have been reported in general use with EMEND. Physicians should instruct their patients to stop taking EMEND and call their doctor right away if they experience an allergic reaction. EMEND may interact with some drugs including chemotherapy; therefore, patients should be advised to report to their doctor the use of any other prescription or nonprescription medication or herbal products. Patients on chronic warfarin therapy should be instructed to have their clotting status closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day regimen of EMEND 125 mg/80 mg with each chemotherapy cycle, or following administration of a single 40-mg dose of EMEND for prevention of postoperative nausea and vomiting. Administration of EMEND may reduce the efficacy of hormonal contraceptives. Patients should be advised to use alternative or backup methods of contraception during treatment with EMEND and for 1 month following the last dose of EMEND. For detailed information, please read the Prescribing Information. Rx only

Copyright Š 2011 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. All rights reserved. ONCO-1001721-0004

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News Notes New Drug Therapy for HER2-Positive Breast Cancer on the Horizon Patients with HER2-positive breast cancer who develop resistance to trastuzumab may soon have an alternative therapy, according to recent findings published in Clinical Cancer Research. This therapy involves HER2-Affitoxin, a protein that combines HER2-specific affibody molecules and a modified bacterial toxin, PE38, according to study investigator Jacek Capala, PhD, DSc, of the National Cancer Institute. Instead of interfering with the HER2 signaling pathway as trastuzumab does, this protein uses HER2 as a means to supply a form of bacterial toxin specifically to the HER2-positive cancer cells. On absorption of the toxin, the cells’ production of protein is inhibited and the cells are destroyed.

Link Among Obesity, Estrogen Status, and Breast Cancer Mortality Maintaining a healthy body weight is important for all patients. But this is especially true for women with a breast cancer diagnosis, as an analysis of the California Teachers Study has shown a correlation between breast cancer deaths and body mass index (BMI). Obesity (defined as BMI ≼30 kg/m²) increased a woman’s risk of dying of her breast cancer by 69%, compared with a woman with a BMI <25. For patients who were overweight at 18 years of age (defined as BMI 25-29), a similar increased risk in breast cancer mortality was detected. In addition, the association between obesity and breast cancer mortality is greatest among obese women who are diagnosed with estrogen receptor (ER)-positive cancer. According to the retrospective data analysis, ER-positive, obese women participating in the study had a 64% increased risk of death from breast cancer, compared with those with a BMI <25.

Combination Therapy Produced Strong Results for Late-Stage Ovarian Cancer Patients Late-stage ovarian cancer patients responded well to an experimental carboplatin/decitabine combination therapy, even though they had become resistant to carboplatin, Indiana University researchers report. Furthermore, the researchers believe they have discovered biomarkers that could assist in identifying patients who are most likely to benefit from this therapy. The carboplatin/decitabine combination produced a positive result in 70% of patients in this phase 2 trial. The combination was tolerated well and did not produce any dose-limiting toxicities. In 12 of 17 carboplatin-resistant patients whose cancer was progressing, tumor growth slowed considerably or stopped altogether following treatment with the experimental drug combination. Moreover, 1 woman’s tumor became undetectable; however, at 336 days her cancer progression resumed. At 6 months, 9 women were still in remission.

Prostate Cancer Risk Shown in New Urine Test A recently developed urine test can assist in the early detection of and treatment decisions regarding prostate cancer, a study from the University of Michigan Comprehensive Cancer Center and the Michigan Center for Translational Pathology finds. Designed to supplement an elevated prostate-specific antigen (PSA) screening result, this test also defines men at highest risk for clinically significant prostate cancer and could delay or negate the need for a needle biopsy in some patients. The test looks for the TMPRSS2:ERG gene fusion as well as the PCA3 indicator. The researcher found that the combination of both markers was more predictive than either marker alone. Evaluating urine samples from 1312 men, patients were categorized into low, intermediate, and high scores. In the low-score group, 21% of men had cancer. Of the men in the intermediatescore group, 43% had cancer. And, cancer was found in 69% of men in the high-score group. Furthermore, the new urine test results also indicated the cancer’s aggressiveness, based on tumor size and Gleason score. In the low-score group, only 7% of men had an aggressive tumor; however, tumors were aggressive in 40% of those in the high-score group. �

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Noteworthy Numbers

Noteworthy Numbers

I

ncreased awareness, earlier detection through screening, and advances in treatment have led to a decline in breast cancer death rates in the United States since 1990. Sadly, breast cancer continues to claim more women’s lives than any other cancer, besides lung cancer. For more statistical data on this prevalent disease, let’s take a look at breast cancer by the numbers.

About 1 in 8 (12%) women in the United States will develop invasive breast cancer over the course of her lifetime. In 2010, an estimated 207,090 new cases of invasive breast cancer were expected to be diagnosed in women in the United States, along with 54,010 new cases of noninvasive breast cancer. About 1970 new cases of invasive breast cancer were expected to be diagnosed in men in 2010… Less than 1% of all new breast cancer cases occur in men. From 1999 to 2006, breast cancer incidence rates in the United States decreased by about 2% per year… Besides skin cancer, breast cancer is the most commonly diagnosed cancer among US women… More than 1 in 4 (about 28%) cancers in women are breast cancer. 12

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Noteworthy Numbers Compared with AfricanAmerican women, white women are slightly more likely to develop breast cancer, but less likely to die of it.

A woman’s risk of breast cancer approximately doubles if she has a first-degree relative who has been diagnosed with breast cancer…

About 20% to 30% of women diagnosed with breast cancer have this family history although some are attributed to chance.

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What happens to the patient caught in the complications of chemotherapy-induced neutropenia? Consider your last patient with neutropenia

Figure. Overall survival by average relative dose intensity (ARDI)

Did your patient experience any consequences from severe or febrile neutropenia? According to a prospective registry study of 2,692 patients encompassing major tumor types, 29.3% overall were impacted by severe or febrile neutropenia in the first 3 cycles of chemotherapy, leaving a large opportunity for risk assessment intervention. This study also showed that the risk of severe or febrile neutropenia was greatest in the first cycle. That risk continued in subsequent cycles.*1

1.0

In a retrospective database analysis (N = 41,779), the inpatient mortality rate for febrile neutropenia–related hospitalization was 9.5%. This inpatient mortality rate was directly related to the number of major comorbidities present at the time of admission. Major comorbidities were defined as any major organ dysfunction requiring diagnostic or therapeutic intervention. Inpatient mortality ranged from 2.6% (556/21,386) for patients with no comorbidities to over 50% (181/358) for those with 4 or more.2

Optimal chemotherapy delivery was shown to improve survival in some tumor types Retrospective studies have shown that dose delays and reductions due to severe or febrile neutropenia may impact treatment plans and result in unfavorable outcomes for some diagnoses.3-7 While there are inherent risks associated with chemotherapy treatment, landmark studies in both non-Hodgkin’s lymphoma (NHL) and early-stage breast cancer have shown that closer adherence to standard doses is one factor that was associated with increased survival rates.8-11 A retrospective analysis demonstrated significantly longer median survival (7.08 years) for patients with NHL who received > 90% average relative dose intensity of CHOP-21 compared with those who received ≤ 90% (N = 210; P = 0.002) (see Figure).12 Multivariate analyses have identified several independent risk factors for reduced relative dose intensity. The risk factors for relative dose intensity < 85% among early-stage breast cancer patients included age, weight, and three-drug regimens (CAF or CMF).3

0.8 Estimated survival

Febrile neutropenia–related hospitalization can lead to mortality

0.9

0.7 0.6

ARDI: ≤ 85%

0.5

ARDI: 86% to ≤ 90%

ARDI: > 90%

0.3 0.0 0

1

2

4 3 5 Years post-chemotherapy

6

7

8

Retrospective chart data of overall survival in 210 patients treated with CHOP-21 according to average relative dose intensity (ARDI). CHOP = cyclophosphamide, doxorubicin, vincristine, and prednisone. Adapted from Bosly A, et al. Ann Hematol. 2008.

For patients with NHL, age > 60 years, advanced disease stage and poor performance status were associated with relative dose intensity < 85%.4

You can intervene for your next patient A comprehensive risk assessment protocol is critical to helping you identify patients at risk for clinically significant febrile neutropenia.

Consider the risk of the chemotherapy regimen ie, chemotherapeutics administered, alone or in combination

Assess patient risk factors eg, age ≥ 65 years, poor performance status

Risk increases with more comorbidities eg, COPD, cardiovascular disease, diabetes mellitus

Evaluate each patient prior to every cycle To request a febrile neutropenia Risk Assessment Checklist, email: FNchecklist@amgen.com.

Assess the risk.

References: 1. Crawford J, et al. J Natl Compr Canc Netw. 2008;6:109-118. 2. Kuderer N, et al. Cancer. 2006;106:2258-2266. 3. Lyman G, et al. J Clin Oncol. 2003;21:4524-4531. 4. Lyman G, et al. J Clin Oncol. 2004;22:4302-4311. 5. Lyman G, et al. J Natl Compr Canc Netw. 2009;7:99-108. 6. Link B, et al. Cancer. 2001;92:1354-1367. 7. Picozzi V, et al. Oncology. 2001;15:1295-1306. 8. Bonadonna G, et al. N Engl J Med. 1995;332:901-906. 9. Bonadonna G, et al. BMJ. 2005;330:217-222. 10. Chirivella I, et al. Breast Cancer Res Treat. 2009;114:479-484. 11. Kwak L, et al. J Clin Oncol. 1990;8:963-977. 12. Bosly A, et al. Ann Hematol. 2008;87:277-283.

MC49941-D

Mutations of the BRCA1 and BRCA2 genes are the most common… Women with these mutations have up to an 80% risk of developing breast cancer during their lifetime, and they are more likely to be diagnosed at a younger age…

0.4

*Crawford J, et al. J Natl Compr Canc Netw. 2008. Nationwide, prospective registry study conducted in 115 community-based, randomly selected, IRB-approved sites, evaluating the incidence and timing of neutropenia and neutropenic events in the first cycle and in cycles 2–3 across major tumor types.

© 2010 Amgen. All rights reserved.

About 5% to 10% of breast cancers can be linked to gene mutations inherited from one’s mother or father…

An increased ovarian cancer risk also is associated with these genetic mutations. In men, about 1 in 10 breast cancers are believed to be associated with BRCA2 mutations and even fewer cases with BRCA1 mutations. About 70% to 80% of breast cancers occur in women who have no family history of breast cancer. The most significant risk factors for breast cancer are gender and age. In 2010, there were more than 2.5 million breast cancer survivors in the United States.

06-10

Source: BreastCancer.org

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Hematologic Cancers Nursing Care of a Patient with B-Cell... Continued from cover Case Presentation Chief complaint: Generalized arthralgia for 5 months. History of present illness: A 35-year-old Hispanic man presented in November 2009 with generalized arthralgias that progressed to continuous shoulder and knee pain. Primary care physician evaluation revealed the complete blood count to be abnormal: complete blood count revealed a white cell count of 83,000/μL, a hemoglobin count of 17.9 g/dL, and a platelet count of 155/μL. In addition, biopsy revealed hypercellular bone marrow with involvement by a B-cell lymphoblastic leukemia. He was referred for emergent evaluation by a hematologist. Flow cytometry revealed 80% to 90% abnormal cells expressing CD34, CD19, dim CD22, CD10, TdT, CD38, and HLA-DR, CD20(-). Fluorescence in situ hybridization for the Philadelphia chromosome fusion protein was negative. Full cytogenetics revealed a male karyotype with a translocation between the long arm of chromosome 1 and the short arm of chromosome 9 and addition to the long arm of chromosome 13 (deletion 13q) was observed in 6 metaphases. Five metaphases showed t(1;9) unbalanced translocation between the long arm of chromosome 1 and the short arm of chromosome 19. Three metaphases showed t(1;9) and der(9)t(1;9). Six metaphases showed a normal male karyotype. The t(1;19)(q23;p13.3) is reported to be associated with B-cell acute lymphoblastic leukemia (B-ALL). Translocations resulting in partial deletion of the short arm of chromosome 9 also are reported in ALL. The final diagnosis was B-ALL.

a cancer is of the blood, we must help them grasp the idea that they have leukemia. Only then can we discuss the treatments they will be receiving and the tests we will be performing, which in this case included frequent blood counts and bone marrow biopsies. Nursing Interventions For this patient, we started with teaching him the basics of reading a complete blood count and chemistry results, and educating him about the types of intensive chemotherapy he would be receiving as an inpatient and as an outpatient. It was very important that he understand the chemotherapy schedule, especially when to expect his counts to nadir, because of the risk for infection resulting from a severely suppressed immune system. As the oncology nurse practitioner, my role involved collaborating and coordinating with the physician, pharmacists, caretakers and family members, social worker, transplant team, and other nurses in the inpatient and outpatient setting to make sure the plan would be carried out to the best capability. Chemotherapy education began with an explanation of the hyperfractionated cyclophosphamide/vincristine/doxorubicin/dexamethasone (Hyper-CVAD) regimen. This regimen requires the patient to receive chemotherapy as both an inpatient and an outpatient. This patient would be scheduled to be admitted for 5 days every 21 days for part A chemotherapy followed by 4 days for part B chemotherapy. Part A chemotherapy consists of cyclophos-

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A baseline computed tomography scan revealed no enlarged lymphadenopathy in the chest, abdomen, and pelvic area. Multigated acquisition scan revealed the left ventricular ejection fraction to be 71%, which is within normal limits. The patient was treated with dexamethasone 40 mg for 4 days until induction chemotherapy was initiated. Induction consisted of hyperfractionated cyclophosphamide/vincristine/doxorubicin/dexamethasone (Hyper-CVAD) for 2 cycles of part A and B every 21 days with side effects related to mucositis, headaches, nausea, and fatigue. The patient also received intrathecal chemotherapy for 3 doses consisting of cytarabine and methotrexate during the induction. Medical history: Unremarkable. Surgical history: Spinal disc surgery (unknown date). Family history: Mother alive with coronary artery disease and type 2 diabetes mellitus; father alive with coronary artery disease; 1 full sister who is not a human leukocyte antigen match and 2 half sisters. No family history of cancer. Social history: Patient is currently married and has 1 daughter. He works for a drinking establishment in New York City. Denies tobacco use and consumes moderate amount of alcohol. Medications: Dexamethasone 40 mg x 4 days, allopurinol 300 mg x 10 days, ciprofloxacin 500 mg twice daily, acyclovir 400 mg twice daily.

Allergies: No known drug allergies. Physical examination: General: Muscularly built Hispanic man, well dressed and well nourished accompanied with wife; no acute distress but appeared to be quite anxious. Vital signs: Temperature: 98.2°F; heart rate: 96 beats/min; blood pressure: 151/83 mm Hg; central venous oxygen saturation: 99%; height: 67 inches; weight 166 lb. Head, ears, eyes, nose, throat: No pallor; icterus. Oropharynx: Clear. Neck: Supple without jugular venous distension; no thyroid masses. Chest: Clear to auscultation. Cardiac: Regular rate and rhythm; no murmurs. Abdomen: Soft, nondistended; no palpable masses. Spleen not appreciated. Extremities: No edema. Skin: No rashes. Neurologic: Grossly nonfocal. Lymphatic: Not palpable. Laboratory values: White blood cell: 92.4/μL; hemoglobin: 15.6 g/dL; platelets: 131/μL.

“We made a calendar so the patient could visualize the chemotherapy cycles, which provided the necessary understanding of the plan.” —Jayshree Shah, NP phamide 300 mg/m2 over 3 hours every 12 hours for 6 doses on days 1 through 3, with mesna at the same total dose as cyclophosphamide but given by continuous infusion starting with cyclophosphamide and ending 6 hours after the last dose; vincristine 2 mg intravenous (IV) days 4 and 11; doxorubicin 50 mg/m2 IV day 4; and dexamethasone 40 mg days 1 through 4 and 11 through 14. Part B chemotherapy consists of highdose methotrexate 200 mg/m2 IV over 2 hours followed by 800 mg/m2 IV over 24 hours on day 1; leucovorin rescue starting 24 hours after completion of methotrexate infusion at 15 mg oral every 6 hours for 8 doses; until methotrexate levels are lower than 0.1 µM; cytarabine 3 g/m2 over 2 hours every 12 hours 4 times on days 2 and 3. In addition, we discussed the need to offer intrathecal (IT) chemotherapy central nervous system (CNS) prophylaxis. CNS prophylaxis is given according to the expected patient risk, based on previous multivariate analysis for prognostic factors for CNS leukemia. Patients are considered at high risk for CNS disease if the lactate dehydrogenase level is >600 U/L (normal laboratory reference level, 25 to 225 U/L). CNS prophylaxis is given with methotrexate 12 mg IT on day 2 and

cytarabine 100 mg IT on day 8 of each cycle for 16 IT treatments for high-risk patients, 4 IT treatments for low-risk patients, and 8 IT treatments for patients of unknown risk.1 We also reviewed the antibiotic prophylaxis regimen, which would include ciprofloxacin 500 mg by mouth twice daily, acyclovir 400 mg by mouth twice daily, and fluconazole 200 mg daily. Supportive care with a granulocyte colony-stimulating factor would include pegfilgrastim 6 mg2 every 21 days for up to 8 cycles. We also discussed the option of having a peripherally inserted central catheter (PICC) to provide easier venous access because he was anticipated to require multiple blood and platelet transfusions, especially during the nadir timeframe. The patient agreed, and a PICC line was inserted during his first admission. We made a calendar so the patient could visualize the chemotherapy cycles, which provided the necessary understanding of the plan. We also had the multidisciplinary team review and edit any changes to plan accordingly. To conclude the discussion, we reviewed the anticipated symptoms, which included chemotherapy-induced nausea and vomiting, mucositis, alopecia, dermatologic changes, myelosuppression,

chemotherapy-induced peripheral neuropathy, and fatigue. This information also was reviewed with the patient’s caregivers. Helping this patient through the side effects and adverse events he would likely experience during his intensive chemotherapy regimen required collaboration among multiple healthcare personnel: pharmacists, social workers, and inpatient and outpatient nurses. Conclusion Our main goal for this patient was for him to achieve lifelong remission. Upon finishing his second part B cycle of Hyper-CVAD, a bone marrow biopsy was performed to assure he was in remission. The biopsy revealed, however, that he had residual leukemia cells thus prompting us to direct him to the transplant service. At the time of diagnosis, human leukocyte antigen typing was performed to identify future matches if he should need to have an allogeneic transplant. His disappointment associated with the lack of complete remission made the patient choose to have an allogeneic transplant done as soon as possible. The bone marrow transplant registry was able to find a donor for him, and an allogeneic transplant was performed 2 weeks later. He is currently disease free and remains ever so grateful for having such a great team of multidisciplinary professionals be part of his care. ● Reference 1. Kantarjian HM, O’Brien S, Smith TL, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol. 2000; 18:547-561.

