http://www.theoncologynurse.com/docs/issues/February-2010

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FEBRUARY 2010

www.TheOncologyNurse.com

VOL 3, NO 1

er d a Le and e h T ews in N eeting e M erag Cov NURSING SCHOOL PROFILE

University of Louisiana, Lafayette Recognized for Innovative Programs

By Karen Rosenberg

PAIN MANAGEMENT

Addressing Concerns about Opioid Use for Cancer Pain An Interview, with Judith A. Paice, PhD, RN

By Karen Rosenberg

O

pioids remain a mainstay of treatment for moderate-tosevere cancer pain. In this interview, Judith A. Paice, PhD, RN, director, Cancer Pain Program, Division of Hematology-Oncology, Northwestern University, Feinberg School of Medicine, Chicago, discusses the issues surrounding the use of opioids for the management of cancer pain and the role of the oncology nurse in assessing pain and addressing patients’ fears about use of these agents.

Despite their demonstrated efficacy, there is still some resistance among healthcare providers, patients, and

Top row left to right: Katie Comeaux, Paul Dressler, and Amy Naquin Middle row left to right: Jaimie Vincent, Amber Rourke, and Tiffany Landry Bottom row left to right: Shawntel Smith, Lindsey Dees, and Megan Ebling

T

he University of Louisiana at Lafayette College of Nursing and Allied Health Professions provides a variety of programs at the undergraduate and graduate levels, including one that offers students the opportunity to achieve the bachelor’s of science in nursing (BSN) degree and to begin the master’s of science in nursing (MSN) program at the same time through the process of articulation. The college, which offers one of the largest undergraduate nursing programs in the Continued on page 18

caregivers to use of opioids for cancer pain. What are the concerns?

For those of us working with people who have cancer, the primary barriers from the patients’ perspective are the fear of side effects, particularly constipation and cognitive blunting, and the perceived meaning of taking an opioid. For many patients, taking morphine, in particular, means that their disease has advanced. From a professional perspective, we are concerned about the side effects. Also, many prescribers are concerned about the regulatory issues involved in prescribing opioids. They are fearful that the Drug

Enforcement Administration is watching their practice, especially because there have been several high-profile cases, not in oncology, that have gotten a lot of publicity.

Continued on page 12

GENITOURINARY CANCERS

CONFERENCE NEWS

The Changing Kidney Cancer Treatment Landscape. Part 2.

Changing the Role of the Oncology Nurse

The ONS 10th Annual Institutes of Learning and Advanced Practice Nursing Conference

By John Schieszer

Tampa, Florida, November 12-15, 2009 Highlights are presented on page 8.

SEATTLE—The past 5 years have ushered in a new era in the treatment of kidney cancer, and new medications are giving patients more options than ever before. In addition, the traditional end points in oncology drug development, such as survival and tumor response, are changing when it comes to this tumor type.

The goal of therapy now is to improve symptomatic and functional ability in patients with renal cell carcinoma (RCC).

Experts in this area say kidney cancer is becoming more of a chronic disease, similar to diabetes, and as such is managed in some of the same ways. For this very reason, patient reported outcomes (PROs) are becoming increasingly important to capture treatment benefits.

“The oncology nurse’s role is huge in PROs,” said David Cella, PhD, an associate director for cancer prevention and control at Continued on page 19

Inside REMS Review Risk management: a new era of patient safety

between pages 18 and 19

Complimentary CE Credit

Psychosocial Issues

Cancer treatment–related bone loss and osteoporosis: a concern for women with breast cancer

An interview with Carolyn Messner, DSW, MSW, LCSW-R, BCD

page 14

page 24 ©2010 Green Hill Healthcare Communications, LLC

SABCS Anthracyclines may not be necessary Based on a presentation by Dennis Slamon, MD, PhD

page 26

r fo ay E d o e C om T er Fre xm.c t is ur coe g Re Yo ww. w

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When treating patients with HER2+ breast cancer

No one touches their HER2-positive status is associated with more aggressive disease and poorer outcomes than HER2-negative breast cancer. Women who received 1 year of Herceptin had a lower risk of HER2+ breast cancer returning.

We applaud you for playing such a critical role in helping patients with HER2+ breast cancer complete the full course of treatment with Herceptin.

