October/November 2008 Vol. 1 No. 5

©iStockphoto.com/ODonnell Photograf

BREAST CANCER Women may overestimate risk for breast cancer

SUPPORTIVE CARE Quality of life directly related to survival in cancer patients

NURSING EDUCATION & TRAINING UNMC College of Nursing trains oncology nurses

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page 17

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OCTOBER/NOVEMBER 2008 • VOL. 1, NO. 5

www.theoncologynurse.com

HEMATOLOGIC CANCERS

BREAST CANCER

Unraveling the Complexities of Non-Hodgkin’s Lymphoma. Part 1.

Advances in Treatment of Metastatic Breast Cancer: Evolving Role of the Taxanes

BY SANDRA KURTIN, RN, MS, AOCN, ANP-C

ARIZONA CANCER CENTER, UNIVERSITY OF ARIZONA, TUCSON

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An interview with Peter Bjerkerot, RN, OCN Private Nurse Consultant, Atlanta, Georgia

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death for women in the United States, lung cancer being number one. Nearly all deaths from breast cancer are attributable to metastatic, or stage IV, breast cancer. It is estimated that nearly 155,000 women in the United States are currently living with metastatic breast cancer, and the number is projected to

elevision specials, fundraising runs, and other special events held around the country in October marked National Breast Cancer Awareness Month.

National Breast cancer is the most common type of cancer among women, other than skin cancer, and the second leading cause of cancer

increase to nearly 162,000 by the year 2011.1 In this interview, Peter Bjerkerot, RN, OCN, provides an overview of treatment options for metastatic breast cancer, focusing on recent advances in taxane therapy.

Complimentary CE Credit

SUPPORTIVE CARE

Oncology Patient Participation in Clinical Trials: Overcoming Challenges to Enrollment

Three-pronged Intervention Removes Barriers to Management of Cancer Pain and Fatigue

he approval of new cancer therapies and new indications for existing therapies relies on patient participation in clinical trials, but several factors can hinder enrollment. Speaking at the 2008 American Society for Clinical Oncology Annual Meeting in Chicago, Joseph Paul Eder, MD, of AstraZeneca LP and the Dana-Farber Cancer Institute, Boston, pointed out that unless the population of

CHICAGO—A National Cancer Institute-funded, phase 2 study showed that an intervention comprising patient education, professional education, and strategies to integrate symptom management into routine oncology practice removed patient, professional, and system barriers to pain and fatigue management and improved outcomes in patients with

Continued on page 16

Continued on page 16 PRESORTED STANDARD

U.S. POSTAGE

PAID LEBANON JUNCTION, KY

PERMIT #651

© 2008 Green Hill Healthcare Communications, LLC

Continued on page 15

Continued on page 10

CLINICAL TRIALS

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on-Hodgkin’s lymphomas (NHLs) represent a group of heterogenous lymphoid malignancies that arise from either B or T lymphocytes at different stages of maturation. These malignancies include more than 30 distinct diagnoses with variable presentation, diagnostic findings, prognosis, and treatment recommendations. NHL is the fifth most common cancer and the most common hematologic malignancy, with an estimated 66,120 new cases and 19,160 deaths in 2008.1 There are many patients living with

College of Nursing Continuing Nursing Education

Program #08CE059d: Finasteride and Prostate Cancer Prevention: The Latest Chapter

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SUPPORTIVE CARE

FDA REPORT

Narcolepsy drug may combat fatigue in cancer patients

Patch to treat chemotherapyinduced nausea and vomiting approved

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With Herceptin, proven results HER2+ breast cancer are In the adjuvant setting: AC* therapy, reduced the risk of recurrence by 52% vs chemotherapy • Herceptin, in combination with paclitaxel following † alone (HR=0.48,CI: 0.39-0.59; P<0.0001) – Benefit was similar regardless of age, hormone-receptor status, or tumor size1

• Herceptin, as a single agent following completion of surgery and chemotherapy with or without radiotherapy, reduced the risk of recurrence by 46% (HR=0.54,CI: 0.44-0.67; P<0.0001).† The benefit was seen: – Regardless of nodal involvement1 – Using a q3w dosing schedule – With a variety of anthracycline-based chemotherapy regimens used prior to Herceptin1

52 weeks of Herceptin significantly

Adjuvant indications Herceptin is indicated for adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR-negative or with one high-risk feature)‡ breast cancer: • As part of a treatment regimen containing doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel • With docetaxel and carboplatin • As a single agent following multi-modality anthracycline-based therapy

reduced the risk

of breast cancer recurrence

AC=anthracycline-based.

HR=hazard ratio; CI=95% confidence interval. ‡ High-risk features for patients with ER/PR+ breast cancer include: tumor size >2 cm, age <35 years, and histologic and/or nuclear grade 2/3. *

†

Boxed WARNINGS and Additional Important Safety Information Cardiotoxicity and cardiac monitoring • Herceptin administration can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure (CHF) and decreased left ventricular ejection fraction (LVEF) – The incidence and severity of left ventricular cardiac dysfunction was highest in patients who received Herceptin concurrently with anthracycline-containing chemotherapy regimens – Discontinue Herceptin treatment in patients receiving adjuvant therapy and strongly consider discontinuation of Herceptin in patients with metastatic breast cancer who develop a clinically significant decrease in left ventricular function • Patients should undergo monitoring for decreased left ventricular function before Herceptin treatment, and frequently during and after Herceptin treatment – More frequent monitoring should be employed if Herceptin is withheld in patients who develop significant left ventricular cardiac dysfunction • In one adjuvant clinical trial, cardiac ischemia or infarction occurred in the Herceptin-containing regimens

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

Reference: 1. Data on file. Genentech, Inc.

www.herceptin.com ©2008 Genentech USA

So. San Francisco, CA

All rights reserved.

9265400

6/08

in within her reach

He rce ad TCH NO ptin rejuvan (the f W gim t non irst AP en) a -AC PR nd A OV C-T E H§

In the metastatic setting: • Patients receiving first-line Herceptin plus chemotherapyll lived 4.8 months longer on average (25.1 months) than those receiving chemotherapy alone (20.3 months) (P=0.05) – Among the subset of patients receiving paclitaxel, those receiving paclitaxel alone lived a median of 18.4 months, vs 22.1 months for patients receiving Herceptin plus paclitaxel (P=0.17)

• Adding Herceptin to chemotherapyll extended time to progression by 60% vs chemotherapy alone (7.2 months vs 4.5 months; P<0.0001)

– Among the subset of patients receiving paclitaxel, combination therapy with Herceptin more than doubled time to progression vs paclitaxel alone (6.7 months vs 2.5 months; P<0.0001)

Metastatic indications Herceptin is indicated: • In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer • As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease §

ll

In the adjuvant setting, AC-TH now approved with docetaxel, and for q3w dosing of Herceptin.

Chemotherapy was either doxorubicin or epirubicin plus cyclophosphamide, or paclitaxel.

Herceptin extended median survival

Boxed WARNINGS and Additional Important Safety Information (continued) Infusion reactions, pulmonary toxicity, and neutropenia • Serious infusion reactions and pulmonary toxicity have occurred; fatal infusion reactions have been reported – In most cases, symptoms occurred during or within 24 hours of administration of Herceptin – Herceptin infusion should be interrupted for patients experiencing dyspnea or clinically significant hypotension – Patients should be monitored until signs and symptoms completely resolve – Discontinue Herceptin for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome

• Exacerbation of chemotherapy-induced neutropenia has also occurred Pregnancy category D • Herceptin can cause oligohydramnios and fetal harm when administered to a pregnant woman Most common adverse events • 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

D

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

WARNING: CARDIOMYOPATHY, INFUSION REACTIONS, and PULMONARY TOXICITY Cardiomyopathy Herceptin can result in sub-clinical and clinical cardiac failure manifesting as CHF and decreased LVEF. The incidence and severity of left ventricular cardiac dysfunction was highest in patients who received Herceptin concurrently 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 strongly consider discontinuation of Herceptin treatment in patients with metastatic breast cancer 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 infusion reactions and pulmonary toxicity. Fatal infusion reactions have been reported. In most cases, symptoms occurred during or within 24 hours of administration of Herceptin. Herceptin infusion should be interrupted for patients experiencing dyspnea or clinically significant hypotension. Patients should be monitored until signs and symptoms completely resolve. Discontinue Herceptin for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. [see Warnings and Precautions]

INDICATIONS AND USAGE Adjuvant Breast Cancer Herceptin is indicated for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/ PR negative or with one high risk feature [see Clinical Studies]) breast cancer • As part of a treatment regimen consisting of doxorubicin, Cyclophosphamide, and either paclitaxel or docetaxel • With docetaxel and carboplatin • As a single agent following multi-modality anthracycline based therapy. Metastatic Breast Cancer Herceptin is indicated: • In combination with paclitaxel for firstline treatment of HER2-overexpressing metastatic breast cancer • As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease. CONTRAINDICATIONS None.

WARNINGS AND PRECAUTIONS Cardiomyopathy Herceptin can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death [see Boxed Warning: Cardiomyopathy]. Herceptin can also cause asymptomatic decline in left ventricular ejection fraction (LVEF). There is a 4–6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving Herceptin as a single agent or in combination therapy compared with those not receiving Herceptin.

The highest absolute incidence occurs when Herceptin is administered with an anthracycline. Withhold Herceptin for ≥16% absolute decrease in LVEF from pre-treatment values or an LVEF value below institutional limits of normal and ≥10% absolute decrease in LVEF from pretreatment values. [see Dosage and Administration] The safety of continuation or resumption of Herceptin in patients with Herceptin-induced left ventricular cardiac dysfunction has not been studied. Cardiac Monitoring Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan. The following schedule is recommended: • Baseline LVEF measurement immediately prior to initiation of Herceptin • LVEF measurements every 3 months during and upon completion of Herceptin • Repeat LVEF measurement at 4 week intervals if Herceptin is withheld for significant left ventricular cardiac dysfunction [see Dosage and Administration] • LVEF measurements every 6 months for at least 2 years following completion of Herceptin as a component of adjuvant therapy. In Study 1, 16% (136/844) of patients discontinued Herceptin due to clinical evidence of myocardial dysfunction or significant decline in LVEF. In Study 3, the number of patients who discontinued Herceptin due to cardiac toxicity was 2.6% (44/1678). In Study 4, a total of 2.9% (31/1056) patients in the TCH arm (1.5% during the chemotherapy phase and 1.4% during the monotherapy phase) and 5.7% (61/1068) patients in the AC-TH arm (1.5% during the chemotherapy phase and 4.2% during the monotherapy phase) discontinued Herceptin due to cardiac toxicity.

Among 32 patients receiving adjuvant chemotherapy (Studies 1 and 2) who developed congestive heart failure, one patient died of cardiomyopathy and all other patients were receiving cardiac medication at last follow-up.

Approximately half of the surviving patients had recovery to a normal LVEF (defined as ≥ 50%) on continuing medical management at the time of last follow-up. Incidence of congestive heart failure is presented in Table 1. The safety of continuation or resumption of Herceptin in patients with Herceptin-induced left ventricular cardiac dysfunction has not been studied.

Table 1 Incidence of Congestive Heart Failure in Adjuvant Breast Cancer Studies

Study Regimen 1 & 2a ACb Paclitaxel+ Herceptin 3 Chemo Herceptin monotherapy 4 ACb Docetaxel+ Herceptin 4 Docetaxel+Carbo+ Herceptin a b

Incidence of CHF Herceptin Control 2% (32/1677)

0.4% (7/1600)

2% (30/1678)

0.3% (5/1708)

2% (20/1068)

0.3% (3/1050)

0.4% (4/1056)

0.3% (3/1050))

Includes 1 patient with fatal cardiomyopathy.

Anthracycline (doxorubicin) and cyclophosphamide.

Table 2 Incidence of Cardiac Dysfunctiona in Metastatic Breast Cancer Studies

Study 5 (AC)b 5 (paclitaxel) 6

Event Cardiac Dysfunction Cardiac Dysfunction Cardiac Dysfunctionc

Incidence NYHA I-IV NYHA III-IV Herceptin Control Herceptin Control 28%

7%

19%

3%

11%

1%

4%

1%

7%

N/A

5%

N/A

a Congestive heart failure or significant asymptomatic decrease in LVEF. bAnthracycline (doxorubicin or epirubicin) and cyclophosphamide. cIncludes 1 patient with fatal cardiomyopathy.

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 postinfusion events with rapid clinical deterioration. For fatal events, death occurred within hours to days following a serious infusion reaction. Interrupt Herceptin infusion in all patients experiencing dyspnea, clinically significant hypotension, and intervention of medical therapy administered, which may include: epinephrine, corticosteroids, diphenhydramine, bronchodilators, and oxygen. Patients should be evaluated and carefully monitored until complete resolution of signs and symptoms. Permanent discontinuation should be strongly considered in all patients with severe infusion reactions.

There are no data regarding the most appropriate method of identification of patients who may safely be retreated with Herceptin after experiencing a severe infusion reaction. Prior to resumption of Herceptin infusion, the majority of patients who experienced a severe infusion reaction were pre-medicated with antihistamines and/or corticosteroids. While some patients tolerated Herceptin infusions, others had recurrent severe infusion reactions despite pre-medications. Exacerbation of ChemotherapyInduced Neutropenia In randomized, controlled clinical trials in women with metastatic breast cancer, the perpatient incidences of NCI CTC Grade 3-4 neutropenia and of febrile neutropenia were higher in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was not significantly increased. [see Adverse Reactions].

Pulmonary Toxicity Herceptin use can result in serious and fatal pulmonary toxicity. Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions [see Warnings and Precautions]. Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity. HER2 Testing Detection of HER2 protein overexpression is necessary for selection of patients appropriate for Herceptin therapy because these are the only patients studied and for whom benefit has been shown. Assessment for HER2 overexpression and of HER2 gene amplification should be performed by laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance, including use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results. Several FDA-approved commercial assays are available to aid in the selection of patients for Herceptin therapy. These include HercepTestTM and Pathway ® HER-2/neu (IHC assays) and PathVysion® and HER2 FISH pharmDxTM (FISH assays). Users should refer to the package inserts of specific assay kits for information on the validation and performance of each assay. Limitations in assay precision (particularly for the IHC method) and in the direct linkage between assay result and overexpression of the Herceptin target (for the FISH method) make it inadvisable to rely on a single method to rule out potential Herceptin benefit. A negative FISH result does not rule out HER2 overexpression and potential benefit from Herceptin. Treatment outcomes for metastatic breast cancer (Study 5) as a function of IHC and FISH testing are provided in Table 9. Treatment outcomes for adjuvant breast cancer (Studies 2 and 3) as a function of IHC and FISH testing are provided in Table 7.

HER2 Protein Overexpression Detection Methods HER2 protein overexpression can be established by measuring HER2 protein using an IHC method. HercepTest ®, one test approved for this use, was assessed for concordance with the Clinical Trial Assay (CTA), using tumor specimens collected and stored independently from those obtained in Herceptin clinical studies in women with metastatic breast cancer. Data are provided in the package insert for HercepTest ®. HER2 Gene Amplification Detection Method The presence of HER2 protein overexpression and gene amplification are highly correlated, therefore the use of FISH to detect gene amplification may be employed for selection of patients appropriate for Herceptin therapy. PathVysion®, one test approved for this use, was evaluated in an exploratory, retrospective assessment of available CTA 2+ or 3+ tumor specimens collected as part of patient screening for clinical studies in metastatic breast cancer (Studies 5 and 6). Data are provided in the package insert for PathVysion ®. Embryo-Fetal Toxicity (Pregnancy Category D) Herceptin can cause fetal harm when administered to a pregnant woman. Post-marketing case reports suggest that Herceptin use during pregnancy increases the risk of oligohydramnios during the second and third trimesters. If Herceptin is used during pregnancy

or if a woman becomes pregnant while taking Herceptin, she should be apprised of the potential hazard to a fetus. [see Use in Specific Populations]. ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: • Cardiomyopathy [see Warnings and Precautions] • Infusion reactions [see Warnings and Precautions] • Exacerbation of chemotherapy-induced neutropenia [see Warnings and Precautions] • Pulmonary toxicity [see Warnings and Precautions] The most common adverse reactions in patients receiving Herceptin are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia. Adverse reactions requiring interruption or discontinuation of Herceptin treatment include CHF, significant decline in left ventricular cardiac function, severe infusion reactions, and pulmonary toxicity [see Dosage and Administration]. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adjuvant Breast Cancer Studies The data below reflect exposure to Herceptin across three randomized, open-label studies, Studies 1, 2, and 3, with (n= 3355) or without (n= 3308) trastuzumab in the adjuvant treatment of breast cancer.

The data summarized in Table 3 below, from Study 3, reflect exposure to Herceptin in 1678 patients; the median treatment duration was 51 weeks and median number of infusions was 18. Among the 3386 patients enrolled in Study 3, the median age was 49 years (range: 21 to 80 years), 83% of patients were Caucasian, and 13% were Asian.

Table 3 Adverse Reactions for Study 3, All Gradesa : MedDRA (v. 7.1) 1 Year Herceptin Adverse Event Preferred Term (n= 1678) Cardiac Hypertension 64 (4%) Dizziness 60 (4%) Ejection Fraction Decreased 58 (3.5%) Palpitations 48 (3%) 40 (3%) Cardiac Arrhythmiasb Cardiac Failure Congestive 30 (2%) Cardiac Failure 9 (0.5%) Cardiac Disorder 5 (0.3%) Ventricular Dysfunction 4 (0.2%) Respiratory Thoracic Mediastinal Disorders Nasopharyngitis 135 (8%) Cough 81 (5%) Influenza 70 (4%) Dyspnea 57 (3%) URI 46 (3%) Rhinitis 36 (2%) Pharyngolaryngeal Pain 32 (2%) Sinusitis 26 (2%) Epistaxis 25 (2%) Pulmonary Hypertension 4 (0.2%) Interstitial Pneumonitis 4 (0.2%) Gastrointestinal Disorders Diarrhea 123 (7%) Nausea 108 (6%) Vomiting 58 (3.5%) Constipation 33 (2%) Dyspepsia 30 (2%) Upper Abdominal Pain 29 (2%) Musculoskeletal & Connective Tissue Disorders Arthralgia 137 (8%) Back Pain 91 (5%) Myalgia 63 (4%) Bone Pain 49 (3%) Muscle Spasm 46 (3%) Nervous System Disorders Headache 162 (10%) Paraesthesia 29 (2%) Skin & Subcutaneous Tissue Disorders Rash 70 (4%) Nail Disorders 43 (2%) Pruritus 40 (2%) General Disorders Pyrexia 100 (6%) Edema Peripheral 79 (5%) Chills 85 (5%) Asthenia 75 (4.5%) Influenza-like Illness 40 (2%) Sudden Death 1 (0.06%) Infections Nasopharyngitis 135 (8%) UTI 39 (3%) Immune System Disorders Hypersensitivity 10 (0.6%) Autoimmune Thyroiditis 4 (0.3%)

Observation (n= 1708) 35 (2%) 29 (2%) 11 (0.6%) 12 (0.7%) 17 (1%) 5 (0.3%) 4 (0.2%) 0 (0%) 0 (0%) 43 (3%) 34 (2%) 9 (0.5%) 26 (2%) 20 (1%) 6 (0.4%) 8 (0.5%) 5 (0.3%) 1 (0.06%) 0 (0%) 0 (0%)

the following investigator-attributed treatment-related adverse reactions: NCI-CTC Grade 4 and 5 hematologic toxicities, Grade 3–5 non-hematologic toxicities, selected Grade 2–5 toxicities associated with taxanes (myalgia, arthralgias, nail changes, motor neuropathy, sensory neuropathy) and Grade 1–5 cardiac toxicities occurring during chemotherapy and/or Herceptin treatment. The following non-cardiac adverse reactions of Grade 2–5 occurred at an incidence of at least 2% greater among patients randomized to Herceptin plus chemotherapy as compared to chemotherapy alone: arthralgia (11% vs.

8.4%), myalgia (10% vs. 8%), nail changes (9% vs. 7%), and dyspnea (2.5% vs. 0.1%). The majority of these events were Grade 2 in severity. Safety data from Study 4 reflect exposure to Herceptin as part of an adjuvant treatment regimen from 2124 patients receiving at least one dose of study treatment [AC-TH: n = 1068; TCH: n = 1056].

The overall median treatment duration was 54 weeks in both the AC-TH and TCH arms. The median number of infusions was 26 in the AC-TH arm and 30 in the TCH arm, including weekly infusions during the chemotherapy phase and every three week dosing in the monotherapy period. Among these patients, the median age was 49 years (range 22 to 74 years). In Study 4, the toxicity profile was similar to that reported in Studies 1, 2, and 3 with the exception of a low incidence of CHF in the TCH arm. Metastatic Breast Cancer Studies The data below reflect exposure to Herceptin in one randomized, openlabel study, Study 5, of chemotherapy with (n=235) or without (n=234) trastuzumab in patients with metastatic breast cancer, and one single-arm study (Study 6; n=222) in patients with metastatic breast cancer. Data in Table 5 are based on Studies 5 and 6. Among the 464 patients treated in Study 5, the median age was 52 years (range: 25–77 years). Eighty-nine percent were White, 5% Black, 1% Asian and 5% other racial/ethnic groups.

All patients received 4 mg/kg initial dose of Herceptin followed by 2 mg/kg weekly. The percentages of patients who received Herceptin treatment for ≥ 6 months and ≥ 12 months were 58% and 9%, respectively. Among the 352 patients treated in single agent studies (213 patients from Study 6), the median age was 50 years (range 28–86 years), 100% had breast cancer, 86% were White, 3% were Black, 3% were Asian, and 8% in other racial/ethnic groups. Most of the patients received 4 mg/kg initial dose of Herceptin followed by 2 mg/kg weekly. The percentages of patients who received Herceptin treatment for ≥ 6 months and ≥ 12 months were 31% and 16%, respectively.

Table 4 Per-Patient Incidence of Adverse Reactions Occurring in ≥ 5% of Patients in Uncontrolled Studies or at Increased Incidence in the Herceptin Arm (Studies 5 and 6) (Percent of Patients) Herceptin Single + Paclitaxel Herceptin ACb a Agent Paclitaxel Alone + ACb Alone n = 352 n = 91 n = 95 n = 143 n = 135 Body as a Whole Pain 47 61 62 57 42 Asthenia 42 62 57 54 55 Fever 36 49 23 56 34 Chills 32 41 4 35 11 Headache 26 36 28 44 31 Abdominal pain 22 34 22 23 18 Back pain 22 34 30 27 15 Infection 20 47 27 47 31 Flu syndrome 10 12 5 12 6 Accidental injury 6 13 3 9 4 Allergic reaction 3 8 2 4 2 Cardiovascular Tachycardia 5 12 4 10 5 Congestive heart failure 7 11 1 28 7 Digestive Nausea 33 51 9 76 77 Diarrhea 25 45 29 45 26 Vomiting 23 37 28 53 49 Nausea and 8 14 11 18 9 vomiting Anorexia 14 24 16 31 26 Heme & Lymphatic Anemia 4 14 9 36 26 Leukopenia 3 24 17 52 34 Metabolic Peripheral edema 10 22 20 20 17 Edema 8 10 8 11 5 Musculoskeletal Bone pain 7 24 18 7 7 Arthralgia 6 37 21 8 9 Nervous Insomnia 14 25 13 29 15 Dizziness 13 22 24 24 18 Paresthesia 9 48 39 17 11 Depression 6 12 13 20 12 Peripheral neuritis 2 23 16 2 2 Neuropathy 1 13 5 4 4 Respiratory Cough increased 26 41 22 43 29 Dyspnea 22 27 26 42 25 Rhinitis 14 22 5 22 16 Pharyngitis 12 22 14 30 18 Sinusitis 9 21 7 13 6 Skin Rash 18 38 18 27 17 Herpes simplex 2 12 3 7 9 Acne 2 11 3 3 <1 Urogenital Urinary tract infection 5 18 14 13 7

16 (1%) 19 (1%) 10 (0.6%) 17 (1%) 9 (0.5%) 15 (1%) 98 (6%) 58 (3%) 17 (1%) 26 (2%) 3 (0.2%) 49 (3%) 11 (0.6%) 10 (0.6%) 0 (0%) 10 (0.6%) 6 (0.4%) 37 (2%) 0 (0%) 30 (2%) 3 (0.2%) 0 (0%) 43 (3%) 13 (0.8%) 1 (0.06%) 0 (0%)

a

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

The data from Studies 1 and 2 were obtained from 3206 patients enrolled, of which 1635 patients received Herceptin; the median treatment duration was 50 weeks.