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Conference News The following articles are based on presentations at the 36th Annual Congress of the Oncology Nursing Society held April 28-May 1, in Boston, Massachusetts.

Guidelines on Screening for Breast, Prostate, and Lung Cancers Oncology Nurses Should Serve as Screening Educators By Christin Melton

BOSTON—The national discourse on cancer screening has come a long way since 1988, when Ronald Reagan became the first president to say “breast cancer” in public, noted Alec Stone, MA, MPA, Health Policy Director, Oncology Nursing Society (ONS). After the US Preventive Services Task Force (USPSTF) recommended mammography screening every 2 years instead of annually, beginning at 50 years of age instead of 40, the public outcry was widespread and loud. Controversy has also been swirling about prostate cancer screening recommendations. Several organizations offer guidelines for breast and prostate cancer screening, but “patients get confusing messages from all of these different organizations about how or when to be screened,” said Heather Greene, RN, MSN, FNP, AOCNP, an oncology nurse practitioner with Blue Ridge Medical Specialists, Bristol, Tennessee. Many oncology nurses care for patients who already have cancer, but ONS believes their role as a cancer educator obligates them to stay current on cancer screening and prevention guidelines. Breast Cancer For years, women were told to undergo annual mammography screening for breast cancer starting at 40 years of age because early detection saves lives. Women were also encouraged to perform a monthly breast self-examination (BSE). Greene said the American Cancer Society (ACS) and the National Comprehensive Cancer Network (NCCN) continue to recommend an annual mammogram once women reach 40 years of age and a clinical breast examination every 1 to 3 years from age 20 to 39 years and annually starting at age 40. “ACS and NCCN don’t recommend that we tell our patients to do monthly self-examinations anymore. They’re more in favor of teaching breast awareness,” said Greene. The BSE can be incorporated in awareness education, but the focus should be on breast changes that might signal a problem, such as heaviness, redness, or nipple concerns. Whereas USPSTF guidelines advise against mammography screening for women older than 75 years, citing insuf-

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ficient evidence of effectiveness, ACS and NCCN guidelines leave it to the physician’s discretion. “If the clinician deems them healthy enough to benefit from intervention, they should have a mammogram,” Greene said. Early detection of breast cancer via mammography clearly reduces mortality and morbidity, said Greene, who opposes implementing the USPSTF guidelines. She suggested nurses talk to patients about mammography risks, such as false positives, which might require additional tests and increase expense and anxiety. Patients also should be told about false negatives and informed that certain tumors, even if detected early, are associated with worse prognosis. Prostate Cancer After years of debate, guidelines are leaning against routine prostate cancer

screening in men with low to average risk. Prostate tumors are often indolent, and men with positive prostate-specific antigen (PSA) tests frequently die of causes other than the malignancy. PSA velocity may be more useful than absolute PSA levels. ACS guidelines recommend talking to men about PSA screening at 50 years of age and encouraging them to take an active role in decision making. Men with a family history of prostate cancer or African-American men should get screened starting at 45 years of age. NCCN continues to advise discussing risks and benefits of prostate cancer screening and offering a baseline PSA screen and digital rectal examination once men reach 40 years of age. USPSTF does not recommend any prostate cancer screening and opposes it in men aged 75 years and

older. The American Urology Association (AUA) suggests screening “well-informed men” starting at 40 years of age if their life expectancy is at least 10 years. For asymptomatic men of low to average risk whose PSA screens suggest prostate cancer, NCCN and AUA guidelines include observation as a follow-up option. Lung Cancer No organization recommends lung cancer screening for asymptomatic individuals, but it might be appropriate for tobacco users with high risk. NCCN’s 2011 guidelines recommend high-risk individuals enter a chemoprevention or screening trial. At least one study has shown that lung cancer screening with low-dose spiral computed tomography scanning reduces mortality among heavy smokers. Stone pointed out that “cost drives everything,” including screening. Some employers are electing not to include cancer screening in their insurance plans. Other plans cover initial mammography but not a repeat test to clarify results. Patients may need help finding financial assistance for screening when it is indicated. ●

Managing Hyperglycemia in Patients... Continued from cover risk of hyperglycemia, a primary symptom of diabetes. The risk of steroidinduced hyperglycemia is greatest in those who use steroids for prolonged periods. Mary Ellen Beitel, BS, BSN, RN, OCN, outlined the important components to include when educating patients with steroid-induced diabetes. Patients should be instructed on personalized insulin regimens that detail blood glucose parameters. They also should be taught how to use insulin delivery devices and their accessories properly to increase their confidence in managing their blood sugar. Visual aids are useful in helping patients recognize symptoms of hyperglycemia and hypoglycemia, according to Beitel, who practices in the ambulatory medical oncology unit at Memorial Sloan-Kettering Cancer Center (MSKCC), New York. Early recognition will prompt appropriate measures to correct the blood sugar imbalance before it causes serious damage. Beitel recommends that all patients on steroids receive a baseline HbA1c test followed by a postprandial test. Ideally, the postprandial test should be conducted

Beitel recommends that all patients on steroids receive a baseline HbA1c test followed by a postprandial test. Ideally, the postprandial test should be conducted with the afternoon meal, when glucose levels are typically highest.

with the afternoon meal, when glucose levels are typically highest. When educating patients on hyperglycemia, Beitel said nurses should use simplified explanations for laboratory studies on “preserving and evaluating critical organ function.” This helps patients recognize the level of damage potential of poorly controlled blood glucose levels and hopefully will encourage better adherence to the plan provided for managing their condition. Beitel noted that no established standards exist for guiding care of patients with cancer and concomitant steroidinduced diabetes. The general goal is to teach patients how to control their blood glucose levels, lowering HbA1c levels to the appropriate range for a patient receiving steroid therapy.

At MSKCC, educating patients in accordance with these recommendations has contributed to increased adherence to methods of blood glucose control and increased the proportion of patients able to maintain HbA1c levels at the preset range. Beitel said steroid-induced diabetes is predictable and manageable, and ambulatory oncology nurses have an excellent opportunity to take a proactive approach to helping patients on steroid therapy avoid the serious complications associated with hyperglycemia. Beitel recommended more efforts to “cultivate nurses’ awareness, knowledge, and clinical skills related to diabetes management,” as a means of improving patients’ ability to provide self-care. ●

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Conference News

Challenges Presented by Morbidly Obese Patients with Cancer Care Plans Should Be Tailored to Patients’ Unique Needs BOSTON—Treating patients with cancer who are morbidly obese presents unexpected challenges according to Vita Norton, RN, BSN, OCN, and Michelle Howard, RN, BSN, of Massachusetts General Hospital in Boston. Data indicate that obesity significantly increases the risk of endometrial and ovarian cancers and is associated with worse outcomes. In a poster, Norton and Howard presented the case of a 60-year-old woman weighing 525 lb who underwent major surgery for adenocarcinoma of the uterus (stage IA, grade 2), followed by vaginal brachytherapy. She had multiple comorbidities, including type 2 diabetes mellitus, hypertension, and restrictive lung disease; and her medical history included papillary thyroid cancer and debridement for lymphedema-related cellulitis. She was hospitalized multiple times after diagnosis for partial small bowel obstructions and infections. Following

an admission for diffuse abdominal pain, she spent 4 days on the surgical unit. Bedbound, the patient needed a Foley catheter to address urinary incontinence. On day 4, she was transferred to the gynecologic oncology unit, which was equipped with a bariatric bed with an assist-to-stand feature; a heavy-duty transfer lift; a bariatric wheelchair and shuttle chair; and a bariatric commode. The patient’s impaired mobility and urinary incontinence resulted in poor skin integrity. The skinfolds of obese patients are susceptible to bacterial, fungal, and viral activity that breaks down the skin and causes infections. She could not reposition herself or get out of bed, and complications of her lung disease left her unable to tolerate being upright. Nevertheless, she insisted the staff remove the catheter, which caused pain. As a result, she urinated on herself over the next 24 hours, accelerating skin breakdown.

For the skin to heal, her mobility needed to improve to where she could use the commode. She also needed to be repositioned every 2 hours, as is common with obese patients, to prevent skin erosion and pressure sores and administer perineal care, a process requiring 4 to 5 staff members. Several obstacles arose in caring for this patient, requiring the interdisciplinary team to collaborate on a care plan. They wanted to move her to the bathroom using the bariatric shuttle chair or wheelchair, but her short legs could not reach the floor so she could stand. She fell when using the standing feature, and the staff decided this was unsafe. Nor could they use the inflatable slide board, because even belting her in provided insufficient stabilization. They tried using the mechanical transfer lift, with 5 staff members moving her to the sling, but she found the sling painful. Her girth

Managing Complications Among Morbidly Obese Patients with Cancer Common complications

Nursing interventions

Wound-healing (dehiscence and/or infections)

• IV antibiotic therapy • Frequent wound care (change dressing 2-3 times per day) • Vacuum-assisted closure • Abdominal binders

Respiratory

• Use of incentive spirometers 10 times per hour during waking hours • Postsurgery epidural anesthesia

Mobility

• Multiple staff members, adjusted staff assignments • Ceiling lifts • Team approach to care, including patient and family • Bariatric technologies (bed, transfer lift, wheelchair or shuttle chair, commode) • Reposition routinely (every 2 hours) • Postsurgery epidural anesthesia

Genotyping: Looking at the Future of Lung Cancer Care Nurses Can Educate Patients About Who Should Be Tested and When BOSTON—As more targeted therapies for non–small-cell lung cancer (NSCLC) become available, experts are assessing which patients’ tumors should be genotyped and when. Although genotyping—not to be confused with genetic testing—is becoming increasingly important in developing a treatment plan, professional guidelines do not yet recommend incorporating it as a

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routine part of care for patients with NSCLC. Whether to test prior to initiating therapy depends on each patient’s clinical situation, according to Michele Myers, BSN, RN, OCN. “I would recommend that patients who have a lifelong history of being a never-smoker, as well as patients with a light smoking history (<10 pack-years) have their

tumors genotype tested,” Myers, who is a thoracic access nurse at Massachusetts General Hospital (MGH) in Boston, told The Oncology Nurse-APN/PA. In April, the American Society of Clinical Oncology issued a provisional clinical opinion (PCO) that recommended genotype testing in patients with advanced NSCLC if first-line therapy with an epithelial growth factor

prevented her from fitting comfortably in the wheelchair or the shuttle chair, and she could not reach the shuttle chair’s foot supports. Both were intolerably painful. The patient asked to use a standard hospital bed, which is closer to the ground. The staff medicated her before moving her to the lift and then the wheelchair. With coaching on how to rise from the wheelchair and help from 2 canes, a nurse, and a physical therapist, she stood and walked safely to the standard bed. She could then move from the bed to the bathroom on her own. Its firmer mattress let her reposition herself and sit up unassisted. Skin integrity rapidly improved, allowing the patient to return home after 2 days, rather than to a rehabilitation center as indicated in the initial care plan. The authors noted that “bariatric technology is not always the solution.” Resolving this patient’s issues required close cooperation with other staff and listening actively to the patient’s concerns, as well as being flexible and thinking critically. As obesity rates climb in the United States, with more than 35.5% of women considered obese in 2009, and as our population ages, oncology nurses will likely encounter more obese or morbidly obese patients. Awareness of and sensitivity to their concerns are critical. The relationship with the patient must take priority, with a care plan tailored to the patient’s unique needs (Sidebar). As new assistance devices become available, facilities and practices should take a proactive approach in preparing to care for more morbidly obese patients. ● —CM

receptor (EGFR) tyrosine kinase inhibitor is being considered. Studies show that the EGFR inhibitors gefitinib and erlotinib are less effective in patients with NSCLC who do not have EGFR mutations. Myers hailed the PCO as a positive step for patients. “My hope is that those patients, especially in the community setting, will now have the same access to genotyping as those patients who are seen and treated in a tertiary care setting.” The most common mutations in NSCLC include HER2, PIK3CA, EGFR, MET, PDGFR, BRAF, ALK, and KRAS, according to Lecia V. Sequist, MD, MP, with MGH’s thoracic division and assistant professor of medi-

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Conference News cine at Harvard Medical School. More than one quarter of patients have none of these, suggesting many more mutations await discovery. Although studies show erlotinib is effective in EGFR-positive NSCLC, it is not approved for the first-line setting. Sequist said the Iressa Pan-Asia Study (IPASS), which compared gefitinib with chemotherapy in patients with NSCLC, showed that EGFR-positive patients had longer progression-free survival and better symptom control and quality of life when treated with gefitinib. Gefitinib, however, is not readily available in the United States and not approved for general use in patients with NSCLC.

“Going forward, nurses will need to have a basic understanding of what genotype tumor-tissue testing entails and how this could benefit their cancer patients.” —Michele Myers, BSN, RN, OCN

Crizotinib is another promising targeted therapy and, if approved by the US Food and Drug Administration, will be indicated for the 2% to 5% of NSCLC patients with an EML4ALK translocation. Other targeted agents under evaluation in NSCLC include PLX4032, a BRAF inhibitor; PF02341066, a c-MET/ALK inhibitor; BEZ235, a PI3K/mTOR inhibitor; afatinib, a HER2/EGFR inhibitor; and imatinib, an inhibitor of BCR-ABL, PDGF, SCF, and c-KIT. Nursing education does not adequately prepare nurses for the transformation under way in how lung cancer is treated. “Nurses right now in general practice are used to the typical drug treatments that are chosen based on where in the body the cancer is found,” said Myers. “Going forward, nurses will need to have a basic understanding of what genotype tumor-tissue testing entails and how this could benefit their cancer patients.” She added that providing general education on which patients with cancer should be tested, along with how and when, and how to use those results “will allow oncology nurses to advocate and participate in decisions and discussions for their cancer patients.” Some larger institutions already genotype tumors in all patients with newly diagnosed NSCLC. MGH uses its custom SNAPSHOT panel for analyzing a core biopsy sample of tumor tis-

sue. “SNAPSHOT provides information on 110 different mutations involving 13 different genes,” Myers said. “Once we know the genetic profile of a patient’s lung cancer, we can then pair the patient with the best targeted therapy for their cancer,” she explained. Different degrees of testing are available commercially and through tertiary care centers, yet “patients can face many different obstacles in getting the

tissue genotype tested,” said Myers. Commercial testing for EGFR, KRAS, and ALK mutations is available but requires patients to follow up with the local oncologist to determine eligibility for a targeted therapy. For much broader “package” testing at tertiary care centers, it is incumbent on patients to locate centers that provide the testing and follow up with their oncologist. Last fall, a 2-year lung cancer muta-

tion consortium was launched at 14 sites around the country. Myers said these institutions are providing free testing to patients with advanced lung adenocarcinoma with the genotyping protocol developed at MGH, to identify 10 genetic mutations. “Patients will then be referred to the appropriate clinical trial or therapies based on the individual molecular profile results,” she said. ● —CM

NOW RECRUITING

Investigators Study of the long-term safety and efficacy of darbepoetin alfa in anemic patients with Non-Small Cell Lung Cancer (NSCLC) receiving chemotherapy Phase 3 study with approximately 3,000 subjects at 500 study sites globally KEY INCLUSION CRITERIA* PRIMARY ENDPOINT • Advanced NSCLC

• Overall survival

• Receiving 1st-line chemotherapy

SECONDARY ENDPOINTS

• Hemoglobin (Hb) ≤ 11 g/dL

• Progression-free survival • Incidence of ≥ 1 red blood cell (RBC) transfusion or Hb ≤ 8.0 g/dL

Darbepoetin alfa 500 mcg Q3W 2:1 Randomization

End of Investigational Product

(darbepoetin alfa: placebo)

End of Treatment Period

Long-term Follow-up

Placebo Q3W

Week 0

Week 1

Disease progression or end of chemotherapy treatment

*Complete inclusion/exclusion criteria can be found in the protocol.

For more information, please visit www.782study.com or call 1-866-965-0782 (US and Canada only).

© 2010 Amgen. All rights reserved.