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: s As part of a treatment regimen containing doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel s With docetaxel and carboplatin s As a single agent following multi-modality anthracyclinebased therapy *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.

Metastatic indications Herceptin is indicated: s In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer s As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease Š2009 Genentech USA

Boxed WARNINGS and Additional Important Safety Information 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 anthracyclinecontaining 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

So. San Francisco, CA

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lives like you

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.

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. Herceptin can cause oligohydramnios and fetal harm

9568900

01/09

when administered to a pregnant woman.

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.

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

www.herceptin.com

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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 multimodality anthracycline based therapy. Metastatic Breast Cancer Herceptin is indicated: • In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer • As a single agent for treatment of HER2overexpressing 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 1 & 2a 3 4 4 a

Regimen ACb Paclitaxel+ Herceptin Chemo Herceptin ACb Docetaxel+ Herceptin Docetaxel+Carbo+ Herceptin

Incidence of CHF Herceptin Control 2% (32/1677) 2% (30/1678)

0.4% (7/1600) 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. b Anthracycline (doxorubicin) and cyclophosphamide

Table 2 Incidence of Cardiac Dysfunctiona in Metastatic Breast Cancer Studies

Study 5 (AC)b 5 (paclitaxel)

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

Event Cardiac 28% 7% 19% 3% Dysfunction Cardiac 11% 1% 4% 1% Dysfunction Cardiac N/A 5% N/A 6 7% Dysfunctionc a Congestive heart failure or significant asymptomatic decrease in LVEF. b Anthracycline (doxorubicin or epirubicin) and cyclophosphamide c Includes 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 post-infusion events with rapid clinical deterioration.

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

There are no data regarding the most appropriate method of identification of patients who may safely be retreated with Herceptin after experiencing a severe infusion reaction. Prior to resumption of Herceptin infusion, the majority of patients who experienced a severe infusion reaction were pre-medicated with antihistamines and/or corticosteroids. While some patients tolerated Herceptin infusions, others had recurrent severe infusion reactions despite pre-medications. Exacerbation of Chemotherapy-Induced 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 (5.2)].

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. Postmarketing 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 64 (4%) Hypertension Dizziness 60 (4%) Ejection Fraction Decreased 58 (3.5%) Palpitations 48 (3%) b Cardiac Arrhythmias 40 (3%) 30 (2%) Cardiac Failure Congestive 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%) 70 (4%) Influenza Dyspnea 57 (3%) URI 46 (3%) Rhinitis 36 (2%) Pharyngolaryngeal Pain 32 (2%) 26 (2%) Sinusitis Epistaxis 25 (2%) Pulmonary Hypertension 4 (0.2%) Interstitial Pneumonitis 4 (0.2%) Gastrointestinal Disorders Diarrhea 123 (7%) Nausea 108 (6%) 58 (3.5%) Vomiting Constipation 33 (2%) Dyspepsia 30 (2%) Upper Abdominal Pain 29 (2%) Musculoskeletal & Connective Tissue Disorders Arthralgia 137 (8%) Back Pain 91 (5%) Myalgia 63 (4%) Bone Pain 49 (3%) Muscle Spasm 46 (3%) Nervous System Disorders Headache 162 (10%) Paraesthesia 29 (2%) Skin & Subcutaneous Tissue Disorders Rash 70 (4%) Nail Disorders 43 (2%) Pruritis 40 (2%) General Disorders Pyrexia 100 (6%) Edema Peripheral 79 (5%) Chills 85 (5%) Aesthenia 75 (4.5%) Influenza-like Illness 40 (2%) Sudden Death 1 (.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%) 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 (.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 noncardiac 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 the following investigator-attributed treatment-related adverse reactions NCICTC Grade 4 and 5 hematologic toxicities, Grade 3–5 nonhematologic 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 7 11 1 28 7 heart failure Digestive Nausea 33 51 9 76 77 Diarrhea 25 45 29 45 26 Vomiting 23 37 28 53 49 Nausea and 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 5 18 14 13 7 infection a Data for Herceptin single agent were from 4 studies, including 213 patients from Study 6. b Anthracycline (doxorubicin or epirubicin) and cyclophosphamide The following subsections provide additional detail regarding adverse reactions observed in clinical 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