The median age was 49.0 years (range: 24-80); 84% of patients were White, and 7% were Black, 4% were Hispanic, and 4% were Asian. In Study 1, only Grade 3–5 adverse events, treatment-related Grade 2 events, and Grade 2–5 dyspnea were collected during and for up to 3 months following protocol-specified treatment. The following non-cardiac adverse reactions of Grade 2-5 occurred at an incidence of at least 2% greater among patients randomized to Herceptin plus chemotherapy as compared to chemotherapy alone: arthralgia (31% vs.

28%), fatigue (28% vs. 22%), infection (22% vs. 14%), hot flashes (17% vs. 15%), anemia (13% vs. 7%), dyspnea (12% vs. 4%), rash/desquamation (11% vs. 7%), neutropenia (7% vs. 5%), headache (6% vs. 4%), and insomnia (3.7% vs. 1.5%). The majority of these events were Grade 2 in severity. In Study 2, data collection was limited to

a

Data for Herceptin single agent were from 4 studies, including 213 patients from Study 6. bAnthracycline (doxorubicin or epirubicin) and cyclophosphamide.

The following subsections provide additional detail regarding adverse reactions observed in clinical

a

For Studies 1, 2 and 3, events are counted from the beginning of Herceptin treatment. For Study 4, events are counted from the date of randomization. bStudies 1 and 2 regimens: doxorubicin and cyclophosphamide followed by paclitaxel (AC T) or paclitaxel plus Herceptin (AC TH). c Study 4 regimens: doxorubicin and cyclophosphamide followed by docetaxel (AC T) or docetaxel plus Herceptin (AC TH); docetaxel and carboplatin plus Herceptin (TCH).

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

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

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

Time 0 is the date of randomization.

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

Time 0 is the date of randomization.

The incidence of treatment emergent congestive heart failure among patients in the metastatic breast cancer trials was classified for severity using the New York Heart Association classification system (I–IV, where IV is the most severe level of cardiac failure) (see Table 2). In the metastatic breast cancer trials the probability of cardiac dysfunction was highest in patients who received Herceptin concurrently with anthracyclines. Infusion Reactions During the first infusion with Herceptin, the symptoms most commonly reported were chills and fever, occurring in approximately 40% of patients in clinical trials. Symptoms were treated with acetaminophen, diphenhydramine, and meperidine (with or without reduction in the rate of Herceptin infusion); permanent discontinuation of Herceptin for infusional toxicity was required in <1% of patients. Other signs and/or symptoms may include nausea, vomiting, pain (in some cases at tumor sites), rigors, headache, dizziness, dyspnea, hypotension, elevated blood pressure, rash, and asthenia. Infusional toxicity occurred in 21% and 35% of patients, and was

October/November 2008

she should be apprised of the potential hazard to a fetus. In the post-marketing setting, oligohydramnios was reported in women who received Herceptin during pregnancy, either alone or in combination with chemotherapy. In half of these women, amniotic fluid index increased after Herceptin was stopped. In one case, Herceptin was resumed after the amniotic fluid index improved, and oligohydramnios recurred. Women using Herceptin during pregnancy should be monitored for oligohydramnios. If oligohydramnios occurs, fetal testing should be done that is appropriate for gestational age and consistent with community standards of care. Additional intravenous (IV) hydration has been helpful when oligohydramnios has occurred following administration of other chemotherapy agents; however, the effects of additional IV hydration with Herceptin treatment are not known. Reproduction studies in cynomolgus monkeys at doses up to 25 times the recommended weekly human dose of 2 mg/kg trastuzumab have revealed no evidence of harm to the fetus. However, HER2 protein expression is high in many embryonic tissues including cardiac and neural tissues; in mutant mice lacking HER2, embryos died in early gestation. Placental transfer of trastuzumab during the early (Days 20-50 of gestation) and late (Days 120-150 of gestation) fetal development period was observed in monkeys. [See Nonclinical Toxicology] Because animal reproduction studies are not always predictive of human response, Herceptin should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Nursing Mothers It is not known whether Herceptin is excreted in human milk, but human IgG is excreted in human milk. Published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Trastuzumab was present in the breast milk of lactating cynomolgus monkeys given 12.5 times the recommended weekly human dose of 2 mg/kg of Herceptin. Infant monkeys with detectable serum levels of trastuzumab did not have any adverse effects on growth or development from birth to 3 months of age; however, trastuzumab levels in animal breast milk may not accurately reflect human breast milk levels. Because many drugs are secreted in human milk and because of the potential for serious adverse reactions in nursing infants from Herceptin, a decision should be made whether to discontinue nursing, or discontinue drug, taking into account the elimination half-life of trastuzumab and the importance of the drug to the mother. Pediatric Use The safety and effectiveness of Herceptin in pediatric patients has not been established. Geriatric Use Herceptin has been administered to 386 patients who were 65 years of age or over (253 in the adjuvant treatment and 133 in metastatic breast cancer treatment settings). The risk of cardiac dysfunction was increased in geriatric patients as compared to younger patients in both those receiving treatment for metastatic disease in Studies 5 and 6, or adjuvant therapy in Studies 1 and 2. Limitations in data collection and differences in study design of the 4 studies of Herceptin in adjuvant treatment of breast cancer preclude a determination of whether the toxicity profile of Herceptin in older patients is different from younger patients. The reported clinical experience is not adequate to determine whether the efficacy improvements (ORR, TTP, OS, DFS) of Herceptin treatment in older patients is different from that observed in patients <65 years of age for metastatic disease and adjuvant treatment.

OVERDOSAGE There is no experience with overdosage in human clinical trials. Single doses higher than 8 mg/kg have not been tested. PATIENT COUNSELING INFORMATION • Advise patients to contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness [see Boxed Warning: Cardiomyopathy].

• Advise women with reproductive potential to use effective contraceptive methods during treatment and for a minimum of six months following Herceptin [see Pregnancy]. • Encourage pregnant women who are using Herceptin to enroll in the Cancer and Childbirth Registry [see Pregnancy].

HERCEPTIN® [trastuzumab] Manufactured by: 4839802 Genentech, Inc. Initial US Approval: Sept. 1998 1 DNA Way Revision Date: May 2008 South San Francisco, CA LK0726 7172910 94080-4990 9317800 ©2008 Genentech USA

News Notes ■ HPV Researcher Receives Nobel Prize in Physiology and Medicine German virologist Dr Harald zur Hausen has been awarded the 2008 Nobel Prize in Physiology and Medicine for his discovery that certain types of human papillomavirus (HPV) cause cervical cancer.

He shares the prize with French virologists Dr Françoise Barré-Sinoussi and Dr Luc Montagnier, who discovered the human immunodeficiency virus, which causes AIDS. Dr zur Hausen’s research contributed to the development of vaccines that protect against cervical cancer.

NEWS NOTES

LVEF <50% and Absolute Absolute LVEF Decrease from Baseline Decrease LVEF ≥ 10% ≥ 16% <20% and <50% decrease decrease ≥ 10% ≥ 20% Studies 1 & 2b AC TH 22.8% 18.3% 11.7% 33.4% 9.2% (n=1606) (366) (294) (188) (536) (148) AC T 9.1% 5.4% 2.2% 18.3% 2.4% (n=1488) (136) (81) (33) (272) (36) Study 3 Herceptin 8.6% 7.0% 3.8% 22.4% 3.5% (n=1678) (144) (118) (64) (376) (59) Observation 2.7% 2.0% 1.2% 11.9% 1.2% (n=1708) (46) (35) (20) (204) (21) Study 4c TCH 8.5% 5.9% 3.3% 34.5% 6.3% (n=1056) (90) (62) (35) (364) (67) AC TH 17% 13.3% 9.8% 44.3% 13.2% (n=1068) (182) (142) (105) (473) (141) AC T 9.5% 6.6% 3.3% 34% 5.5% (n=1050) (100) (69) (35) (357) (58)

severe in 1.4% and 9% of patients, on second or subsequent Herceptin infusions administered as monotherapy or in combination with chemotherapy, respectively. In the postmarketing setting, severe infusion reactions, including hypersensitivity, anaphylaxis, and angioedema have been reported. Anemia In randomized controlled clinical trials, the overall incidence of anemia (30% vs. 21% [Study 5]), of selected NCI-CTC Grade 2–5 anemia (12.5% vs. 6.6% [Study 1]), and of anemia requiring transfusions (0.1% vs. 0 patients [Study 2]) were increased in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. Following the administration of Herceptin as a single agent (Study 6), the incidence of NCI-CTC Grade 3 anemia was <1%. Neutropenia In randomized controlled clinical trials in the adjuvant setting, the incidence of selected NCI-CTC Grade 4–5 neutropenia (2% vs. 0.7% [Study 2]) and of selected Grade 2–5 neutropenia (7.1% vs. 4.5 % [Study 1]) were increased in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. In a randomized, controlled trial in patients with metastatic breast cancer, the incidences of NCI-CTC Grade 3/4 neutropenia (32% vs.

22%) and of febrile neutropenia (23% vs. 17%) were also increased in patients randomized to Herceptin in combination with myelosuppressive chemotherapy as compared to chemotherapy alone. Infection The overall incidences of infection (46% vs. 30% [Study 5]), of selected NCI-CTC Grade 2–5 infection/febrile neutropenia (22% vs.

14% [Study 1]) and of selected Grade 3–5 infection/febrile neutropenia (3.3% vs. 1.4%) [Study 2]), were higher in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. The most common site of infections in the adjuvant setting involved the upper respiratory tract, skin, and urinary tract. In Study 4, the overall incidence of infection was higher with the addition of Herceptin to AC-T but not to TCH [44% (AC-TH), 37% (TCH), 38% (AC-T)]. The incidences of NCI-CTC grade 3-4 infection were similar [25% (AC-TH), 21% (TCH), 23% (AC-T)] across the three arms. In a randomized, controlled trial in treatment of metastatic breast cancer, the reported incidence of febrile neutropenia was higher (23% vs. 17%) in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to chemotherapy alone. Pulmonary Toxicity Adjuvant Breast Cancer: Among women receiving adjuvant therapy for breast cancer, the incidence of selected NCI-CTC Grade 2–5 pulmonary toxicity (14% vs. 5% [Study 1]) and of selected NCI-CTC Grade 3–5 pulmonary toxicity and spontaneous reported Grade 2 dyspnea (3.4% vs. 1% [Study 2]) was higher in patients receiving Herceptin and chemotherapy compared with chemotherapy alone. The most common pulmonary toxicity was dyspnea (NCI CTC Grade 2–5: 12% vs. 4% [Study 1]; NCI-CTC Grade 2–5: 2.5% vs. 0.1% [Study 2]). Pneumonitis/pulmonary infiltrates occurred in 0.7% of patients receiving Herceptin compared with 0.3% of those receiving chemotherapy alone. Fatal respiratory failure occurred in 3 patients receiving Herceptin, one as a component of multi-organ system failure, as compared to 1 patient receiving chemotherapy alone. In Study 3, there were 4 cases of interstitial pneumonitis in Herceptin-treated patients compared to none in the control arm. Metastatic Breast Cancer: Among women receiving Herceptin for treatment of metastatic breast cancer, the incidence of pulmonary toxicity was also increased. Pulmonary adverse events have been reported in the post-marketing experience as part of the symptom complex of infusion reactions. Pulmonary events include bronchospasm, hypoxia, dyspnea, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, and acute respiratory distress syndrome. For a detailed description, see Warnings and Precautions.

Thrombosis/Embolism In 4 randomized, controlled clinical trials, the incidence of thrombotic adverse events was higher in patients receiving Herceptin and chemotherapy compared to chemotherapy alone in three studies (3.0% vs.

1.3% [Study 1], 2.5% and 3.7% vs. 2.2% [Study 4] and 2.1% vs. 0% [Study 5]). Diarrhea Among women receiving adjuvant therapy for breast cancer, the incidence of NCICTC Grade 2–5 diarrhea (6.2% vs. 4.8% [Study 1]) and of NCI-CTC Grade 3–5 diarrhea (1.6% vs. 0% [Study 2]), and of Grade 1–4 diarrhea (7% vs. 1% [Study 3]) were higher in patients receiving Herceptin as compared to controls. In Study 4, the incidence of Grade 3–4 diarrhea was higher [5.7% AC-TH, 5.5% TCH vs. 3.0% AC-T] and of Grade 1–4 was higher [51% AC-TH, 63% TCH vs. 43% AC-T] among women receiving Herceptin. Of patients receiving Herceptin as a single agent for the treatment of metastatic breast cancer, 25% experienced diarrhea. An increased incidence of diarrhea was observed in patients receiving Herceptin in combination with chemotherapy for treatment of metastatic breast cancer. Glomerulopathy In the postmarketing setting, rare cases of nephrotic syndrome with pathologic evidence of glomerulopathy have been reported.

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

Complications included volume overload and congestive heart failure. Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. Among 903 women with metastatic breast cancer, human antihuman antibody (HAHA) to Herceptin was detected in one patient using an enzyme-linked immunosorbent assay (ELISA). This patient did not experience an allergic reaction. Samples for assessment of HAHA were not collected in studies of adjuvant breast cancer. The incidence of antibody formation is highly dependent on the sensitivity and the specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Herceptin with the incidence of antibodies to other products may be misleading. USE IN SPECIFIC POPULATIONS Pregnancy Teratogenic Effects: Category D [see Warnings and Precautions] Herceptin can cause fetal harm when administered to a pregnant woman. Post-marketing case reports suggest that Herceptin use during pregnancy increases the risk for oligohydramnios during the second and third trimester. If Herceptin is used during pregnancy or if a woman becomes pregnant while taking Herceptin,

■ Chemotherapy May Delay Need for Radiation in Children with Brain Tumors Using chemotherapy alone and delaying or even avoiding radiation may be an effective alternative approach for children with unresectable or progressive low-grade glioma, a Children’s Oncology Group study suggests.

The results of the multi-institutional study “confirmed the ability of chemotherapy to control the disease,” said Joann Ater, MD, professor of pediatrics at the Children’s Cancer Hospital at M.D. Anderson Cancer Center, Houston, Tex, speaking at the 40th Annual International Society of Pediatric Oncology meeting in Berlin, Germany. The 401 patients enrolled in the trial were treated with one of two different chemotherapy regimens—carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and vincristine (TPCV). The TPCV regimen was more effective than the CV regimen and resulted in a 5-year event-free survival rate of nearly 50%. “If we can delay radiation, then we can allow more time for our youngest patients to develop physically, which could decrease some of the long-term effects from treatment,” Ater said in a press release. Longterm effects of radiation include mental impairment, hormonal deficiencies, and increased rate of stroke late in life, causing some physicians and families to avoid radiation treatment.

■ Bone Cancer Foundation Provides Information to Healthcare Professionals, Patients The newly formed Bone Cancer Foundation (BCF) provides information on cancer that affects the bone to healthcare providers and cancer patients on its website (http://www.boneandcancerfoundation.org) and in its publications, all of which are free.

Six patient publications are now available in print and on the website, covering bone metastases and treatment-related bone loss in breast, prostate, lung cancer, and myeloma as well as osteonecrosis of the jaw and vitamin D deficiency. More information about the BCF can be obtained by phone (888-862-0999) or e-mail (bcfdn@aol.com).

G REEN H ILL H EALTHCARE C OMMUNICATIONS

3

NEWS NOTES

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

Following initiation of Herceptin therapy, the incidence of new-onset dose-limiting myocardial dysfunction was higher among patients receiving Herceptin and paclitaxel as compared to those receiving paclitaxel alone in Studies 1 and 2, and in patients receiving Herceptin monotherapy compared to observation in Study 3 (see Table 5, Figures 1 and 2).

Table 5 a Per-patient Incidence of New Onset Myocardial Dysfunction (by LVEF) Studies 1, 2, 3 and 4

Vol. 1, No. 5

October/November 2008

The

Departments

Feature Articles

Oncology Nurse

The Official Newspaper of Record for the Hem/Onc Nurse

™

PUBLISHING STAFF

CONTENTS

12 Breast Cancer

3

News Notes

6

Editor’s Letter

8

Medical Minutes

Publisher Philip Pawelko phil@greenhillhc.com

Women may overestimate risk for breast cancer

17 Supportive Care

Editorial Director Karen Rosenberg karen@greenhillhc.com

Narcolepsy drug may combat fatigue in cancer patients

19 Continuing Education Finasteride and prostate cancer prevention: The latest chapter

24 Supportive Care For opiod-induced constipation, try second or third dose of methynaltrexone

27 Nursing Life

Senior Production Manager Stephanie Laudien

32 Recent FDA Approvals

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

33 Meetings

26 Nursing & Education Training

Complementary and alternative medicine and the oncology patient

The

Oncology Nurse

The Official Newspaper of Record for the Hem/Onc Nurse

™

EDITORIAL BOARD EDITOR-IN-CHIEF

Beth Faiman, RN, MSN, APRN, BC, AOCN Cleveland Clinic Taussig Cancer Institute Cleveland, OH Isabell Castellano, RN Bristol-Myers Squibb Children’s Hospital Robert Wood Johnson University Hospital New Brunswick, NJ Deena Damsky Dell, RN, MSN, AOCN, BC Fox Chase Cancer Center Philadelphia, PA Wendy DiSalvo, BSN, MSN, FNP, AOCN Dartmouth Hitchcock Medical Center Norris Cotton Cancer Center Lebanon, NH

CONTENTS

Denice Economou, RN, MN, AOCN City of Hope National Medical Center Duarte, CA Amy Ford, RN, BSN, OCN Creative Cancer Concepts, Inc. Rockwall, TX

4

Russell Hennessy russell@greenhillhc.com Director of Human Resources Blanche Marchitto blanche@greenhillhc.com

UNMC College of Nursing offers postgraduate programs in oncology

16 Alternative/Complementary Therapies

Managing Editor Lara J. Reiman

Circulation circulation@greenhillhc.com

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: online at www.theoncologynurse.com

GH Green Hill Healthcare Communications

, LLC ™

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Constance Engelking, RN, MS, OCN The CHE Consulting Group, Inc. Mt. Kisco, NY

Gary Shelton, MSN, ARNP, AOCN NYU Cancer Institute New York, NY

Lyssa Friedman, RN, MPA, OCN Veracyte, Inc South San Francisco, CA

Lori Stover, RN, BSN Western Pennsylvania Cancer Institute Pittsburgh, PA

Sharon S. Gentry, RN, MSN, AOCN Derrick L. Davis Forsyth Regional Cancer Center Winston-Salem, NC Marilyn L. Haas, PhD, RN, CNS, ANP-C Mountain Radiation Oncology Asheville, NC Cassandra J. Hammond, RN, MSN, CRNP Avid Education Partners, LLC Sharpsburg, MD Taline Khoukaz, NP, MSN, ACNP-C University of Southern California Norris Cancer Center & Hospital Los Angeles, CA Sandra E. Kurtin, RN, MS, AOCN, ANP-C Arizona Cancer Center Tucson, AZ Ann McNeill, MSN, RN, NP-C, OCN The Cancer Center at Hackensack University Medical Center Hackensack, NJ Kena C. Miller, RN, MSN, FNP Roswell Park Cancer Institute Buffalo, NY Dolores “Jeff” Nordquist, RN, MS, CS, FNP Mayo Clinic Rochester, MN Melinda Oberleitner, RN, DNS, APRN, CNS College of Nursing and Allied Health Professions University of Louisiana Lafayette, LA

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Joseph D. Tariman, RN, MN, ARNP-BC, OCN University of Washington School of Nursing Seattle, WA Pamela Hallquist Viale, RN, MS, CS, ANP, AOCN Saratoga, CA Connie Visovsky, RN, PhD, APRN University of Nebraska, College of Nursing Omaha, NE Jeanne Westphal, RN Meeker County Memorial Hospital Litchfield, MN Rita Wickham, OCN, PhD, RN Rush University College of Nursing Rush-Presbyterian-St. Luke’s Medical Center Chicago, IL Karla Wilson, RN, MSN, FNP-C, CPON City of Hope National Medical Center Duarte, CA

OTHER SPECIALTIES Susan Goodin, PharmD, FCCP, BCOP Cancer Institute of New Jersey New Brunswick, NJ Barbara Savage, LISW Cleveland Clinic Taussig Cancer Institute Cleveland, OH Amanda Saldivar, MS, RD, LD Cleveland Clinic Taussig Cancer Institute Cleveland, OH

October/November 2008

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EDITOR’S LETTER

A Letter from the Editor O BETH FAIMAN, RN, MSN, APRN, BC, AOCN

EDITOR-IN-CHIEF

ctober was National Breast Cancer Awareness Month and so was an appropriate time to review advances in treatment of breast cancer. The introduction of the taxanes in the 1990s provided an important new option for the treatment of metastatic breast cancer, and these agents are now widely used. In this issue, Peter Bjerkerot reviews the role of the taxanes in metastatic breast cancer and discusses recent advances in taxane therapy, including a new solvent-free formulation that reduces some of the side effects associated with these agents and combination therapy with a taxane and a targeted therapy, which has shown promise in early clinical trials Participation in clinical trials affords patients access to the latest treatment advances, but enrollment in trials remains low. A report from the annual meeting of the American Society of Clinical Oncology discusses barriers to clinical trial participation and ways to overcome them. Other sessions covered new interventions to prevent or reduce side effects of cancer therapies.

The continuing education article this month addresses prevention of prostate cancer and raises interesting questions about risks versus benefits. Initial results of the large Prostate Cancer Prevention Trial (PCPT), which were reported in 2003, showed that treatment with finasteride, a drug approved for the treatment of benign prostatic hyperplasia, significantly reduces the risk of prostate cancer. This promising finding was tempered, however, by

Coming Soon CE article: Quality of Life in Metastatic Renal Cell Carcinoma New Technologies in HER2 Testing Navigating the Journey of Breast Cancer Increasing Oncology Patient Participation in Clinical Trials: The Coalition of Cancer Cooperative Groups Recognizing Structural Oncologic Emergencies

EDITOR’S LETTER

Reports from ASCO Breast Cancer Symposium, European Society for Medical Oncology

For a free subscription go to www.theoncologynurse.com 6

G REEN H ILL H EALTHCARE C OMMUNICATIONS

the apparent increase the risk of high-grade disease in men who took finasteride. A new analysis of the PCPT data shows that this concern was unfounded and suggests the drug be offered as an option for men concerned about the risk of prostate cancer. The new analysis received much media attention, so it is important for oncology nurses to be aware of the findings and be prepared to answer their patients’ questions about how and when to use finasteride or other measures for prostate cancer prevention.

The Practical Applications review by Kerry Mahar highlights another area of professional and personal concern for oncology nurses and their colleagues. Nurses who administer chemotherapeutic agents and other hazardous substances are themselves at risk, but in caring for their patients, sometimes neglect to take care of themselves. Mahar makes it clear that nurses must take precautions to protect themselves and their coworkers as well as their patients.

Hospitals and clinics must develop and implement policies and procedures to ensure safe handling of hazardous materials in keeping with national guidelines, and professional education is needed to ensure that all healthcare providers understand the importance of adhering to established guidelines and procedures.

As this issue goes to press, the 2008 presidential election is being decided. Healthcare is an issue of importance to voters of all parties, and we hope that the new administration will make cancer and other health issues a priority.