MC45038-D-6

04-10

2:29:08 PM

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Breast Cancer Differences and Similarities Among Ixabepilone... Continued from cover Ixabepilone is the first of a new class of cytotoxic agents: the epothilones. This relatively newly approved agent may still be unfamiliar to many oncology nurses; they may equate ixabepilone to taxanes because both are microtubule-stabilizing agents. Ixabepilone, however, is highly active in several tumor types and is less susceptible to many of the cellular resistance mechanisms that affect the use of taxanes.3 In preclinical models of taxane-resistant cancer, for example, ixabepilone has higher anticancer activity than the taxanes in cell lines that overexpress drug efflux pump proteins, presumably because ixabepilone is less susceptible than taxanes to binding and removal from the cell by this mechanism.4 In addition, although taxanes and ixabepilone both bind to β-tubulin to mediate their cytotoxic activity, ixabepilone maintains efficacy in cancer cells that have high levels of class III β-tubulin, a form of β-tubulin to which taxanes cannot bind effectively.4 This preclinical efficacy has translated into clinical benefit for patients with taxane-pretreated breast cancer, as this article will discuss.5-7 Currently, ixabepilone is indicated for use in combination with capecitabine in patients with metastatic or locally advanced breast

Ixabepilone is highly active in several tumor types and is less susceptible to many of the cellular resistance mechanisms that affect the use of taxanes. —Teresa Davis, RN, OCN

cancer after failure of an anthracycline and a taxane (or following taxane failure when further anthracycline therapy is contraindicated).5 Ixabepilone also is indicated as monotherapy in metastatic or locally advanced breast cancer after failure of an anthracycline, a taxane, and capecitabine.5 Although ixabepilone is similar to the taxanes in many ways, oncology nurses should be aware of important differences in their clinical response and tolerability profiles (Table 1). Clinical Efficacy Taxanes are one of the many approved therapies for metastatic breast cancer, either alone or in combination with anthracyclines or other agents, such as

Table 1 Comparison of Ixabepilone with Paclitaxel and Docetaxel Paclitaxel Class Taxane Mechanism of action Microtubule stabilizer Most common severe adverse effects Nonhematologica Myalgia/arthralgia, peripheral neuropathy, alopecia

Hematologicd

Contraindications

capecitabine and gemcitabine. Taxanes are of particular value when patients have already been treated with anthracyclines.2 Regimens combining taxanes with anthracyclines or other agents such as capecitabine and gemcitabine produce response rates of about 40% to 60%, median progression-free survival (PFS) of 6 to 9 months, and median overall survival of 15 to 22 months.11-14 To explore the clinical benefits of ixabepilone, 2 clinical trials involving nearly 2000 patients combined assessed the efficacy of ixabepilone plus capecitabine in patients with locally advanced or metastatic breast cancer who had been pretreated with an anthracycline and a taxane.6,7 In the first trial, all patients met strict resis-

tance criteria for taxanes and anthracyclines.6 In the subsequent confirmatory trial, all patients had been pretreated with a taxane and an anthracycline, but only about half met the strict definition of resistance used in the original trial.7 In both trials, patients received 21-day cycles of either intravenous ixabepilone 40 mg/m2 on day 1 plus oral capecitabine 2000 mg/m2/day on days 1 through 14, or oral capecitabine 2500 mg/m2/day alone on days 1 through 14. The combination of ixabepilone plus capecitabine showed superior efficacy on a range of outcome measures. In the original and confirmatory trials, respectively, the median PFS was 5.3 months and 6.2 months with ixabepilone plus capecitabine, respectively, approximately 1.5 months longer than with capecitabine alone. In addition, response rates associated with ixabepilone plus capecitabine were approximately 40%, more than 1.5-fold greater than with capecitabine alone.6,7 Direct comparisons of ixabepilone with taxane therapy currently are under way in multiple stages of breast cancer, mostly in sequence or combination with a variety of other agents (Table 2, page 20). Interim data from a 3-arm phase 2 trial comparing ixabepilone (Arm A: 16 mg/m2 weekly; Arm B: 40

nab-paclitaxel Taxane Microtubule stabilizer

Docetaxel Taxane Microtubule stabilizer

Ixabepilone Epothilone Microtubule stabilizer

Peripheral neuropathy, fatigue/asthenia, myalgia/arthralgia, alopecia

Fatigue/asthenia, myalgia/arthralgia, stomatitis/mucositis, peripheral neuropathy, cutaneous reactions, diarrhea, alopecia, fluid retentionb

Peripheral neuropathy, fatigue/asthenia, myalgia/arthralgia, stomatitis/mucositis, hand-foot syndrome,c diarrheac

Neutropenia

Neutropenia

Neutropenia, leukopenia, febrile neutropeniab

Neutropenia, leukopenia

Neutrophils <1500/mm3; previous hypersensitivity reaction to paclitaxel or Cremophor EL

Neutrophils <1500/mm3

Hepatic impairment,e neutrophils <1500/mm3; previous severe hypersensitivity reaction to docetaxel or polysorbate 80

Moderate/severe hepatic impairment,f neutrophils <1500/mm3, platelets <100,000/mm3; previous severe hypersensitivity reaction to Cremophor EL

a Grade 3/4 severity and affecting ≥5% of patients, with the exception of alopecia, which was not graded for severity. Alopecia is included because of its significance for patients and high incidence (≥75% of patients). Listed in order of incidence. b

Dose-dependent. Incidence ≥5% with docetaxel 100 mg/m2, but less common with 60 mg/m2.

c

Ixabepilone in combination with capecitabine.

d

Severe (grade 3/4) in ≥40% of patients.

e

Not defined as a contraindication, but labeling carries a boxed warning that docetaxel should generally not be given to patients with bilirubin levels above the ULN, or to patients with AST and/or ALT >1.5 x ULN concomitant with ALP >2.5 x ULN. f

The use of ixabepilone in combination with capecitabine is contraindicated in patients with AST or ALT levels >2.5 x ULN or bilirubin levels above the ULN.

ALP indicates alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; nab, nanoparticle albumin-bound; ULN, upper limit of normal. Sources: References 5, 8-10.

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In relapsed and refractory disease

The complications of multiple myeloma present clinical challenges The care of patients with relapsed and refractory multiple myeloma can be complicated by a number of factors related to the patient, prior therapies, stage of disease, and comorbidities.1 • 65% of patients with multiple myeloma are 65 years of age or older2 • Cumulative toxicities from prior therapies can impact treatment options1 • Multiple myeloma itself can damage the patient’s organs and nervous system3

Seeking a new approach to your patients’ needs Onyx Pharmaceuticals is committed to pursuing advances to address the unmet needs of patients with relapsed and refractory multiple myeloma.

©2011 Onyx Pharmaceuticals, Inc., South San Francisco, CA

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References: 1. Richardson P, Mitsiades C, Schlossman R, et al. The treatment of relapsed and refractory multiple myeloma. Hematology Am Soc Hematol Educ Program. 2007;317-323. 2. Palumbo A, Gay F. How to treat elderly patients with multiple myeloma: combination of therapy or sequencing. Hematology Am Soc Hematol Educ Program. 2009;566-577. 3. Munshi NC, Anderson KC. Plasma cell neoplasms. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. Cancer: Principles & Practice of Oncology. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:2305-2342.

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Breast Cancer mg/m2 every 3 weeks) with paclitaxel (Arm C: 90 mg/m2 weekly), each in combination with the antiangiogenic agent bevacizumab (10 mg/kg every 2 weeks in Arms A and C; 15 mg/kg every 3 weeks in Arm B), reveal equivalent response rates and 24-week PFS for all 3 arms, suggesting that ixabepilone produced results that were comparable with weekly paclitaxel in this setting.15 Tolerability Overall, ixabepilone and the taxanes exhibit fairly similar tolerability profiles, because both ixabepilone and the taxanes operate by inhibiting the function of microtubules within cancer cells. However, because ixabepilone is chemically unrelated to taxanes and interacts with microtubules in a different manner, it does have a distinct adverse event profile. In patients with advanced breast cancer, these adverse events are generally predictable and manageable with supportive care, dose reductions, and treatment delays. Nonhematologic adverse events. Whether used alone or with capecitabine, one of the most common adverse effects with ixabepilone is sensory chemotherapy-induced peripheral neuropathy (CIPN). CIPN affects approximately 60% of patients treated with ixabepilone and is severe (grade 3/4) in about 15% to 25% of patients.6,16,17 CIPN is also a common adverse effect with taxanes, with reported incidence of severe CIPN more variable and highly dependent on the cumulative and per-cycle dose.18 Incidence rates range from 2% to 32% with conventional paclitaxel to 4% to 11% with nab-paclitaxel to 0% to 17% with docetaxel. For ixabepilone-induced CIPN, even grade 3/4 events are responsive to dose reduction or delays,6,17,18 and guidelines for managing dose reduction based on the severity of symptoms have been established (Table 3). Notably, in the original ixabepilone trial, patients with grade 1 neuropathy were able to receive the same amount of therapy as the general population.6 Also in this trial, the onset of grade 3/4 neuropathy occurred after a median of 4 cycles.6 These events are reversible in most patients after discontinuation of ixabepilone, with a median time to resolution to baseline or grade 1 of 5 to 6 weeks,6,16,17 which is more rapid than that reported with conventional taxanes.19 Ixabepilone should be used with caution in patients with diabetes mellitus or preexisting moderate-to-severe neuropathy, both of whom may be at increased risk for CIPN.5,17,19 There are no proven agents or interventions that prevent or eliminate CIPN more effectively than early detection by routine clinical assessment of neurologic function. The

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Table 2 Clinical Trials Comparing Ixabepilone with Taxanes in Breast Cancer Clinical trial identifier Phase Patients Study design NCT00490646 2 Locally advanced and/or metastatic • Ixabepilone 40 mg/m² vs docetaxel 100 mg/m² (day 1 every 21 days) • Each with trastuzumab 2 mg/kg (loading dose, 4 mg/kg; day 1 every 21 days) NCT00789581

3

Triple-negative, early stage

• Ixabepilone 40 mg/m² (day 1 every 21 days) vs paclitaxel 80 mg/m² (weekly) • Each following cyclophosphamide 600 mg/m² and doxorubicin 60 mg/m² (day 1 every 21 days)

NCT00630032a

3

• Ixabepilone vs docetaxel • Following combination chemotherapy (tamoxifen, aromatase inhibition, anthracyclines)

NCT00785291a

3

Locally recurrent stage IIIB or IV

• Ixabepilone vs nab-paclitaxel vs paclitaxel (days 1, 8, and 15 every 28 days) • Each with bevacizumab (days 1 and 15 every 28 days)

a

Dosing and/or schedule not provided.

National Comprehensive Cancer Network (NCCN) Task Force for Management of Neuropathy in Cancer strongly recommends that patients be questioned directly regarding common signs and symptoms of neuropathy, because patients may tend to bucket neuropathic symptoms together with other forms of cancer pain when selfreporting. Patients also should be given neurologic assessments before initial treatment, to establish a baseline, and periodically thereafter. For a more extensive review of commonly used grading scales, critical questions to ask patients, and functional assessments, please refer to the recently published NCCN Task Force report.19 Several of the main themes of supportive care in patients receiving ixabepilone therapy have parallels in the taxane drug class, and experience with taxanes will be useful in managing ixabepilone-treated patients. In addition to neuropathy, both taxanes and ixabepilone are associated with a predictable assortment of other nonhematologic adverse events, such as fatigue/ asthenia, myalgia/arthralgia, stomatitis/mucositis, nausea and vomiting, and diarrhea.8-10 Although not mandatory, a 20% reduction in the dose of ixabepilone is an option for mitigating transient grade 3 fatigue.5 Patients with symptoms of fatigue may benefit from reducing activity levels overall, planning activities around times when energy levels tend to be highest, and structured routines; nurses should be prepared to provide guidance in these areas. Nurses also should consider addressing underlying contributors to fatigue, such as inadequate nutrition or nighttime sleep, anemia, or stress,

Table 3 Dose-Adjustment Guidelines for Ixabepilone in Chemotherapy-Induced Peripheral Neuropathy Grade

Dosage adjustment

Grade 2 (moderate) lasting ≥7 days

Decrease by 20%

Grade 3 (severe) lasting <7 days

Decrease by 20%

Grade 3 (severe) lasting ≥7 days

Discontinue treatment

Grade 4 or disabling

Discontinue treatment

Source: Reference 5.

should symptoms occur.20 Alopecia occurs as well, but is notably more common with taxanes than with ixabepilone, affecting 75% to 90% of patients treated with taxanes8-10 compared with 48% of patients treated with ixabepilone monotherapy and 31% of patients treated with ixabepilone plus capecitabine.5 Although the risk is lower, nurses should prepare their patients for the possible onset of alopecia during ixabepilone therapy and discuss potential coping mechanisms when relevant. As a general rule, the dose of ixabepilone should be reduced by 20% for persistent grade 3 nonhematologic reactions, including transient fatigue if necessary, and treatment should be stopped for grade 4 reactions (refer to prescribing information). Resumption of treatment may be considered if toxicities resolve or improve to grade 1 (mild). Hematologic adverse events. At least 90% of patients treated with ixabepilone alone or in combination with capecitabine will experience some hematologic toxicity.6,16 As with the taxanes, myelosuppression is the most common dose-limiting toxicity with ixabepilone. Common toxicities in this category include anemia and thrombocytopenia (mild to moderate in most

cases), severe (grade 3/4) neutropenia (affecting approximately 50% to 70% of patients), and severe leukopenia (affecting approximately 50% to 60% of patients). Despite the high incidence of neutropenia, the incidence of ixabepilone-related serious febrile neutropenia is low, approximately 3% to 5%.6,16 Moderate or transient hematologic toxicity and febrile neutropenia generally can be managed by reducing the ixabepilone dose by 20%. In addition, although not required, hematopoietic growth factor support (ie, colony-stimulating factors) may be provided. Patients should not begin a new treatment cycle with ixabepilone until neutrophil counts are ≥1500 cells/mm3. To help ensure that neutropenia is managed promptly, patients treated with ixabepilone should receive complete blood counts before treatment begins to establish a baseline, and periodically thereafter. Patients should be counseled in the areas of hygiene, protecting themselves from infections, and recognizing early signs of an infection. Hepatic impairment. The risk of toxicity and neutropenia-related death associated with the ixabepilone plus capecitabine combination regimen is increased in patients with significant

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Need a reason to choose Evercare™ Hospice and Palliative Care? How about seven? Within our power, we are committed to providing the best hospice and palliative care experience available. That commitment is expressed in our Seven Point Pledge.

4. Respond to all patient-related calls within 15 minutes, 24 hours a day, 7 days a week. A patient’s condition doesn’t take a day off, and neither do we.

Evercare Hospice & Palliative Care pledges to:

5. Provide a hospice staff presence at the time of death. We’ll be there at this important time, as we have throughout the process, to provide comfort and support.

1. Admit all hospice-eligible referrals the same day, unless requested otherwise. Patients deserve timely care and action, especially as they approach end-of-life. 2. Provide direct, extensive physician involvement in the care of each patient. Experts highly trained in hospice and palliative care are involved and available to make personal visits. 3. Achieve acceptable pain control on all patients. No patient should live in pain. That’s why we place such an emphasis on delivering pain management in a timely and caring manner.

6. Maintain an Unrestricted Options Philosophy regarding patient admissions. We believe in making hospice care available to all those who are eligible. 7. Offer palliative care consults and advanced care planning services. These continuing health care services are important, so we offer expertise in both areas.

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Breast Cancer baseline hepatic impairment.6 Thus, this regimen is contraindicated in patients with preexisting moderate and severe hepatic impairment; specifically, those with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels that exceed 2.5 x the upper limit of normal (ULN), or those with bilirubin levels that exceed ULN. Ixabepilone monotherapy can be used cautiously, at a lower dose, in patients with mildto-moderate baseline hepatic impairment. If a patient’s AST and ALT levels do not exceed 2.5 x ULN and bilirubin does not exceed ULN, she may receive the full dose of ixabepilone monotherapy, 40 mg/m2. As long as a patient’s AST and ALT levels do not exceed 10 x ULN and if bilirubin levels do not exceed 1.5 x ULN, she may receive ixabepilone at 32 mg/m2, or she should receive between 20 mg/m2 and 30 mg/m2 if her bilirubin

levels exceed 1.5 times ULN but do not exceed 3 x ULN (refer to the prescribing information for details).5 Hypersensitivity reactions. There is a risk of hypersensitivity reactions to the solvents used in ixabepilone preparations and in the conventional formulations of the taxanes. Standard paclitaxel (containing Cremophor EL) and docetaxel (containing polysorbate 80) may cause severe hypersensitivity in 2% to 4% of patients, necessitating a recommendation for standard premedication with corticosteroids and H1/H2 antagonists (nab-paclitaxel is solventfree and does not need premedication).8-10 The incidence of severe hypersensitivity reactions (including anaphylaxis) is lower with ixabepilone, which contains Cremophor EL but less than standard paclitaxel—about 1%. H1/H2 antagonist premedication is required (eg, oral diphenhydramine 50 mg and oral ranitidine 150 mg to 300

13 Comorbid Conditions Decrease Survival, Increase Mortality in Elderly Breast Cancer Patients By Dawn Lagrosa

F

or breast cancer patients aged 66 years and older, nurses should consider comorbidities when discussing prognosis, according to an analysis of Surveillance, Epidemiology and End Results–Medicare data. In a US population of 64,034 patients diagnosed with breast cancer at a median age of 75 years, Patnaik and colleagues identified 13 comorbid conditions associated with decreased overall survival and increased all-cause mortality (Table). Among the study population, 58% had none of the selected comorbidities, 28.0% had 1 comorbidity, 8.8% had 2 comorbidities, and 4.9%

had ≥3 of the conditions. Kaplan-Meier survival curves showed that comorbidities are associated with survival, meaning that for a patient with comorbid conditions diagnosed at an early stage, that patient had similar or worse survival than a patient with no comorbid conditions diagnosed at a later stage. The investigators concluded that their findings suggest that “careful attention to the effective management of comorbid conditions, as well as to the management of a patient’s cancer, may result in longer overall survival for older breast cancer patients.” ●

Table

Comorbid Conditions Associated with Decreased Survival Hazard ratio Comorbid condition Patients, % (95% confidence interval) Previous cancer 1.27 (1.23-1.30) 16.3 1.41 (1.36-1.45) Diabetes 13.0 Chronic obstructive 8.8 1.52 (1.47-1.58) pulmonary disease Congestive heart failure 6.7 1.70 (1.64-1.76) Stroke 4.3 1.35 (1.28-1.42) Liver disease 0.3 2.32 (1.97-2.73) Myocardial infarction 1.7 1.11 (1.03-1.19) Peripheral vascular disease 2.6 1.36 (1.28-1.44) Dementia 1.4 1.96 (1.82-2.10) Paralysis 0.6 1.23 (1.09-1.38) Chronic renal failure 0.9 2.20 (2.02-2.41) Stomach ulcer 1.1 1.12 (1.02-1.23) Rheumatoid arthritis 2.0 1.27 (1.18-1.37) Source: Patnaik JL, Byers T, DiGuiseppi G, et al. The influence of comorbidities on overall survival among older women diagnosed with breast cancer. J Natl Cancer Inst. 2011;103:1101-1111.