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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 5a Per-patient Incidence of New Onset Myocardial Dysfunction (by LVEF) Studies 1, 2, 3 and 4 LVEF <50% and Absolute Decrease from Baseline

Studies 1 & 2b AC TH (n=1606) AC T (n=1488) Study 3 Herceptin (n=1678) Observation (n=1708) Study 4c TCH (n=1056) AC TH (n=1068) AC T (n=1050)

LVEF ≥10% ≥16% <50% decrease decrease

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

22.8% 18.3% (366) (294) 9.1% 5.4% (136) (81)

11.7% (188) 2.2% (33)

33.4% (536) 18.3% (272)

9.2% (148) 2.4% (36)

8.6% (144) 2.7% (46)

7.0% (118) 2.0% (35)

3.8% (64) 1.2% (20)

22.4% (376) 11.9% (204)

3.5% (59) 1.2% (21)

8.5% (90) 17% (182) 9.5% (100)

5.9% (62) 13.3% (142) 6.6% (69)

3.3% (35) 9.8% (105) 3.3% (35)

34.5% (364) 44.3% (473) 34% (357)

6.3% (67) 13.2% (141) 5.5% (58)

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. b Studies 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 severe in 1.4% and 9% of patients, on second or

www.TheOncologyNurse.com

subsequent Herceptin infusions administered as monotherapy or in combination with chemotherapy, respectively. In the post-marketing setting, severe infusion reactions, including hypersensitivity, anaphylaxis, and angioedema have been reported. Anemia In randomized controlled clinical trials, the overall incidence of anemia (30% vs. 21% [Study 5]), of selected NCI-CTC Grade 2–5 anemia (12.5% vs. 6.6% [Study 1]), and of anemia requiring transfusions (0.1% vs. 0 patients [Study 2]) were increased in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone.

Following the administration of Herceptin as a single agent (Study 6), the incidence of NCI-CTC Grade 3 anemia was < 1%. 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 NCICTC 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 NCI-CTC Grade 2–5 diarrhea (6.2% vs. 4.8% [Study 1]) and of NCI-CTC Grade 3–5 diarrhea (1.6% vs. 0% [Study 2]), and of grade 1-4 diarrhea (7% vs. 1% [Study 3]) were higher in patients receiving Herceptin as compared to controls. In Study 4, the incidence of Grade 3–4 diarrhea was higher [5.7% AC-TH, 5.5% TCH vs. 3.0% AC-T] and of Grade 1–4 was higher [51% AC-TH, 63% TCH vs. 43% AC-T] among women receiving Herceptin. Of patients receiving Herceptin as a single agent for the treatment of metastatic breast cancer, 25% experienced diarrhea.

An increased incidence of diarrhea was observed in patients receiving Herceptin in combination with chemotherapy for treatment of metastatic breast cancer.

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 anti-human 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. Postmarketing 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, she should be apprised of the potential hazard to a fetus. In the postmarketing 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. Registry Pregnant women with breast cancer who are using Herceptin are encouraged to enroll in MotHER- the Herceptin Pregnancy Registry: phone 1-800-690-6720. 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 MotHER- the Herceptin Pregnancy Registry [see Pregnancy].

HERCEPTIN® [trastuzumab] Manufactured by: 4839803 Genentech, Inc. Initial US Approval: Sept. 1998 1 DNA Way Revision Date: March 2009 South San Francisco, CA LK0726 7172911 94080-4990 7172713 ©2009 Genentech, Inc.

News Notes ASCO and ONS Release Chemotherapy Administration Safety Standards The American Society of Clinical Oncology (ASCO) and the Oncology Nursing Society (ONS) have released standards for safe chemotherapy administration to adult cancer patients in the outpatient setting. The document lists 31 standards encompassing seven domains: • Review of clinical information and selection of a treatment regimen • Treatment planning and informed consent • Ordering a treatment • Drug preparation • Assessment of treatment compliance • Administration and monitoring • Assessment of response and toxicity monitoring.

Over the past 5 years, recommendations to improve safety in chemotherapy administration have been developed in response to reports of chemotherapy administration errors. These recommendations have included standardizing approaches, developing policies and procedures for system improvements, and having errors reviewed by interdisciplinary professional staff.