EDITORIAL CORRESPONDENCE should be addressed to EDITORIAL DIRECTOR, The Oncology Nurse™, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. E-mail: karen@greenhillhc.com. YEARLY SUBSCRIPTION RATES: United States and possessions: individuals, $105.00; institutions, $135.00; single issues $17.00. Orders will be billed at individual rate until proof of status is confirmed. Prices are subject to change without notice. Correspondence regarding permission to reprint all or part of any article published in this journal should be addressed to REPRINT PERMISSIONS DEPARTMENT, Green Hill Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. The ideas and opinions expressed in The Oncology Nurse™, do not necessarily reflect those of the Editorial Board, the Editorial Director, or the Publisher. Publication of an advertisement or other product mention in The Oncology Nurse™, should not be construed as an endorsement of the product or the manufacturer’s claims.

Readers are encouraged to contact the manufacturer with questions about the features or limitations of the products mentioned. Neither the Editorial Board nor the Publisher assumes any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this periodical. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosage, the method and duration of administration, or contraindications. It is the responsibility of the treating physician or other healthcare professional, relying on independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Every effort has been made to check generic and trade names, and to verify dosages. The ultimate responsibility, however, lies with the prescribing physician. Please convey any errors to the Editorial Director. ISSN #1944-9798.

The Oncology Nurse™, is published 6 times a year by Green Hill Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. Telephone: 732.656.7935. Fax: 732.656.7938.

Copyright ©2008 by Green Hill Healthcare Communications, LLC. All rights reserved. The Oncology Nurse™ logo is a trademark of Green Hill Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the Publisher. Printed in the United States of America.

October/November 2008

MEDICAL MINUTES

Medical Minutes

BY JOHN SCHIESZER

Nurses Simplify Chemotherapy in the Hopes of Improving Care at the Bedside John Schieszer is an award-winning national journalist and radio broadcaster of The Medical Minute.

He can be reached at medminutes@aol.com.

Strategies that simplify and improve the chemotherapy process may be able to transform care at the bedside, decrease medical errors associated with chemotherapy administration, and improve nursing confidence and satisfaction.

Chemotherapy administration can be a complex process that can be anxiety-producing, especially for new nurses or those not experienced in this field. Direct care nurses from Roswell Park Cancer Institute who are involved in the administration of chemotherapy identified several issues contributing to the complexity of this process.

These nurses then simplified the process by designing a roadmap that outlines the order of administration and associated instructions of specific chemotherapy regimens. In addition, they created a pocket-sized booklet that in-

cludes the side effects and special instructions for the chemotherapy agents prescribed most often.

“Chemotherapy continues to be challenging because of new agents and the combination of agents in cancer treatment. It is imperative that bedside nurses are empowered to identify issues and transform the care that they provide through the safest method possible,” said researcher Mary Ann Long, MS, RN, director of patient care services at Roswell Park Cancer Institute, Buffalo, NY. Because of concerns raised by nurses, Long and colleagues set up a chemotherapy task force made up of nurses from the medical surgical units and the chemotherapy infusion clinic. They identified problems faced by the nursing staff and established a roadmap, which was an algorithm for the entire process of chemotherapy administration. This roadmap did not contain the same amount of detail as the orders but rather provided direction for the nurses in what to do first, second, third, etc. Interestingly, the nurses, not the doctors, developed the roadmaps and modified them as well.

“Nurses identified the problem and came up with the solution.

So that is the key. The end users are the ones who drove the whole process. Chemotherapy administration is a very complex process and it needs to get simplified as much as possible,” Long said. “We need to do this to ensure patient safety and make it as efficient as possible for the nurses. We need to make sure the information is available. [To obtain the booklet, write to MaryAnn.Long@ RoswellPark.org.]

New Study Suggests the Role of Hormones in Sexuality May Be Limited

MEDICAL MINUTES

Most long-term cervical cancer survivors report they have satisfy- desired sexual activity, and 90.9% indicated they enjoyed sexual ing sex lives after surgical intervention, according to a new study activity at least some of the time. When asked if cervical cancer had that challenges public perceptions of the role hormones play in sex- a negative effect on their relationships, two thirds disagreed.

“This observation is important because the public places so much ual activity.

The University of Southern California (USC)-Yale University emphasis on hormones in sex, and the pharmaceutical industry is study is significant because researchers documented the sexual expe- poised to release a whole new generation of hormone-based drugs for riences of women who presumably had no hormonally motivated female sexuality,” said Greenwald. “A person’s outlook, relationsexual behavior or interest. Surgical intervention for cervical cancer ships, and other factors may be just as important or even more often involves removing the ovaries, which reduces or eliminates important.” circulating testosterone, which is a factor in both male and female sexual behavior.

“Our findings, which demonstrate the Improving Pain Management for Cancer Patients existence of widespread interest and satisfaction with sex in the absence of a crucial A new study suggests that nurses and Rather surprisingly, however, 80% of those hormone, underscore the importance of other clinicians may be able to help patients said they did not use medication to nonhormonal components of sexual interimprove pain management for patients with manage their pain.

Most patients said the main reason they est and satisfaction,” said lead study author cancer by simply requiring documentation Howard Greenwald, who is a professor in of patients’ pain levels and their responses did not take pain medication was that their healthcare provider did not recommend it. the School of Policy, Planning, and to pain medications.

Development at USC. “That may mean Many cancer patients do not receive ade- This reason was followed by a fear of addicthe key to sexual satisfaction is less about quate therapy for the pain caused by their tion or dependence and the inability to pay. biology and more about psychology.” disease or treatments, according to a study Some patients also reported using alternaHe said that during the first months and by researchers at the University of tive therapies for pain relief, including years after treatment for cervical cancer, Pennsylvania, Department of Radiation physical therapy, massage therapy, and women often struggle with what they perOncology in Philadelphia and the acupuncture.

“To eliminate barriers to optimal pain ceive to be an assault on their sexual Radiation Oncology Branch of the organs and identity. Most studies of cancer National Cancer Institute (NCI). They management for cancer patients, healthcare survivors follow patients no more than 5 sought to determine the main reasons that providers should talk with their patients years after diagnosis and treatment, but in patients fail to receive optimal pain therapy. about pain symptoms and pain medicathis study, the researchers found that after Between November 2005 and April tions,” said lead study investigator Charles 6 years, most women’s sexual desire and 2006, 106 radiation therapy patients Simone, MD, a resident at the NCI radiaenjoyment rebounds. The investigators responded to an Internet-based question- tion oncology branch, Bethesda, MD. “At interviewed women 6 to 28 years after naire that evaluated their medication use, our institution, we have taken these steps their initial diagnosis. pain control, and attitudes toward pain by transitioning to an electronic medical They found based on interviews with medications, including prescription and record system that has been designed to 179 women that more than 80% of the over-the-counter pain medications. The require an evaluation and documentation of cervical cancer survivors reported being researchers found that 58% reported pain patient pain levels and pain medication sexually active. A total of 81.4% said they from their cancer treatment, and 46% responses by healthcare providers at each “sometimes,” “almost always,” or “always” reported pain directly from their cancer. patient encounter.”

8

G REEN H ILL H EALTHCARE C OMMUNICATIONS

October/November 2008

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issue with paclitaxel is the neuropathies, such as numbness and tingling of the hands and feet. It may be necessary to interrupt treatment if neutropenia or neuropathy occurs. There are no evidence-based interventions for neuropathy, but there are some pharmacologic and nonpharmacologic interventions that are effective. [For a fact sheet on assessment and management of peripheral neuropathies, write to Peter.

Bjerkerot@mindspring.com.]

Continued from cover

BREAST CANCER

What are the major treatment options for metastatic breast cancer?

Surgical intervention is generally how all women enter into their journey with breast cancer. We’ve gotten better at screening women, educating them about the importance of doing self breast examinations and getting routine mammograms. And the technology has gotten so much better that we can pick up a lot more cases while it’s still early.

When breast cancer is detected early, it can usually be surgically treated, and then we follow up with chemotherapy and radiation therapy, depending on factors such as the individual characteristics of the woman and the type of tumor. When breast cancer spreads beyond the breast and lymph nodes, however, more aggressive treatment approaches are needed. There are three broad types of medical therapies for metastatic breast cancer—hormone therapy, chemotherapy, and biologic or novel targeted therapy.

How do these different types of therapies work?

Hormone therapy. Hormone therapy is generally used for women whose breast cancer expresses or overexpresses estrogen receptor or progesterone receptor positivity. In a nutshell, hormonal therapies work by blocking production of estrogen, or by sequestering the estrogen that is produced.2 Therefore, those tumors that feed on estrogen to grow do not have an estrogen supply.

Chemotherapy. We also have a variety of chemotherapy agents, which stop growth of cancer cells, either by killing the cells or preventing them from dividing.3 The four types most commonly used for breast cancer are the anthracyclines, alkylating agents, antimetabolites, and taxanes.

Targeted therapies. The biologic or novel targeted therapies specifically target proteins that are overexpressed in cancer cells, leading to cancer growth and spread.4 Target therapies commonly used to treat metastatic breast cancer include agents that inhibit the activity of HER2 and those that inhibit vascular endothelial growth factor. Often, targeted therapies are given in combination with standard chemotherapy.

BREAST CANCER

What are some factors to consider when selecting therapy?

We now can do more intense or indepth analysis of the genetic makeup of the breast cancer itself to see which drug is going to be better than the other for an individual patient. You also then look into the woman’s preference as far as which one she would prefer to use.

That’s an important part to remember— that patients have 51% of the vote.

The drugs have different side effect profiles. Some are more aggressive than others. For some, treatment time is shorter than for others. Another factor to consider is how bad the disease is. Do we just need to buy some time, or are we going to be aggressive and try to cure it?

Of course, we also have to consider that patient’s underlying condition as well. It’s always benefits versus risks, just 10

Figure. Mechanism for the transport and accumulation of nab-paclitaxel in tumors. The transcytosis of albumin-bound paclitaxel across the endothelial barrier is facilitated by the binding to the gp60 receptor and caveolar transport. In the tumor intestinal space, albumin-paclitaxel complexes bind to SPARC (secreted protein, acidic and rich in cysteine) and are rapidly internalized in tumor cells via a nonlysosomal pathway. like with any other form of medicine.

The problem with oncology is that there are always risks. We don’t give benign drugs.

Oncology has gotten to be very sophisticated in that we’re looking at gene lines. We’re looking at chromosomes. We really are taking huge steps forward, and it’s going to continue to be that way for decades to come. It’s an exciting time to be in oncology.

The taxanes paclitaxel and docetaxel are among the most widely used drugs for metastatic breast cancer, and new developments in taxane therapy have been reported recently. Could you tell us more about the evolution of taxanes and their role in treatment of metastatic breast cancer?

In 1994, solvent-based paclitaxel (Taxol), became available for treatment of breast cancer. Then, in 1996, the second taxane, docetaxel (Taxotere) was introduced. Originally, paclitaxel was approved for women with metastatic disease who had progressed through one other chemotherapy regimen or who had had chemotherapy in the adjuvant setting. If, within 6 months of stopping the chemotherapy, the patient’s tumor began to grow or new lesions were found, she was able to get paclitaxel.

Docetaxel was also approved for use in the adjuvant setting. Taxane-containing regimens have been shown to prolong overall survival, time to progression, and overall response in women with metastatic breast cancer; they are widely used, but there are some problems associated with their use.5

What are some challenges associated with taxane use?

Probably the biggest challenge is that the taxanes cannot be dissolved in water and so they have to be combined with solvents. The problem is the solvents can prolong infusion time and cause side effects beyond those caused by the drug itself.6,7 Regardless of which solvent is used, there’s a variety of side effects associated with them, such as neuropathy, neutropenia, and allergic reactions, even to the point of anaphylactic reactions, and premedication is

G REEN H ILL H EALTHCARE C OMMUNICATIONS

need to prevent these hypersensitivity reactions. Sometimes therapy has to be discontinued because of side effects.

With cancer therapy, basically what we do is give somebody who feels pretty good drugs that make them feel pretty bad while we’re fighting their cancer.

And so, it is important to try to minimize those side effects as much as possible. That was the impetus for the development of an albumin-based, solvent-free formulation of paclitaxel known as nanoparticle albumin-bound (nab)-paclictaxel (Abraxane), which was approved as monotherapy in 2005.

How does this new formulation compare with conventional taxanes?

Basically what they did was to combine the paclitaxel molecule with human albumin, which made it possible to put it into solution (Figure). That eliminated the need for the solvent, so there are no solvent-related side effects, and there is no need to premedicate patients with steroids or antihistamines to prevent hypersensitivity reactions.

Also, because we’ve taken the solvent out and thus eliminated the solventrelated side effects, we can give about 49% more of the drug to the patient without increasing the side effects or affecting the patient’s quality of life.

Another advantage is that the drug can be infused in 30 minutes compared with up to 3 hours with solvent-based paclitaxel.8 You don’t need to have intravenous tubing, which is necessary with solvent-based taxanes, because the solvents would actually leech out the plastic particles in the tubing.

You mentioned the side effects of solvents, but what about the side effects of paclitaxel itself?

The paclitaxel molecule itself does cause side effects. Neutropenia is one of them, and it can be severe. We have to watch patients closely for that, and use appropriate interventions, such as advising them to avoid crowds and take antibiotics when their blood count is low. One of the most important things we can do is to start them on bone marrow–stimulating drugs to keep their blood count up. Probably the biggest

Have there been any large clinical trials of nab-paclitaxel?

It has been studied both as monotherapy and, more recently, in combination with other agents. In two large phase 3 studies of its use as monotherapy, nabpaclitaxel without premedication was compared with solvent-based forms of paclitaxel with premedication in patients with metastatic breast cancer.9,10 In both studies, response rate and time to tumor progression were greater in patients treated with the nab-paclitaxel regimen than with standard paclitaxel.

At the 2008 American Society of Clinical Society (ASCO) meeting, a few studies were presented of use of nabpaclitaxel in combination therapy, and the results are very promising (Sidebar).

Combination Therapy for Metastatic Breast Cancer At the 2008 annual meeting of ASCO, Danso and colleagues reported interim results of a phase 2 study in which nab-paclitaxel was given in combination with the targeted agent bevacizumab (Avastin) as first-line treatment of metastatic HER2negative breast cancer. In the 45 evaluable women, the overall response rate was 33%, and 18% of women had stable disease for more than 16 weeks.11 In another ongoing study, Seidman and associates treated 30 women with HER2-positive metastatic breast cancer with nab-paclitaxel in combination with carboplatin and trastuzumab (Herceptin).12 Of the 26 evaluable patients, 12 had a complete or partial response, and the median progression-free survival was 16 months.

What is the rationale for combining nab-paclitaxel with another agent?

To put it simply, combining drugs allows you to come at the cancer in more than one direction. With this twopronged approach, the goal is to get more drug available to kill the cancer kill, without increasing the number or severity of side effects. The drugs have different mechanisms of action and different side effect profiles. You may see different side effects, but the severity is not going to be much greater than with either drug used individually.

The clinical trials presented at Continued on page 12

October/November 2008

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Balloon Kyphoplasty

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New Study Shows that Many Women May Overestimate Their Risk for Breast Cancer CHICAGO—Many women appear to have a distorted view of their true risk of getting breast cancer.

However, educational efforts can reduce inaccuracies in women’s perceptions of breast cancer risk, according to a new study presented at the 44th Annual Meeting of the American Society of Clinical Oncology. In addition, the study found that a majority of women (53%) would participate in chemoprevention trials if they could lower their overall breast cancer risk by at least 35%.

Researchers at New York University theorize that women’s perceptions of breast cancer risk and how they assess the value of prevention strategies are likely to determine if they are willing to take up prevention strategies or join breast cancer risk reduction clinical trials. So, they conducted a study to assess the effectiveness of an educational intervention on women’s perceptions of breast cancer risk. They also investigated women’s perceptions of the effectiveness of risk reduction interventions and what level of risk reduction would be required to justify their participation in chemoprevention trials.

Questionnaires administered before and after edu-

cational intervention provided data to calculate Gail risk scores and assess risk perception. A total of 65 women completed both questionnaires, but the study population was restricted to just 38 women who had no prior history of breast cancer and were able to provide information to compute a Gail score. The median age of the 38 study participants was 56 years (range: 28-72 years).

Of the 38 women, 12 (32%) had a strong family history of breast cancer. The mean Gail score was 2.2%, and 17 (45%) of 38 women had Gail scores of 1.7% or greater. The investigators concluded that 34% of the women overestimated the average lifetime risk of developing breast cancer. However, their perception decreased significantly to just 8% after the educational intervention. Most of the women rated diet as the “most effective” risk reduction intervention, followed by physical activity.

The researchers concluded that specific educational efforts can reduce inaccuracies in women’s perception of breast cancer risk. In addition, they found that women have a marked interest in participating in potential risk reduction interventions, including vita-

Individualized Sleep Intervention Holds Promise for Chemotherapy-related Sleep Disturbances and Fatigue CHICAGO—Sleep issues and fatigue are significant problems for breast cancer patients treated with chemotherapy, and one third of breast cancer survivors report persistent fatigue and sleep disturbances. A National Institutes of Health–funded, randomized, controlled trial demonstrated that an individually tailored intervention significantly improved sleep over time in women with

breast cancer receiving chemotherapy and at 30 days after the last treatment.

Women who had lower levels of fatigue at baseline and who adhered to the intervention also experienced reduced fatigue.

This type of intervention should be offered to all women with breast cancer beginning adjuvant chemotherapy who report poor sleep, said lead author Anne

BREAST CANCER Continued from page 10

ASCO of nab-paclitaxel combined with another agent suggest that this can be acomplished. You have to remember, however, that these were phase 2 studies with small numbers of patients, so it is hard to generalize from the results.

Larger studies are needed to confirm the results, but the results so far suggest that combination therapy is a promising approach for the treatment of metastatic breast cancer.

—Karen Rosenberg

References

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1. Data on file. DA-ABR-03. Abraxis Bioscience Inc. 2. National Cancer Institute. Breast cancer treatment (PDQ), Patient Version. http://www. cancer.gov/cancertopics/pdq/treatment/breast/ patient. Accessed October 27, 2008.

3. National Cancer Institute. Dictionary of cancer terms, “Systemic chemotherapy.” http:// cancer.gov/templates/db_alpha.aspc?cdrID= 301626. Accessed October 27, 2008.

4. American Cancer Society. Detailed guide: Breast cancer, Targeted therapy. http://www. cancer.org/docroot/CRI._2_4_4x_Targeted_ Therapy_5.asp?sitearea+. Accessed October 27, 2008.

5. Ghersi D, Wilcken N, Simes J, et al. Taxane containing regimens for metastatic breast cancer. Cochrane Database Syst Rev. 2005; 2:CD003366.

12

6. ten Tije AJ, Verweij J, Loos WJ, et al.

Pharmacological effects of formulation vehicles: implications for cancer chemotherapy.

Clin Pharmacokinet. 2003;42:665-685.

7. van Zuylen L, Verweij J, Sparreboom A. Role of formulation vehicles in taxane pharmacology.

Invest New Drugs. 2001;19:125-141.

8. Abraxane [prescribing information]. Los Angeles, CA: Abraxis Oncology; 2007.

9. O’Shaughnessy JA, Tjulandin S, Davidson N, et al. ABI-007 (Abraxane), a nanoparticle albumin-bound (nab) paclitaxel demonstrates superior efficacy vs Taxol in MBC: a phase III trial. Presented at the 26th Annual San Antonio Breast Cancer Symposium; December 3-6, 2003. Abstract 44.

10. Gradishar WJ, Tjulandin S, Davidson N, et al.

Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005;23:7794-7803.

11. Danso M, Blum J, Robert N, et al. Phase 2 trial of weekly nab-paclitaxel in combination with bevacizumab as first-line treatment in metastatic breast cancer. Presented at the 44th Annual Meeting of the American Society of Clinical Oncology; May 30-June 2, 2008. Abstract 1075.

12. Seidman AD, Conlin AK, Bach AM, et al.

Phase II trial of weekly nanoparticle albumin bound (nab) paclitaxel in combination with carboplatin and transtuzumab as first-line therapy for patients with HER2-positive metastatic breast cancer (MBC). Presented at the 44th Annual Meeting of the American Society of Clinical Oncology; May 30-June 2, 2008.

Abstract 1047.

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min therapy, diet, and chemoprevention trials.

“Until now nobody has ever asked women what they are looking for,” said lead study investigator Freya Schnabel, MD, professor of surgery at New York University. “Diet, alcohol, and exercise are the interventions that people want. Chemoprevention efforts should look at these. Women don’t want pharmaceuticals.” She said that because women favor lifestyle modification to lower their risk, there is a need to develop appropriate strategies to accomplish that.

“The take-home message for oncology nurses is that most women don’t know their true risk of breast cancer. …We need to get them to a place where they are not overestimating or underestimating their true risk,” Schnabel said in an interview with The Oncology Nurse. “It is nice to validate for our nurses that doing accurate family history and prior history of breast disease is important, and that is something that oncology nurses do well because they tend to have intimate relationships with their patients.”

—John Schieszer

M. Berger, PhD, RN, professor and Dorothy Hodges Olson Endowed Chair in Nursing at the University of Nebraska Medical Center in Omaha.

apy and 7 days after each chemotherapy treatment, and again 30 days after treatments were completed. The Piper Fatigue Scale and the Fatigue Intensity

This type of intervention should be offered to all women with breast cancer beginning adjuvant chemotherapy who report poor sleep.

She said that the women who are most likely to benefit are those who prefer a behavioral intervention over sleep medications and who respond to motivators such as using fewer sick days at work and feeling well for an important life event. Another suggestion was to involve an experienced sleep expert in tailoring strategies for specific types of sleep disturbance if the initial plan does not improve sleep.

The intervention, called the Individualized Sleep Promotion Plan (ISPP), consists of four components: stimulus control, modified sleep restriction, relaxation therapy, and sleep hygiene. Patients were randomized to the intervention or to a healthy eating control group. The intervention group developed an ISPP before initial chemotherapy, and this plan was regularly reinforced and revised according to response. Control group participants were given information about healthy eating and equal time and attention as the intervention group.

The study enrolled 219 women 19 years of age or older with a first diagnosis of stage I, III, or IIIA breast cancer. Patients were free of unstable comorbidities. The subjects were recruited from two academic-based practices and 10 community oncology clinics. Data were collected in the home setting 2 days before chemother-

Item on that scale were used to assess fatigue; sleep was assessed with the Pittsburgh Sleep Quality Index.

Over time, the intervention significantly improved sleep quality compared with controls (P <.049). Fatigue increased in both groups over the period of chemotherapy treatment and returned to pretreatment levels by day 30.

No differences in fatigue were reported between the two arms at 30 days.

Berger said that future research should focus on women receiving chemotherapy who are most likely to benefit from this type of intervention.

—Alice Goodman

New Website Matches Breast Cancer Patients with Trials Information on breast cancer clinical trials taking place at more than 1100 medical facilities nationwide is available on a website recently launched by the University of California, San Francisco Center of Excellence for Breast Cancer Care. Breast CancerTrials.org, a free, nonprofit, clinical trials matching service matches patients with or at risk for breast cancer with trials that are specific to their personal health situation. The site provides contact information for the trial and criteria for enrollment.

October/November 2008

Table 1. Most Common Subtypes of Non-Hodgkin’s Lymphoma Lymphoma subtype Cases Diffuse large B-cell 31% Follicular 22% Small lymphocytic/chronic lymphocytic leukemia 6% Mantle cell 6% Peripheral T-cell 6% Marginal zone B-cell (MZL) 5% Mucosa-associated lymphoid tissue 5% Remaining subtypes: <2% Splenic MZL Lymphoblastic Nodal MZL AIDS-related B-cell Burkitt’s Mycosis fungoides/Sézary syndrome Established treatment guidelines provided by the National Comprehensive Cancer Network based on the Non-Hodgkin’s Lymphoma Project.

Sources: References 3 and 6.

Figure. Ann Arbor Staging System for Lymphoma

Adapted from the American Cancer Society website.

the disease who may require intermittent therapy over an extended period of time. Few subtypes of the disease are considered curable, but most are considered highly treatable. Therefore, familiarity with the nomenclature, diagnostic evaluation, staging criteria, treatment selection, and toxicity management is critical to selection of the most effective therapy for each individual patient throughout the disease continuum.