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mg, or equivalent). Unlike taxanes, however, corticosteroid premedication is required only in cases of a history of hypersensitivity to ixabepilone.5 As with taxanes, if a severe hypersensitivity reaction occurs, ixabepilone must be stopped immediately and aggressive supportive care started. Patients should not receive ixabepilone if any previous reaction to a Cremophor EL–containing agent was severe. Because of the risk of hypersensitivity to ixabepilone, patients should be monitored for signs of hypersensitivity, such as hives, itching (pruritus), rash, flushing, swelling, or difficulty breathing or swallowing, either during or shortly after treatment. Conclusions Like the taxanes, ixabepilone kills tumor cells by inhibiting the function of microtubules. It is associated, therefore, with a similar spectrum of adverse events. Ixabepilone is chemically unrelated to the taxanes, however, which yields clinical benefit in patients whose disease has progressed after taxanes fail, as well as unique features of its adverse event profile. CIPN associated with ixabepilone is more likely to be reversible, generally resolving to grade 1 or baseline in a median time of 5 to 6 weeks. Like the taxanes (with the exception of nab-paclitaxel), ixabepilone is given intravenously and carries the risk of hypersensitivity reactions to its polyethoxylated diluent. Most patients receiving ixabepilone, however, need only receive prophylactic H1/H2 antagonists to prevent hypersensitivity reactions, and corticosteroid premedication is needed only in patients with a history of hypersensitivity reactions to ixabepilone. As yet, no randomized comparative data are available from head-to-head trials comparing ixabepilone and the taxanes in breast cancer patients, but several trials are ongoing. In addition, several other trials are evaluating ixabepilone, either as a single agent or as part of sequential or combination therapy, in earlier lines of breast cancer therapy. As the patients in these trials are less heavily pretreated than the patients in the registrational trials, it is expected that ixabepilone may show promising results. Acknowledgment The author takes full responsibility for the content of this publication and confirms that it reflects her viewpoint and medical expertise. She also wishes to acknowledge StemScientific, funded by Bristol-Myers Squibb, for providing writing and editing support. Neither Bristol-Myers Squibb nor StemScientific influenced the content of the

manuscript, nor did the author receive financial compensation for authoring the manuscript. ● References 1. O’Shaughnessy J. Extending survival with chemotherapy in metastatic breast cancer. Oncologist. 2005; 10(suppl 3):20-29. 2. O’Shaughnessy J, Twelves C, Aapro M. Treatment for anthracycline-pretreated metastatic breast cancer. Oncologist. 2002;7(suppl 6):4-12. 3. Lee FY, Borzilleri R, Fairchild CR, et al. Preclinical discovery of ixabepilone, a highly active antineoplastic agent. Cancer Chemother Pharmacol. 2008;63:157-166. 4. Lee FY, Smykla R, Johnston K, et al. Preclinical efficacy spectrum and pharmacokinetics of ixabepilone. Cancer Chemother Pharmacol. 2009;63:201-212. 5. Ixempra kit (ixabepilone) for injection [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2010. 6. Thomas ES, Gomez HL, Li RK, et al. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007;25:5210-5217. 7. Hortobagyi G, Perez E, Vrdoljak E, et al. Analysis of overall survival among patients with metastatic breast cancer receiving either ixabepilone plus capecitabine or capecitabine alone and a review of results from two randomized phase III trials. Presented at: American Society of Clinical Oncology Breast Cancer Symposium. September 5-7, 2008; Washington, DC:Abstract 186. 8. Abraxane for injectable suspension (paclitaxel protein-bound particles for injectable suspension) [package insert]. Bridgewater, NJ: Abraxis BioScience; 2010. 9. Taxol (paclitaxel) injection [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2011. 10. Taxotere (docetaxel) injection [package insert]. Bridgewater, NJ: sanofi; 2010. 11. Piccart-Gebhart MJ, Burzykowski T, Buyse M, et al. Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer. J Clin Oncol. 2008;26:1980-1986. 12. Nabholtz JM, Falkson C, Campos D, et al; for the TAX 306 Study Group. Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol. 2003;21:968-975. 13. O’Shaughnessy J, Miles D, Vukelja S, et al. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol. 2002;20:2812-2823. 14. Albain KS, Nag SM, Calderillo-Ruiz G, et al. Gemcitabine plus paclitaxel versus paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment. J Clin Oncol. 2008; 26:3950-3957. 15. Rugo HS, Campone M, Amadori D, et al. Randomized phase II study of weekly versus every-3week ixabepilone plus bevacizumab (ixa/bev) versus paclitaxel plus bev (pac/bev) as first-line therapy for metastatic breast cancer (MBC). J Clin Oncol. 2009;27(15S):Abstract 1029. 16. Perez EA, Lerzo G, Pivot X, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007;25:3407-3414. 17. Perez EA, Pivot X, Vrdoljak E, et al. A prospective characterization of the resolution of ixabepilone induced peripheral neuropathy: data from a large registrational program in patients with metastatic breast cancer. Cancer Res. 2009;69(suppl):Abstract 6140. 18. Swain SM, Arezzo JC. Neuropathy associated with microtubule inhibitors: diagnosis, incidence, and management. Clin Adv Hematol Oncol. 2008;6:455-467. 19. Stubblefield MD, Burstein HJ, Burton A, et al. NCCN Task Force Report: management of neuropathy in cancer. J Natl Compr Canc Netw. 2009;7(suppl 5): S1-S28. 20. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Cancer-Related Fatigue. V.1.2011. www.nccn.org/professionals/physician_gls/ pdf/fatigue.pdf. Accessed June 20, 2011.

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Genetic Counseling

Understanding the Evolution of and Term “Genetic Counselor”: Is the Term Being Used Appropriately in Your Community? By Cristi Radford, MS, CGC Sarasota Memorial Health Care System, Sarasota, Florida

G

enetic counseling as a profession began in 1969 with the establishment of the first Master’slevel graduate program in genetic counseling. As a process, however, genetic counseling has evolved over a longer period of time. The term was coined in 1947 by Sheldon Reed, a geneticist, who used the term “genetic counseling” to describe the process of providing genetic information and support to families. He believed that an “important requirement of the counselor was to have a deep respect for the sensitivities, attitudes, and reactions of the patient.”1 Physicians who worked in the early medical genetics clinics hoped to gain an understanding of the genetics involved in disease. At that time, laboratory tests for genetic conditions did not exist and the practice of genetic counseling was limited. During the 1950s and 1960s, however, cytogenetics advanced and amniocentesis emerged. It became possible for physicians to diagnose chromosomal abnormalities in their patients. In addition, amniocentesis could be used to detect Barr bodies in fetal cells. Barr bodies allowed the prediction of fetal sex.2 This information could be applied to families at risk for a sex-linked genetic disorder. Eventually, by the mid-1960s, amniocentesis was used to construct a human karyotype of the fetus.3 Amniocentesis did not come without risks. Therefore, not only did the information from amniocentesis have to be conveyed to the family, but also the risks, limitations, and benefits of the procedure had to be

explained. At this point, genetic counseling was no longer limited to a few specialty centers. The number of centers offering these services grew from 10 in 1951 to 287 in 1977.4 Medical professionals realized that conveying genetic information required a particular subset of skills, and the first genetic counseling program opened. As society progressed into the 1980s, cytogenetics, molecular genetics, and biochemical genetics progressed too. The role of the genetic counselor in the prenatal setting expanded to include information obtained from examining enzymes in amniotic fluid.5 In addition, genetic counselors entered predisposition testing when the gene for Huntington disease was mapped with DNA markers.6 Predisposition testing continued to grow in the 1990s. At which time, several cancer-predisposing genes were cloned. These genes caused an increased risk for cancers, such as colon, breast, and ovarian.7 As centers began offering predictive DNA testing to affected individuals and family members at risk, genetic counselors entered a new sector: cancer counseling. Cancer Counseling The sequencing of the human genome and identification of cancer predisposition genes, such as BRCA1 and BRCA2, rapidly increased the need for individuals with cancer genetic expertise and experience in genetic counseling. Now, we have direct-to-consumer marketing of hereditary cancer genetic testing, which has increased public awareness of genetic testing. And healthcare professionals face increased pressure to incorporate genetic testing into their practice— either by providing genetic counseling

Did you know that in many states the term “genetic counselor” does not have title protection? When collaborating with a “genetic counselor,” a healthcare provider cannot assume the term genetic counselor denotes an individual with graduate training, certification, or even experience in genetics. Only 11 states currently issue licensure for genetic counselors: California, Delaware, Illinois, Indiana, Massachusetts, New Mexico, Oklahoma, South Dakota, Tennessee, Utah, and Washington. Source: Reference 15.

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Professional guidelines, insurance carriers, and case review demonstrate the importance of genetic counseling by trained experts.

in-house or referring to experts for consultation. Multiple professional guidelines, including the American College of Medical Genetics, American College of Obstetricians and Gynecologists, American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network, National Society of Genetic Counselors (NSGC), Oncology Nursing Society, and Society of Gynecologic Oncologists, state the importance of both pre- and posttest genetic counseling. Often, community hospitals are looked upon to meet the needs of their community and physicians. Creating a position and hiring the correct individual can be challenging for an administrator. In the rapidly evolving field of cancer risk assessment, however, the task has an additional layer of complexity. Not only is the field in its infancy, but it also is largely unregulated. Concern has been expressed about the potential for harm when genetic testing is performed outside of an expert in genetics.8 Brierley and colleagues identified 3 themes of negative outcomes when cancer genetic testing was performed without genetic counseling by an expert in genetics9: wrong genetic test ordered, genetic test results misinterpreted, and inadequate genetic counseling. An abstract presented at the 2011 ASCO annual meeting identified similar themes and concluded that physicians appear to be the most vulnerable group for lawsuits related to genetic technologies and the number of cases likely will increase substantially. Case review demonstrated that physicians were held liable for various aspects of genetic counseling and testing, including failure to take an adequate family history, recommend the appropriate testing, refer to a geneticist or genetic counselor, interpret the test results correctly, interpret the test results in a timely manner, recommend the appropriate risk mitigation strategies,

and failing to disclose their patients’ test results to at-risk family members.10 In addition, healthcare payers have expressed similar concerns. In 2009, UnitedHealthcare launched the BRCA Genetic Testing Notification and Counseling program, which consists of prior notification of BRCA genetic testing and improved access to genetic counseling by certified genetic counselors. The document states that although genetic tests “may provide valuable information to both doctors and patients, many genetic tests are ordered and performed with incomplete information, unclear indications, and insufficient support services such as test interpretation and genetic counseling.”11 Aetna is funding a study to help address questions “…about whether these tests are being offered to the women who can most benefit—consistent with the evidence-based guidelines for this testing—and whether the information learned from testing is being put to best use.”12 Priority Health states that for hereditary cancer syndromes, “Genetic Counseling must be done prior to testing by a board certified Genetic Counselor or Geneticist that is independent of the laboratory performing the test.”13 Certification Standards Professional guidelines, insurance carriers, and case review demonstrate the importance of genetic counseling by trained experts. Genetic counseling has been provided by a variety of professionals with genetics expertise, including MD and PhD geneticists, genetic counselors, and nurses with specialized training in genetics. However, the use of the term “genetic counselor” or another title containing the term “genetic” by an individual does not necessarily denote he or she has obtained a certain proficiency in genetic counseling. Although the NSGC defines genetic counselors as “… healthcare professionals with special-

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Genetic Counseling ized graduate training in the areas of medical genetics and counseling,”14 in many states genetic counselors do not have licensure. Without title protection, anyone in that state can use the term genetic counselor. A healthcare provider, therefore, could unknowingly be referring to an individual using the term genetic counselor who does not have graduate training in genetic counseling or even a basic level of proficiency. Not only does this place consumers at risk, but it also potentially places healthcare providers using these untrained individuals at risk. So how does an administrator or provider know an individual they are using has expertise in genetics? In addition to asking a professional about their training and experience, an individual can look for particular credentials to determine a provider’s level of expertise. There are 3 main groups of professionals with advanced degrees and experience in genetics. Each group uses particular acronyms to designate their credentials and has their own unique strengths.

A healthcare provider, therefore, could unknowingly be referring to an individual using the term genetic counselor who does not have graduate training in genetic counseling or even a basic level of proficiency. • Advanced Practice Nurse in Genetics (APNG). An APNG has graduated from a graduate nursing program and completed a professional portfolio review process (www. geneticnurse.org/advancedpractice apng.html). • Certified Genetic Counselor (CGC). A CGC has at least a Master’s degree in genetic counseling and has passed a board examination (www.abgc.net). • Diplomate, American Board of Medical Genetics (DABMG) or Fellow, American College of Medi cal Genetics (FACMG). Individuals using the acronym DABMG or FACMG are physicians who have completed a residency in genetics and passed a board examination. DABMG, although not widely used, is a physician certified by the ABMG, whereas FACMG is an individual certified by the ABMG and is a member of the American College of Medical Genetics (www.abmg.org). ●

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References 1. Reed S. Counseling in Medical Genetics. Philadelphia, PA: WB Saunders Co; 1955. 2. Fuchs F, Riis P. Antenatal sex determination. Nature. 1956;177:330. 3. Steele MW, Breg WR. Chromosome analysis of human amniotic-fluid cells. Lancet. 1966;1(7434):383-385. 4. Marks JH. Masters level training programs for genetic counselors: an eight year report. In: Porter IH, Hooks EB, eds. Service and Education in Medical Genetics. New York, NY: Academic Press; 1979:351-360. 5. Boué A, Muller F, Nezelor C, et al. Prenatal diagnosis in 200 pregnancies with a 1-in-4 risk of cystic fibrosis. Hum Genet. 1986;74:288-297. 6. Gusella JF, Wexler NS, Conneally PM, et al. A polymorphic DNA marker genetically linked to Huntington’s disease. Nature. 1983;306:234-238.

7. Offit K. Clinical Cancer Genetics: Risk Counseling and Management. New York, NY: Wiley-Liss, Inc; 1998. 8. Greendale K, Pyeritz RE. Empowering primary health professionals in medical genetics: how soon? how fast? how far? Am J Med Genet. 2001;106:223-232. 9. Brierley KL, Campfield D, Ducaine W, et al. Errors in delivery of cancer genetic services: implications for practice. Conn Med. 2010;74:413-423. 10. Lindor RA, Marchant GE. A review of medical malpractice claims related to clinical genetic testing. J Clin Oncol. 2011;29(suppl):Abstract 6073. 11. UnitedHealthcare. BRCA Genetic Testing Notification and Expanded Access to Genetic Counseling. August 16, 2009. www.unitedhealthcareon line.com/b2c/CmaAction.do?channelId=f3478c10d2152 210VgnVCM1000002f10b10a____. Accessed August 5, 2011.

12. Aetna supports first national study on communitybased use of genetic tests for cancer risk [press release]. September 15, 2010. www.aetna.com/news/new Releases/2010/0915_BRCAesting.html. Accessed August 5, 2011. 13. Priority Health. Genetics: counseling, testing, screening. Medical Policy No. 91540-R5. August 2010. www.priorityhealth.com/provider/manual/auths/~/media/ documents/medical-policies/91540.ashx. Accessed August 5, 2011. 14. National Society of Genetic Counselors. Patient FAQs. www.nsgc.org/Home/ConsumerHomePage/Patient FAQs/tabid/338/Default.aspx. Accessed August 5, 2011. 15. National Society of Genetic Counselors. States issuing licenses for genetic counselors. July 1, 2011. www.nsgc.org/Advocacy/StatesIssuingLicensesforGenetic Counselors/tabid/347/Default.aspx. Accessed August 5, 2011.

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For conference program details visit www www.oncnurseed.com .oncnurseed.com Register on line at www.chemotherapyfoundationsymposium.org www.chemotherapyfoundationsymposium.org Contacts: Gina Amatruda at gina@oncnurseed.com, (203) 915-3975 jaclyn.silverman@mssm.edu, (212) 866-2813 Jointly sponsored/co-provided by:

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CONTINUING EDUCATION PROGRAM CE21 • RELEASE DATE: AUGUST 22, 2011 • EXPIRATION DATE: AUGUST 22, 2012 ESTIMATED TIME TO COMPLETE: 1.0 HOUR • COMPLETE THE POSTTEST AT WWW.THEONCOLOGYNURSE.COM

Cancer Burden in the HIV-Infected Population in the United States By Meredith S. Shiels, PhD, MHS Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland

STATEMENT OF NEED In the United States, improved antiretroviral therapy has significantly prolonged survival among those infected with HIV. As a result, increasing numbers of the HIV-infected population are at risk of non–AIDS-defining cancers that typically occur at older ages. In recent years, several studies have addressed the incidence rates of cancer among those with HIV infection; however, there have been no published estimates on the number of cancers or the types of cancers that occur annually among HIV-infected individuals in the United States. This study will identify these cancers, which as the HIVinfected population continues to grow and to age will emerge as an important public health issue. TARGET AUDIENCE Advanced practice nurses, registered nurses, and other interested healthcare professionals, especially those caring for cancer patients LEARNING OBJECTIVES After completing this activity, the reader should be able to: • Discuss significant changes in the cancer burden in people with HIV and AIDS. • Describe possible causes of the shift in types of cancer experienced by people with HIV and AIDS.

C

ompared with the population at large, people who have HIV infection and AIDS have a higher risk for developing many types of cancer.1-9 Kaposi sarcoma (KS), nonHodgkin lymphomas (NHLs), and cervical cancer have been termed AIDSdefining cancers by the Centers for Disease Control and Prevention (CDC).10 However, the longevity of people in the United States infected with HIV has increased dramatically since the advent of highly active antiretroviral therapy (HAART) in 1996,11,12 and this aging population, with or without AIDS, is now at risk of developing numerous non–AIDSdefining cancers that typically occur at older ages. HIV-infected individuals have a 3640-fold increased risk of KS caused by human herpesvirus 8 (HHV8); a 77-fold increased risk of NHL, some caused by Epstein-Barr virus; and a 6-fold increased risk of cervical cancer caused by oncogenic subtypes of human papillomavirus (HPV).8 Non–AIDS-defining cancers include some associated with coinfections, such as HPV infection (anal and oropharyngeal cancers), hepatitis B and C viruses (liver cancer), and Epstein-Barr virus infection (Hodgkin

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lymphoma), or with smoking (lung cancer).5,6,8,13 From 1991 to 2005, the US AIDS population increased slightly more than 4-fold, from 96,179 to 413,080. During this period, AIDS-defining cancers decreased by more than 3-fold, whereas non–AIDS-defining cancers increased by 3-fold (Figure). In recent years, several studies have addressed the incidence rates of cancer among those with HIV infection.1-9 However, there have been no published estimates on the number of cancers—the cancer burden—or the types of cancers that occur annually among HIV-infected individuals in the United States. Study Population and Protocol The current study shows that the growth in size and the increase in age in the HIV-infected population coupled with its elevated cancer risk have led to an increase in the number of non–AIDS-defining cancers in this group. The study was divided into 3 calendar periods: 1991 to 1995 (preHAART), 1996 to 2000 (early HAART), and 2001 to 2005 (late HAART). It examined trends in the cancer burden among people with AIDS in the United States. Estimated counts of specific AIDS-defining and non–AIDSdefining cancers were based on data from the HIV/AIDS Cancer Match Study and the CDC. The study also estimated the cancer burden in HIV-infected people without AIDS from 2004 to 2007 using data from 34 states. Results

Characteristics of AIDS and HIVOnly Populations The number of people living with AIDS in the United States increased from 96,179 in 1991 to 413,080 in 2005, representing 3,955,556 person-years at risk for developing cancer. The proportion of person-years attributed to those aged younger than 30 years decreased from 15.1% in 1991 to 1995 to 5.9% in 2001 to 2005, whereas the proportion for those aged 50 years or older increased from 9.8% to 24.8%. This represents a substantial age shift, and the increase in the size of the AIDS population is largely a result of the increased number of people aged 40 years or older.

Compared with the AIDS population of 1991 to 1995, it was noted that those living with AIDS in 2001 to 2005 were less likely to be men but more likely to be African American, Hispanic, or of other race and ethnicity. Also, infection through heterosexual contact increased, although men who have sex with men (MSM) were still the largest HIV transmission risk group. The HIV-only population evaluated in 34 US states during 2004 to 2007 represented 946,936 personyears at risk of cancer. People with HIV only were younger than people with AIDS and were more likely to be women, but both groups had similar findings in race, ethnicity, and HIVtransmission categories.