The new standards also incorporate the need for extravasation management procedures and accessible antidote order sets and antidotes.

In addition, the new standards call for providing patients on oral chemotherapeutic agents written or electronic education materials that include the preparation, administration, and disposal of the chemotherapy. Including family members, caregivers, or others in the education plan is also highlighted.

In addition to the standards, ASCO and ONS recognize that the increased use of electronic medical record systems may improve the safety and quality of outpatient chemotherapy administration.

The standards are available at www.asco.org and www.ons.org.

COMPLETE International Registry for Patients with PTCL Allos Therapeutics has launched a new international registry designed to help understand treatment patterns and outcomes for patients with peripheral T-cell lymphoma (PTCL). The Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment (COMPLETE) registry is a global observational study that will enroll patients with newly diagnosed PTCL and obtain data regarding longitudinal treatment patterns and outcomes.

COMPLETE is expected to add much needed information on PTCL disease management across various treatment regimens to existing registries collecting data on incidence and prognosis at diagnosis. Approximately 75 sites are projected to participate, including academic, hospital, and community practices in the United States and Europe. Sites will collect data on a real-time basis over 3 years of patient enrollment and 2 years of follow-up.

Physicians interested in participating or learning more can visit www.mednetregistry. com/mednet/allos. ●

February 2010 I VOL 3, NO 1

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Editorial Board EDITOR-IN-CHIEF

Sharon S. Gentry, RN, MSN, AOCN

Dolores “Jeff” Nordquist, RN, MS, CS, FNP

Karla Wilson, RN, MSN, FNP-C, CPON

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

Mayo Clinic Rochester, MN

City of Hope National Medical Center Duarte, CA

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

Cassandra J. Hammond, RN, MSN, CRNP

Nutrition Karen Connelly, RD

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Avid Education Partners, LLC Sharpsburg, MD

Melinda Oberleitner, RN, DNS, APRN, CNS

Deena Damsky Dell, RN, MSN, AOCN, BC

Taline Khoukaz, NP, MSN, ACNP-C

Gary Shelton, MSN, ARNP, AOCN

Fox Chase Cancer Center Philadelphia, PA

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

NYU Cancer Institute New York, NY

Wendy DiSalvo, BSN, MSN, FNP, AOCN

Sandra E. Kurtin, RN, MS, AOCN, ANP-C

Lori Stover, RN, BSN

Dartmouth Hitchcock Medical Center Norris Cotton Cancer Center Lebanon, NH

Arizona Cancer Center Tucson, AZ

Western Pennsylvania Cancer Institute Pittsburgh, PA

Denice Economou, RN, MN, AOCN

Ann McNeill, MSN, RN, NP-C, OCN

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

City of Hope National Medical Center Duarte, CA

The Cancer Center at Hackensack University Medical Center Hackensack, NJ

Saratoga, CA

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

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

Somerset Medical Center Somerville, NJ

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

Susan Goodin, PharmD, FCCP, BCOP Cancer Institute of New Jersey New Brunswick, NJ

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

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

Kena C. Miller, RN, MSN, FNP

Connie Visovsky, RN, PhD, APRN

Roswell Park Cancer Institute Buffalo, NY

University of Nebraska, College of Nursing Omaha, NE

Veracyte, Inc South San Francisco, CA

Jeanne Westphal, RN Meeker County Memorial Hospital Litchfield, MN

Amy Ford, RN, BSN, OCN Innovex Dallas, TX

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February 2010 I VOL 3, NO 1

Patricia Molinelli, RN, MSN, AOCNS Somerset Medical Center Somerville, NJ

Rita Wickham, OCN, PhD, RN Rush University College of Nursing Rush-Presbyterian-St. Luke’s Medical Center Chicago, IL

Social Work Barbara Savage, LISW Cleveland Clinic Taussig Cancer Institute Cleveland, OH

www.TheOncologyNurse.com

TON_Feb2010_FINAL:TON 2/6/10 11:50 AM Page 5

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

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

KYPHON® Balloon Kyphoplasty

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

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

TON_Feb2010_FINAL_TON 2/4/10 10:44 AM Page 6

FROM THE EDITOR

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

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s we enter our third year of publication, we are introducing some changes and new features to better serve your needs. First, you will notice that we’ve updated our appearance. But the changes are not only skin deep. We have also established a new collaboration with Veritas Institute for Medical Education, Inc. to provide a seamBeth Faiman, RN, way to receive continuing eduless MSN, APRN, BC, cation (CE) credit online. One artiAOCN in each issue of The Oncology cle Editor-in-Chief Nurse will offer complimentary CE credit. After reading the article, readers can apply for CE credits by completing a posttest and registering to receive a statement of completion online.