Robust scientific discoveries over the past decade have led to an improved understanding of the pathobiology of the disease, including molecular characteristics, which have provided novel targets for treatment. Effective management of the patient using a life-span approach provides the opportunity to preserve future treatment options and reduce potentially debilitating toxicities. This is the first in a series of articles that will explore recent advances in the diagnosis, risk stratification, and treatment of NHL.

Disease nomenclature NHL arises from either B or T lymphocytes. B-cell NHL is the most common type (90%). Until recently, the International Working Formulation was used to describe NHL based on morphology, immunophenotyping, and clinical features. The subtypes were further divided into low-grade, intermediOctober/November 2008

ate-grade, and high-grade lymphomas.

The World Health Organization

Staging and prognostic criteria Prognosis for NHL varies widely based on information obtained during the diagnostic process. Successful treatment of NHL is based on a complete evaluation of the disease, including location and extent of organ involvement and an adequate tissue

Table 2. Prognostic Indexes for Non-Hodgkin’s Lymphoma International Prognostic Index Risk factors (1 point each) Age >60 years Ann Arbor stage III or IV >1 extranodal site Elevated LDH ECOG PS ≥2

Score 0-1 2 3 4-5 0

CR (%) 87 67 55 44 92

5-year survival (%) 73 51 43 26 83

Age-adjusted risk for >60 years Ann Arbor stage III or IV Elevated LDH ECOG PS ≥2

1 2 3

78 57 46

51 26 32

Follicular Lymphoma International Prognostic Index (FLIPI) Risk factors (1 point each) Score 5-year 10-year survival (%) survival (%) Age >60 years 0-1 73 71 Ann Arbor stage III or IV 2 51 51 Hgb <12 g/dL ≥3 43 36 Elevated LDH 26 LDH indicates lactic dehydrogenase; ECOG, Eastern Cooperative Oncology Group; Hgb, hemoglobin.

diagnosis. It is generally accepted that a fine-needle aspirate is not adequate for accurate characterization of newly diagnosed NHL based on the distinct variations among each subtype. Specific elements of the tissue diagnosis and radiologic imaging will be reviewed in detail in subsequent articles in this series. The Ann Arbor staging classification system (Figure) is used for describing distribution and number of nodal sites, the presence or absence of extranodal sites, or constitutional symptoms. Two systems have been developed to provide key prognostic factors–the International Prognostic Index (IPI) for aggressive lymphoma and the Follicular Lymphoma International Prognostic Index for follicular lymphoma, which is the most common subtype of indolent NHL (Table 2).7,8 These systems are effective in identifying high-risk patients within each diagnostic subgroup who may require more aggressive initial therapy.2 The IPI system is further subdivided by age.

HEMATOLOGIC CANCERS

(WHO) revised the classification system in 2001 with added criteria based on morphology, immunophenotyping, molecular characteristics, and cytogenetics with 35 subtypes of NHL described.2 The International Lymphoma Classification Project evaluated 1403 patients thought to have NHL across nine international practice sites.

After expert hematopathology review, 25 of these patients were found not to have NHL, emphasizing the complexity of accurate diagnosis in this disease.

Based on the 1378 evaluable patients, the 13 most common subtypes of NHL were identified.

Epidemiological studies investigating the recent increase in incidence for NHL also report a number of cases that were reclassified after further expert pathology review.4,5 Many of the subtypes described in the WHO criteria were not found in this analysis, underscoring the number of rare entities classified as NHL. In addition, this underscores the importance of including these subsets in clinical trials to further characterize the disease, develop standardized criteria for diagnosis and response evaluation, and facilitate development of new therapies.

The National Comprehensive Cancer Network Guidelines for 2008 are focused on the 13 most common histological subtypes of NHL based on this analysis (Table 1).3,6

Continued from cover

Summary NHL represents a group of hematologic diseases that are common, have a wide variation in prognosis, and may require treatment over many years.

Treatment for each stage and subtype of disease may vary, and treatment within a specific subtype may vary based on prognostic evaluation. Familiarity with the nomenclature for the subtypes of this disease and the prognostic and staging criteria will provide the foundation for effective nursing management and education of the patient with NHL. Future articles in this series will provide evaluation of specific elements of the tissue diagnosis and radiologic imaging and how these are used to select the most effective therapy for an individual patient with NHL. References 1. American Cancer Society. Cancer Facts & Figures 2008. Atlanta, GA: American Cancer Society. Available at: http://www.cancer.org/ downloads/STT/2008CAFFfinalsecured.pdf.

Accessed July 30, 2008.

2. Ansell SM, Armitage J. Non-Hodgkin lymphoma: diagnosis and treatment. Mayo Clin Proc. 2005;80:1087-1097.

3. Armitage JO, Weisenberger DD. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histological subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol. 1998;16:2780-2795.

4. Clarke CA, Glaser SL, Dorfman RF, et al. Expert review of non-Hodgkin’s lymphomas in a population-based cancer registry: reliability of diagnosis and subtype classifications. Cancer Epidemiol Biomarkers Prev. 2004;13:138-143.

5. Turner JJ, Hughes AM, Kricker A, et al.

WHO non-Hodgkin’s lymphoma classification by criterion-based report review followed by targeted pathology review: an effective strategy for epidemiology studies. Cancer Epidemiol Biomarkers Prev. 2005;14:2213-2219.

6. National Comprehensive Cancer Network.

NCCN Clinical Practice Guidelines in Oncology: Non-Hodgkin’s Lymphoma, v3, 2008. http://www.nccn.org/professionals/physician_gls/ PDF/nhl.pdf. Accessed July 30, 2008.

7. Solal-Céligny P, Roy P, Colombat P, et al.

Follicular lymphoma international prognostic index. Blood. 2004;104:1258-1265.

8. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma.

N Engl J Med. 1993;329:987-994.

Source: Reference 7.

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NON-HODGKIN’S LYMPHOMA

CLINICAL TRIALS

patients in a clinical trial represents the general population of patients with that disease, there is a major risk for errors in assessing the safety and efficacy of the trial therapy. This can result in a lack of apparent benefit in larger trials, resulting in rejection of a potentially beneficial treatment, or in conducting prolonged, expensive, and ultimately failed trials of an ineffective treatment.

Challenges in trial enrollment Eder noted that it is in everyone’s self interest to enroll patients and complete trials rapidly. Sponsors and investigators not only make money conducting trials, but the less time a trial takes to complete, the less it costs, and newer, more effective therapies may become available to patients earlier. However, trials must be conducted properly. Eder says that there are large numbers of patients who want to be included in phase 1 trials despite not meeting eligibility criteria. He attributes that, in part, to some groups of patients acquiring and sharing information about potential benefits of drugs that are still in early stages of trials long before safety data are collected.

“I think we all agree we can improve on cancer therapy. The chance to participate in clinical trials gives patients a choice,” Eder says. “One guarantee every patient can take is that they have done something for somebody else.

Even negative information does help us with the next patient.”

Eligibility criteria are among the factors that affect speed of accrual. Several posters presented at the meeting addressed age, which per se is not an impediment to enrollment in trials.

Eder says that elderly patients are much less likely to enroll than younger patients, sometimes because of comorbid disease, but this may not be a valid reason for exclusion, given that elderly patients do well when treated. Hyman B. Muss, MD, of the University of Vermont and Vermont Cancer Center, believes that there is an age bias in not offering clinical trial participation to older patients, and that older patients with cancer are underserved; Eder agrees. Primary care physicians refer elderly patients to oncologists less often, and oncologists are less likely to recom-

mend trials to the elderly. For their part, nicity, or sex to be significant, but did the elderly are less likely to seek out tri- suggest that patients with higher als on their own. This could reflect gen- socioeconomic status (SES) are less erational views on care. likely to enroll. Eder says this contraOther factors affecting eligibility dicts other studies, although small include the site and severity of disease. numbers in the Wisconsin study, as Patients with primary or metastatic well as less disparity between higher brain tumors may be excluded, although and lower levels compared with other they may respond well to therapy, and parts of the country, might be responsithese patients may be overrepresented in ble. He speculated that patients with older patient populations. Eder notes higher SES might have access to investhat race and ethnicity are wellWhen patients trust their care represented in clinical trials, providers, they are more likely to although trends suggest this may accept a recommendation to connot continue to be the case. Pa- sider participation in a clinical trial. tients who have more severe disease may be more likely tigational therapies without the diffito enroll in trials. Patients with breast culties that go with trial participation. cancer may be overrepresented in trials, This may be particularly true for trials which Eder attributes to the good sup- of combinations of therapies in which port systems available to these patients. the individual agents are already Additionally, distance from a trial site approved. If insurance or a patient will may play a role in patients’ willingness pay for the agents off trial, it is easier to participate. for that patient not to participate. Eder Overly restrictive eligibility criteria also suggested that patients covered by and competing trials also affect enroll- insurance perhaps should not be ment. Other impediments to trial enrolled, so patients who could not enrollment can be attributed to trial otherwise afford treatment could be design (eg, the “equality” of treatment better served by trial participation. He in the arms of randomized trials). In a noted that Medicare and the State trial for treatment of prostate cancer, for Children’s Health Insurance Program instance, patients are likely to have have increased trial enrollment with strong opinions about surgery versus only a small incremental cost increase. radiation therapy, and it is hard to com- Patients with more education are more pare those two arms. The option of likely to enroll and may view trial parcrossing over from one study arm to ticipation as an opportunity to receive another may be attractive to potential the latest, improved treatment rather trial participants. than being “experimented” on, although elderly patients do not seem to Communication and education have that attitude.

Fay J. Hlubocky, MA, of the UniTim Wassenaar, MD, MS, of the University of Wisconsin School of versity of Chicago Medical Center, and Medicine and Public Health, pointed her group found that only 25% of out that patients must be satisfied with patients were able to identify the purtheir care. When patients trust their pose of phase 1 trials and concluded care providers, they are more likely to that cognitive impairment was quite accept a recommendation to consider common among these patients. This participation in a clinical trial. Eder may be because of multiple prior sees this as evidence of the importance chemotherapy treatments, patient age, of communication between patient and comorbidities. Although younger, and healthcare providers at all levels. better-educated patients appear to be The Wisconsin study did not find tra- less impaired, it may be that they simply ditional factors, such as age, race/eth- test better. Eder suggests larger numbers

of patients need to be studied and notes that twice as many patients with cancer self-report cognitive impairment than are identified by testing. There may also be better ways to identify impaired patients (eg, by brain scans, rather than verbal testing).

Obtaining trial information Patients can obtain information about clinical trials from several websites, including the American Cancer Society (www.cancer.org) and www. clinicaltrials.org. This self-referral information, however, is not available to those without the knowledge or comfort level to use computers. Here, again, the elderly may be at a disadvantage, as are those who do not own a computer. Eder is concerned, therefore, about putting trial information on websites, easy and inexpensive as it is, when many potentially eligible participants do not get their information that way.

The Coalition of Cancer Cooperative Groups reports that only about 3% of adults in the United States participate in clinical trials. Wassenaar’s group in Wisconsin reports that 60% of patients are unaware of clinical trials.

Eder cited survey results showing up to 85% of patients may be unaware of clinical trials, but 75% of these patients would have participated in a trial had they known about trials at the time of their diagnosis. The Coalition of Cancer Cooperative Groups has as its mission to improve patient awareness of clinical trials, facilitating access, and promoting participation. The Coalition’s TrialCheck (http://www.trialcheck. org/Services/) can be used to find cancer trial information.

Conclusions Eder concludes that challenges to enrollment in clinical trials can be met with dedication of considerable institutional resources for the conduct of trials, availability of complete trial information to referring healthcare providers, and acceptance on the part of institutions, investigators, and patients that clinical trials are an option for cancer treatment.

—Lynne Lederman

SUPPORTIVE CARE MANAGEMENT OF CANCER PAIN AND FATIGUE Continued from cover

CLINICAL TRIALS

breast, lung, colon, and prostate cancer.

The intervention was in line with National Comprehensive Cancer Network Pain and Fatigue Guidelines, explained lead author Betty Ferrell, RN, PhD, a research scientist at the City of Hope in Duarte, California. Ferrell presented this study at a poster session during the 2008 Annual Meeting of the American Society of Clinical Oncology.

According to Ferrell, results of this study suggest that continual patient education is needed to address concerns of addiction to pain medications, tolerance, and other misconceptions about analgesic use and to promote understanding about the role of exercise and activity for fatigue. System changes are also needed to expedite earlier referral to supportive services to assist with pain and fatigue management. She said too that enhanced professional education is needed to ensure that oncologists and other professionals provide optimum relief of pain and fatigue.

16

The study enrolled 187 outpatients who experienced pain and/or fatigue; 40% had breast cancer, 25% had lung cancer, 20% had colon cancer, and 15% had prostate cancer. Patients were randomized to the intervention (n = 104) or to usual care (n = 83).

Patients were assessed at baseline, 1 month, and 3 months using the Pain and Fatigue Knowledge Scales, Psychological Distress Thermometer, City of Hope Quality of Life Tool, Karnofsky Scale, and Piper Fatigue Scale.

All patients were 18 years of age or older (mean, 59.7 years) and had at least 6 months to live; and they had a pain and/or fatigue score of >4 on a 0 to 10 scale.

Sixty percent were women; 11% had pain symptoms, 56% had fatigue symptoms, and 33% had both.

Twenty-three percent had stage I-II cancer, and 77% had stage III-IV cancer. Seventy-eight percent had received prior chemotherapy, 8% had had radiation therapy, and 19% had received supportive services.

G REEN H ILL H EALTHCARE C OMMUNICATIONS

Total knowledge about pain increased significantly from baseline to 3 months. For example, at baseline only 45% of patients agreed with the statement that cancer is the most common cause of pain compared with 80% at the end of the study.

Barriers to pain management decreased significantly only for the intervention group. Compared with the usual care group, the intervention significantly improved on knowledge about pain (P <.001), while knowledge about pain decreased in the usual care group; fatigue decreased significantly in the intervention sample (P = .006 to P <.001); and often increased in the usual care group. Knowledge of fatigue increased significantly in the intervention group only (P <.001).

A phase 3 study will explore dissemination and integration of the tested intervention in routine oncology practice.

—Alice Goodman October/November 2008

patients who had the most severe fatigue at the beginning of the study showed the most significant improvement after taking the drug, whereas patients with mild or moderate fatigue showed no significant improvement.

Modafinil improved symptoms of sleepiness, but not depression, compared with the placebo group.

“Although this drug did not have a positive effect for everyone, until now there was nothing reliable to prescribe for people who are most severely fatigued,” said principal investigator Gary R. Morrow, PhD, a professor of radiation oncology and psychiatry at the University of Rochester Medical

Cancer Patients’ Quality of Life May Directly Relate to Their Overall Survival

your quality of life?” Patients had a variety of cancer types, and the question

screen for baseline quality of life, we have found that it is prognostic for

The patients who had the most severe fatigue at the beginning of the study showed the most significant improvement.

CHICAGO—Baseline quality of life (QOL) appears to be a strong and independent prognostic factor for overall survival over and above performance score in a wide variety of oncology patient populations. In addition, QOL should be considered for routine inclusion as a stratification factor for all future randomized oncology treatment trials, according to researchers at the Mayo Clinic. They presented data at the 44th Annual Meeting of the American Society of Clinical Oncology that showed baseline QOL is a strong predictor of overall survival regardless of cancer type (gastrointestinal, genitourinary, lung, breast, and brain).

“Quality of life appears to affect the survival of cancer patients,” said study lead author Angelina Tan, MD, a cancer researcher at the Mayo Clinic, Rochester, Minn. “If physicians can

QOL should be considered for routine inclusion as a stratification factor for all future randomized oncology treatment trials. was asked during their participation in one of 24 different North Central Cancer Treatment Group clinical trials.

The unifying factor for the patients was that all had late-stage disease. All of the results were converted to a 100-point scale.

The investigators found that baseline QOL was a strong and independent prognostic factor and there was a distinct difference when dividing patients by the median score of 83: there was a 6.1-month increased survival time for patients with scores >83. The investigators also divided the group into those with scores of >50 and <50, defining those in the <50 category as having clinically deficient QOL. In this analy-

Nurses assess patient quality of life with virtually every clinical interaction they have with a patient. identify patients who are not doing well, they will be able to intervene and, we hope, improve not only their patients’ sense of well-being but also their length of life.”

Tan and her colleagues compared overall survival with responses from 3704 patients to one question: “On a scale of 1 to 10, how would you rate October/November 2008

sis, the results were even more striking, with increased survival of 7.5 months for the nonclinically deficient patients.

The investigators determined that these numbers were independent of performance status (a traditionally used survival prediction method evaluating a patient’s ambulatory status).

“Using a very simple, single-item

approach is that we now have data to support a simple way of facilitating their care programs,” said Sloan in an interview with The Oncology Nurse.

He noted that he and his colleagues now plan to use this tool in all of their clinical trials with cancer patients. He said it is sensitive enough to pick up problems clinically and he hopes that this measurement will be used in much the same way as pain is measured for clinical purposes.

patient survival across a broad spectrum of cancer patients,” said study principal investigator Jeff Sloan, PhD, a professor of oncology at the Mayo Clinic.

—JS Sloan, who presented the study findings at the meeting, said it is hoped that future research will identify both how and when clinicians can best support their patients’ feelings of well-being. For example, if the QOL deficit were found to be related to patient fatigue and emotional distress, interventions (pharmaceutical, psychosocial, etc) could be offered to improve patient well-being.

“The take-home message for oncology nurses is that they are really the front-line people when it comes to assessing patient quality of life. They spend the most time with the patients in terms of dealing with their ongoing symptoms and quality of life issues. So, what we are hoping to do is incorporate this measure into clinical practice so nurses can have a systematic and efficient way of assessing patient quality of life.

Nurses assess patient quality of life with virtually every clinical Jeff Sloan, PhD interaction they have with a patient. The advantage with this

Continued on page 24

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SUPPORTIVE CARE

CHICAGO—A large phase 3 clinical study is showing that the narcolepsy drug modafinil may help alleviate

patient who reported a fatigue value greater than two was randomly assigned to receive either 200 mg daily of modafinil or a placebo. A total of 320 patients were randomized to the modafinil group and 322 to the placebo group.

The investigators found that the

SUPPORTIVE CARE

severe cancer-related fatigue for a significant number of patients, paving the way for possibly the first reliable treatment for this common and debilitating side effect.

The randomized trial included 642 patients who were receiving chemotherapy for a variety of cancers. The investigators asked patients to complete a survey assessing their level of fatigue, sleepiness, and depression during the second and fourth cycles of chemotherapy.

A standard scale, similar to the one used to measure pain, was used to rate patients’ level of fatigue from zero (none) to 10 (as bad as it can be). Any

noticeable,” he said.

Center, New York.

He said another interesting aspect of Eugeroic agents such as modafinil promote wakefulness without interfering the study was that modafinil appeared with sleep or causing addiction con- to have no impact on depression, which cerns. These agents are cleared from the is often linked to fatigue. “Our data body in approximately 12 hours. The show that fatigue and depression are US Food and Drug Administration has very different,” he said. “We’ve also approved modafinil for the treatment of tested antidepressants such as paroxenarcolepsy, sleep apnea, and other tine in cancer patients and, as expected, sleep-related disorders. Researchers at it helped their depression but it did the University of Rochester Medical nothing for fatigue.”

Center have also been testing modafinil to treat “chemo brain.”

—John Schieszer Morrow said managing cancer-related fatigue is important because most patients seek to go on with their lives as they undergo treatment. He and his colleagues have shown in previous studies that 80% to 85% of patients receiving chemotherapy report fatigue, as do nine of 10 patients receiving radiation therapy.

Morrow said it is not fully understood why modafinil appears to work best in the most severely fatigued patients.

However, he suggested the benefits may simply be more evident in this group of patients.

“If you think about it, in the context of severe nausea or a pounding headache, any amount of relief is going to be Gary R. Morrow, PhD

Narcolepsy Drug May Help Combat Fatigue in Cancer Patients

Complimentary

Continuing Education Program #08CE059d • RELEASE DATE: November 15, 2008 • EXPIRATION DATE: November 14, 2009

Finasteride and Prostate Cancer Prevention: The Latest Chapter

EDITORIAL BOARD Amy K. Darke, MS Public Health Services Division Fred Hutchinson Cancer Research Center Seattle, WA 98109

BY MARY W. REDMAN PHD Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington

Helen McFarland, PharmD, BCOP Clinical Pharmacist—Oncology and Pain Management Department of Pharmacy Union Memorial Hospital Baltimore, MD 21218

HOW TO RECEIVE NURSING CREDIT To receive continuing education credit, learners must: • Read the article in its entirety • Take the CE self-assessment test and complete the evaluation test: 1. Log onto www.theoncologynurse.com.

2. Click on UNMC logo on homepage.

3. Register to participate.

4. Enter program number #08CE059d.

• Complete and submit the evaluation form online (enter program number #08CE059d).

Nurses must answer at least 70% of the questions on the post-test correctly. If Internet access is not available, please fax a request for an evaluation form to 402-559-6379, attn: Anji Wittman, (please include return fax number) or e-mail concne@unmc.edu • The estimated time to complete this activity is 1 hour. Your continuing education certificate can be printed by following the directions online after successful completion of the post-test.

DISCLAIMERS The opinions or views expressed in this continuing education activity are those of the faculty and do not necessarily reflect the opinions or recommendations of the University of Nebraska Medical Center College of Nursing Continuing Nursing Education.

While the University of Nebraska Medical Center College of Nursing Continuing

O

ur recently published reanalysis of the Prostate Cancer Prevention Trial (PCPT) appears to settle the issue of finasteride’s role in prostate cancer prevention. My colleagues and I reported that the 5-alpha-reductase inhibitor reduced risk of prostate cancer detection by 30% in healthy men >55 years of age without the increased rate of detecting high-grade tumors (Gleason grade >7) seen in the initial study.1,2 An accompanying editorial supports our findings, stating that “finasteride is a safe and effective prevention option that should be offered to men at risk for prostate cancer.”3 Increased detection of high-grade malignancies in the initial study appeared to primarily reflect improved screening properties of prostate-specific antigen (PSA) testing and digital rectal examination (DRE) as well as an increased sensitivity for detecting such tumors on biopsy in men receiving finasteride rather than any effect of finasteride on the biology of cancer progression.1 The increased biopsy sensitivity most likely resulted from the prostate gland shrinkage associated with finasteride, in line with its approved use in benign prostatic hypertrophy.1,4 FACULTY/PLANNER DISCLOSURES All planners and faculty participating in continuing education activities provided by the University of Nebraska Medical Center, College of Nursing Continuing Nursing Education are expected to disclose to the audience any significant support or substantial relationship(s) with providers of commercial products and/or devices discussed in this activity and/or with any commercial supporters of the activity. In addition, all faculty are expected to openly disclose any off-label, experimental, or investigational use of drugs or devices discussed in their presentation. The planners and faculty and have been advised that this activity must be free from commercial bias and based upon all the available scientifically rigorous data from research that conforms to accepted standards of experimental design, data collection, and analysis.

October/November 2008

Nursing Education is an ANCC accredited organization, this does not imply endorsement by the UNMC or ANCC of any commercial products affiliated with this activity.

PROGRAM GOAL To educate oncology nurses about recent findings about the potential role of finasteride in prostate cancer prevention.

LEARNING OBJECTIVES After completing this activity, the reader should be better able to: • Summarize the initial findings of the Prostate Cancer Prevention Trial.

• Explain how finasteride may affect prostate cancer detection by prostate-specific antigen testing or digital rectal examination.

• Discuss how the use of a risk calculator may be helpful for patients and their physicians when evaluating prostate cancer risk and making decisions about prevention.

TARGET AUDIENCE Advanced practice nurses, registered nurses, and other interested healthcare professionals, especially those caring for cancer patients.

COST This program is complimentary for all learners.