Cancer Burden in the AIDS Population During 1991 to 2005, an estimated 79,657 cancers occurred in the US AIDS population (incidence rate = 2013 per 100,000 person-years). Estimated numbers for the most common types of cancer were: KS, 31,037; NHL, 26,038; lung cancer, 4140; anal cancer, 2540; Hodgkin lymphoma, 2004; and cervical cancer, 1276. 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. FACULTY DISCLOSURES As a provider accredited by the California Board of Registered Nursing, Science Care must ensure balance, independence, objectivity, and scientific rigor in all its activities. All course directors, faculty, planners, and any other individual in a position

Trends from 1991 to 2005 indicate that most age groups experienced some decline in AIDS-defining cancers, with the largest decline seen among those 20 to 39 years old. There was an increase, however, in the cancer burden of non–AIDS-defining cancers, which was limited to people aged 40 years or older. As a result of these changes, the total cancer burden in the AIDS population decreased during 1991 to 1998 but later increased as a result of the rise in the number of non– AIDS-defining cancers. The number of AIDS-defining cancers declined and the number of non–AIDS-defining cancers increased across the 3 calendar periods (Ptrend <.001 for both). Although only 8.2% of cancers among people with AIDS were non–AIDSdefining cancers in 1991 to 1995, by 2001 to 2005 non–AIDS-defining cancers represented 48.3% whereas AIDSdefining cancers represented 49.6%. Among AIDS-defining cancers, KS counts decreased approximately 82% and NHL decreased 53% from 1991 to 2005. Of the KS cases, 89% occurred in MSM. In women with AIDS, a statistically significant increase in the number of cervical cancers occurred to control the content of this educational activity are required to disclose to the audience any relevant financial relationships with any commercial interest. Science Care must determine if the faculty’s relationships may influence the educational content with regard to exposition or conclusion and resolve any conflicts of interest prior to the commencement of the educational activity. Disclosures are as follows: • Rosemary Hansen has nothing to disclose. • Dawn Lagrosa has nothing to disclose. • Meredith S. Shiels, PhD, MHS, has nothing to disclose. The staff of Science Care have nothing to disclose. DISCLAIMER The opinions and recommendations expressed by faculty, authors, and other experts whose input is included in this program are their own and do not necessarily represent the viewpoint of Science Care or Green Hill Healthcare Communications, LLC. COPYRIGHT STATEMENT Copyright © 2011 Science Care. All rights reserved.

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2004

2003

2002

Incidence Rate 100,000 Person-Years

2005 2005

0

2004

2005

2004

2003

2002

2001

2000

1999

1998

1997

1996

1995

1994

1993

0

Incidence Rate per 100,000 Person-Years

1000

1000

2003

100

250

2000

2000

1998

200 500

1997

750

3000 3000

1996

300

1995

1000

4000 4000

1994

400

1993

1250

5000 5000

1992

500

1500

6000

6000

1991

1750

7000

7000

Number of Cancers

600

2001

8000 Poorly specified cancer Non–AIDS-defining cancer AIDS-defining cancer

8000

700

2000

9000

60 years and older

2000

0

0

1999

2005

2004

2003

2002

2001

2000

1999

1998

1997

1996

1995

1994

1993

50-59 years

0

D

1000

1000

2002

2250

800

13-19 years 30-39 years

0-12 years 20-29 years 40-49 years

2000

2000

2001

2500

1992

1991

0

3000 3000

2000

50,000

4000 4000

1999

100,000

5000

1998

150,000

6000 5000

1997

200,000

7000

13-19 years 30-39 years 50-59 years

6000

1996

250,000

proportion of people with AIDS aged older than 40 years. In addition, although the overall incidence rate for non–AIDS-defining cancers decreased over time, the incidence rates for some of these cancers increased, which, when applied to the population at risk, magnified the estimated number of incident cancers. There are likely several reasons for the drop in the number of cases of the

60 years and older

1995

300,000

7000

1994

350,000

TheOncologyNurse.com

0-12 years 20-29 years 40-49 years

1993

60 years and older

8000

1992

400,000

Number of AIDS-Defining Cancers

13-19 years 30-39 years 50-59 years

0-12 years 20-29 years 40-49 years

1992

Number of Non–AIDS-Defining Cancers

C

B

450,000

1991

Number of People in the US AIDS Population

A

Discussion The data from this study demonstrate that the cancer burden and the types of cancers occurring among HIV-infected

people in the United States changed dramatically during the period from 1991 to 2005. Among the AIDS population, which increased slightly more than 4-fold from 1991 to 2005, the number of AIDS-defining cancers decreased dramatically between 1991 and 1997 and continued to decline gradually in subsequent years. During the same period, 1991 to 2005, the number of non–AIDS-defining cancers increased steadily and, since 2003, has surpassed the annual number of AIDS-defining cancers. The total cancer burden in people with AIDS has increased since 1998. The significant increase in the estimated number of non–AIDS-defining cancers can be attributed to several factors, including the growing size of the AIDS population and the increased

1991

Cancer Burden in the HIV-Infected Population in 34 US States Among HIV-infected people in the 34 US states surveyed, an estimated 15,884 cancers occurred between 2004 and 2007. Of these, 7869 (49.5%) were AIDS-defining cancers, and 7563 (47.6%) were non–AIDS-defining cancers. Of the non–AIDS-defining cancers, 29.0% occurred in the HIV-only population. In this population, an estimated 2191 non–AIDS-defining cancers occurred, including 454 lung cancers, 166 female breast cancers, 154 anal cancers, 150 cases of Hodgkin lymphoma, and 147 prostate cancers.

from the calendar periods of 1991 to 1995 and 2001 to 2005, despite a declining incidence rate. During 1991 to 2005, increases were noted in the number of most non–AIDS-defining cancers, including lung cancer, liver cancer, Hodgkin lymphoma, and colorectal cancer, despite stable or decreasing standardized incidence rates. The number of anal and prostate cancers also increased, partially due to increasing incidence rates. In people with AIDS younger than 50 years, the number of lung cancers remained relatively consistent over time, whereas in people older than 50 years, the estimated number of lung cancers increased from 35 in 1991 to 283 in 2005. In addition, 89% of prostate cancers occurred in men older than 50 years, 83% of all anal cancer occurred in MSM, and 51% of liver cancers occurred in injection drug users.

To Receive cRediT, compleTe The posTTesT aT

0

Figure. Number of people living with AIDS, AIDS-defining cancers, non–AIDS-defining cancers, and all cancers in the United States during 1991-2005. A) US AIDS population by calendar year and age group. B) The estimated counts and standardized rates of AIDS-defining cancers among people living with AIDS in the United States by calendar year and age group. C) The estimated counts and standardized rates of non–AIDS-defining cancers among people living with AIDS in the United States by calendar year and age group. Of note, the bars for 0 to12-year-olds in panels (B) and (C) are difficult to see because of small numbers of cancers in this age group during 1991-2005 (122 AIDS-defining cancers and 25 non–AIDS-defining cancers). D) The estimated counts and standardized incidence rates of total cancers among people living with AIDS in the United States, stratified by AIDS-defining cancers, non–AIDS-defining cancers, and poorly specified cancers. Bars depict the estimated number of cancers, and points connected by lines depict incidence rates standardized to the 2000 US AIDS population by age group, race, and sex. Shiels MS, Pfeiffer RM, Gail MH, et al. Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst. 2011;103:753-762. Reprinted by permission of Oxford University Press.

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CONTINUING EDUCATION

Cancer Burden in the AIDS and HIV-Infected Populations in the United States AIDS-defining cancers KS and NHL despite the increase in numbers for the AIDS population. Initial declines may have been due to the use of early combination antiretroviral therapy regimens or, in the instance of KS, changes in HHV8 epidemiology.1,14,15 In 1996, the introduction of HAART led to further declines in incidence.1,4,16,17 NHL and KS remain the most common cancers in the US AIDS population, however; and the risk of both malignancies remains greater in people with AIDS than in the general population.1 NHL is now more common than KS. Compared with the general population, people infected with HIV are also at an increased risk of developing many non–AIDS-defining cancers.1,57,9,13 Notably, the incidence rates are increased for lung cancer, anal cancer, liver cancer, and Hodgkin lymph oma.1,2,4,13 Contributing to the increased risk are a greater prevalence of infection with HPV and the hepatitis viruses coupled with an inability to fight the infections resulting from a suppressed immune system.5 The increased risk of lung cancer may be associated with cigarette smoking, which is far more common in HIV-infected individuals than in the general population18 as well as frequent pulmonary infections, chronic inflammation, or nutrient deficiencies.19 Lung cancer, anal cancer, liver cancer, and Hodgkin lymphoma comprised 50% of all non–AIDS-defining cancers in the AIDS population in the United States between 1991 and 2005 compared with only 16% of cancers in the general population.20 The cancer burden of each of these 4 cancers increased over time. The increase in lung cancer occurred only in people aged 50 years or older and was most likely driven by the growth of this population. The largest increase was seen in anal cancer, predominantly concentrated among MSM. An observed increase in the standardized incidence

rate of anal cancer during 1991 to 2005 paralleled an increase in the rates of anal cancer seen in the general US population.21 HIV-infected people do not have an increased risk of prostate and colorectal cancers compared with the general population, but the number of cases of those cancers has increased over time.8,22 This study found an increase in the burden of reproductive cancers in women, which occurred despite a decline in the incidence rate. As the population of women with AIDS continues to grow and age, these cancers likely will become a rising source of morbidity. Cancers in people with HIV-only infection represent approximately 29% of all non–AIDS-defining cancers occurring in the HIV-only population. Because data on this population were more limited than for people with AIDS, neither the number of non– AIDS-defining cancers occurring in the entire HIV-only population in the United States nor time trends could be estimated from this study. In addition, the number of cancers occurring among people with HIV-only infection are undoubtedly underestimated, because many HIV cases are undiagnosed in the United States (21% in 2006).23,24 Conclusion The use of the HIV/AIDS Cancer Match Study and CDC surveillance data to estimate cancer counts was the main strength of this study, whereas the major limitation was the insufficient data for the HIV-only population. The study, however, emphasized the growing burden of non–AIDSdefining cancers and the need for cancer prevention and early detection among people with HIV infection. The data show that the increased cancer burden among those infected with HIV is not limited to cancers known to occur more frequently in the HIV population or to cancers with rising inci-

dence rates. As the HIV-infected population in the United States continues to grow and to age, cancer will emerge as an important public health issue. ● References 1. Engels EA, Pfeiffer RM, Goedert JJ, et al; for the HIV/AIDS Cancer Match Study. Trends in cancer risk among people with AIDS in the United States 19802002. AIDS. 2006;20:1645-1654. 2. Engels EA, Biggar RJ, Hall HI, et al. Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer. 2008;123:187-194. 3. Long JL, Engels EA, Moore RD, Gebo KA. Incidence and outcomes of malignancy in the HAART era in an urban cohort of HIV-infected individuals. AIDS. 2008;22:489-496. 4. Patel P, Hanson DL, Sullivan PS, et al; for the Adult and Adolescent Spectrum of Disease Project and HIV Outpatient Study Investigators. Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992-2003. Ann Intern Med. 2008;148:728-736. 5. Silverberg MJ, Chao C, Leyden WA, et al. HIV infection and the risk of cancers with and without a known infectious cause. AIDS. 2009;23:2337-2345. 6. Clifford GM, Polesel J, Rickenbach M, et al; for the Swiss HIV Cohort. Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. J Natl Cancer Inst. 2005;97:425-432. 7. Dal Maso L, Polesel J, Serraino D, et al; for the Cancer and AIDS Registries Linkage (CARL) Study. Pattern of cancer risk in persons with AIDS in Italy in the HAART era. Br J Cancer. 2009;100:840-847. 8. Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007;370:59-67. 9. Goedert JJ, Coté TR, Virgo P, et al. Spectrum of AIDS-associated malignant disorders. Lancet. 1998; 351(9119):1833-1839. 10. Schneider E, Whitmore S, Glynn KM, et al; for the Centers for Disease Control and Prevention (CDC). Revised surveillance case definitions for HIV infection among adults, adolescents, and children aged <18 months and for HIV infection and AIDS among children aged 18 months to <13 years–United States, 2008. MMWR Recomm Rep. 2008;57(RR-10):1-12. 11. Detels R, Muñoz A, McFarlane G, et al. Effectiveness of potent antiretroviral therapy on time to AIDS and death in men with known HIV infection duration. Multicenter AIDS Cohort Study Investigators. JAMA. 1998;280:1497-1503. 12. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998;338:853-860. 13. Shiels MS, Cole SR, Kirk GD, Poole C. A metaanalysis of the incidence of non-AIDS cancers in HIVinfected individuals. J Acquir Immune Defic Syndr. 2009;52:611-622. 14. Eltom MA, Jemal A, Mbulaiteye SM, et al. Trends

PALLIATIVE CARE

Are We Meeting the Needs of Family Members of Patients in Palliative/Hospice Care? By Christin Melton

T

he healthcare system is only beginning to recognize what nurses who tend patients with cancer have always known: The loved ones of dying patients also need help managing pain. Julie Cronin, BSN, RN, OCN, an oncology nurse at Massachusetts General Hospital (MGH) in Boston, says failing to

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address family members’ distress has serious consequences. “If the spiritual, emotional, physical, and mental needs of these loved ones are neglected, the rates of morbidity and mortality, depression, and risk for ineffective coping can skyrocket.” Cronin is leading a small pilot study to identify nursing interventions that

might benefit family members of a patient with gynecologic cancer who is near the end of life. Via an in-person interview, researchers will ask 10 to 15 first- and second-degree relatives of patients receiving end-of-life care at MGH to suggest steps nurses can take to “improve [the family member’s] comfort and well-being during this time.”

in Kaposi’s sarcoma and non-Hodgkin’s lymphoma incidence in the United States from 1973 through 1998. J Natl Cancer Inst. 2002;94:1204-1210. 15. O’Brien TR, Kedes D, Ganem D, et al. Evidence for concurrent epidemics of human herpesvirus 8 and human immunodeficiency virus type 1 in US homosexual men: rates, risk factors, and relationship to Kaposi’s sarcoma. J Infect Dis. 1999;180:1010-1017. 16. Biggar RJ, Chaturvedi AK, Goedert JJ, Engels EA; for the HIV/AIDS Cancer Match Study. AIDS-related cancer and severity of immunosuppression in persons with AIDS. J Natl Cancer Inst. 2007;99:962-972. 17. Shiels MS, Cole SR, Wegner S, et al. Effect of HAART on incident cancer and noncancer AIDS events among male HIV seroconverters. J Acquir Immune Defic Syndr. 2008;48:485-490. 18. Tesoriero JM, Gieryic SM, Carrascal A, Lavigne HE. Smoking among HIV positive New Yorkers: prevalence, frequency, and opportunities for cessation. AIDS Behav. 2010;14:824-835. 19. Engels EA. Inflammation in the development of lung cancer: epidemiological evidence. Expert Rev Anticancer Ther. 2008;8:605-615. 20. SEER*Stat Database: Incidence—SEER 17 Regs Limited-Use + Hurricane Katrina Impacted Louisiana Cases, Nov 2007 Sub (1973–2005 varying) - Linked to County Attributed—Total U.S., 1969–2005 Counties. Rockville, MD: National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch; 2008. 21. Joseph DA, Miller JW, Wu X, et al. Understanding the burden of human papillomavirus-associated anal cancers in the US. Cancer. 2008;113(10 suppl):28922900. 22. Shiels MS, Goedert JJ, Moore RD, Platz EA, Engels EA. Reduced risk of prostate cancer in U.S. men with AIDS. Cancer Epidemiol Biomarkers Prev. 2010;19:29102915. 23. Centers for Disease Control and Prevention. HIV prevalence estimates—United States, 2006. MMWR Morb Mortal Wkly Rep. 2008;57:1073-1076. 24. Campsmith ML, Rhodes PH, Hall HI, Green TA. Undiagnosed HIV prevalence among adults and adolescents in the United States at the end of 2006. J Acquir Immune Defic Syndr. 2010;53:619-624.

Acknowledgment Rosemary Hansen contributed to the preparation of this article.

This is a condensed version of an article published in the Journal of the National Cancer Institute: Shiels MS, Pfeiffer RM, Gail MH, et al. Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst. 2011;103:753-762.