Veritas Institute for Medical Education provides a variety of CE/CME activities designed to help nurses, physicians, pharmacists, and other healthcare professionals better treat and educate their patients. In 2007, Veritas Institute received 6-year Accreditation with Commendation from the Accreditation Council for Continuing Medical Education, one of an elite group of accredited providers to receive this recognition. We look forward to working

CONTENTS

REMS programs lead to added responsibilities for nurse practitioners Redesigned lung cancer management process decreases time to diagnosis and treatment Diastolic blood pressure may predict efficacy of axitinib Virtual classroom fosters collaborative relationships across the country

14 Continuing Education Cancer treatment–related bone loss and osteoporosis: a concern for women with breast cancer

20 Conference News: ASH Nilotinib: first-line treatment option for chronic-phase CML? Rituximab improves overall survival in previously untreated CLL patients Sustained improvements in quality of life observed with bortezomib in multiple myeloma Aprepitant improves emesis control in transplant patients with no adverse effect on clinical outcomes

24 Psychosocial Issues Interdisciplinary approach best for addressing emotional, practical issues associated with cancer

26 Conference News: SABCS Anthracyclines may not be necessary for HER2-positive breast cancer

34 Books and Media Book review: Woman Cancer Sex

36 Nursing Life Nursing excellence award honors oncology nurse who goes above and beyond the call of duty Recipe: spaghetti squash bruschetta

DEPARTMENTS 3 News Notes Cervical cancer

37 International Oncology News February 2010 I VOL 3, NO 1

February 2010 • VOL 3, NO 1

FEATURE ARTICLES 8 Conference News: ONS Institutes of Learning

30 Oncology Drug Codes

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with Veritas Institute to provide high-quality educational programs that will help enhance your professional development.

Another new feature is a series discussing the psychosocial issues experienced by patients with cancer, their families, and caregivers. The first article in this series is an interview with Carolyn Messner, president of the Association of Oncology Social Work, who speaks of the need for nurses and social workers to work together to best help patients and their caregivers navigate the practical and emotional issues associated with a diagnosis of cancer.

In another interview, Judith Paice, a well-known expert on pain management, offers insights into patient and professional barriers to use of opioids for relief of cancer pain and suggests how nurses can work with patients and their caregivers to overcome these barriers and assure safe, effective use of these agents. The US Food and Drug Administration recently announced that manufacturers of opioids will need to develop Risk Evaluation and Mitigation Strategies (REMS) for these products. The REMS Review featured in this issue explains what REMS are and why they are being implemented. In a presentation at the 2009 ONS Institutes of Learning/Advanced Practice Nursing Conference, Marilyn Haas provided a nurse’s perspective on what REMS will mean for clinical practice. Her presentation and others are summarized in this issue. ●

REMS REVIEW Risk management: a new era of patient safety Between pages 18 and 19

www.TheOncologyNurse.com

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A pioneer in cancer innovation — exploring new directions

At Genentech BioOncology, we’re leading the fight against cancer with innovative science and are working to transform cancer treatment.

A family of firsts — Our proven therapeutics are standards of care in 5 of the 6 leading causes of cancer mortality in the United States.

A robust pipeline — Our molecules in development target the fundamental mechanisms of cancer growth and include a HER dimerization inhibitor, a Hedgehog pathway inhibitor, an antibody–drug conjugate, and antibodies targeting cancer cell-surface antigens.

A commitment to patients — We actively pursue ways to ensure patient access to therapeutics through a variety of patient support programs so healthcare providers can remain focused on patient care.