Initial PCPT findings We first studied finasteride as a possible protective agent because it blocks conversion of testosterone to the more potent androgen dihydrotestosterone involved in prostate cancer development. The large (N = 18,882), National Cancer Institute–funded PCPT followed lowrisk men >55 years of age treated with placebo or finasteride (5 mg daily) for 7 years to determine the drug’s effect on prostate cancer detection.2 Men underwent annual PSA testing and DRE. Those with abnormal DRE or annual PSA >4 ng/mL, adjusted for finasteride’s effect, were referred for biopsy. This analysis revealed that: • Finasteride reduced the risk of prostate cancer detection by 24.8% overall (detection rates, 18.4% in the finasteride group vs 24.4% in the placebo group, 95% confidence interval [CI], 18.6% to 30.6%, P <.001) • Finasteride was associated with a higher risk of detecting highgrade malignancy. Gleason grade >7 tumors were identified in 6.4% of men in the finasteride group compared with 5.1% of men in the placebo group, for a 27% higher risk (95% CI, 1.07 to 1.50, P = .005).

The following authors, reviewers, and planning committee members listed below have stated they have no significant or substantial relationship with providers of commercial products and/or devices discussed in this activity and/or with any commercial supporter of this activity.

• Lisa Anzai, RN, MA • Catherine Bevil, RN, EdD • Jennifer Ludwig, PharmD • Lara J. Reiman • Karen Rosenberg • Gary C. Yee, PharmD, FCCP, BCOP • Amy K. Darke, MS • Helen McFarland, PharmD, BCOP • Mary W. Redman, PhD • Gary Shelton, MSN, ARNP, AOCN

The following author has stated that he has the following financial relationships: Ian M. Thompson, MD, states that he is a consultant for Veridex and Mission.

CONTINUING NURSING EDUCATION ACCREDITATION AND CONTACT HOURS STATEMENT The University of Nebraska Medical Center College of Nursing Continuing Nursing Education is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

This activity is provided for 1.0 contact hours under ANCC criteria.

Provided for 1.2 contact hours under Iowa Provider #78. Provider Approved by the California Board of Registered Nursing, Provider #13699 for 1.2 contact hours.

Mary W. Redman, PhD Public Health Services Division Fred Hutchinson Cancer Research Center Seattle, WA 98109 Gary Shelton, MSN, ARNP, AOCN Clinical Research Program NYU Cancer Institute New York, NY 10016 Ian M. Thompson, MD Department of Urology The University of Texas Health Science Center at San Antonio San Antonio, TX 78229 PLANNING COMMITTEE Lisa Anzai, RN, MA Nurse Planner University of Nebraska Medical Center College of Nursing 985330 Nebraska Medical Center Omaha, Nebraska 68198-5330 Catherine Bevil, RN EdD Director, Continuing Nursing Education and Evaluation University of Nebraska Medical Center College of Nursing 985330 Nebraska Medical Center Omaha, Nebraska 68198-5330 Lara J. Reiman Managing Editor Green Hill Healthcare Communications, LLC 241 Forsgate Drive Monroe Twp, NJ 08831 Karen Rosenberg Editorial Director Green Hill Healthcare Communications, LLC 241 Forsgate Drive Monroe Twp, NJ 08831 REVIEWERS Jennifer Ludwig, pharmD Oncology Pharmacist University of Nebraska Medical Center Omaha, NE 68198 Gary C. Yee, PharmD, FCCP, BCOP Professor of Pharmacy Practice Associate Dean for Academic Affairs College of Pharmacy University of Nebraska Medical Center Omaha, NE 68198

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Continuing Education Program #08CE059d • RELEASE DATE: November 15, 2008 • EXPIRATION DATE: November 14, 2009 Because of this apparently elevated rate of aggressive disease, finasteride did not enter common use as a chemopreventive agent.

Continued investigation The impact of finasteride on prostate gland size and PSA levels was known before the PCPT. Therefore, before ruling out finasteride as an effective chemopreventive agent, the study team undertook a series of analyses to investigate finasteride’s effect on detection of prostate cancer and high-grade disease. To determine whether finasteride improved cancer screening, we compared the predictive value of a positive DRE and/or PSA levels between the placebo and finasteride arms with biopsy findings. To determine whether finasteride improved biopsy sensitivity to detect high-grade disease, we compared biopsy findings with radical prostatectomy samples. These studies revealed that: • Finasteride significantly increased the sensitivity of PSA testing for detecting prostate cancer (P <.001) and high-grade (Gleason grade >7) disease (P = .003).5 • Finasteride significantly increased the sensitivity of DRE for detecting prostate cancer (P = .015).6 • Finasteride significantly increased the sensitivi-

ty of biopsy for Figure. Prostate Cancer Detection Rates detecting highgrade malignancies, based on comparison of Gleason score at biopsy and p r o s t a t e c t o m y.

Biopsy detected 69.7% of Gleason grade > 7 malignancies identified at prostatectomy in the finasteride group versus 50.5% of such cancers in the placebo group (P = .01).4 We proposed that the increased sensitivity for high-grade cancers most likely resulted from the reduction of median prostate gland volume seen with finasteride (25.1 cm3 finasteride vs

C A S E S T U DY

Case Study of Five Prostate Cancer Prevention Trial Participants

BY MARY W. REDMAN PHDa; AMY K. DARKE MSa; IAN M. THOMPSON, MDb a Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington b Department of Urology, The University of Texas Health Science Center at San Antonio, Texas

T

he Prostate Cancer Prevention Trial randomized 18,882 men to receive finasteride, a selective inhibitor of type 2 five-alpha reductase or placebo to be followed for annually up to 7 years for prostate cancer. The study, which closed in 2003, showed that finasteride reduced the risk of prostate cancer by at least 25%.1 Based on study data, a calculator for the risk of prostate cancer and high-grade cancer (Gleason score >7) was developed.2 Presented here are five cases from the placebo arm that illustrate the diversity of prostate cancer risk and the use of the risk calculator. The calculator is intended to help inform the decision process for patients and their physicians on the risk of prostate cancer and the possible benefit of finasteride use for prevention of prostate cancer.

Case 1 is a white man, 62 years old at study entry, with no family history of prostate cancer.

During his 7 years of follow-up in the study, he had no clinical indications for biopsy of the prostate.

At his 7-year and final annual study visit, results of his digital rectal examination (DRE) were normal, and his prostate specific antigen (PSA) level was 1.1 ng/mL. His end-of-study biopsy found no cancer. According to the risk calculator, this patient has a 15% chance of prostate cancer and a 2% chance of high-grade prostate cancer.

Case 2 is a white man, 67 years old at study entry, with no family history of prostate cancer.

During his 7 years of follow-up in the study, he had no clinical indications for biopsy of the prostate. At his final visit, his DRE results were normal, and his PSA level was 2.5 ng/mL. Prostate cancer was detected on biopsy with a Gleason score of 6, indicating low-grade disease.

This man has a 27% and 6% chance of prostate

cancer and high-grade cancer, respectively.

Case 3 is a white man, 68 years old at study entry, with a family history of prostate cancer. At his 2-year visit, his PSA level was 2.4 ng/mL, and his DRE results were abnormal. Results of a biopsy of the prostate were negative. At his 6-year visit, his PSA level was elevated at 4.3 ng/mL, and he again had abnormal DRE results. He again underwent a biopsy, and prostate cancer was detected with a Gleason score of 6, indicating low-grade disease. This man has a 47% and 19% chance of prostate cancer and high-grade cancer, respectively.

Case 4 is a white man, 60 years old at study entry, with no family history of prostate cancer. At his 7-year visit, his PSA level was 5 ng/mL, and his DRE results were normal. Results on biopsy of the prostate were negative. This man has a 39% and 11% chance of prostate cancer and high-grade cancer, respectively.

Case 5 is a black man, 72 years old at study entry, with no family history of prostate cancer. At his 1-year visit, his PSA level was 0.3 ng/mL, and his DRE results were abnormal. Prostate cancer was detected on biopsy with a Gleason score of 6, indicating low-grade disease. This man has a 13% and 3% chance of prostate cancer and high-grade cancer, respectively.

References 1. Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349:215-224.

2. Comprehensive Center for the Advancement of Scientific Strategies, Fred Hutchinson Cancer Research Center. Cancer Risk Calculator. http://www.compass.fhcrc.org/edrnnci/bin/ calculator/main.asp?t=prostate&sub=disclaimer&v=prostate& m=&x=Prostate%20Cancer. Accessed October 28, 2008.

34.4 cm3 with placebo; P< .001).1,4 We also suggested that finasteride may have selectively inhibited lowgrade cancers, leaving high-grade tumors constituting a greater proportion of the total cancers detected.4 Counterbalancing these factors, men in the placebo group were more likely to undergo biopsy. This latter finding would bias results toward greater cancer detection in the placebo group.1 We then conducted a series of analyses in an effort to control for these detection biases. We also incorporated 3 months of data not included in the 2003 report.

These additional data were gathered from when the data set was frozen after the trial was stopped, up to its unblinding.1

Latest findings Our team recently published the latest findings from these analyses.1 • Increased sensitivity of PSA and DRE did not significantly affect initial findings that finasteride significantly reduced risk of prostate cancer detection.

Increased likelihood of biopsy in the placebo group also did not substantially change results.

• Specifically, after accounting for these biases, finasteride reduced the risk of prostate cancer detection by 30% (detection rates: 14.7% in the finasteride group vs 21.1% in the placebo group [Figure]; 95% CI, .64–.76, P <.0001) and there was a now-nonsignificant increased risk of high-grade cancer (14%, 95% CI, .96–1.35; P = .12) • Last, we controlled for the heightened biopsy sensitivity for the high-risk malignancies seen with finasteride. This analysis showed that finasteride significantly reduced the rate of both high-grade (Gleason >7) and low-grade (Gleason <6) prostate cancer, by an estimated 27% (95% CI, .56-.96; P = .02) and 34% (95% CI, .55–.80, P <.0001), respectively. We corrected for the increased biopsy sensitivity to high-grade cancer seen with finasteride by attempting to estimate the rate of high-grade prostate cancer that would have been identified if all men with biopsy-detected malignancies had undergone prostatectomy. About 25.5% of study subjects with biopsy-detected malignancies had their prostate removed and had prostatectomy samples and biopsy grade information available for analysis.4 Continued on page 21

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October/November 2008

Continuing Education Program #08CE059d • RELEASE DATE: November 15, 2008 • EXPIRATION DATE: November 14, 2009 Continued from page 20

Recommendations • Whether healthy men should take finasteride for prostate cancer prevention depends on many factors. These include the risk of prostate cancer, significance of the cancers that can be prevented, and finasteride’s risk/benefit profile.

• Prostate cancer is common. Primarily because of frequent screening, the estimated lifetime risk for men in the United States is one in seven.1 • Identification of even low-grade cancer often prompts men to seek treatment. Treatment has its own costs and side effects; it also exacts an emotional toll on patients and their families.

• Finasteride significantly reduced the risk of both low- and high-grade cancers. It decreases urinary

symptoms and complications of prostatic hypertrophy. We identified no evidence that finasteride increased the risk of high-grade prostate cancer.

• Finasteride’s side effects include reduced sexual function.

• Evidence supports offering finasteride to men at risk for prostate cancer.

• Studies are needed to determine the optimal duration of therapy to prevent prostate cancer while minimizing risk of side effects.3

References 1. Redman MW, Tangen CM, Goodman PJ, Lucia MS, Coltman CA Jr., Thompson IM. 2008. Finasteride does not increase the risk of high-grade prostate cancer: a bias-adjusted modeling approach.

Cancer Prev Res. 2008;1:174-181.

2. Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349:215-224.

3. Logothetis CJ, Schellhammer PF. High-grade prostate cancer and the Prostate Cancer Prevention Trial. Cancer Prev Res. 2008;1:151152.

4. Lucia MS, Epstein JI, Goodman PJ, et al. Finasteride and highgrade prostate cancer in the Prostate Cancer Prevention Trial.

J Natl Cancer Inst. 2007;99:1375-1383.

5. Thompson IM, Chi C, Ankerst DP, et al. Effect of finasteride on the sensitivity of PSA for detecting prostate cancer. J Natl Cancer Inst.

2006;28:1128-1133.

6. Thompson IM, Tangen CM, Goodman PJ, et al. Finasteride improves the sensitivity of digital rectal examination for prostate cancer detection. J Urol. 2007;177:1749-1752.

Eileen McCaffrey contributed to the preparation of this manuscript.

Continued on page 22

C O M M E N TA R Y

Finasteride and Prostate Cancer Prevention: The Latest Chapter: A Nurse’s Perspective

BY GARY SHELTON, MSN, ANP-BC, AOCN New York University Cancer Institute, New York

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ncology nurses tackle new knowledge and balance it against old behavior.

Advanced practice nurses embrace this role, allowing them a framework to promote change that influences practice and ultimately improves outcomes. We welcome research like fresh air, hoping that findings will lead to evidence-based care that healthcare providers will accept and promote. Prevention of cancer is of primary interest.

A fresh look at the maturing data from the Prostate Cancer Prevention Trial, in which men took finasteride 5 mg daily for 7 years, reveals interesting bias-adjusted data.1 It is now clearer that finasteride not only reduces the incidence of prostate cancer (chemoprevention), but also allows for more accurate grading of the disease when found through screening/early detection. With better understanding of the mechanism of action of finasteride (ie, shrinking the prostate gland and blocking the conversion of testosterone to dihydrotestosterone), we see how finasteride increases the sensitivity of prostate-specific antigen testing and digital rectal examination for detecting prostate.

Men with benign prostatic hyperplasia take finasteride as indicated to shrink the prostate gland, thereby lessening urinary obstructive symptoms. For many of these men, this benefit outweighs the sexual side effect of erectile dysfunction. Men without urinary obstructive symptoms may not see themselves as being at risk for prostate cancer, and they may not be ready to hear about medical interventions to prevent the disease. Men without known health problems may not actively be seen in clinics or seek healthcare interventions.

As with all attempts at prevention of disease, the proposed intervention must be seen as beneficial and with acceptable side effects. In

October/November 2008

the case of prostate cancer, there are a number of questions to consider: Do men see themselves at risk of prostate cancer? Would they consider an intervention to prevent cancer as necessary? Are they aware of these new data?

How do we introduce the topic? Are men coming to our offices or are we reaching out to them? An asymptomatic population may not be aware of their risk of prostate cancer. All men deserve the option of an intervention that may either prevent disease or allow for easier detection.

Nurses must be knowledgeable about prostate cancer and comfortable about discussing it with their patients. They should discuss both the overall and relative risk for prostate cancer and outline what is known about the disease and its prevention. All men deserve to be informed of ways to improve their quality of life, especially through diet and lifestyle changes.

Finasteride is not currently approved for prostate cancer prevention and may not be available to all men; however, evidence sup-

finasteride, we may be able to stave off the development of prostate cancer in some men.

Treatment with finasteride may also allow for more accurate staging when cancer is detected, making it possible to treat more aggressive disease earlier.

When men understand the risk/benefit ratio of an intervention, they are more likely to consider the option. Being up front and candid about side effects allows for discussion of possible treatments and approaches to dealing with side effects. Referral to specialists may be necessary at times.

Although finasteride cannot currently be promoted for prostate cancer prevention, it is our role and duty to make our patients aware of recent research and their treatment options.

Cancer prevention interventions are routinely discussed in all contact moments. Oncology nurses should be up-to-date on research findings and offer education to peers and populations at risk to facilitate decision making and patient advocacy.

1. Redman MW, Tangen CM, Goodman PJ, et al. Finasteride does not increase the risk of high-grade prostate cancer: a biasadjusted modeling approach. Cancer Prev Res. 2008;1:174-181.

All men deserve to be informed of ways to improve their quality of life, especially through diet and lifestyle changes. ports offering finasteride to men at risk for prostate cancer. The incidence of prostate cancer is high, perhaps due in part to overscreening. By implementing chemoprevention with

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Continuing Education Program #08CE059d • RELEASE DATE: November 15, 2008 • EXPIRATION DATE: November 14, 2009 C O M M E N TA R Y

Finasteride and Prostate Cancer Prevention: The Latest Chapter: A Pharmacist’s Perspective

BY HELEN MCFARLAND, PHARMD, BCOP Union Memorial Hospital, Baltimore, Maryland

T

he Prostate Cancer Prevention Trial (PCPT) was the largest prostate cancer prevention trial ever completed.1 The positive results were tainted by the increased incidence of high-grade tumors found in the finasteride arm, thus muting the enthusiasm of the medical community to use finasteride as a preventative agent.

The current reanalysis of the PCPT data presented in the Redman article is one of many attempts to evaluate the PCPT results to determine the real role of finasteride as a preventative agent for prostate cancer. Redman and colleagues used advanced statistical modeling to determine whether finasteride is truly increasing the risk of high-grade tumors or if there are other factors that are lending bias to the interpretation of the data. The authors thoroughly discuss the difference between the original data and their findings and conclude that finasteride does not increase the risk of high-grade prostate cancer after 7 years of therapy.

The PCPT investigators suggest that finasteride increases the sensitivity of prostate-specific antigen (PSA) and digital rectal examination (DRE) for detecting prostate cancer.2,3 Finasteride decreases the prostate gland volume, therefore if there was tumor present, it would be easier to detect by DRE or biopsy.

Finasteride decreases PSA levels to a greater extent in the setting of benign prostatic hyperplasia, thus those men receiving finasteride with persistently elevated PSA levels are more likely to have prostate cancer, and the risk of high-grade disease increases proportionally with higher PSA levels. When the PCPT data

were adjusted for prostate gland size, the biopsy results showed there was no increase in highgrade tumors in the finasteride group.2 The amount of data that has been released which contradicts the original conclusion of the 2003 PCPT data certainly has offered some clarification of the risks and benefits of finasteride for prostate cancer prevention. Patients and providers should feel comfortable that finasteride in the preventive setting is not selecting out for high-grade tumors.

So what is the final recommendation for the use of finasteride in prostate cancer prevention?

Patients and providers should feel comfortable that finasteride in the preventive setting is not selecting out for high-grade tumors.

The American Urological Association and the American Society of Clinical Oncology have yet to make formal recommendations on the subject. The most common side effects reported in the PCPT finasteride group were sexual dysfunction (reduced ejaculate volume, erectile dysfunction, and decreased libido) and gynecomastia. Older age predicts increased sexual dysfunction with finasteride. The increase in adverse effects in the finasteride arm was small

and decreased over the 7 years of treatment.4 Patients in the PCPT received finasteride 5 mg orally every day for up to 7 years of therapy.

Additional studies are required to determine the minimally effective duration of therapy to decrease potential adverse effects.

Thompson and colleagues developed a risk calculator taking into account variables such as PSA, DRE, age, race, family history, and history of a prior negative biopsy.5 The calculator predicts a patient’s risk for developing prostate cancer and risk of high-grade disease. Use of these results in combination with consideration of the risks and potential benefits of finasteride therapy should be part of the counseling session with all men older than 55 years of age. This can assist the patient in determining the best course of action based on the potential aggressiveness of his disease and potentially decrease unnecessary systemic therapy in tpatients with low-risk disease.

References 1. Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349:215-224.

2. Yael CC, Liu KS, Heyden NL, et al. Detection bias due to the effect of finasteride on prostate volume: a modeling approach for analysis of the prostate cancer prevention trial. J Natl Cancer Inst. 2007;99:1366-1374.

3. Thompson IM, Chi C, Ankerst DP, et al. Effect of finasteride on the sensitivity of PSA for detecting prostate cancer. J Natl Cancer Inst. 2006;98:1128-1133.

4. Moinpour CM, Darke AK, Donaldson GW, et al. Longitudinal analysis of sexual function reported by men in the prostate cancer prevention trial. J Natl Cancer Inst. 2007;99:1025-1035.

5. Thompson IM, Ankerst DP, Chen C, et al. Assessing prostate cancer risk: results from the prostate cancer prevention trial. J Natl Cancer Inst. 2006;98:529-534.

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October/November 2008

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SUPPORTIVE CARE

For Opioid-induced Constipation, Try Second or Third Dose If No Response to First Dose of Methylnaltrexone CHICAGO—Many patients with advanced illness who suffer from opioid-induced constipation but fail to respond to a first dose of methylnaltrexone will respond to a second or third dose, said Robert J. Israel, MD, at the 44th annual meeting of the American Society of Clinical Oncology.

Methylnaltrexone is a selective muopioid receptor antagonist that blocks peripheral opioid side effects without affecting central analgesia.

A previous randomized trial by

Israel and his colleagues (N Engl J Med. 2008;358:2332-2343) established the efficacy of subcutaneous methylnaltrexone (0.15 mg/kg of body weight) for treating opioid-induced constipation in patients with advanced disease (incurable cancer or other end-stage disease). In that study, significantly more patients treated with methylnaltrexone than placebo had a laxation response within 4 hours after the first double-blind dose (48.4% vs 15.5%). More than 80% of the patients enrolled had taken contact laxatives without success before study entry, and the median number of laxatives used before entry was two.

Patients in the study were receiving a median opioid dose of approximately 100 mg of oral morphine equivalent.

“The question has been what do you for those people who don’t respond to the first dose? Should you continue to

Hyperglycemia Increases Infection Risk in Stem Cell Recipients CHICAGO—Hyperglycemia is a significant risk for infection following stem cell transplant, and should be managed aggressively in the peritransplant period to potentiate this risk, according to Vince D. Cataldo, MD, a second-year medical oncology and hematology fellow at M.D. Anderson in Houston, Texas, at the 44th annual meeting of the

glycemia results from the catabolic effects of induction chemotherapy and the use of corticosteroids.

The effect of hyperglycemia during the peritransplant period was investigated in a retrospective review of all patients admitted to M.D. Anderson Cancer Center for an initial stem cell transplant over a 3-month period. The

Table. Infection data Characteristic Patients with valid infections Total Types of infections Blood-borne Urinary tract Line-associated Sputum/bronchial Cerebrospinal fluid

43 (39.1%) 15 (34.9%) 14 (32.6%) 7 (16.3%) 6 (13.9%) 1 (2.3%)

SUPPORTIVE CARE

American Society of Clinical Oncology.

In critically ill patients, hyperglycemia is associated with increased mortality, organ dysfunction, and a number of blood-borne infections. In stem cell transplant recipients, hyper-

incidence of hyperglycemia with respect to the development of documented infections (blood-borne, line-associated, sputum/bronchial [excluding normal flora and yeast], and urinary tract) was assessed.

Sexual Dysfunction Underrecognized and Usually Not Treated

ed, and the implication is that oncologists and others who treat breast cancer survivors should be alerted to this potential problem.

“Sexual dysfunction is probably being underreported by our breast cancer survivors, partly because patients are too embarrassed or ashamed to bring it up with their doctors. Many doctors probably don’t actively screen for sexual dysfunction, because they are afraid of opening up a can or worms and because there are limited interventions available for sexual dysfunction among breast cancer patients,” said lead author Katherine Crew, MD, assistant professor of medicine at Columbia University Medical Center in New York. “Oncologists should be more

CHICAGO—Although physicians may not routinely ask cancer survivors about sexual dysfunction, and patients may not feel comfortable about volunteering that information, it appears that sexual dysfunction is a significant problem for women who have had chemotherapy and/or radiation. A study presented at the 2008 American Society of Clinical Oncology’s annual meeting suggests that sexual dysfunction in patients with breast cancer is more prevalent and severe than has been previously report24

G REEN H ILL H EALTHCARE C OMMUNICATIONS

try to treat or do you stop treating, assuming that they won’t respond?” said Israel, senior vice president of medical affairs, Progenics Pharmaceuticals, Inc, Tarrytown, New York.

His group compared the clinical response (rescue-free laxation within 4 hours post-dosing) between methylnaltrexone and placebo to previous doses during the seven doses of the double-blind phase of the previously reported trial. Of the patients who failed to respond to the first dose, 34% responded to a second dose of methylnaltrexone, and 9% responded to placebo (P = .006). Of those who failed to respond to the first two doses, 26% responded to a third dose of methylnaltrexone, and 12% responded to placebo (P = .16).

“We showed that if you continue to treat, by the third dose, 75% will respond,” Israel said. “So the recom-

mendation is that when treating patients with methylnaltrexone, if they don’t respond to the first dose, treat again. One third of them will then have a response to the second dose, and then on dose three, another one third will have a response.”

Of patients who did not respond to the first three doses, there was no difference in the response to either a fourth dose of methylnaltrexone or placebo (7% vs 8%, respectively). “If they don’t respond to three doses, at that point it’s probably not worth giving additional doses,” Israel noted.