Researchers will conduct a phone interview 4 to 6 weeks after the patient’s death to elicit additional suggestions from the participants, along with their views on what needs were not met. The lack of research surrounding this issue prompted Cronin to initiate the study, and she is optimistic that the findings will prompt changes in nursing care that enhance the quality of life for patients and families. “The needs of patients and families are not separate, but rather incorporated together and equally important,” she told The Oncology NurseAPN/PA, noting that hospitalized Continued on page 29

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Cancer Center Profile Baptist Memorial Hospital-Memphis Continued from cover Opened in 2000, the surgical oncology unit joined the medical and myelosuppression units already onsite at the Tennessee hospital. From postoperative care to discharge, these registered nurses and patient care assistants care for all of their patients’ needs. “It starts out with the drains, the dressings, the clinical interventions, and along with those things we are educating patients, preparing them for discharge, and keeping their families informed,” Brooks, who is a founding member of the unit, tells The Oncology NurseAPN/PA. Caring for surgical oncology patients requires the nurses to have what amounts to 2 specialties, says Patricia Davidson, head nurse of the unit: “I consider oncology a specialty and surgery a specialty.” This level of professionalism necessitates a knowledgeable and experienced staff who “have more information about what these types of patients need,” explains Brooks. Surgical oncology patients may receive chemotherapy or go for radiation therapy from the unit. In addition, many patients, because of the complexity of their surgery, experience multiple medical issues that require nurse follow-up. “Many people require TPN [total parenteral nutrition] and a lot of management of their glucose levels. Many of our patients also have a lot of comorbidities so they are at a higher risk,” says Brooks. For this reason, “the doctors tend to want to send their patients to an area where the nurses are used to taking care of these types of illness,” Davidson shares. “The same doctors request our

“In the oncology world, some of our patients get a diagnosis where they have to get beyond the major surgery but they also have to deal with other issues postoperatively— follow-up care, chemotherapy.” —Betsy Brooks Manager, Surgical Oncology Unit

unit because they know the continuity of care is here; they know we are used to taking care of their patients, we understand the surgical part of it and we understand the oncology part of it.” And this dedication to both specialties is welcomed by patients. “I think patients sense that we are knowledgeable in both areas, and we are here to get them through this dire time in their life. Usually they get a bad diagnosis, and in my opinion we handle it very well and are able to help the patients through it,” says Davidson, a surgical nurse who went on to become oncology-certified because of her love of the specialty and desire to give her patients “the best that I have.” Teamwork “We have a great group of people to work with. They are all very well educated and very caring. Teamwork is a must; we don’t accept anything less. The doctors and the patients see that and they do appreciate that,” Davidson explains. This means that along with hands-on nursing interventions, the unit’s staff provides patients a full continuum of

care. “In the oncology world, some of our patients get a diagnosis where they have to get beyond the major surgery but they also have to deal with other issues postoperatively—follow-up care, chemotherapy, those types of things—or just getting well from the major surgery, which takes them a little bit longer. So our team has social workers and our patients have a case manager, who is in and out of everybody’s room every day, helping them to plan for home IVs, home antibiotics, catheter placement, and those types of things,” explains Brooks. “We try to meet everyone within 24 hours of getting on the unit, just to introduce ourselves initially,” says Kathy Ketchum, a case manager with the surgical oncology unit. “Then we look at how they functioned prior to hospitalization and prior to surgery. Next, we start looking at where they are planning to be on discharge.” In a population consisting of elderly and fragile patients, often with comorbid chronic conditions, many require help with placement after discharge. “We try to begin [getting everything ready] initially, so when the

patient is ready for discharge, we are prepared also. If we know they are going home and they are young enough to learn how to give their own TPN or IV antibiotics, we start that process, verifying their benefits for home coverage and teaching the family members who are going to be with them how to flush lines, how to do dressing and drain changes. We try to start that early, so that we don’t lengthen their stay for teaching at the very end.” The nursing staff also participates in bedside rounds, including the families in the bedside report, plus discharge callbacks, says Brooks. And the unit also helps out when needed. “We are adjacent to the myelosuppression unit, and we do take some overflow of those patients who are not neutropenic. They might have a leukemia or an issue with their cancer, so sometimes we have that overflow,” Brooks explains. Patient Success All this work has its rewards for the surgical oncology team. Patients often return to express their appreciation. “They come back to us, you don’t even recognize them because they look so different, thanking us, bringing us gifts, just thanking us for really making a difference in their life at that time and that means so much to us,” shares Davidson. And for patients who require additional surgical interventions, “they do come back sometimes for additional surgery or maybe they get dehydrated and they want to come back to the surgical area because they feel comfortable with our care on this area,” Brooks explains. ●

patients often worry as much about the well-being of family members as family members worry about their well-being. “Patients want to be reassured that, after they pass, their loved ones will be able to carry on with a full, happy life.” Cronin considers supporting family members visiting the hospital an important first step toward realizing the patient’s wish and helps make the patient’s transition into death more peaceful. Although nurses generally take a holistic approach to patient care that encompasses the patient’s family, Cronin says “alleviating the patient’s suffering…and provid[ing] a seamless, peaceful, and dignified transition from life to death” take top priority; as a result, the family’s needs often get overlooked. This is a problem because, as Cronin explains, “These family members and loved ones will be carrying on with their lives after the passing of the patient, which often entails caring for children or other fami-

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ly members, continuing to work, maintaining a home, etc.” Cronin’s unit at MGH has already implemented measures to enhance the care a terminal patient’s loved ones receive, and her study will try to determine which ones are considered most beneficial. “We offer a ‘comfort cart’ to family members that provides family members with food and drink for physical nourishment; spiritual readings of a variety of faiths; music and aromatherapy; diversional material, such as magazines and books; note cards; tissues; journal; and more.” The nurses also try to keep the patient’s room quiet, maintain flexible visiting hours, and make sleeping arrangements for family members who wish to stay overnight with the patient. “We also make it a priority to keep family members informed of their loved one’s status and provide therapeutic communication and listening at all times,” she said.

©iStockphoto.com/Nick Free

Are We Meeting the Needs... Continued from page 28

In addition to evaluating the effectiveness of MGH’s current interventions, researchers hope the study will provide guidance on developing new measures to

support family members whose loved ones are receiving hospice/palliative care. Cronin says they anticipate presenting initial findings in May 2012. ●

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Conference News The following articles are based on presentations at the 2011 Annual Meeting of the American Society of Clinical Oncology held June 3-7, in Chicago, Illinois.

Exemestane Effective for Primary Prevention of Breast Cancer CHICAGO—Exemestane appears to be a good alternative to tamoxifen for prevention of breast cancer in postmenopausal women, according to results of the randomized, placebo-controlled MAP.3 trial. Exemestane reduced the risk of a first invasive breast cancer by 65% in healthy postmenopausal women with risk factors for breast cancer, and also reduced the risk of known breast cancer precursor lesions, including ductal carcinoma in situ, lobular carcinoma in situ, atypical ductal hyperplasia, and atypical lobular hyperplasia, which would suggest further reductions in invasive cancers as time goes by. Exemestane did not increase the incidence of serious side effects, including osteoporosis and clinical fracture, cardiovascular events, and second malignancies, or treatmentrelated deaths, compared with placebo. Although tamoxifen is approved by the US Food and Drug Administration for prevention of breast cancer, only about 4% of eligible women actually take the drug, explained lead author Paul Goss, MD, director of breast cancer

Photo by © GMG/Todd Buchanan 2011.

Risk for First Invasive Breast Cancer Reduced by 65%

Paul Goss, MD

research, Harvard Medical School and Massachusetts General Hospital in Boston. Tamoxifen carries serious, but relatively rare, risks of venous throm-

boembolism and endometrial cancer. Unlike tamoxifen, exemestane is not approved for prevention of breast cancer. The drug is about to go off-patent, and it is not clear whether Pfizer will try to file for the prevention indication. “It is extraordinary that we can reduce the incidence of breast cancer by 65%. That is a massive benefit. In our opinion, exemestane represents a new option for consideration for breast cancer prevention in postmenopausal women who meet the criteria of the MAP.3 trial. This study provides a rationale for wider implementation of preventive use of exemestane,” Goss stated. Between 2004 and 2010, the study enrolled 4560 postmenopausal women older than age 37 (median age, 62 years) with at least 1 risk factor for breast cancer (age 60 or older, Gail score >1.66%, prior atypical ductal hyperplasia, and atypical lobular hyperplasia). At baseline, median Gail score was 2.3% and average body mass index was 28 kg/m2. About half of participants were older than 50 years, 40% had a Gail score

Flaxseed No More Effective Than Placebo for Hot Flashes Hunt Continues for Complementary Treatments for Reduction By Bonnie Gillis

CHICAGO—Flaxseed failed to have a significant effect on reducing hot flashes in women compared with placebo, according to results of a randomized, placebo-controlled trial supported by the North Central Cancer Treatment Group. The study included breast cancer survivors as well as women who had never had breast cancer who experienced frequent hot flashes throughout the day and night. These results were disappointing, said lead investigator Sandhya Pruthi, MD, Mayo Clinic, Rochester, Minnesota. “Hot flashes are bothersome, and although there are effective therapies, these have side effects. We need to balance side effects with efficacy. Although the present study was disappointing, we need to continue to try to identify com-

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plementary treatments [with fewer side effects] that can relieve hot flashes,” she said at a presentation.

In both groups, about one third of the women received a 50% reduction in their hot flashes. Hot flashes compromise quality of life. They can be socially awkward as well as interfere with sleep. At present, there are 2 effective options for treatment of hot flashes—venlafaxine and gabapentin—but both have side effects that may not be acceptable. After hearing anecdotal evidence that flaxseed controlled hot flashes, Pruthi and col-

leagues conducted a pilot study in 30 women with hot flashes, and results showed that flaxseed decreased both the severity and frequency of hot flashes. That pilot trial led to the randomized, placebo-controlled trial. The current study enrolled 188 participants who experienced >28 hot flashes per week at baseline; 75% were aged 50 years and older; 51% had a history of breast cancer. Among women with a breast cancer history, 15% were taking an aromatase inhibitor and 25% were taking tamoxifen. Patients were randomized to 1 flaxseed bar per day containing 410 mg lignans and fiber or to 1 placebo bar per day with 2 g protein and fiber; treatment was continued for 6 weeks. The flaxseed bars achieved a 33%

>1.66%, and 11% had prior intraepithelial neoplasia. During the 3-year follow-up, 11 cases of breast cancer were diagnosed in the exemestane arm compared with 32 in the placebo arm. The benefit of exemestane was in the reduction of estrogen receptor–positive tumors (7 in the exemestane arm vs 27 in the placebo arm) and in HER2-negative tumors (10 vs 26, respectively). The superiority of exemestane to placebo was evident across all risk groups, including Gail score, age, body mass index, prior lobular carcinoma in situ, and prior ductal carcinoma in situ. Side effects that were increased with exemestane included hot flashes, fatigue, insomnia, gastrointestinal effects, and arthritis. Hot flashes occurred in 40% of women treated with exemestane and 32% of those in the placebo group. The incidence of bone fracture, osteoporosis, cardiovascular events, and other malignancies was similar in both arms. “The elephant in the kitchen [in women at risk for breast cancer] is prophylactic mastectomy. Exemestane is now another treatment option for these women,” said Andrew Seidman, MD, of the Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center in New York City. Seidman chaired the press conference where these data were presented. ●

decrease in hot flash score from baseline compared with a 29% decrease for placebo bars. Mean hot flash scores were reduced by 4.9 units in the flaxseed group and 3.5 units in the placebo group. This difference between treatment arms was not significant, Pruthi said. In both groups, about one third of the women received a 50% reduction in their hot flashes. No significant differences in toxicity were observed between the 2 arms. Abdominal distension, gas, and diarrhea were common in both arms, presumably as a result of fiber content, she said. “As oncologists, we need to deal with the rollercoaster effects of our research. [Some trials appear promising and then pan out not to have efficacy.] Hot flashes have a negative impact on quality of life and we need to find the most effective treatment. There are some effective treatments for hot flashes. Patients should discuss treatment options with their doctors,” said Mark G. Kris, MD, chief of Thoracic Oncology Service at Memorial Sloan-Kettering Cancer Center in New York City, who moderated the press conference where Pruthi presented the results. ●

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BUILDING

pillars of knowledge IN SUPPORTIVE CARE

BONE HEALTH

LOG ON TODAY TO PARTICIPATE

www.coexm.com/ace05 Release Date: June 24, 2011 Expiration Date: June 23, 2012

TARGET AUDIENCE The educational series is intended for nurses, pharmacists and others with clinical, research, and management interests in the treatment of bone health in cancer

EDUCATIONAL OBJECTIVES On completion of this activity, participants should be able to: • Describe the potentially serious consequences of skeletal-related events (SREs) associated with cancer and cancer-related treatments • Review recent advances in the management of bone health in cancer patients, with emphasis on treatment with the bisphosphonates and denosumab • Examine approaches for improving bone health and outcomes for patients with skeletal complications, based on key clinical evidence and practice guidelines

ACCREDITATION STATEMENTS Creative Educational Concepts, Inc. (CEC) is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This knowledge-based activity has been assigned ACPE # 0245-0000-11015-H01-P and will award 1.0 contact hour (0.10 CEUs) of continuing pharmacy education credit. CEC complies with the Criteria for Quality for continuing education programming.

FACULTY Regina Cunningham, PhD, RN, AOCN Senior Director, Oncology The Tisch Cancer Institute Mount Sinai Medical Center New York, NY

R. Donald Harvey, PharmD, BCPS, BCOP, FCCP Assistant Professor, Hematology/ Medical Oncology Director, Phase I Unit Winship Cancer Institute Emory University School of Medicine Atlanta, GA

For further information and to participate, please go to: www.coexm.com/ace05

NURSING Creative Educational Concepts, Inc. (CEC) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. CEC provides this activity for 1.0 contact hour. Learners are advised that accredited status does not imply endorsement by the provider or ANCC of any commercial products displayed in conjunction with an activity. Your statement of credit will be issued immediately upon successful completion of the posttest and evaluation form.

This activity is supported by an educational grant from Amgen Inc.

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Conference News

Nutrition Interventions for Cancer Patients Personalized Care Extends to Diet and Exercise By Dawn Lagrosa

CHICAGO—O ncology men, especially expected nurses know that nutrition side effects, to help the interventions can help patient and caregiver pretheir patients, both during pare to maintain nutritional and after active treatment. status through those side But the evidence is scant, effects. and personalizing it for each Psychologic factors also patient can be a challenge. come into play. A patient’s To help, nutrition experts and/or caregiver’s goals for provided useful tips for the nutritional intervennurses, along with a discustion as well as for cancer Wendy Demarksion of the evidence. treatment should be Wahnefried, PhD, RD Although a specialized assessed, said Robien. “If dietitian can best help patients, oncol- choosing to [pursue the intervention] ogy nurses are key partners in nutrition for palliative measures, we might not and physical activity interventions. be as aggressive as someone who wants Communication and coordination is to continue as an Olympic athlete.” In essential, ideally with a nutrition con- addition, the dietitian evaluates the sultation before treatment. Plus, suc- patient’s and caregiver’s readiness and cessful counseling often requires multi- motivation toward dietary change. ple sessions, according to Kim Robien, “Some patients will come to lifestyle PhD, RD, CSO, FADA. Nurses changes as their way of coping. It is should, therefore, regularly apprise the something they understand. They may dietitian of any changes in the not understand medical terminology, patient’s health or treatment. they may not understand the planned treatment regimen, but they probably The Intervention understand diet and physical activity; When designing the right nutrition that may be their coping mechanism,” intervention for the right patient, she explained. “Other patients just keep in mind the “3 general nutrition aren’t at that stage and need to get goals for a patient going through through cancer treatment before we do treatment,” said Robien, assistant pro- something more aggressive for them.” fessor in the Division of Epidemiology and Community Health, University What Is the Evidence? of Minnesota, Masonic Cancer Center, Using the Institute of Medicine’s defiMinneapolis, as she detailed her nition of survivorship, from diagnosis to end of life, Wendy Demarkprocess. Nutrition interventions should pre- Wahnefried, PhD, RD, professor vent nutrient deficiencies, maintain and Webb Endowed Chair of nutrition lean body mass (not to be confused sciences, University of Alabama at with body weight), and minimize the Birmingham, and associate director, impact of treatment-related side University of Alabama at Birmingham effects, she said. However, “the active Comprehensive Cancer Center, sumtreatment phase for most people is a marized the available evidence and time of coping, anxiety, and just get- guidelines (Sidebar). Her literature ting through the treatments; and we review identified the level of evidence need to be respective of that,” noted associating nutrition and physical Robien. “It is not the time for us to be activity with outcomes: making major lifestyle changes… • Possible benefit • Depression unless that helps with managing their • Fatigue side effects. It is small baby steps and • Adverse body composition change helping them to make sure that they • Functional decline preserve lean body mass and prevent • Probable benefit nutrient deficiencies.” • Recurrent and progressive disease When developing a personalized nutrition plan, a specialist in oncology • Convincing benefit • Comorbidity, especially cardionutrition begins by taking baseline nutrivascular disease. tional status. “Many of our patients come Although the evidence is sparse, she to us already nutrient depleted as a result of the cancer itself,” explained Robien, highlighted those studies that have assonoting that, in addition, the number of ciated diet and exercise with outcomes patients with diet-manageable comorbid among cancer survivors. Kroenke and conditions, such as diabetes and hyper- colleagues found that an increase in tension, is on the rise. Next, the dietitian weight after breast cancer increases the considers the planned treatment regi- risk for recurrence, disease-specific mor-

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tality, and all-cause mortality (J Clin Oncol. 2005;23:1370-1378). In addition, Meyerhardt and colleagues associated 1 hour per day of physical exercise with a decreased risk for recurrence, disease-specific mortality, and all-cause mortality among survivors of colorectal cancer (J Clin Oncol. 2006;24:3535-3541). Other studies highlighted associated food choices with outcomes, but these studies failed to correlate outcomes directly with cancer diagnoses. For example, Kroenke and colleagues found that a prudent diet (avoidance of sugar and fat with an emphasis on plant-based sources) made no difference in breast cancer–specific mortality, but did make a significant impact on all-cause mortality (J Clin Oncol. 2005;23:9295-9303), an outcome Demark-Wahnefried noted was likely attributed to improved cardiac function. And Meyerhardt, in his study of colorectal cancer survivors, found similar survival outcomes, with a Western diet predisposing patients to all-cause

mortality (JAMA. 2007;298:754-764). Demark-Wahnefried highlighted still other studies that present conflicting data on the protective effect of diet on recurrence. Pierce and colleagues followed breast cancer survivors for up to 10 years, finding no difference in recurrence rates, disease-specific death rates, or overall death rates (JAMA. 2007;298: 289-298). These findings, DemarkWahnefried noted, may have been caused by location bias. The Californiabased study participants reported high consumption (≥7 servings per day) of fruits and vegetables at baseline. In their study, however, Chlebowski and colleagues found that reducing the fat consumption among breast cancer survivors did produce a protective effect, especially among estrogen receptor–negative women (J Natl Cancer Inst. 2006; 98:1767-1776). Because participants lost an average of 6 lb, Demark-Wahnefried noted that their outcomes may be attributable to a weight-loss phenomenon. ●

Nutrition and Physical Activity Guidelines for Cancer Survivors American Cancer Society • Balance caloric intake with physical activity. • Engage in at least 30 minutes of moderate-to-vigorous exercise, 5 or more days per week (45-60 minutes preferred). • Eat 5 or more servings of vegetables and fruits per day. • Choose whole grains over processed grains. • Limit consumption of processed and red meats. • Limit alcoholic beverages to no more than 1 per day for women/2 per day for men.

American Institute for Cancer Research • Engage in physical activity for at least 30 minutes per day. • Avoid sugary drinks; limit processed, high-sugar, and high-fat foods. • Eat more vegetables, fruits, whole grains, and legumes. • Limit consumption of red meats. • Limit alcoholic beverages to no more than 1 per day for women/2 per day for men. • Limit consumption of salty foods. • Do not use supplements to protect against cancer. Sources: Doyle C, Kushi LH, Byers T, et al; for the 2006 Nutrition, Physical Activity and Cancer Survivorship Advisory Committee. Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices. CA Cancer J Clin. 2006;56:323-353; Nutrition and the Cancer Survivor. Washington, DC: American Institute for Cancer Research; 2010.