Our goal is to fundamentally change the way cancer is treated — not just with incremental advances, but with new standards of care.

www.BioOncology.com

© 2009 Genentech USA, Inc. All rights reserved. 9708100 Printed in USA.

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Conference News ONS IOL The following articles are based on presentations at the Oncology Nursing Society’s 10th Annual Institutes of Learning/Advanced Practice Nursing Conference held in Tampa, Florida, November 12-15, 2009.

REMS Programs Lead to Added Responsibilities for Nurse Practitioners

By Deborah Brauser

T

he US Food and Drug Administration (FDA) has identified six opioid products that will require Risk Evaluation and Mitigation Strategies (REMS). Advanced practice nurses (APNs) who want to continue prescribing opioids will need to follow several new practices, according to an educational presentation by Marilyn Haas, PhD, RN, CNS, ANP-BC, nurse practitioner for palliative and supportive care at Care Partners in Asheville, North Carolina.

“REMS are strategies to manage a potential or known serious risk of a drug or biological product,” explained Haas during her presentation. “In other words, REMS will help all parties understand the side effects and reduce prescription problems. The overall goal is to improve patient safety.”

She reported that on February 6, 2009, the FDA sent letters requiring that pharmaceutical companies manufacturing certain opioids develop REMS programs, including medication guides, communication plans (such as special brochures to

prescribers and educational materials to patients), and an implementation system for healthcare practitioners.

The FDA’s focus was on opioids containing fentanyl, hydromorphone, methadone, morphine, oxycodone, and oxymorphone—and includes more than 60 products. Prescribing APNs will be required to obtain training certifications by enrolling in the pharmaceutical companies’ REMS. In addition, APNs will be responsible for creating a new system, incorporating order sets, protocols, and evaluation procedures “to ensure drugs are dispensed only to patients with evidence of safe use.”

APNs must work with the nursing staff on setting up protocols for educating patients on how they’re going to be receiving their medications, how to take them, and that they must enroll in patient-registry programs. “The new process is really going to be a collaborative effort between the nurse practitioner, the nurse, and the patients,” said Haas.

Physicians and pharmacists will also be required to take training and certification. “Right now, the programs just use specialty pharmacies, which can be a really positive thing as only one pharmacy will know about the patient and what medications he or she is taking.

So there will be more control over potential abuse of the drug and some good safeguards.

“Of course there are also barriers to using specialty pharmacies,” admitted Haas. “It takes some time to get that medicine processed and then to the patient. It’s not like they can just go out and get it filled everywhere.”

Many of the products now have a medication guide, communication plan, elements to assure safe use, and an implementation plan; others have medication guides only. “So it’s really important that APNs educate themselves on the specifics of each product’s REMS requirements, including listening to webinars,” Haas said.

She advised that the first step for APNs should be to register online as

prescribers as soon as possible to avoid any delays in getting medications to their patients. “Ultimately, you don’t want to deny patients that medication just because you are not a prescriber that has gone through the process. I’d also advise asking for support from nurse navigators to help enroll patients in the registries.”

She cautioned that numerous surveys from the pharmaceutical companies will also need to be filled out documenting safe use, per FDA requirements.

“The educational process is actually pretty easy. It just takes time out of your busy schedule to get approval to prescribe the needed medication. But if you do it now, then you won’t get caught with having to do a whole bunch of REMS programs at once,” concluded Haas.

Further information can be found at: www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformation forPatientsandProviders/ucm111350. htm. ●

Redesigned Lung Cancer Management Process Decreases Time to Diagnosis and Treatment

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medical center’s redesigned lung cancer management protocol decreased both the time to diagnosis and the time from diagnosis to actual treatment to less than 20 days, according to a new study.

“Although 215,000 new cases of lung cancer were diagnosed in 2008, past studies have shown that this diagnosis can take up to 4 months after a suspicious finding, especially if patients are undergoing consecutive procedures,” said Ivy Tuason, RN, MSN, FNP, from Pomona Valley Hospital Medical Center in Pomona, California, during her presentation.

“Many lung cancers are just found too late for successful treatment.”

She reported that because her center often did not perform timely followups on suspicious chest x-ray (CXR) findings coming from emergency department visits, preoperative testing,

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February 2010 I VOL 3, NO 1

and other routine tests, her team sought to expedite this process through a new lung cancer program.