“The problem is probably not opioidinduced constipation at that point; these patients are all very sick so a lot of them have other problems; they may have a tumor obstructing the intestine, for example.”

Of the 110 patients included, 35 patients had acute myelogenous leukemia, 21 had multiple myeloma, 21 had non-Hodgkin’s lymphoma, 11 had Hodgkin’s lymphoma, seven had acute lymphoblastic leukemia, six had chronic lymphocytic leukemia, five had chronic myelogenous leukemia, and four had other cancers.

Forty-three (39.1%) patients developed valid infections (Table). The incidence of infection was significantly higher in those who met the American Diabetes Association’s criteria for a diagnosis of diabetes versus those who did not: the incidence of infection during the hospitalization was 52.5% in the 40 patients with diabetes and 31.4% in the patients who did not have hyperglycemia (P = .04).

In addition, the average hospital stay was longer in those patients with diabetes versus those without diabetes: length of hospital stay averaged 35.0 days in those with diabetes versus 24.3 days in those without diabetes (P = .002).

“Confounding factors were acute graft-versus-host disease, which leads to steroid induction, which causes more hyperglycemia; so there is the issue that those with graft-versus-host disease were sicker patients and is confounding the presence of diabetes,” Cataldo said.

Eighteen patients (45%) with diabetes developed acute graft-versus-host

disease compared with 5 (7.1%) of those without hyperglycemia (P <.0001).

Corticosteroids were used in 19 of the 40 patients with diabetes compared with only 14 of the 70 patients without diabetes (P = .002).

Even with these confounders, “hyperglycemia is certainly a risk factor and one that we can intervene on to potentially fix the hyperglycemia, and decrease the amount of infections that we’re having at our institution during transplant,” Cataldo said.

“There’s no protocol yet to say that all patients need point-of-care [bedside] monitoring but that is something that we’re also looking into,” he noted. “We control hyperglycemia on the floor as aggressively as we can with sliding scale insulin, but there’s an argument whether sliding scale insulin is actually aggressive control or not. The best part of our aggressive control happens in the intensive care unit on an insulin drip, which is not something we’re able to implement in patients who are just getting a transplant.”

A protocol for more aggressive glucose management is being implemented at M.D. Anderson and may be assessed in a future prospective study, Cataldo said.

aware of the problem and more research should focus on interventions to treat sexual dysfunction, which will have a significant impact on quality of life,” she stated.

As a first step, she suggested that doctors, nurses, and other healthcare professionals who treat breast cancer survivors should ask about sexual dysfunction and offer interventions that can improve pain associated with sexual intercourse and lubrication.

Scores on the Female Sexual Function Index (FSFI) were compared with published scores of normal female controls and also those with female sexual arousal disorder (Rosen R, et al. J Sex Marital Ther. 2000;26:191-208). An abnormal score was defined as >2 standard deviations below the mean of female controls.

The patients’ mean age was 52 years; 18% were premenopausal; 41% had chemotherapy/surgery-induced menopause; and 41% had natural menopause.

Ten percent had stage 0 (ductal carcinoma in situ) breast cancer, 32% had stage I, 41% had stage II, and 16% had

Study details The study focused on women with early-stage breast cancer treated at Columbia University. Of 206 consecutive women screened, 167 (81%) responded; of these, 117 were evaluable.

—Wayne Kuznar

—WK

Continued on page 25

October/November 2008

dard of chemotherapy and radiation after surgery, despite compelling clinical data available since 2001.

It is encouraging, however, to see that there has been a significant increase in the use of chemoradiotherapy since it became the standard of care,” said study principal investigator Kristian Enestvedt, MD, a cancer researcher at Oregon Health & Science University Cancer Institute, Portland.

In 2001, a seminal study showed that using chemotherapy and radiation after gastric cancer surgery significantly increased survival rates.

Other studies also have recommended What patients should know is that at least 15 lymph nodes should be removed with gastric resection surgery. that they should routinely ask Until now, however, there has been little about whether this recommended practheir physicians if their tice is being followed.

Using a statewide cancer registry, treatment plan includes the Enestvedt and his colleagues identified 313 patients who had undergone stomlatest clinical trial data that ach cancer surgery. They found that chemo/radiation therapy was used in only pertain to their 14.2% of patients before 2001 compared with 33.3% after that date. “That still particular situation. leaves almost 67% of cases left in which patients did not get the appropriate and potentially life-extending therapy. We found that “We were surprised to learn that there are still there was a 5-month survival advantage for patients many patients who are not receiving the gold stanCHICAGO—It appears that there are still significant numbers of patients across the United States who are not getting the recommended therapy after surgery to remove stomach cancer. Researchers from Oregon presented data at the 44th Annual Meeting of the American Society of Clinical Oncology suggesting that a majority of these patients are not benefiting from a major study that has shown chemotherapy and radiation prolong life after stomach cancer surgery.

who received chemoradiotherapy,” Enestvedt said.

The researchers also found that only 35% of the patients had at least 15 nodes removed to check for cancer. The number of lymph nodes, however, did not affect survival.

“What patients should know is that they should routinely ask their physicians if their treatment plan includes the latest clinical trial data that pertain to their particular situation,” said study coauthor, Charles Thomas, MD, who is chairman and professor of radiation medication at Oregon Health & Science University.

“There is a significant increase that is occurring and that is good news. That is what we would hope to see. However, we are still seeing a number of patients who are missing out on chemotherapy and radiation,” Enestvedt pointed out in an interview with The Oncology Nurse. “The message for the oncology nurses is that when patients inquire about what the standard of care is, then it is important for all the members of the healthcare team to be aware of what it is. The nurses need to advocate for patients to get into clinical trials. Nurses tend to know about these trials, where the patients may not be aware of them. So, the nurses can be great advocates.”

SUPPORTIVE CARE

New Study Suggests Many Patients May Not Be Receiving Recommended Treatment After Surgery for Stomach Cancer

—John Schieszer

New Research Finds Possible Cause of “Chemo Brain” in Breast Cancer Patients West Virginia University’s Mary Babb Randolph Cancer Center, Morgantown.

A study by Abraham and his colleagues documented the extent of changes to the brain’s white matter in women who received chemotherapy for breast cancer (Abraham J, et al.

Clin Breast Cancer. 2008;8:88-91). The preliminary study involved 10 breast cancer patients who had received chemotherapy and complained of cognitive changes. A control group of nine healthy women of similar age, education, and intelligence quotient, who never received chemotherapy, was also studied.

All participants were screened for

medical, neurologic, and psychiatric conditions that could affect brain structure or function. Participants were tested for depression, anxiety, and processing speed. Each subject in the study also underwent diffusion tensor imaging magnetic resonance imaging scans to assess changes in the white matter of the brain.

“The images indicated differences in the white matter in the front part of the brain in women who had received chemotherapy,” said study investigator Marc Haut, PhD, who is in the Department of Behavioral Medicine and Psychiatry, Neurology and Radiology at West Virginia University. “This

SEXUAL DYSFUNCTION

or type of hormonal therapy.

Continued from page 24

Potential treatments Most of the symptoms of sexual dysfunction in patients with breast cancer are related to estrogen deprivation due to premature menopause caused by chemotherapy and antiestrogen hormonal therapy. Unfortunately, the best methods for treating menopausal symptoms are estrogen replacement therapy and topical estrogen. “Estrogen replacement is a relative contraindication in breast cancer patients. Nonestrogen– containing lubricants are a start for patients with vaginal dryness, but are sometimes ineffective. Estrogen-containing topical agents should be used with caution in breast cancer patients with moderate-to-severe vaginal symptoms,” Crew commented. Because of the complex and multifactorial nature of sexuality, she suggested sexual counseling for breast cancer survivors with sexual dysfunction.

stage III. Forty percent had mastectomy and 60% had lumpectomy. Eighty-three percent had chemotherapy; and 72% had radiation therapy. Thirty-one percent had no hormonal therapy, 32% were taking tamoxifen, and 37% were taking an aromatase inhibitor.

Mean FSFI scores of patients with breast cancer were similar to those of women with known sexual arousal disorder and lower than controls. Patients with breast cancer had abnormal scores for desire (43%), arousal (54%), lubrication (62%), orgasm (46%), satisfaction (50%), pain (63%), and total score (57%). Multivariate analysis showed that low total FSFI scores were significantly correlated with unmarried marital status (P = .02), postmenopausal status (P = .05), and receipt of adriamycin chemotherapy (P = .03). No association was found with sexual dysfunction and age, body mass index, October/November 2008

—Alice Goodman

difference in white matter correlated with how quickly the breast cancer patients could process information.”

Women who received chemotherapy performed significantly worse in processing speed than their counterparts in the control group. The changes in the white matter of the brain did not appear to be caused by depression or anxiety.

“Our preliminary findings suggest that chemotherapy may change the brain and those changes affect the patient’s cognitive skills,” said Abraham.

—John Schieszer

Risk factors for chemobrain • Factors that increase the risk of memory problems in cancer survivors include: • Brain cancer • Chemotherapy given directly to the central nervous system • Higher doses of chemotherapy or radiation • Radiation therapy to the brain • Younger age at time of cancer diagnosis and treatment Source: MayoClinic.com.

G REEN H ILL H EALTHCARE C OMMUNICATIONS

25

SUPPORTIVE CARE

T

hanks to early diagnosis and improved chemotherapy, more women survive breast cancer than ever before. However, following treatment, approximately 25% of survivors experience mild-to-moderate memory, concentration, and cognitive problems known as “chemo brain.” A new study suggests that changes in the brain may explain this condition.

“Several studies have investigated chemotherapy’s cause and effect on memory problems, but until now scientists had no clue what changes in the brain lead to memory loss,” said Jame Abraham, MD, director of the Comprehensive Breast Cancer Program at

NURSING EDUCATION & TRAINING

UNMC College of Nursing Offers Postgraduate Programs in Oncology

NURSING EDUCATION & TRAINING

Courtesy of UNMC College of Nursing

Established in 1917, the University of Nebraska Medical Center (UNMC) College of Nursing celebrated its 90th anniversary last year. The UNMC College of Nursing is the oldest state-supported and largest nursing school in Nebraska. It currently has four campuses—in Omaha, Lincoln, Kearney, and Scottsbluff—and, in response to community demand, a fifth in Norfolk is in the planning stages. The college offers three levels of nursing programs: the baccalaureate, the master’s, and the doctoral. The Oncology Nurse recently spoke with editorial board member Constance Visovsky, RN, PhD, APRN, director of the master’s program.

The College offers two programs at the master’s level, she explained: The Master of Science (MSN) in Nursing degree is for those who have undergraduate degrees in nursing while the Post Master’s certificate is for those who already have a master’s degrees in another area. “We also offer an RN [registered nurse] to MSN option for nurses who have the RN but lack the baccalaureate and would like ultimately to have a master’s degree,” Visovsky said.

The master’s program offers a broad range of specialties, including acute care and oncology, which fall under the Adult Health and Illness program. Within each of these specialties, students can prepare to become a Clinical Nurse Specialist (CNS) or a Nurse Practitioner (NP). Students in the acute care and

the oncology specialty get clinical experience in both inpatient and outpatient settings so they see patients undergoing acute care as well as follow-up care.

Students choose to specialize in oncology for a variety of reasons, Visovsky said. “Sometimes people go into oncology because that was the job they could get at the time and then they find they love it. Some, like myself, go into oncology voluntarily. We love the patients. We love the experience.” Oncology, she continued, is “a growing field with the new targeted therapies and people living longer into survivorship, and it offers many opportunities for a career and many opportunities to intervene for patients.” The serious nature of the illness, she said, “forms bonds between the healthcare team and the patients.”

Earning an advanced degree offers nurses several advantages, according to Visovsky, including a better salary and expanded job opportunities in clinical practice, research, and teaching. “The biggest shortage in nursing is in faculty….We would encourage our next generation of students to consider teaching as a career.”

Trends in oncology nursing Visovsky received her master’s degree from the University of Rochester in 1995 and her doctorate in nursing from Case Western University in 2002 and has worked as an acute care nurse practitioner as well as a nursing instructor. In her years of practice, she has observed a number of trends in oncology nursing. One of these, she said, is the change from a disease-based approach to more of a symptom-management approach. “We’re learning and having to teach more about specific symptom-management strategies for targeted therapies.”

With the widespread use of oral chemotherapeutic drugs, adherence has become a major issue.

“We now have to teach strategies for adherence,” she said. The increasing number of long-term cancer survivors has brought new emphasis on the importance of a healthy lifestyle, and nurses have to be prepared to counsel patients on tobacco cessation, weight control, cardiovascular disease, and diabetes risk reduction. Genetics too has received increasing attention, and nurses Students In the acute care and oncology must be prepared to answer patient’s questions about the specialties can train to become both genetic basis of disease, available tests, who should be tested, and a CNS and an NP. what the results mean. Other oncology specialties can train to become both a CNS trends she noted are increasing focus on palliative, and an NP. This unique feature of the program, end-of-life care, and quality improvement, “working Visovsky explained, came about because curriculum well in interprofessional teams toward providing the planners in the 1990s wanted to prepare students to best and safest quality care for our patients.”

Nursing is “a very powerful profession,” Visovsky play a “blended role” with the skills of both a CNS noted, and more men are entering the field. One and an NP. Students must have undergraduate courses in attraction is that “the job market is robust,” and nursresearch and physical assessment and are required to es can look forward to a good job with a good salary take a graduate course in statistics. Previous work and opportunities for advancement. Admission stanexperience in the field is desirable but not a require- dards at the UNMC College of Nursing are high for both undergraduates and graduates, and the quality of ment for admission.

Currently, 365 students are enrolled in the master’s students is high. “The new young person is choosing and post-master’s programs, 14 specializing in oncolo- nursing for its opportunities, for its advancement, for gy, Visovsky said. The MSN program requires four its prestige. We are the most trusted profession, and semesters of full-time study, but part-time study is also we’re well recognized in the healthcare arena…. available. Like the undergraduate program, the MSN Nursing is a force to be reckoned with,” Visovsky said. program includes a mix of classroom and clinical training. Internet-based learning is also offered. Students in —Karen Rosenberg 26

G REEN H ILL H EALTHCARE C OMMUNICATIONS

UNMC College of Nursing: A student’s view Kari Lockhart recently completed the Master of Science in Nursing program at UNMC and started her career in oncology nursing.

Where did you do your undergraduate training?

I did my undergrad training at Creighton University College of Nursing from August 2001 to May 2004. My first year of undergraduate work was at the University of St. Thomas in St. Paul, Minn. I was pre-med there, but decided to switch to nursing so that I could provide direct patient care all of the time.

Why did you decide to specialize in oncology?

Ever since I was young I was interested in the oncology field. I think it was because I have had a lot of close family members and friends diagnosed with cancer and some who eventually died.

I wanted to do more for the patients and wanted to show them that there is always hope. Cancer patients also have a wonderful attitude toward life, and I have always felt this was my calling in life. Oncology/hematology is also such an interesting field, and it is constantly changing or something new is being discovered about it. So it challenges me to keep up-to-date with new developments, and I always love a challenge.

Why did you choose UNMC? I picked UNMC because they were the only university in the Omaha and southwest Iowa area that offered the Adult Acute Care Oncology Track, which was exactly what I wanted to do What did you like best about the program?

What I liked best about the program would have to be the support and encouragement from everyone involved in this university. The instructors always encouraged us to do more, learn more, want more, and never degraded or insulted us. They gave us pointers on how to do things better or where we could find more information.

Many of the instructors are also currently practicing as nurse practitioners themselves, so we learned a lot from their stories and past experiences. They also understood that we were graduate students who had to carry on our lives outside the classroom. They understood that a lot of us worked full-time and went to school full-time, so they were very considerate when it came to schedules and due dates.

What are you doing now?

I just received my ultimate dream job. I am a nurse practitioner at UNMC in the bone marrow transplant unit. I will be working mostly with inpatients, but will see some outpatients when needed.

For more information about programs offered by the UNMC College of Nursing, call 800-626-8431 x94120 or log onto http://www.unmc.edu/nursing October/November 2008

Using Upfront Contracts to Cure Mutual Mystification

H

ave you ever thought that your communication with people was crystal clear and then find that the other person didn’t get it? Typically we think, “How could they not understand? They just don’t listen.” But maybe your communication wasn’t as clear as you thought it was. When two or more people engage in communication but the end result is neither person clearly understands what the other expressed, we call that mutual mystification. If this is happening on a regular basis, a system of agreement might help. We call it an upfront contract.

People communicate through different methods. Up-front contracts are the mutually agreed upon expectations between individuals, established before moving forward in any endeavor. In any professional setting, whether it is business or the practice of medicine, when you set an up-front contract with a prospect or patient, both of you have agreed on what you want to accomplish and what will happen next, provided a specific set of events occurs. The mechanics are more involved, but the concept is that simple.

An up-front contract in a typical discussion might set the parameters for what will be discussed, what information will be provided by both the nurse and the patient, and what the outcome of the action might be at the end of the discussion.

The

Oncology Nurse

The Official Newspaper of Record for the Hem/Onc Nurse

ic set of events occurs.

Up-front contracts often ease anxiety that patients have due to the unknown.

Think of a child going the dentist. In the old days, the dentist would command the child to get in the chair and keep his mouth open while the dentist poked, picked, and shoveled power tools into his mouth. Today, the dentist knows a little more about up-front contracts and makes the child feel more comfortable. The dentist may explain that he will only be in the chair for 20 minutes and that he is only inspecting and cleaning the child’s teeth.

He may also explain that none of the tools he will use will hurt and may even ask the child if he would like to watch a cartoon. Now, the child may still feel a little stress, but it’s much easier than the initial situation.

October/November 2008

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and what will happen next, provided a specif-

Oncology

A Newsletter Series for Cancer Care Professionals

prospect or patient,

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CONSIDERATIONS IN MULTIPLE MYELOMA

front contract with a

agreed on what you

The

The Official Newspaper of Record for the Hem/Onc Pharmacist

Presents The First Annual 2008 Curriculum for

When you set an up-

both of you have

The Sandler Sales Institute is an international sales and management training/consulting firm since 1967. For more information, in NJ call 732-764-0200 or visit their website at PerformanceSellingLLC.com.

Multidisciplinary Cancer Care newsletters provide a forum for sharing expert interdisciplinary treatment perspectives on patient care with the ultimate goal of promoting ongoing professional education to physicians, nurses, and pharmacists in the hematology/oncology community.

Pharmacists

Target Audience This educational publication is designed for physicians, nurses, and pharmacists who wish to enhance their knowledge concerning the management of patients with multiple myeloma and renal dysfunction.

Learning Objectives At the completion of this educational activity, you should be able to: • Describe the prevalence of renal insufficiency among patients with multiple myeloma (MM) • Recognize the special challenges in pharmacologic treatment of the many patients with MM who also have renal insufficiency, especially those requiring dialysis • Discuss the results of studies showing treatments that are active and safe in MM patients with renal impairment, including those with advanced renal failure requiring dialysis

Accreditation Physicians This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of CME Consultants and Center of Excellence Media. CME Consultants is accredited by the ACCME to provide continuing medical education for physicians.

CME Consultants designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

CME Consultants is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

This activity has been designated for 1 contact hour (0.100 CEU). In order to receive credit, all participants must complete an evaluation, request for credit form, and a posttest. Statements of Credit will be mailed to participants within six weeks. ACPE #309-999-08-012-H01-P Initial Release Date: 05/07/08. Planned Expiration Date: 05/07/09.

Nurses CME Consultants is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

NURSING LIFE

By Jim

need training to achieve a particular outcome. Or, specific coaching may be necessary to keep an employee on behaviors to achieve an outcome. Certain supervisory checkpoints may be described and then established to maintain the flow and pace of work.

Up-front contracts require work. First, there is the frontend learning curve—gaining an understanding about how to set up-front contracts. Second, there is the effort involved in actually setting the contract with the other person, a step most people are not currently doing. Third, there is the continual process of improving how you set contracts with others.

Contracts make your life easier, but they do require more effort—an investment in time and energy that pays back many times over.

NURSING LIFE

In establishing an up-front contract, you are establishing the ground rules for a working relationship Barnoski between yourself and others.

The contract describes which behaviors are expected to achieve those aspects of the goal for which they will be responsible. For a computer analyst, the goal could be a component of a software package; for a salesperson, the goal might be expressed as a sales quota; for a nurse, the goal could be a higher level of satisfaction for the patients.

By discussing mutual expectations, you establish what is expected of the others and what you need to provide. This may be stated explicitly. For instance, the employee may

Leadership and Communication Skills for Nurses

CME Consultants designates this program for 1 contact hour. Participants should claim only those contact hours actually spent in the educational activity.

In order to receive credit for this program, each participant must complete the evaluation form, posttest, and certificate request form. Certificates will be mailed to program participants in approximately four to six weeks after receipt of the completed evaluation form, posttest, and certificate request form.

CO Center of Excellence Media, LLC E ™

™

Your Innovative Partners in Continuing Education

Supported by an educational grant from Millennium Pharmaceuticals, Inc.

G REEN H ILL H EALTHCARE C OMMUNICATIONS

27

Nursing Life

—DMK

NURSING LIFE

Corn Salsa Courtesy of Kurt Rummel 1 cup diced tomatoes 3/4 cup fresh roasted corn 28

G REEN H ILL H EALTHCARE C OMMUNICATIONS

Career Builder: Tips for Successful Negotiations

S

uccessful negotiations start before the parties ever get to the negotiation table or other such setting. “Deal making and negotiation is really around relationship building, and relationships shouldn’t start at the negotiation table,” according to Kevin Sowers, RN, MSN. “You should figure out strategies on how you’re going to do that before you get to the negotiation table.” He presented a Career Builder mini-session at the Oncology Nursing Society (ONS) annual meeting in Philadelphia in May. As Chief Operating Officer of Duke University Hospital, Durham, North Carolina, Sowers advised listeners that the first principle is to always go into a negotiation with an understanding of what the other person may want to get out of it and what is important to that person or organization. Ask questions about needs and concerns, he said.

As an example, he said he recently negotiated a deal with a company but first had called its president and asked what the company’s overall business objectives were and what were some of the challenges it faced in the marketplace. “So that first phone call was more of a relationship-building phone call and was more me looking at what it was like to run their business,” he said. “So I actually spoke to that during the negotiations, where I built on that to build my business case as to why the deal should look a certain way.”

The second piece for a successful negotiation is to understand and gather the data points that you will need to build your case. Using graphics can tell a more powerful story than words alone depending on the audience. State not only what you need but also why, and how you would like to achieve it. Both parties may have similar goals but may differ

1/4 cup diced onions 1/4 cup diced peppers or jalapenos 1/4 cup seeded diced cucumber 1/2 bunch cilantro chopped fine Juice of 1 fresh lime Salt and pepper to taste

on how they want to reach them.

Preparing alternative goals and methods may be useful in case your first suggestion is not accepted.

“The third piece is to know your messaging,” Sowers said. “What are the most important three points you want to get across to the person you are negotiating with? If you go beyond three points, you start to lose the negotiation.”

You should anticipate questions and objections before starting to present your case. This point gets back to seeing the situation from the other party’s side of the table—their objectives, concerns, and even fears.

“Spend time thinking through what

©iStockphoto.com/Phillip Jones Photography

of the discussion and bring it back to the listener’s values, projects, etc.

The Expectations step requires clearly communicating what the outcome should look like. Hochberg gave an example of telling one’s child to clean up his/her room. The idea of clean may be very different for the parent and the child, so a clear picture of the result needs to be communicated. Similarly, patient education about wound care requires a mental picture of what a good outcome should look like.

As the Ability step implies, it is imperative to speak to someone who can make your ideas happen. Telling your ideas to a nursing assistant may be good practice, but you have to pitch them, for example, to your director of nursing or hospital CEO to make them happen. “If you need to get to the head of your hospital, often the best person to talk to is the person doing their scheduling, not necessarily the physician [him/her]self,” Hochberg said.

One or two specific examples or stories can be helpful in supporting the main message, and everything you say should be consistent with that message.