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Newsletter Series

YOUR QUESTIONS ANSWERED

Editor in Chief

Editor in Chief

Sagar Lonial, MD

Stephanie A. Gregory, MD

Associate Professor of Hematology and Oncology Emory University School of Medicine

The Elodia Kehm Chair of Hematology Professor of Medicine Director, Section of Hematology Rush University Medical Center/Rush University

Topics include: • Newly Diagnosed Patients • Maintenance Therapy • Transplant-Eligible Patients • Retreatment • Transplant-Ineligible Patients • Cytogenetics • Side-Effect Management • Bone Health

Topics include: • Hodgkin Lymphoma • Follicular Lymphoma • Mantle Cell Lymphoma • Waldenstrom’s Macroglobulinemia • Diffuse Large B-Cell Lymphoma • T-Cell Lymphoma

This activity is supported by an educational grant from Millennium Pharmaceuticals, Inc.

This activity is supported by educational grant from Cephalon Oncology, Millennium Pharmaceuticals, Inc., and Seattle Genetics, Inc.

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

Accreditation This activity has been approved for 1.0 AMA PRA Category 1 Credit™ (a total of 14.0 credit hours will be issued for completion of all activities). Nursing and Pharmacy credit hours will also be provided. For complete learning objectives and accreditation information, please refer to each activity. This activity is jointly sponsored by Global Education Group and Medical Learning Institute, Inc. Coordination for this activity provided by Center of Excellence Media, LLC.

For information about the physician accreditation of this activity, please contact Global at 303-395-1782 or inquire@globaleducationgroup.com. COEKsize40611MM

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Conference News

Turning Psychosocial Screening Into Outcomes Nurse-Led Model Improves Quality of Life CHICAGO—Both patients and practitioners realize the importance of psychosocial issues, but today’s cancer care often fails to address them. Steps to resolve this problem are under way, according to experts at an education session. Standards for assessing psychosocial concerns were included in the American Society of Clinical Oncology (ASCO)/Oncology Nursing Society Chemotherapy Administration Safety Standards released in 2009. And beginning in 2012, psychosocial distress screening will be a required standard for American College of Surgeons Commission on Cancer accreditation. Inclusion of psychosocial concerns in these standards will likely increase awareness and assessment of patients’ needs; but how to translate screening into outcomes? “We need to assist practices seeking to improve psychosocial care,” said Paul B. Jacobsen, PhD, chair, Department of Health Outcomes and Behavior, H. Lee Moffitt Cancer Center & Research

Institute, Tampa, Florida. To do that, his group examined the quality indicators in psychosocial care, seeking to determine if clinician improvement in performance indicators enhances patients’ quality of life. Where We Are The team began by developing methods to identify quality indicators from medical records. They reviewed more than 1600 cases of colorectal, breast, and non–small-cell lung cancer treated in 2006 at 11 cancer centers in Florida. Presenting their findings, Jacobsen detailed the indicators. • Evidence in the medical chart that current emotional well-being was assessed within 1 month of the first visit with a medical oncologist. This could include a copy of a distress, depression, or anxiety screening measure; a copy of a form indicating a patient selfreport; or a note using any one of the terms coping, adjustment, emotional distress, depression, or anxiety

RECENT FDA APPROVAL

Vemurafenib and Companion Diagnostic Test for Late-Stage Melanoma The US Food and Drug Administration (FDA) has approved vemurafenib (Zelboraf, Genentech, a member of the Roche Group) for metastatic or unresectable melanoma. Vemurafenib, a BRAF inhibitor, is able to block the function of the V600E-mutated BRAF protein. Vemurafenib is indicated only for patients with melanoma which expresses the BRAF V600E mutation. The drug has not been studied in patients whose melanoma tests negative for that mutation. Therefore, vemurafenib has been approved in conjunction with a first-of-a-kind diagnostic test, the Cobas 4800 BRAF V600 Mutation Test (Roche Molecular Systems). Approved under the FDA’s priority review program, vemurafenib has been approved with a Medication Guide to inform healthcare professionals and patients of potential risks. Vemurafenib was approved based on a single international trial of 675 chemotherapy-naïve patients with late-stage melanoma with the BRAF V600E mutation who were randomized to vemurafenib or dacarbazine. Median survival has not been reached (77% still living) in the vemurafenib group and was 8 months (64% still living) in the dacarbazine group. Approval of the Cobas 4800 BRAF V600 Mutation Test was based on data from the same study, which collected melanoma tissue samples from patients and tested them for the mutation. The most common side effects reported with vemurafenib included joint pain, rash, hair loss, fatigue, nausea, and skin sensitivity when exposed to the sun. About 26% of patients developed a cutaneous squamous cell carcinoma, which was managed with surgery.

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Making practitioners aware of their shortcomings can improve the rate of psychosocial screening. This does not hold true, however, for increasing the rate of action. in reference to patient status. • If a problem with emotional well-being was identified, evidence action was taken to address the problem or an explanation provided for no action being taken. This could include care provided by the primary oncology team, referral to another professional, or a note describing why no action was taken. Their findings suggest that making practitioners aware of their shortcomings can improve the rate of psycho social screening. This does not hold true, however, for increasing the rate of action. For assessing emotional well-being, performance ranged widely among the 11 practices, from 12% to 86% (overall rate, 46%). For action taken, performance ranged even wider, from 13% to 100% (overall rate, 53%). For perspective, Jacobsen noted that “these same practices rated between 55% and 97% for assessing pain (overall rate, 85%).” In fall 2008, ASCO’s Quality Oncology Practice Initiative (QOPI) adopted Jacobsen and colleagues’ indicators for psychosocial care, which provided the team information from 166 practices. In comparing these data from fall 2008 with fall 2009, they found assessment rates to range from 64% to 73%. This represents a substantial increase over the 1-year period compared with nonpsychosocial QOPI indicators. The high rate of increase suggests that feedback works well for increasing assessment, according to Jacobsen. For action taken, however, the rate increased only slightly, from 74% to 78%. Jacobsen noted that this small increase suggests that feedback alone is not going to solve this issue. Where We Can Go “A treatment model that engages frontline cancer care practitioners and provides support resources as well as guidance can make a difference,” said David Goldstein, MBBS, FRACP, FRCP (UK), Department of Medical Oncology, Prince of Wales Hospital, New South Wales, Australia, who presented a model that “systematically introduces multidisciplinary care of the psychosocial needs

of patients with cancer, [which] can be a reality in a practice of any size.” Studies in oncology practices have shown that screening is feasible, but often does not lead to improvement in psychosocial care or quality of life, according to Goldstein. Studies outside of oncology, however, have presented models that can help (Unutzer J, et al. JAMA. 2002;288:2836-2845; Katon WJ, et al. N Engl J Med. 2010;363:26112620). By adapting these models, cancer centers have achieved success. Goldstein detailed a model that uses nurses, nurse practitioners, and/or physician assistants as care managers. Although each pilot study used slightly different intervention designs, all of them had key components in common: • Frontline cancer care practitioners act as care managers. • These frontline oncology health professionals, who are trained in oncology first, receive additional mental health training. • A small number of mental health professionals supply support and manage the intervention. Forms of this model enhanced quality of life in elderly patients with depression and cancer (50% vs 34% reduction in symptoms at 6 months; 39% vs 20% reduction at 12 months; Fann JR, et al. J Gen Intern Med. 2009;24[suppl 2]: S417-S424) and in patients with major depressive disorder being treated as outpatients in a large UK cancer center (53% vs 34% reduction in depression; 68% vs 45% remission rate; Strong V, et al. Lancet. 2008;372:40-48). In addition, adapting the model for regional and rural practices produced similar results by using remote care managers. Using a telephone-based service, nurse care managers increased the percentage of patients who responded to treatment for cancer-related depression (33.7% vs 27.9% at 12 months) as well as reduced the percentage of incidences of depressive episodes (from 61% to 21.4% in the intervention group vs from 61.9% to 35.2% in the usual care group; Kroenke K, et al. JAMA. 2010;304:163-171). ● —DL Conference News continued on page 42

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Nurse & Patient Navigator Association Best Practices A selection of member-submitted best practices for others to learn from and comment on.

Continuing Education Learn how to advance your understanding of the complexities of cancer care through our live, online, and printed educational activities.

Networking Opportunities Coordinated events throughout the year both in person and online to help you connect with members and leaders.

Community Resources A collection of resources to help you and your patients better navigate their cancer treatment.

Expert Opinion Blogs Thought-provoking articles from the leaders in navigation and survivorship on various subject areas.

Publications Subscriptions to the Journal of Oncology Navigation & Survivorship速 and The Oncology Nurse速-APN/PA.

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The Whole Patient

When Hair Is Not “Just Hair” By Susan Beausang

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t is not “just hair.” Often referred to as a woman’s “crowning glory,” much of a woman’s female identity is defined by her hair—from her femininity, to age, to confidence, to style, women communicate a great deal about themselves by how they wear and style their hair. Without hair, women feel stripped of their identity, and in the context of cancer, women often feel as if they are systematically being stripped of themselves. Many women feel guilty or vain for caring about their hair when faced with a life-threatening disease like cancer. Loved ones may try to support them with well-meaning statements such as “it’s just hair” or “it’ll grow back”—statements that may feel dismissive. Rather than have their feel-

Many cancer survivors recommend cutting the hair short before hair loss begins and then shaving the head when hair loss begins so as not to prolong the emotionally difficult process.

ings dismissed, many women prefer to cope alone. Many women find hair loss to be one of the most emotionally difficult side effects of cancer treatment. Hair loss strips women of their anonymity and privacy as they undergo treatment. Up until a woman loses her hair to chemotherapy, she will often put most of her energy into maintaining a sense of normalcy for the benefit of loved

The Beaubeau Difference: A Scarf That Is “Heads Above the Rest” Susan Beausang, President of 4Women.com and designer of the patented beaubeau head scarf, comes from 3 generations of breast cancer survivors. Having watched her grandmother, aunt, mother, and 2 of 4 sisters battle breast cancer, she and her siblings underwent genetic testing. Susan learned she carried the BRCA2 gene and had an estimated 85% lifetime chance of developing breast cancer. She opted to have a prophylactic double mastectomy and oophorectomy. Eleven years later, she is healthy, but bald. Shortly after her surgeries, she began losing her hair in profuse amounts. In just 3 months, she was completely bald from alopecia universalis. Trying to adjust to hair loss in our appearance-conscious society, Susan found a complete disconnect between the worlds of medical headwear and fashion. She set out to unite the two worlds with her own solution, the beaubeau. The beaubeau is designed as a pretied head scarf that can be styled in a variety of ways. No tying skills are needed as the scarf is sewn to appear as if it’s been tied and styled professionally. The beaubeau is offered in over 300 high-fashion fabric styles and comes in 4 women’s and 2 girl’s sizes so that no one has to settle for less than a perfect fit. 4Women.com also offers soft sleep caps, transitional head scarves, swim caps, and the beaubag, a smart tote bag to accompany patients to their treatment. The beaubeau is not just a head covering, but a fashionable accessory and a chic alternative to wearing a wig. Just because a woman loses her hair does not have to mean she has to surrender her sense of style. ●

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ones, especially children. Many women find that it is their hair loss that pushes their parents, partners, and children over the edge with fear. Although some women enjoy receiving attention for their style or intelligence, no one enjoys the attention that comes with what feels like the “cancer image.” Women need to know that regardless of how they cope and respond, they are not alone, their feelings are valid, and they have every right to want to feel good about themselves. At no time is such love of self more important than when fighting cancer.

Women should be encouraged to explore many styles and have a sample assortment on hand before they lose their hair. On learning they will lose their hair, many women will immediately begin anticipating the change and the impact it will have on themselves and others. They may envision the worstcase scenarios, possibly making the anticipation of hair loss worse than the event itself. Rather than anticipate hair loss with a growing sense of helplessness, women should be encouraged to use this time to be proactive, inform themselves, research options, make deliberate choices, and take specific actions to plan for and determine their appearance without hair. By doing so, they empower themselves not just to cope, but to rise above the drastic assault to their selfesteem posed by sudden hair loss. A greater sense of control and positive self-image can help women to take control of other aspects of their lives that contribute to a greater quality of life during cancer treatment. Helping Women to Take Control of Hair Loss Chemotherapy-induced hair loss is almost always temporary. Women should keep this in mind when choosing a wig. Encourage them to talk to

other women who have purchased wigs and to research reputable wig salons. Many women are advised to purchase a wig before they lose their hair, but in some cases, the scalp sensitivity that comes with chemotherapy-induced hair loss can make wigs especially difficult to wear. Wigs are also generally very hot, an important factor to keep in mind for women who live in a warm climate or who plan to wear their wig in the summer. Watching the hair fall out can be very traumatic. Some women try to pamper every last hair on their head in the hope that they will not lose all of it. This can prolong and intensify feelings of grief and sadness. Many cancer survivors recommend cutting the hair short before hair loss begins and then shaving the head when hair loss begins so as not to prolong the emotionally difficult process. Taking such steps can help women to feel more in control and avoid some of the most difficult emotions triggered by sudden hair loss. Until a woman actually loses her hair, it may be hard to determine which headwear options she will prefer. Women should be encouraged to explore many styles and have a sample assortment on hand before they lose their hair. After a woman loses her hair, she can determine her preferences and then purchase additional items according to her style. Comfort, convenience, and customfit are key elements when shopping for headwear options. Women should be reminded that they may be wearing something on their head for many hours each day. Tight hats, scarves, or wigs can cause headaches. Headwear that is not sufficiently snug will have them feeling insecure, wondering if it will stay in place. Tying and styling head scarves or turbans on a daily basis is a less than optimal option for women battling cancer who may be unable to comfortably lift or hold their arms above their heads. Rather than face the emotional side of chemotherapy-induced hair loss alone, women need more understanding, more resources, and more options for coping with the drastic assault on their self-esteem that often accompanies hair loss. Because there is no onesize-fits-all means of addressing women’s emotions, the first step is to acknowledge the fact that hair loss can be of deep emotional and healing significance to women. When women find emotional understanding and support to be as comprehensive as diagnosis and treatment, the healing journey will be that much easier. ●

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31ST ANNUAL

Oncology Nurses Symposium SUNDAY – WEDNESDAY, OCTOBER 2–5, 2011 – /03;65 :(5 +0,.6 9,:69; :(5 +0,.6 *(30-6950(

Course Overview

Scripps Cancer Center’s Oncology Nurses Symposium is designed for nurses dedicated to the field of hematologyoncology. During this three and a half day conference, attendees will benefit from an intimate learning environment in which renowned faculty will present the latest in oncology care and provide practical strategies and tools to improve nursing practice and patient outcomes. The program itself is designed to provide a generous amount of CE credits while offering participants the chance to interact and network with like-minded colleagues. Conference Highlights

s s s s s

Comprehensive presentations of the latest advances in cancer diagnosis and treatment with a strong patient care focus Small group workshops allowing for additional interaction with expert faculty on pertinent topics Audience Response System used for instant feedback and interactive learning Multiple networking and one-on-one discussion opportunities throughout the course Conference recording sent to all attendees 4-6 weeks after the conference

California Board of Registered Nursing CE credits available!

Get 15% off when you register with promo code “ON2011”!

FOR ADDITIONAL INFORMATION:

Scripps Conference Services & CME Email: med.edu@scrippshealth.org

Phone: 858-652-5400 Visit: www.scripps.org/oncologynursessymposiumCE 10:32 AM

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Navigation & Survivorship

Brought to you by

Patient Navigation After Diagnosis Reduces Treatment Interruptions

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atient navigation decreased treatment interruptions among American Indian patients receiving radiation treatment (RT) with curative intent in a recent study conducted at the Rapid City Regional Hospital Cancer Care Institute in South Dakota. The study also found a high rate of clinical trial participation among its patients. Similar patients who underwent treatment between 1991 and 2004 and did not receive navigation services acted as controls. The importance of these findings are magnified when you take into account that treatment interruptions during curative RT have been shown to affect patient outcomes negatively (McCloskey SA, et al. Am J Clin Oncol. 2009;32:587-591). Known disparities in care for this population as well as high cancer mortality rates (Espey DK, et al. Cancer. 2007; 110:2119-2152) and low clinical trial enrollment rates (Murthy VH, et al. JAMA. 2004;291:2720-2726) among American Indians further amplify the significance of these results.

The Intervention Building on knowledge from a previous review, the investigators designed a culturally tailored patient navigation program that followed American Indian patients from diagnosis through follow-up after cancer treatment completion. “There was an intense focus on trying to understand what the barriers were for people. The navigators were either members of the community or closely tied to the community,” lead investigator B. Ashleigh Guadagnolo tells the Academy of Oncology Nurse Navigators. “They paid intensive attention to each patient’s treatment course, with an eye toward culturalspecific understanding of the healthcare experience for the patients they were serving.” For this population the intervention focused on many aspects of a patient’s experience of cancer care including but not limited to logistical and financial barriers, and understanding the “social stigma around cancer diagnosis and treatment.” In addition, navigators focused on the socioeconomic barriers

for this population that “is among one of the most economically disadvantaged in the country; and they live very far from this or any other cancer treatment center,” says Guadagnolo. Pine Ridge Reservation, home to most of the patients, is a 2-hour drive from the cancer institute, making transportation and housing main barriers to care. “The navigators sometimes gave gas money, sometimes meal money, and helped patients arrange lodging if they needed it, calling hotels or arranging other lodging,” she explains. Patients were either recruited into the program by a community program staff member, by their treating physician or oncology nurse, or self-referred. Initially, most patients were referred for financial assistance or logistical support, as well as for cancer education or advocacy. After the first visit with the navigator, however, patients’ needs shifted. “The financial assistance needs to be pretty consistent because it was hard for people to come [for their treatment], but they needed less education about cancer as they progressed through their treatment course

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and advocacy and more psychosocial support,” says Guadagnolo. The navigation efforts also led to higher rates of clinical trial participation. Guadagnolo attributes this to education. “This is a population that has very hardearned reasons to be wary of research, and the navigators were able to explain things very intensively and answer questions. And also each navigator was assigned to make sure that patients were offered a clinical trial, which often was as simple as making sure a doctor assess if they are eligible.” This program, initially funded through a National Cancer Institute cancer disparities research grant, is now faced with finding hard funding for the future. “The challenge for us is to show that navigation is actually effective and, hopefully, to eventually get payers to reimburse for this service. That is not standard yet.” The complete study is published in the June 15, 2011, issue of Cancer. In addition, details of the program’s development are available in Cancer Control (Petereit DG, et al. 2008; 15:254-259).●

Annual Healthcare Costs Higher for Survivors

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©iStockphoto.com/spxChrome

ach year, adult cancer survivors spend, on average, $4000 to $5000 more on total medical expenditures than people who have never had cancer, according to a study of survivors younger than 65 years. “These ongoing expenditures signal what oncology nurses already know…when people finish their treatment for cancer, that is

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not necessarily the end of it. They require ongoing support. There’s a need for heightened surveillance that extends for the rest of their lives. Perhaps they’ll need other kinds of services, too,” lead author Pamela Farley Short, PhD, tells the Academy of Oncology Nurse Navigators. Using the National Cancer Institute’s

definition of cancer survivor—from diagnosis through end of life—investigators at Penn State University focused on prime-age survivors because this population has been underrepresented in previous research, yet the implications of the economic impact upon them can help inform the national health reform debate. “To my way of thinking, cancer survivors are poster children for healthcare reform,” says Short. “It is people like cancer survivors who will particularly benefit from the new system where people are guaranteed insurance at an affordable price, and moving away from a system where their health history can affect what they have to pay for insurance.” Short and colleagues analyzed annual expenditures for newly diagnosed survivors (in that calendar year), previously diagnosed survivors (in a previous calendar year), and those with no history of cancer. Although the high cost for newly diagnosed survivors is expected (as they undergo active treatment), the financial burden for longer-term survivors remains significant. They found that survivors 1 to 5 years after diagnosis averaged almost $6000 more per year than people with no history of cancer, and survivors >5 years

after diagnosis averaged $4000 more. Separating out cancer-related expenses from those for comorbid conditions reduced the estimates by approximately $1000. Prescription costs contributed particularly to expenses paid out of pocket (OOP) by survivors, accounting for 44% of the total. For many, the additional economic burden of cancer survivorship is covered by public or private insurance. But not for all. The investigators identified uneven distribution of OOP expenses. For example in survivors aged between 40 and 64 years, approximately 60% spent ≤$1000 per year OOP, but 5% spent >$5000 per year OOP. “I think it goes to show that having good insurance is particularly important for survivors. Those who find themselves without access to good health insurance for some reason are at a disadvantage compared with other people,” shares Short, highlighting the public health implications of the findings. Prescription coverage, in particular, “is an area where there is a lot more variation among private health insurance plans in terms of how well they cover specific drugs and whether they cover some drugs at all.” ●

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The Healthy Benefits of Tomatoes

©iStockphoto.com/Laura Stanley

By Karen Connelly, RD, CSO he hot, hazy days of summer are the perfect time uble, which means that to optimize absorption they need for some of nature’s best produce. The tomato to be consumed along with a source of fat. For example, easily could be the unspoken mascot of the sum- using oil and vinegar dressing on a tomato salad will promer season. From July through September, make sure you vide a sufficient amount of fat to aid absorption of the take advantage of this delicious, nutrient-dense summer lycopene. A piece of low-fat mozzarella consumed with a favorite. Although a fruit by definition, tomatoes usually slice of tomato also is an acceptable combination. Unlike are prepared in meals similar to vegetables, which is why other foods, cooking the tomato increases its antioxidant they often fall into this category. Whether you like to eat content and the bioavailability of lycopene. them like an apple straight from the garden, simmered In addition to the tomato’s stellar phytonutrient coninto a savory sauce, or as the classic condiment known as tent, they also contain a powerhouse of vitamins and ketchup, the nutritional benefit you will receive is minerals. Tomatoes are an excellent source of vitamin C, incomparable. vitamin A, and vitamin K. They Despite the popularity and are a good source of thiamin, Tomatoes are not only vitamin B6, folate, niacin, riboassociation of tomatoes with Italian cuisine, the tomato did flavorful but also offer flavin, and magnesium. These vitamins and minerals are impornot originate in Europe. The first a host of nutritional tant in maintaining overall good tomato was native to South health. America and then eventually was benefits. They have Tomatoes also offer a good cultivated in Mexico. It wasn’t been associated with way to increase your dietary until the Spanish conquistadors fiber. For optimal health, you came to Mexico and brought reducing the risk of try to consume 30 g/day this wonderful fruit back to their certain types of cancer should of fiber. To reach your fiber homeland that Europe experias well as other goals, try adding tomatoes to enced the wonderful world of salads, sandwiches tomatoes. Settlers in what would chronic, inflammatory omelets, and, of course, pasta dishes. become the United States were illnesses. Exciting research is being connext in discovering tomatoes’ ducted to investigate the ability advantages, and they have been of lycopene to prevent certain types of cancer as well as gaining popularity in the American diet ever since. Tomatoes are not only flavorful but also offer a host other chronic conditions, such as diabetes and macular of nutritional benefits. They have been associated with degeneration. Lycopene has been linked to the prevenreducing the risk of certain types of cancer as well as tion of prostate cancer as well as the ability to slow disother chronic, inflammatory illnesses. Tomatoes con- ease progression in more advanced stages of this cancer.1,2 tain a variety of vitamins, minerals, and phytonutrients. It has been shown to have a possible impact on the prePhytonutrients are naturally occurring compounds vention of lung, stomach, colon, and pancreatic cancers, found in plant foods such as vegetables, fruits, grains, as well.1,3,4 The antioxidant profile of lycopene and the legumes, and nuts. These compounds help enhance the other phytonutrient compounds in tomatoes may be the immune system and protect the body against chronic answer to its disease-fighting properties. Antioxidants are illness. One of the tomato’s phytonutrients has been scavengers of free radicals that circulate in the body. Free studied extensively—lycopene. As a member of the radicals are highly reactive molecules that are responsible carotenoid group, lycopene gives plants their red, yellow, for cell damage and initiate the cascade of detrimental and orange pigments. In addition, carotenoids are fat-sol- cell alterations.A healthy diet that includes foods high in antioxidants may help prevent many of these negative cell changes from occurring.5 Ms Connelly is a Registered A consistent theme throughout research is the imporDietitian and Certified Specialist tance of consuming the whole food versus taking an isoin Oncology Nutrition at the lated supplement of a particular compound. Researchers Steeplechase Cancer Center in are finding that isolated compounds may not be as effecSomerville, New Jersey. As tive taken alone as they are when consumed in their natpart of her responsibilities, she ural state and in conjunction with other compounds.6 For provides nutrition counseling, example, the health benefits of lycopene in tomatoes group classes, and monthly could be dependent on the synergistic effect of the cooking classes to patients lycopene along with the fiber and folate in the tomato, and families. not just the lycopene itself. It is important, therefore, to

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try to eat a variety of fruits and vegetables each day to reap the full benefit of the many antioxidants, phytonutrients, fiber, vitamins, and minerals that these foods have to offer. The summer months are the perfect time to try one of the many varieties of tomatoes. Heirloom tomatoes are a type of tomato plant that has been pollinated by wind and bees and has been cultivated for more than 50 years. You can find these tomatoes in a variety of shapes, sizes, and colors. For example, the Brandywine tomato is a type of beefsteak tomato that can come in yellow, red, pink, or purple. In contrast to the big beefsteak, try the sungold, a small orange cherry tomato. There are so many varieties of tomatoes that you can use in so many dishes—from breakfast to dessert. Look for these different tomatoes at your local farm markets. Local produce will have the richest flavor and retain the most amounts of their nutritional benefits compared with produce that travels across the country. Organic tomatoes are another option. They tend to have a higher lycopene and antioxidant content than nonorganic tomatoes.7,8 If organic produce is too expensive or unavailable in your area, try to purchase organic canned tomato products or organic ketchup. These canned or bottled organic products also may have increased lycopene content compared with the nonorganic variety. Research on the role of phytonutrients and cancer prevention is ongoing and lycopene continues to be a main subject. More research is needed to definitively link lycopene to cancer prevention, but at this time there is no denying that it is essential to a healthy and balanced diet. Think creatively and let tomatoes be a part of every meal. The possibilities are endless, so start letting tomatoes enhance your diet today. ● References 1. Giovannucci E. A review of epidemiologic studies of tomatoes, lycopene, and prostate cancer. Exp Biol Med (Maywood). 2002;227:852-859. 2. Mohanty NK, Saxena S, Singh UP, et al. Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia. Urol Oncol. 2005;23:383-385. 3. Nkondjock A, Ghadirian P, Johnson KC, Krewski D; for the Canadian Cancer Registries Epidemiology Research Group. Dietary intake of lycopene is associated with reduced pancreatic cancer risk. J Nutr. 2005;135:592-597. 4. Erhardt JG, Meisner C, Bode JC, Bode C. Lycopene, beta-carotene, and colorectal adenomas. Am J Clin Nutr. 2003;78:1219-1224. 5. Di Mascio P, Devasagayam TP, Kaiser S, Sies H. Carotenoids, tocopherols and thiols as biological singlet molecular oxygen quenchers. Biochem Soc Trans. 1990;18:1054-1056. 6. Boileau TW, Liao Z, Kim S, et al. Prostate carcinogenesis in N-methylN-nitrosourea (NMU)-testosterone-treated rats fed tomato powder, lycopene, or energy-restricted diets. J Natl Cancer Inst. 2003;95:1578-1586. 7. Ishida BK, Chapman MH. A comparison of carotenoid content and total antioxidant activity in catsup from several commercial sources in the United States. J Agric Food Chem. 2004;52:8017-8020. 8. Crinnion WJ. Organic foods contain higher levels of certain nutrients, lower levels of pesticides, and may provide health benefits for the consumer. Altern Med Rev. 2010;15:4-12.

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Recipes

Compliments of Peter Pascale, Executive Chef, CCC, Somerset Medical Center, Somerville, New Jersey. Bon Appetit!

■ Pico De Gallo Ingredients ½ cup chopped fresh cilantro 1 tablespoon lime juice ½ teaspoon salt ½ jalapeno, diced

8 plum tomatoes, seeded and diced 4 tomatillos, diced 1 red onion, diced 2 garlic cloves, chopped

1. Combine all ingredients and serve. Nutritional Information Serves 4 45 calories; 0.5 g fat; 0 g saturated fat; 0 mg cholesterol; 300 mg sodium; 10 g carbohydrate; 3 g dietary fiber; 6 g sugars; 2 g protein

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■ Pasta Fagioli Ingredients 1⁄8 cup olive oil 4 garlic cloves, chopped 1 small white onion, chopped 2 tablespoons basil, chiffonade 1 15-oz can white beans

1 15-oz can plum tomatoes ½ pound whole-wheat ditalini ½ teaspoon oregano Salt and pepper to taste Grated Parmesan to taste

1. Cook pasta and set aside. 2. In a medium saucepan heat olive oil. 3. Add onion and sauté for 5 minutes. 4. Add garlic, basil, and oregano and cook for 1 more minute. 5. Add white beans and plum tomatoes. 6. Cook for about 15 minutes. 7. Add salt and pepper to taste. 8. Mix in pasta. 9. Finish with grated Parmesan.

©iStockphoto.com/SVETLANA KOLPAKOVA

Nutritional Information Serves 4; serving size 1⁄3 cup 380 calories; 9 g total fat; 0 mg cholesterol; 150 mg sodium; 63 g carbohydrate; 17 g dietary fiber; 16 g protein

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■ Spicy Gazpacho with Cucumber Cilantro Granita Gazpacho Ingredients 4 tomatoes, diced 1 cucumber, peeled and diced 1 green bell pepper, diced 1 red onion, diced

2 cups low-sodium spicy tomato juice 1 tablespoon cilantro, chopped Lime zest (garnish)

Granita Ingredients 1 cucumber, peeled and chopped Juice of 1 lime 1 tablespoon sugar

¼ teaspoon black pepper ¼ teaspoon salt 1 tablespoon cilantro, chopped

1. Combine first 6 ingredients for the gazpacho and set aside. 2. Combine all of the ingredients for the granita in a shallow pan and place in the freezer. 3. Check granita every 5 minutes and stir so it does not freeze solid. 4. Place gazpacho in soup cups and garnish with lime zest and granita. Nutritional Information Serves 6 70 calories; 0.5 g fat; 0 g saturated fat; 0 mg cholesterol; 160 mg sodium; 15 g total carbohydrate; 3 g dietary fiber; 10 g sugars; 2 g protein

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August 2011 I VOL 4, NO 5

■ Garden Fresh Tomato Sauce Ingredients 10 plum tomatoes, peeled ½ bunch basil, chiffonade 6 garlic cloves, chopped 1 tablespoon no-salt seasoning ½ teaspoon oregano 1 tablespoon olive oil 1. Heat pan and add oil. 2. Add garlic and basil. Sauté for 30 seconds. 3. Add tomatoes and seasoning. 4. Simmer for 15 minutes. 5. Using an immersion blender, puree sauce together. 6. Simmer for an additional 10 minutes. Nutritional Information Serves 4; serving size ½ cup 70 calories; 4 g fat; 0.5 g saturated fat; 0 mg cholesterol; 10 mg sodium; 9 g carbohydrate; 3 g dietary fiber; 4 g sugars; 2 g protein

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Pushing Your Limits

Scan Here to Register.

Current activities at www.COEXM.com include:

To use 2D barcodes, download the ScanLife app: • Text “scanâ€? to 43588 • Go to www.getscanlife.com on your smartphone’s web browser, and select “Downloadâ€? • Visit the app store for your smartphone

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Conference News ASCO ANNUAL MEETING

Continued from page 34

Decitabine Improves Overall Survival in Older AML Patients Phase 3 Trial Also Finds 20% Reduction in the Risk of Mortality By Wayne Kuznar

CHICAGO—Decitabine extends overall survival and improves response rates compared with standard therapies in the treatment of older patients with newly diagnosed acute myelogenous leukemia (AML), said Xavier G. Thomas, MD, PhD. The treatment options for older patients with AML are limited. Intensive chemotherapy is generally poorly tolerated in this group, the initial mortality rate is high (exceeding 30% at 8 weeks), the response rate to chemotherapy is poor, and relapse rates are high. Recently, DNA hypermethylation has been demonstrated in the promoter region in AML. Hypomethylating agents may affect tumor suppression genes and have been shown to be beneficial in AML cell lines, said Thomas, who is with the department of hematology, Edouard-Herriot Hospital, Lyon, France. Among the hypomethylating agents, decitabine has been approved for patients with myelodysplastic syndrome, and has demonstrated activity in a previous phase 2 trial of patients older than 60 years with AML.

Hypomethylating agents may affect tumor suppression genes and have been shown to be beneficial in AML cell lines. Based on these results, a phase 3 multicenter, controlled, open-label trial was designed to compare decitabine with patients’ choice of treatment on overall survival in patients 65 years and older with newly diagnosed de novo or secondary AML and poor- or intermediaterisk cytogenetics. The 485 patients enrolled were randomized to decitabine, 20 mg/m2 as a 1-hour intravenous infusion once daily for 5 consecutive days, every 4 weeks, or treatment of choice. Patients assigned to treatment of choice could select low-dose cytarabine, 20mg/m2 subcutaneous injection once daily for 10 days, every 4 weeks (n = 243), or supportive care (n = 28). Patients assigned to decitabine had a median duration of treatment of 4.4 months compared with 2.4 months for those on the treatment-of-choice arm. The protocol-specified final analysis (after 396 deaths) showed a nonsignificant but favorable trend for increased overall survival for patients treated with decitabine, with a median survival of 7.7 months compared with 5.0

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August 2011 I VOL 4, NO 5

months in the treatment-of-choice arm (P = .10). Seventy-five patients received disease-modifying therapy after treatment

failure following randomization. When these 75 patients were censored from the analysis, median overall survival improved to 8.5 months in the decitabine

PROVENGE® (sipuleucel-T) Suspension for Intravenous Infusion

Rx Only

BRIEF SUMMARY — See full Prescribing Information for complete product information

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group and 5.3 months in the treatmentof-choice arm, corresponding to a 20% reduction in the risk of mortality in the decitabine arm, and the difference be-

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Any Adverse Event Chills Fatigue )HYHU %DFN SDLQ Nausea Joint ache Headache Citrate toxicity Paresthesia Vomiting $QHPLD Constipation Pain Paresthesia oral Pain in extremity 'L]]LQHVV Muscle ache $VWKHQLD Diarrhea ,QŶXHQ]D OLNH LOOQHVV 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)

247 (41.1)

186 (30.9)

7 (1.2)

291 (96.0)

Grade 3-5 n (%) 97 (32.0)

(Table 1 continued on next page.)

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TON_August2011_11_TON 8/18/11 12:31 PM Page 43

Conference News came statistically significant (P = .044). An updated unplanned overall analysis was performed with 446 deaths, or approximately an additional year of patient follow-up. This updated analysis showed the same median survival in the 2 groups (7.7 vs 5.0 months) but the effect became significant (nominal P = .037). “This analysis increases the strength and validity of the first clinical cutoff,� said Thomas.

The secondary end point of complete remission with incomplete platelet recovery or complete remission with incomplete blood count recovery was achieved by 17.8% of the decitabine arm compared with 7.8% on treatment of choice. Adverse event rates were consistent with the known decitabine safety profile and without major differences between the treatment arms. â—?

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

Hypertension $QRUH[LD %RQH SDLQ Upper respiratory tract infection ,QVRPQLD Musculoskeletal chest pain Cough Neck pain Weight decreased Urinary tract infection Rash Sweating Tremor

Control* (N = 303)

All Grades n (%)

Grade 3-5 n (%)

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Cerebrovascular Events. ,Q FRQWUROOHG FOLQLFDO WULDOV FHUHEURYDVFXODU HYHQWV LQFOXGLQJ KHPRUUKDJLF DQG LVFKHPLF VWURNHV ZHUH UHSRUWHG LQ RI SDWLHQWV LQ WKH 3529(1*( JURXS FRPSDUHG ZLWK RI SDWLHQWV LQ WKH FRQWURO JURXS (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.

Dendreon Corporation Seattle, Washington 98101

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AugusT 2011 I VOL 4, NO 5

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In asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer

Before, Frank's immune cells could barely recognize a prostate cancer cell.

Now, they are focused on it.

PROVENGE is the first in a new class of therapy that is designed to activate a patient’s own antigen-presenting cells to stimulate an immune response against prostate cancer.

« Extends 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) « Therapy completed in 3 cycles—3 infusions, at approximately 2-week intervals† « Most common adverse events are primarily mild or moderate— chills, fatigue, fever, back pain, nausea, joint ache, and headache *

Control was nonactivated, autologous, peripheral blood mononuclear cells. The dosing interval ranged from 1 to 15 weeks in controlled clinical trials.

†

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 adjacent page.

©2011 Dendreon Corporation. All rights reserved. February 2011. Printed in the U.S.A. Dendreon, the Dendreon logo, and PROVENGE are registered trademarks of Dendreon Corporation. P-A-02.11-007.00

www.PROVENGE.com

Stimulate a Response

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