Repetition, passion, and humor are good tools. Do your homework, know your audience, and tailor the message specifically to them. In a short encounter, the message needs to be simple. A good test is if you can explain it in one or two sentences. The final step is to ask the listener if he or she has any questions.

Hochberg advised that nurses work up and practice a few pitches using the CLEAR format. As public relations director for the ONS, she suggests a good pitch to start with may be one to patients on the value of oncology nursing (eg, how nurses have played a leadership role in managing symptoms or what is the knowledge and evidence behind a practice).

©iStockphoto.com/David Smith Photography

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ou have to have a point to make a point. Actually, you have to have a few well-supported points but not too many if you want to get your point across to decision makers. That was the message of a mini session by Karen Hochberg, director of marketing for the Oncology Nursing Society (ONS) during its annual meeting in Philadelphia.

Hochberg said getting your point across involves five tactics: • Getting out the message • Framing the issue • Defining the audience • Defining the desired outcome • Determining what you need to communicate to best bring about that outcome.

This model relies on focus, brevity, and clarity of communication and is intended to be used as a quick pitch, what she calls “your elevator speech,” to a colleague, boss, prospective employer, or other decision maker.

Simplicity and clarity are key to getting the message out, Hochberg said. Two or three points are optimal. A listener most likely cannot retain more than that from a quick pitch. The speaker should refine the talk to be able to deliver each point in two or three sentences.

“Paragraphs are too long,” she said.

“People like two-point or three-point plans. Our ears immediately perk up.”

The first step is to know what you want to communicate. A useful message framework is CLEAR: Connections to the listener’s values, ideas, or projects—how a desired outcome will serve their needs, benefit patients, staff, families, the institution, etc List the steps you want done Expectations for success—what the desired outcome will look like Ability and know-how (ie, whether the listener has the tools to make it happen) Review—briefly reiterating the points

©iStockphoto.com/Angus Plummer

NURSING LIFE

Career Builder: Getting Your Point Across Quickly

they might object to, and go ahead and address that on the front end so that you’ve fielded their questions before they’ve even asked them,” Sowers advised.

Finally, you have to know the “deal breakers,” those things that you cannot agree to and would end the negotiation. Such points may conflict with one’s vision for a program or institution or may violate personal or institutional philosophy or guiding principles.

According to the ONS brochure “Building Your Dream Job,” timing of negotiations is important. Avoid negotiating when participants are tired, angry, stressed, or preoccupied.

The goal of negotiating is about finding solutions.

Further tips for negotiating can be found at www.work911.com/articles/ negotiate.htm.

—DMK

Roast corn on the grill for 5 minutes or until golden brown on all sides. Do not burn.

Let the corn cool and shave off the kernels.

Mix all ingredients in a bowl and serve with chips, rice, or as a side dish.

Husk corn, season with salt, pepper, and olive oil.

October/November 2008

Gelclair ® can bring a smile to the face of patients with oral mucositis

Soothing the way to relief

GELCLAIR ® provides soothing, long-lasting pain relief1 at the first sign of oral mucositis.

Contains no alcohol and no lidocaine, so patients won’t experience drying, stinging or numbing.

GELCLAIR® Coating Mucosa

Prescribe 6 boxes of GELCLAIR® for a 30 day supply GELCLAIR® is available at your local pharmacy and at:

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Now serving patients nationwide Toll Free: 877-977-9118

For additional information, visit www.gelclair.com or call 1-877-GELCLAIR. Ingredients: Water, Maltodextrin, Propylene Glycol, Polyvinylpyrrolidone (PVP), Sodium Hyaluronate, Potassium Sorbate, Sodium Benzoate, Hydroxyethylcellulose, PEG-40 Hydrogenated Castor Oil, Disodium Edetate, Benzalkonium Chloride, Flavoring, Saccharin Sodium, Glycyrrhetinic Acid. Contents: 15 mL per single-use packet. Commercial boxes contain 15 single-use packets. (NDC 24477-010-15) Indications: GELCLAIR® has a mechanical action indicated for the management of pain and relief of pain by adhering to the mucosal surface of the mouth, soothing oral lesions of various etiologies, including oral mucositis/stomatitis (may be caused by chemotherapy or radiation therapy), irritation due to oral surgery, traumatic ulcers caused by braces or ill-fitting dentures, or disease. Also indicated for diffuse aphthous ulcers. Contraindications: The administration of GELCLAIR® is contraindicated in any patient with a known or suspected hypersensitivity to any of its ingredients. Side effects: At the time of producing this leaflet, no adverse effects have been reported in clinical trials with the use of GELCLAIR®. Postmarketing reports have included infrequent complaints of burning sensation in the mouth.

Reference: 1. Innocenti M, Moscatelli G, Lopez S. Efficacy of Gelclair® in reducing pain in patients with oral lesions: preliminary findings from an open pilot study. J Pain Symptom Manage. 2002;24:455-457.

GELCLAIR® is a registered trademark of Helsinn Healthcare SA, Lugano, Switzerland. Manufactured for Helsinn Healthcare SA, Lugano, Switzerland. Marketed and distributed by EKR Therapeutics, Inc., Cedar Knolls, NJ 07927.

© 2008 EKR Therapeutics, Inc. All rights reserved.

GEL070

Complementary and Alternative Medicine and the Oncology Patient

BY AMANDA SALDIVAR, MS, RD, LD

T

TAUSSIG CANCER INSTITUTE, CLEVELAND, OHIO

ALTERNATIVE AND COMPLEMENTARY THERAPIES 30

he use of complementary and alternative medicine (CAM), which is defined as any practice, group, or system not considered to be a part of conventional medicine,1 is often of interest to oncology patients. Complementary medicine is designed to be used alongside conventional medicine and is also termed integrative medicine. Because of the increasing number of high-quality studies showing its safety and benefits, complementary medicine is also becoming more mainstream; professionals such as chiropractors, massage therapists, osteopaths, and dietitians are becoming part of healthcare teams and having their services covered by health insurance.2 Alternative medicine is a subgroup of CAM that is designed to replace conventional medicine and tends to spark the most controversy, especially throughout the oncology field, because there is no substantial scientific evidence supporting its use, and it may cause more harm than benefit.

Six major subcategories of CAM are listed by the Office of Cancer Complementary and Alternative Medicine (OCCAM), a division of the National Cancer Institute3: Alternative medical systems are defined by a complete system of theory and practice; acupuncture, homeopathy, and Chinese medicine are examples of these.

Energy therapies involve the use of energy fields and are broken down into two subcategories: biofield, designed to affect the energy surrounding and contained within the body (eg, Qi gong and Reiki therapies); and electromagnetic-based, involving pulsed magnetic fields and magnet therapy.

Manipulative and body-based therapies include chiropractics, therapeutic massage, osteopathy, and reflexology.

Mind-body therapies include meditation, hypnosis, art therapy, support groups, dance therapy, and aromatherapy.

Pharmacologic and biologic treatments are defined as off-label use of prescription drugs, hormones, vaccines, and other biologic products not yet accepted into mainstream medicine.

Spiritual therapies include prayer and spiritual healing.

According to OCCAM, all types of nutritional therapies are considered CAM, including nutrients, nonnutrients, and bioactive food components used as chemopreventive agents, as well as diets or specific foods used as cancer prevention or treatment strategies.3 Also included are use of specific diet therapies, such as macrobiotics, the Gerson diet, Kelly/Gonzalez regimens, and any type of dietary supplement/vitamin. Although most of these examples are not recommended and, in fact, often discouraged by registered dietitians, our main goal working with oncology patients is to help manage side effects to lower the morbidities associated with malnutrition and to provide information to help lower risk of recurrence after treatment.

Nutrition in relation to cancer is being increasingly studied and is becoming a key component of complementary care for oncology patients.4-6 Regardless of practitioners’ perceptions of CAM, patients need and expect our guidance

G REEN H ILL H EALTHCARE C OMMUNICATIONS

in making decisions about its use.7 Most types of CAM are unregulated and, given that it is a multimillion dollar business in the United States, patients are increasingly seeking these types of therapies, with or without physician support. This lack of support may cause underreporting of CAM use to oncologists. It is vital for all practitioners to be aware of the types of CAM and have reliable resources to which they can direct patients.

A search for “complementary alternative medicine cancer” resulted in 767,000 results on Google. This vast array of information can be overwhelming for both providers and patients seeking reliable, objective information on CAM. Fortunately, government agencies have recognized the widespread use of CAM among Americans and have developed organizations to help patients and clinicians become more educated.

A recent review by Boddy and Ernst lists resources found to provide quality information on CAM for cancer patients based on the DISCERN rating instrument, a validated questionnaire that assesses information on treatment choices for health conditions.8 This list also included those that would be beneficial for patients, researchers, clinicians, or all three.

Among the sources listed are the National Cancer Institute’s complementary and alternative medicines summary, the Office of Complementary and Alternative Medicine, the World Health Organization, the Society for Integrative Oncology, the National Center for Complementary and Alternative Medicine (National Institutes of Health).

The growing acceptance of what was once “nontraditional” is providing more options to patients, and clinicians need to be informed about CAM so that they can help their patients make informed decisions about its use. This is yet another reason why having a

©iStockphoto.com/Stock Photo NYC

comprehensive care team can provide benefit to the patient.

References 1. National Cancer Institute. Complementary and Alternative Medicine in Cancer Treatment (PDQ). http://www.cancer.gov/cancertopics/pdq/cam/camcancer-treatment. Accessed July 29, 2008.

2. Pelletier KR, Astin JA. Integration and reimbursement of complementary and alternative medicine by managed care and insurance providers: 2000 update and cohort analysis. Altern Ther Health Med. 2002;8:3839,42,44.

3. Office of Complementary and Alternative Medicine Understanding CAM. http://www.cancer.gov/cam/ health_understanding.html. Accessed May 6, 2008.

4. National Cancer Institute. Nutrition in Cancer Care (PDQ). http://www.cancer.gov/cancertopics/pdq/supportivecare/nutrition/healthprofessional. Accessed May 6, 2008.

5. American Cancer Society. Nutrition for the Person with Cancer. http://www.cancer.org/docroot/MBC/ MBC_6.asp?sitearea=ETO. Accessed May 6, 2008.

6. American Institute for Cancer Research. Diet and Cancer: What’s the Link? http://www.aicr.org/site/Page Server?pagename=dc_diet. Accessed May 6, 2008.

7. Ben-Arye E, Frenkel M, Klein A, Scharf M. Attitudes toward integration of complementary and alternative medicine in primary care: perspectives of patients, physicians and complementary practitioners. Patient Educ Couns. 2007;70:395-402.

8. Boddy K, Ernst E. Review of reliable information sources related to integrative oncology. Hemat/Oncol Clin North Am. 2008;22:619-630.

CARTOON Cartoon courtesy of Joseph Farris

ALTERNATIVE AND COMPLEMENTARY THERAPIES

Alternative/Complementary Therapies

October/November 2008

avoid common investment pitfalls: (1) do not chase performance (last year’s winner may be heading for a loss); (2) do not try to time the market (predicting which market sectors will perform well is part voodoo and part guess); (3) do not concentrate your holdings in one sector or one type investment (the “too many eggs in one basket” mistake); and (4) do not create a portfolio of too many funds (a few well chosen funds can provide excellent diversification).

By Sylvia Maurin

Market risk Markets tend to move in cycles that can fluctuate widely. Periods of rising and falling stock prices fuel both joy and sorrow for investors. A diversified asset allocation may be an investor’s only means of sharing in upside appreciation while gaining a measure of protection in times of falling stock values. And it is not only the American market that bears watching. The prices of foreign stocks and the prices of US stocks often move in opposite directions. Words to the wise here: seek a diversified portfolio that suits your risk tolerance and time horizon, and unless and until there are significant changes in one or both factors, avoid making changes to it.

Investment risk While we know that even money hidden under our mattress will lose value over time, we cannot easily predict which types of investments hold the key to our gaining the best possible financial security. Understanding the underlying strengths and weaknesses of assets in our portfolio enables us to make informed decisions about our holdings. Coming to an understanding of these aspects of investment risk takes time—but what activity of value does not? In general, non-US growth stocks tend to go through cycles that outpace or trail the stock market. Such periods usually last for a number of years.

Country risk Domestic events taking place within a specific country’s securities markets have an impact on the risk of holding assets from that country. Events such as natural disasters, political turmoil, and both good and bad news from various market sectors within the country of interest have an effect on investment performance. With the constant feed of global news, it is not as hard as it may seem to become a keen market watcher.

Successful investing While achieving investment success even in rosy financial markets may seem a daunting task, success during most market conditions can be achieved at least in part by avoiding commonly known pitfalls. In other words, concentrate on doing a few things very well. To

Sylvia Maurin is president of Source One, LLC, a consulting services firm. Information presented in this is not intended to furnish or replace the expert guidance and/or advice of a financial planning professional familiar with your particular financial situation, goals, and objectives.

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

ON DEMAND FREE CONTINUING EDUCATION CREDITS www.COEXM.com strives to provide the most up-to-date clinical information that will improve cancer care and outcomes for patients through specialty products, across multimedia platforms, reaching multiple stakeholders and customers.

Current activities at www.COEXM.com include: • Considerations in Multiple Myeloma •Emerging Therapies for Myelodysplastic Syndromes • New Therapeutic Approaches to Metastatic Melanoma • Skin Toxicities Associated with EGFRInhibitor Therapy • Current and Future Perspectives on the Treatment of Colorectal Cancer Interactive online presentations with polling questions at www.COEXM.com

FREE CE newsletters at www.COEXM.com www.coexm.com

FREE CE newsletters at www.COEXM.com

August 2008 • Volume 1 • Number 3

September 2008 • Vol. 1 • No. 2 A Supplement to

Visit us at: www.coexm.com

Considerations in Multiple Myeloma: Hard-to-Treat Patients

Editorial Director Susan Berry susan@coexm.com

MULTIDISCIPLINARY TEAM PRESENTATIONS BY Elizabeth Bilotti, MSN, APRN, BC, OCN® St Vincent’s Comprehensive Cancer Center

Kamakshi Rao, PharmD, BCOP University of North Carolina Hospitals

Shaji Kumar, MD Mayo Clinic

• Updates from the 44th Annual Meeting of the American Society of Clinical Oncology • Multidisciplinary Perspectives on Melanoma Treatment LeAnn B. Norris, PharmD, BCPS Sandra Beam, RN, BS, OCN, CCRC

INTRODUCTION

Russell Hennessy russell@coexm.com

Dear Colleague: It is my distinct pleasure to offer this newsletter entitled “Considerations in Multiple Myeloma: Hard-to-Treat Patients,” the third issue in a series of newsletters featuring topics relevant to your multidisciplinary team approach to caring for patients with multiple myeloma (MM).

Together with a faculty of hematologists/oncologists, oncology nurses, and oncology pharmacists, we focus our discussion on one topic for each newsletter. While the previous issues focused on patients with renal dysfunction (another hard-to-treat population of MM patients) and on treatment-naive patients, this issue discusses treatment of patients with relapsed/refractory disease, as well as those with high-risk factors, including elderly patients, patients with abnormal cytogenetics, and those with elevated β2-microglobulin levels.

Topics in upcoming issues will include health economics and side effect management.

It is our sincere hope that the information presented here is of value to you in your care of patients with MM. Visit us at: www.coexm.com Sincerely,

Millennium Pharmaceuticals, Inc.

IN THIS ISSUE:

Copy Editor Bonnie Nickel Senior Production Manager Alaina Pede Directors of Client Services John W. Hennessy john@coexm.com

LETTER TO OUR READERS

Supported by an educational grant from

New Therapeutic Approaches to Metastatic Melanoma

Publisher Philip Pawelko phil@coexm.com

Editor in Chief Sagar Lonial, MD Emory University

Sagar Lonial, MD Associate Professor of Hematology and Oncology Emory University

Publisher Philip Pawelko phil@coexm.com

Editorial Director Susan Berry susan@coexm.com dits e Cr d Copy Editor CE re E/ ffe Bonnie Nickel © 2008 Center of Excellence Media, LLC CM O Senior Production Manager Alaina Pede

Russell Hennessy russell@coexm.com Circulation Department circulation@coexm.com Director of Human Resources Blanche Marchitto

Supported by an educational grant from

M

elanoma, the most deadly form of skin cancer, arises from melanocytes, the pigment-producing cells of the skin. Melanoma is expected to be diagnosed in approximately 62,480 individuDirector of Human als (34,950 men and 27,530 women) and Resources deaths in the Blanche Marchitto September 2008 • Vol. 1 • No. 3 cause an estimated 8420 United States in 2008.1,2 The incidence of melanoma is increasing faster than any other malignancy. In 1935, an individual’s lifetime risk for developing invasive melanoma in this country was 1 in 1500; in 2010, this risk is projected to be 1 in 50.

According to the World Health Organization, approximately 132,000 melanoma skin cancers occur globally each year, and the incidence of melanoma is Supported by increasing faster than any other maligan educational grant from nancy worldwide.3-5 Approximately 80% of melanomas are Circulation Department circulation@coexm.com

August 2008 • Vol. 1 • No. 1

A Supplement to

A Supplement to

Visit us at: www.coexm.com

Emerging Therapies for Myelodysplastic Syndromes IN THIS ISSUE: • Updates from the 44th Annual Meeting of the American Society of Clinical Oncology

Senior Production Manager Alaina Pede

with Myelodysplastic Syndromes

by Erin P. Demakos, RN, CCRC Mount Sinai School of Medicine, New York, NY

Directors of Client Services John W. Hennessy john@coexm.com

MDS are older than 60 years; the condition is rare in young adults.1 MDS can cause many different signs and symptoms. Most patients experience complications of blood cell deficiencies that cause a wide array of highly debilitating symptoms. Many patients with MDS experience severe, chronic anemia, requiring red blood cell (RBC) transfusions as frequently as every 2 weeks. In addition to disrupting and diminishing quality of life, frequent transfusions are associated with an increased risk of iron overload, transfusion reactions, and infection from agents transmitted through the transfused blood.1,2 Leukopenia (especially neutropenia or granulocytopenia) can cause serious infections with high fevers. Thrombocytopenia can cause excessive bruising and bleeding, which can become lifethreatening as the disease progresses.1,2

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

© 2008 Center of Excellence Media, LLC

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• Updates from the 44th Annual Meeting of the American Society of Clinical Oncology • Management Strategies for Skin and Nail Toxicities Pamela Hallquist Viale, RN, MS, CS, ANP, AOCNP University of California, San Francisco Laura Zitella, RN, MS, NP, AOCN® Stanford University Medical Center

Circulation Department circulation@coexm.com Director of Human Resources Blanche Marchitto

Supported by an educational grant from

INTRODUCTION

T

he development of epidermal growth factor receptor inhibitors (EGFRIs) has expanded treatment options for patients with cancer. Although these agents are generally well tolerated, skin toxicities, including papulopustular rash, xerosis, pruritus, fissures, and hair and nail alterations, are often associated with their use. These adverse events can affect patients both physically and psychosocially and may lead to dose reduction, interruption of therapy, or discontinuation of therapy. Therefore, the timely and effective management of skin

toxicities related to treatment is imperative to ensure consistent EGFRI administration and maintenance of patient quality of life.

Oncology nurses who care for patients receiving EGFRI therapy must be equipped with practical strategies for assessing and managing toxicities related to treatment. This newsletter provides an overview of the pathophysiology and clinical presentation of skin reactions associated with EGFRI therapy, as well as current recommendations for grading and treating these toxicities.

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

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

Celgene Corporation

© 2008 Center of Excellence Media, LLC

diagnosed at a localized stage and the 5year survival rate associated with this form of the disease is about 99%.1 In contrast, the 5-year survival rates for regional and distant stages of the disease are much lower (65% and 15%, respectively).1 Patients diagnosed with stage IV melanoma have very poor prognoses and relatively few treatment options. These patients continue to pose a significant challenge to clinicians.

Over the past decade, several novel agents have been developed for the treatment of metastatic melanoma. Encouraging safety and efficacy results from recent clinical trials evaluating many of these therapies were presented at the 44th annual meeting of the American Society of Clinical Oncology (ASCO), held May 30June 3, 2008, in Chicago, Illinois, and are highlighted in this publication.

Pfizer, Inc.

IN THIS ISSUE:

Russell Hennessy russell@coexm.com

INTRODUCTION yelodysplastic syndromes (MDS) are a group of blood disorders in which the bone marrow does not function properly and produces defective blood cells. These abnormal blood cells usually die before they leave the bone marrow or shortly after entering the bloodstream. As a result, patients with MDS have low blood cell counts, or cytopenias. Approximately 30% of patients with MDS will progress to acute myeloid leukemia (AML),1 a rapidly growing cancer of bone marrow cells that is difficult to treat and has a poor prognosis.

According to the American Cancer Society, an estimated 10,000 to 15,000 new cases of MDS occur annually.1 The number of new cases diagnosed each year is likely to increase in prevalence as the elderly population continues to grow.

About 80% to 90% of all patients with

Effective Management Strategies for Skin Toxicities Associated With Epidermal Growth Factor Receptor (EGFR)-Inhibitor Therapy

Copy Editor Bonnie Nickel

• Nursing Strategies and Interventions for Managing Patients

M

Publisher Philip Pawelko phil@coexm.com Editorial Director Susan Berry susan@coexm.com

Jointly sponsored by CME Consultants and Center of Excellence Media.

Directors of Client Services John W. Hennessy john@coexm.com

Credit risk Put simply, credit risk refers to the potential for default of an underlying debt investment. Lenders bear the risk of borrower default. We have lately seen extraordinary defaults in the housing industry. Following closely and related to the record mortgage defaults, financial markets have been losing their ability to issue credit. When lenders cannot make money from loans, their ability to repay existing debt service is often adversely affected. When such a situation spreads broadly, a negative ripple effect, such as the one now in progress, is the outcome.

about how to transfer funds from one IRA to another, seek information from a bank officer or other financial professional. A slip here could cause you to have to recognize taxes on the money and/or incur penalties.

ing, now may be the time to take a look at your bank holdings. In general, up to $100,000 per depositor per institution in taxable savings (eg, checking accounts, money market deposits, and certificates of deposit) are federally insured. If you have more than that amount in any one bank, you may want to move the excess to another bank. Up to $250,000 held in individual retirement accounts (IRAs) is also federally insured. Again, if you have more than that amount in any bank IRA, you may want to transfer the excess to another IRA at a different bank. If in doubt

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Registered participants will receive email announcements as new educational activities become available.

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Risk minimization In addition to understanding the various types of risk associated with investOctober/November 2008

G REEN H ILL H EALTHCARE C OMMUNICATIONS

31

PERSONAL FINANCE

V

arious types of risk are associated with investing. As of this writing, there are continuing struggles within the financial sector.

Understanding some of the various types of investment risk may help you minimize the anxiety associated with securing your financial future.

PERSONAL FINANCE

Your Financial Future: Retirement Planning

FDA Report FDA REPORT

New Patch Approved for Treating Chemotherapy-Induced Nausea and Vomiting SEATTLE—Oncology nurses now have a new tool to help them better manage chemotherapy-induced nausea and vomiting (CINV). The Granisetron Transdermal System (Sancuso; ProStrakan), approved in September 2008, is the first patch to provide up to 5 consecutive days of control of nausea and vomiting for patients receiving a moderately and/or highly nausea-inducing chemotherapy regimen.

If left untreated, CINV can lead to dehydration, malnutrition, treatment delay, or even discontinuation of treatment.

It is hoped that this new patch may work in combination with other approaches to help improve the quality of life among patients receiving chemotherapy.

“We’ve made significant progress in our understanding of chemotherapy and how to prevent its side effects, yet undergoing chemotherapy remains a challenging experience on many levels,” said Barbara Rogers, CRNP, MN, an adult hematology-oncology nurse practitioner at Fox Chase Cancer Center, Philadelphia. “We should have zero tolerance for CINV. A patch that can be applied before treatment, releasing medication consistently into the bloodstream over a number of days, has the potential to impact patient comfort and quality of life.”

Despite recent advances in treatment, CINV today remains a significant issue. More than 50% of 581 oncology nurses surveyed at the 2008 Oncology Nurses Society’s Annual Congress in Philadelphia in May said they have delayed or halted their patients’ treatment due to CINV. The survey findings highlighted the need for improved strategies for combating CINV. The new patch delivers granisetron through a thin layer of adhesive that attaches the patch to the skin. Granisetron, the active component of the patch, is an established inhibitor of nausea and vomiting. The patches contain 34.3 mg of granisetron and release 3.1 mg of the drug every 24 hours for 7 days. In adults, the patch is applied up to a minimum of 24 hours before chemotherapy, but may be applied up to a maximum of 48 hours before chemotherapy. The patch should be removed a minimum of 24 hours after completion of chemotherapy.

“This patch is going to be utilized in conjunction with what we already have. The drug is already available orally and intravenously [IV]. So, it is now in a new form. The benefits of this new form are that the patients don’t have to get the IV form in the office, and with the pill, they have to take it two or more times a day depending on their regimen. But with the patch you just put it on and it lasts for more than 5 days,” said Rogers in an interview with The Oncology Nurse.

The US Food and Drug Administration (FDA) approved the patch for the prevention of CINV based on results of a multicenter phase 3 randomized, double-blind, doubledummy controlled study. The investigators compared the efficacy, tolerability and safety of the patch with once-daily oral granisetron (2 mg) in 641 patients receiving moderately or highly nausea-inducing multiday chemotherapy. The trial met its primary end point of achieving complete control of CINV, working as well as oral granisetron. Complete control was defined as no vomiting and/or retching, no more than mild nausea and no rescue medication from first administration of the patch until 24 hours after the last day of chemotherapy.

FDA REPORT

The benefits of this new form are that the patients don’t have to get the IV form in the office.

In clinical trials, the patch was generally well-tolerated.

Adverse reactions considered drug-related by investigators occurred in 8.7% of patients receiving the patch.

Constipation was the most common drug-related adverse reaction. Application site reactions were reported but were 32

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mild and did not lead to drug discontinuation. The incidence of skin reactions was comparable to that with placebo.

“It is easier to prevent nausea than to treat it when it does happen. We expect it will be used with some other IV medications. So it won’t get rid of those, but it will add to those agents already being used,” said Rogers. “The most important take-home message for oncology nurses is that we now have an additional option that we didn’t have before. It is a different delivery route and the only patch of its kind on the market. It may be beneficial for patients who have more longterm nausea from their treatment. Oncology nurses are the educators and front-line providers so they need to be aware of it.”

The patch is contraindicated in patients with known hypersensitivity to granisetron or to any of the components of the patch. The makers of the patch say granisetron may mask a progressive ileus and/or gastric distention caused by the underlying condition. In addition, patients should avoid direct exposure of application site to natural or artificial sunlight by covering with clothing while wearing the patch and for 10 days after removing it.

—John Schieszer

Casopitant Bolsters Prevention of Chemotherapy-related Nausea and Vomiting STOCKHOLM—The use of casopitant in combination with standard care is superior to standard care alone for the prevention of chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC), according to phase 3 results released at the 33rd Congress of the European Society for Medical Oncology.

Casopitant is a novel neurokinin-1 receptor antagonist.

Steven Grunberg, MD, an oncologist at the University of Vermont in Burlington, and coworkers tested the use of a single oral dose or a 3-day intravenous (IV)/oral regimen of casopitant plus standard care (ondansetron plus dexamethasone) in 810 cancer patients receiving HEC. Overall, 99% of patients received cisplatin-based HEC regimens for up to six cycles.

Patients were randomized to a control arm, single oral dose casopitant arm, or a 3-day IV/oral dosage casopitant arm and continued on the same treatment arm throughout the study.

The primary end point was the proportion of patients achieving a complete response (CR), defined as no vomiting/retching and no use of rescue medications during the first 120 hours.

Results showed that patients who received the single oral dose and 3-day IV/oral dosage casopitant regimens had statistically significant improvements in CR rates compared with the control (86% and 80% vs 66%, respectively).

Significantly more patients in each casopitant arm achieved CR versus patients in the control arms in both the acute phase and the delayed phase. The benefits with casopitant were maintained in the first four cycles of chemotherapy.

The study also found that significantly more patients who received casopitant had no significant nausea, no nausea, and no vomiting overall compared with the control group.

Both casopitant-based regimens were well tolerated with minimal and manageable side effects. The most commonly observed adverse events were those typically associated with myelosuppressive cisplatin-base chemotherapy.

Recent FDA Approvals • Full Approval for Denileukin diftitox for CTCL The US Food and Drug Administration (FDA) has approved an efficacy supplemental biologics license application for denileukin diftitox solution (Ontak; Eisai) for intravenous treatment of patients with persistent or recurrent cutaneous Tcell lymphoma whose malignant cells express the CD25 component of the IL-2 receptor. The FDA’s action marks the conversion of an accelerated approval indication to full approval based on results of a phase 3 trial.

• New Indications Vaccine

for

HPV

The FDA has approved the human papillomavirus quadrivalent (types 6, 11, 16, and 18) vaccine, recombinant (Gardasil; Merck) for prevention of vaginal and vulvar cancer caused by HPV types 16 and 18 in girls and women 9 to 26 years of age. The vaccine was originally approved in 2006 for prevention of cervical cancer, precancerous genital lesions, and genital warts.

• Third US Pemetrexed

Approval

for

The FDA has granted approval for use of pemetrexed for injection (Alimta; Lilly) in combination with cisplatin as first-line treatment of locally advanced and metastatic non–small-cell lung cancer (NSCLC) in patients with nonsquamous histology. This is the third US approval for the drug, which was approved in 2004 in combination with cisplatin for unresectable malignant pleural mesothelioma and as a single agent for second-line treatment of locally advanced or metastatic NSCLC after prior chemotherapy.

• Device to Assess Lymphedema ImpediMed has received FDA 510(k) clearance for the L-Dex U400, bioimpedance spectroscopy device to assist physicians and other medical professionals in the clinical assessment of unilateral lymphedema of the arm in women with breast cancer. The device, which uses the characteristics of frequency-dependent current flow to quantify changes in extracellular fluid in the patient’s limb, can be used preoperatively and postoperatively. It provides an immediate result and accompanying software can be used to track changes in the patient’s L-Dex value over time.

—Jill Stein October/November 2008

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www.avalerehealth.net

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

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

Progressive Multifocal Leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving Rituxan [see Warnings and Precautions, Adverse Reactions].

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INDICATIONS AND USAGE Non-Hodgkinís Lymphoma (NHL) Rituxan® (rituximab) is indicated for the treatment of patients with: Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent; Previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy; Non-progressing (including stable disease), low-grade, CD20positive B-cell NHL, as a single agent, after first-line CVP chemotherapy; Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens. WARNINGS AND PRECAUTIONS Infusion Reactions Rituxan can cause severe, including fatal, infusion reactions. Severe reactions typically occurred during the first infusion with time to onset of 30–120 minutes. Rituxan-induced infusion reactions and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, or anaphylactoid events. Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medical management (e.g., glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion reactions as needed. Depending on the severity of the infusion reaction and the required interventions, consider resumption of the infusion at a minimum 50% reduction in rate after symptoms have resolved.

Closely monitor the following patients: those with preexisting cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells (>25,000/mm3). [See Boxed Warning, Warnings and Precautions, Adverse Reactions.] Tumor Lysis Syndrome (TLS) Rapid reduction in tumor volume followed by acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia, can occur within 12–24 hours after the first infusion. Fatal TLS cases have occurred after administration of Rituxan. A high number of circulating malignant cells ( 25,000/mm3) or high tumor burden confers a greater risk of TLS after rituximab. Consider prophylaxis for TLS in patients at high risk.

Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated. [See Boxed Warning.]

Severe Mucocutaneous Reactions Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with Rituxan. These reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of these reactions has varied from 1–13 weeks following Rituxan exposure. Discontinue Rituxan in patients who experience a severe mucocutaneous reaction. The safety of readministration of Rituxan to patients with severe mucocutaneous reactions has not been determined. [See Boxed Warning, Adverse Reactions.] Progressive Multifocal Leukoencephalopathy (PML) JC virus infection resulting in PML and death can occur in Rituxan-treated patients with hematologic malignancies or with autoimmune diseases for which Rituxan has not been approved. The majority of patients with hematologic malignancies diagnosed with PML received Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell transplant. The patients with autoimmune diseases had prior or concurrent immunosuppressive therapy and were diagnosed with PML within 12 months of their last infusion of Rituxan. Consider the diagnosis of PML in any patient presenting with new-onset neurologic manifestations. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Discontinue Rituxan and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML. [See Boxed Warning, Adverse Reactions.] Hepatitis B Virus (HBV) Reactivation Hepatitis B Virus (HBV) reactivation with fulminant hepatitis, hepatic failure, and death can occur in patients with hematologic malignancies treated with Rituxan. The median time to the diagnosis of hepatitis was approximately 4 months after the initiation of Rituxan and approximately one month after the last dose. Screen patients at high risk of HBV infection before initiation of Rituxan.

Closely monitor carriers of hepatitis B for clinical and laboratory signs of active HBV infection for several months following Rituxan therapy. Discontinue Rituxan and any concomitant chemotherapy in patients who develop viral hepatitis, and institute appropriate treatment including antiviral therapy. Insufficient data exist regarding the safety of resuming Rituxan in patients who develop hepatitis subsequent to HBV reactivation. [See Adverse Reactions.] Other Viral Infections The following additional serious viral infections, either new, reactivated, or exacerbated, have been identified in clinical studies or postmarketing reports. The majority of patients received Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell transplant. These viral infections included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis C. In some cases, the viral infections occurred as late as one year following discontinuation of Rituxan and have resulted in death. [See Adverse Reactions.] Cardiovascular Discontinue infusions for serious or lifethreatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of Rituxan for patients who develop clinically significant arrhythmias or who have a history of arrhythmia or angina. [See Adverse Reactions.] Renal Severe, including fatal, renal toxicity can occur after Rituxan administration in patients with hematologic malignancies. Renal toxicity has occurred in patients with high numbers of circulating malignant cells (>25,000/mm3) or high tumor burden who experience tumor lysis syndrome and in patients with NHL administered concomitant cisplatin therapy during clinical trials. The combination of cisplatin and Rituxan is not an approved treatment regimen. Use extreme caution if this non-approved combination is used in clinical trials and monitor closely for signs of renal failure. Consider discontinuation of Rituxan for patients with a rising serum creatinine or oliguria. Bowel Obstruction and Perforation Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving Rituxan in combination with chemotherapy.

In postmarketing reports, the mean time to documented gastrointestinal

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MARCH 2009

11 - 15 HOLLYWOOD, FL NCCN 14th Annual Conference: Clinical Practice Guidelines & Quality Cancer Care www.nccn.org

14 - 18 LAS VEGAS, NV 19th Annual National Interdisciplinary Breast Cancer Conference www.breastcare.org

October/November 2008

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and 4 adverse reactions and serious adverse reactions. In Study 7, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R-CHOP vs.

1.0% for CHOP). The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs. 7%) and lung disorder (6% vs. 3%). Other Grade 3 or 4 adverse reactions occurring more frequently among patients receiving RCHOP were viral infection (Study 7), neutropenia (Studies 7 and 8), and anemia (Study 8). Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Rituxan with the incidence of antibodies to other products may be misleading. Using an ELISA assay, antihuman anti-chimeric antibody (HACA) was detected in 4 of 356 (1.1%) patients with low-grade or follicular NHL receiving single-agent Rituxan. Three of the four patients had an objective clinical response. The clinical relevance of HACA formation in rituximab treated patients is unclear. Postmarketing Experience The following adverse reactions have been identified during postapproval use of Rituxan in hematologic malignancies. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to Rituxan. Hematologic: prolonged pancytopenia, marrow hypoplasia, and late-onset neutropenia, hyperviscosity syndrome in Waldenstrom’s macroglobulinemia. Cardiac: fatal cardiac failure.

Immune/Autoimmune Events: uveitis, optic neuritis, systemic vasculitis, pleuritis, lupus-like syndrome, serum sickness, polyarticular arthritis, and vasculitis with rash. Infection: viral infections, including progressive multifocal leukoencephalopathy (PML), increase in fatal infections in HIV-associated lymphoma, and a reported increased incidence of Grade 3 and 4 infections in patients with previously treated lymphoma without known HIV infection.

Neoplasia: disease progression of Kaposi’s sarcoma. Skin: severe mucocutaneous reactions. Gastrointestinal: bowel obstruction and perforation. Pulmonary: fatal bronchiolitis obliterans and pneumonitis (including interstitial pneumonitis). DRUG INTERACTIONS Formal drug interaction studies have not been performed with Rituxan. USE IN SPECIFIC POPULATIONS Pregnancy Category C: There are no adequate and well-controlled studies of rituximab in pregnant women. NonHodgkin’s lymphoma and severe rheumatoid arthritis are serious conditions that require treatment. Rituximab should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Rituximab is a genetically engineered IgG molecule, and IgG crosses the human placenta.

Reproduction studies in cynomolgus monkeys at maternal exposures similar to human therapeutic exposures showed no evidence of teratogenic effects.

However, B-cell lymphoid tissue was reduced in the offspring of treated dams. The B-cell counts returned to normal levels, and immunologic function was restored within 6 months of birth. Other than target B lymphocytes, rituximab is not known to bind to any normal human tissues in an ex vivo assay. However, it is not known if binding occurs to unique embryonic or fetal tissue receptors in vivo. Nursing Mothers It is not known whether Rituxan is secreted into human milk. However, Rituxan is secreted in the milk of lactating cynomolgus monkeys, and IgG is excreted in human milk. Published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts. The unknown risks to the infant from gastrointestinal or limited systemic exposure to Rituxan should be weighed against the known benefits of breastfeeding.

Pediatric Use The safety and effectiveness of Rituxan in pediatric patients have not been established. Geriatric Use Diffuse Large B-Cell NHL Among patients with DLBCL evaluated in three randomized, active-controlled trials, 927 patients received Rituxan in combination with chemotherapy. Of these, 396 (43%) were age 65 or greater and 123 (13%) were age 75 or greater. No overall differences in effectiveness were observed between these patients and younger patients.

Cardiac adverse reactions, mostly supraventricular arrhythmias, occurred more All Grades (%) Grade 3 and 4 (%) All Grades (%) Grade 3 and 4 (%) frequently among elderly patients. Serious pulmonary adverse reactions were also Any Adverse Events 99 57 Respiratory System 38 4 more common among the elderly, including pneumonia and pneumonitis. LowBody as a Whole 86 10 Increased Cough 13 1 Fever 53 1 Rhinitis 12 1 Grade or Follicular Non-Hodgkin’s Lymphoma Clinical studies of Rituxan in Chills 33 3 Bronchospasm 8 1 low-grade or follicular, CD20-positive, B-cell NHL did not include sufficient Infection 31 4 Dyspnea 7 1 Asthenia 26 1 Sinusitis 6 0 numbers of patients aged 65 and over to determine whether they respond Headache 19 1 Metabolic and Nutritional Abdominal Pain 14 1 Disorders 38 3 differently from younger subjects. OVERDOSAGE There has been no experience Pain 12 1 Angioedema 11 1 with overdosage in human clinical trials. Single doses of up to 500 mg/m2 have Back Pain 10 1 Hyperglycemia 9 1 Throat Irritation 9 0 Peripheral Edema 8 0 been given in dose-escalation clinical trials. NONCLINICAL TOXICOLOGY Flushing 5 0 LDH Increase 7 0 Heme and Lymphatic System 67 48 Digestive System 37 2 Carcinogenesis, Mutagenesis, Impairment of Fertility No long term animal Lymphopenia 48 40 Nausea 23 1 Leukopenia 14 4 Diarrhea 10 1 studies have been performed to establish the carcinogenic or mutagenic potential Neutropenia 14 6 Vomiting 10 1 of Rituxan or to determine potential effects on fertility in males or females.

Thrombocytopenia 12 2 Nervous System 32 1 Anemia 8 3 Dizziness 10 1 PATIENT COUNSELING INFORMATION Patients should be provided the Rituxan Skin and Appendages 44 2 Anxiety 5 1 Night Sweats 15 1 Musculoskeletal System 26 3 Medication Guide and provided an opportunity to read prior to each treatment Rash 15 1 Myalgia 10 1 session. Because caution should be exercised in administering Rituxan to patients Pruritus 14 1 Arthralgia 10 1 Urticaria 8 1 Cardiovascular System 25 3 with active infections, it is important that the patient’s overall health be assessed Hypotension 10 1 Hypertension 6 1 at each visit and any questions resulting from the patient’s reading of the Medication Guide be discussed. Rituxan is detectable in serum for up to six a Adverse reactions observed up to 12 months following Rituxan. bAdverse reactions graded for severity by months following completion of therapy. Individuals of childbearing potential NCI-CTC criteria.

In these single-arm Rituxan studies, bronchiolitis obliterans occurred during and should use effective contraception during treatment and for 12 months after up to 6 months after Rituxan infusion. Rituxan in Combination With Rituxan therapy.

Chemotherapy Adverse reactions information below is based on 1250 patients who received Rituxan in combination with chemotherapy or following chemotherapy. Rituxan in Combination With Chemotherapy for Low-Grade NHL In Study 4, patients in the R-CVP arm experienced a higher incidence of Revised 1/2008 (4835504) infusional toxicity and neutropenia compared to patients in the CVP arm. The Jointly Marketed by: following adverse reactions occurred more frequently ( 5%) in patients receiving Biogen Idec Inc. 5200 Research Place San Diego, CA 92122 R-CVP compared to CVP alone: rash (17% vs. 5%), cough (15% vs. 6%), flushing Genentech USA, Inc. 1 DNA Way South San Francisco, CA 94080-4990 (14% vs. 3%), rigors (10% vs. 2%), pruritus (10% vs. 1%), neutropenia (8% vs.

3%), and chest tightness (7% vs. 1%). In Study 5, the following adverse reactions were reported more frequently ( 5%) in patients receiving Rituxan following CVP compared to patients who received no further therapy: fatigue (39% vs. 14%), anemia (35% vs. 20%), peripheral sensory neuropathy (30% vs. 18%), infections (19% vs. 9%), pulmonary toxicity (18% vs. 10%), hepato-biliary toxicity (17% vs. ©2008 Biogen Idec Inc. and Genentech, Inc. 7140916 March 2008 7%), rash and/or pruritus (17% vs. 5%), arthralgia (12% vs. 3%), and weight gain (11% vs. 4%). Neutropenia was the only Grade 3 or 4 adverse reaction that occurred more frequently ( 2%) in the Rituxan arm compared with those who received no further therapy (4% vs. 1%). Rituxan in Combination With Chemotherapy for DLBCL In Studies 6 and 7, the following adverse reactions, regardless of severity, were reported more frequently ( 5%) in patients age 60 years receiving R-CHOP as compared to CHOP alone: pyrexia (56% vs. 46%), lung disorder (31% vs. 24%), cardiac disorder (29% vs. 21%), and chills (13% vs. 4%).

Detailed safety data collection in these studies was primarily limited to Grade 3

perforation was 6 (range 1–77) days in patients with NHL. Perform a thorough diagnostic evaluation and institute appropriate treatment for complaints of abdominal pain, especially early in the course of Rituxan therapy. [See Adverse Reactions.] Immunization The safety of immunization with live viral vaccines following Rituxan therapy has not been studied and vaccination with live virus vaccines is not recommended. For NHL patients, the benefits of primary or booster vaccinations should be weighted against the risks of delay in initiation of Rituxan therapy. Laboratory Monitoring Because Rituxan binds to all CD20positive B lymphocytes (malignant and non-malignant), obtain complete blood counts (CBC) and platelet counts at regular intervals during Rituxan therapy and more frequently in patients who develop cytopenias [see Adverse Reactions]. The duration of cytopenias caused by Rituxan can extend months beyond the treatment period. ADVERSE REACTIONS The most common adverse reactions of Rituxan (incidence 25%) observed in patients with NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia. The most important serious adverse reactions of Rituxan are infusion reactions, tumor lysis syndrome, mucocutaneous toxicities, hepatitis B reactivation with fulminant hepatitis, PML, other viral infections, cardiac arrhythmias, renal toxicity, and bowel obstruction and perforation. Clinical Trials Experience Non-Hodgkin’s Lymphoma Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to Rituxan in 1606 patients, with exposures ranging from a single infusion up to 6–8 months. Rituxan was studied in both single-agent and active-controlled trials (n = 356 and n = 1250). These data were obtained in adults with low-grade, follicular, or DLBCL NHL. Most patients received Rituxan as an infusion of 375 mg/m2 per infusion, given as a single agent weekly for up to 8 doses, in combination with chemotherapy for up to 8 doses, or following chemotherapy for up to 16 doses.

Infusion Reactions In the majority of patients with NHL, infusion reactions consisting of fever, chills/rigors, nausea, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, dizziness, or hypertension occurred during the first Rituxan infusion. Infusion reactions typically occurred within 30 to 120 minutes of beginning the first infusion and resolved with slowing or interruption of the Rituxan infusion and with supportive care (diphenhydramine, acetaminophen, and intravenous saline). The incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion. [See Boxed Warning, Warnings and Precautions.]

Infections Serious infections (NCI CTCAE Grade 3 or 4), including sepsis, occurred in less than 5% of patients with NHL in the single-arm studies. The overall incidence of infections was 31% (bacterial 19%, viral 10%, unknown 6%, and fungal 1%). [See Warnings and Precautions.] In randomized, controlled studies where Rituxan was administered following chemotherapy for the treatment of follicular or low-grade NHL, the rate of infection was higher among patients who received Rituxan. In diffuse large B-cell lymphoma patients, viral infections occurred more frequently in those who received Rituxan. Cytopenias and hypogammaglobulinemia In patients with NHL receiving rituximab monotherapy, NCI-CTC Grade 3 and 4 cytopenias were reported in 48% of patients. These included lymphopenia (40%), neutropenia (6%), leukopenia (4%), anemia (3%), and thrombocytopenia (2%). The median duration of lymphopenia was 14 days (range, 1–588 days) and of neutropenia was 13 days (range, 2–116 days). A single occurrence of transient aplastic anemia (pure red cell aplasia) and two occurrences of hemolytic anemia following Rituxan therapy occurred during the single-arm studies. In studies of monotherapy, Rituxan-induced B-cell depletion occurred in 70% to 80% of patients with NHL. Decreased IgM and IgG serum levels occurred in 14% of these patients. Single-Agent Rituxan Adverse reactions in Table 1 occurred in 356 patients with relapsed or refractory, lowgrade or follicular, CD20-positive, B-cell NHL treated in single-arm studies of Rituxan administered as a single agent. Most patients received Rituxan 375 mg/m2 weekly for 4 doses.

Table 1 Incidence of Adverse Events in 5% of Patients with Relapsed or Refractory, LowGrade or Follicular NHL, Receiving Single-agent Rituxan (N = 356)a,b

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Leading patients toward improved outcomes

You help patients reach their treatment goals RITUXAN is a proven path for many patients battling non-Hodgkin’s lymphoma (NHL), but they can’t complete the journey alone.

Oncology nurses are central members of a cancer care team—working together to achieve improved outcomes. Your guidance and leadership help patients reach their treatment goals. We recognize your commitment and support your continued efforts with innovative patient-education materials and services.

RITUXAN is indicated for the treatment of patients with: • Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent • Previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy • Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy • Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens

To learn more, ask a RITUXAN representative or visit

www.rituxan.com/lymphoma

BOXED WARNINGS and Additional Important Safety Information The most important serious adverse reactions of RITUXAN are fatal infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, progressive multifocal leukoencephalopathy (PML), hepatitis B reactivation with fulminant hepatitis, other viral infections, cardiovascular events, renal toxicity, and bowel obstruction and perforation. The most common adverse reactions of RITUXAN (incidence ≥25%) observed in patients with NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia.1

Reference: 1. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2008.

Please see brief summary of prescribing information on adjacent page.

Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion.

PROVE N. POWE R FU L.

©2008 Genentech, Inc., and Biogen Idec Inc. All rights reserved. 9231900 April 2008