The process put in place through the new program included hiring an advanced practice nurse (APN) to lead

In addition to the new protocol, the team also created and implemented a color-coded intranet webpage, called “virtual tumor board,” to function as a central repository where the physicians could review patient radiographs and

“With this process, we were able to get the times down to less than 3 weeks instead of the 4 months shown in the [previous] studies.”

—Ivy Tuason, RN, MSN, FNP

the program and to determine whether a patient needed further work-up based on daily reports of abnormal CXRs and computed tomography (CT) chest scans. The APN then followed-up on each case until a diagnosis was made.

evaluations. “We wanted to create an automated solution to the issue of accelerating the time it takes for multiple cancer care physicians to review data and, ultimately, determine the correct course of treatment,” Tuason explained.

Finally, the team started creating a series of short web-based patient-education videos, targeting those who were newly diagnosed and featuring providers from the Pomona Valley Hospital Medical Center. “We felt that patients would be able to better relate to the information if their actual providers were the ones featured as content experts,” Tuason said.

The overall aim of the new program was to decrease diagnosis time to less than 25 days and decrease time from diagnosis to treatment to less than 25 days. In an evaluation of 103 patients going through the new protocol between August 2008 and August 2009, the investigators found that the time to diagnosis averaged 18.23 days, and the time to treatment averaged an additional 20.03 days.

“This team approach to fighting the Continued on page 9

www.TheOncologyNurse.com

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Conference News Redesigned Lung Cancer Management...

Diastolic Blood Pressure May Predict Efficacy of Axitinib

Continued from page 8

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disease led to thorough and timely evaluation, treatment, and follow-up,” said Tuason. “With this process, we were able to get the times down to less than 3 weeks instead of the 4 months shown in the [previous] studies. We truly believe that the earlier you diagnose lung cancer and the earlier you initiate treatment, the better the outcomes will be for your patient.”

According to the poster, “The APN had the knowledge and expertise to add value not just in coordinating care but in clinical decision making, collaboration, education, and continuous process improvement.”

Tuason, who was hired as her center’s lung cancer program APN, said that patients appreciate having someone who follows them through the entire process. “It’s a stressful time and they know that I’m there for them, making sure their scans and tests are being read in a timely manner, researching information for their questions, or just available to talk over concerns.”

She added, “This is absolutely a program that can be easily adopted by other centers.” Her program’s new protocol for a suspicious CXR (that turns out to be lung cancer) now includes these steps: • Report received by APN, who contacts patient’s primary care provider (PCP) and CT ordered • After CT, new report received by APN • APN reviews report with the program’s team and PCP; diagnostic study recommended; patient education offered • Diagnosis made based on results • Results given to the patient by PCP; case placed on the new virtual tumor board • Lung cancer team and specialist follow treatment protocol based on test outcome; patient and family receive additional education • Treatment performed • Continued treatment and surveillance ●

iastolic blood pressure (dBP) ≥90 mm Hg may identify whether a patient will benefit from therapy with axitinib, a selective inhibitor of vascular endothelial growth factor (VEGF) receptors, a new study suggests.

Angel Bair, PhD, AOCNP, from Pfizer Oncology in San Diego, Cali-

fornia, presented the results. “Anticancer treatments targeting VEGF pathways have demonstrated success in the clinic, but predicting individual patient benefit remains a challenge,” said Bair during her presentation.

“The use of valid, predictive biomarkers of treatment outcome is important to nurses, particularly if the biomark-

ers are easily measurable and the procedures are inexpensive.”

For this retrospective study, the investigators selected five phase 2 axitinib studies and assessed the association between patient blood pressure and the efficacy of the drug. A total of 230 patients with cytokine- and Continued on page 10

In moderate-risk* chemotherapy regimens

Start every cycle with confidence by helping reduce the risk of febrile neutropenia

Neulasta® is given once per chemotherapy cycle and should not be administered in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

Neulasta® (pegfilgrastim) is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

Important Safety Information Splenic rupture (including fatal cases), acute respiratory distress syndrome, and sickle cell crises have been reported. Allergic reactions, including anaphylaxis, have also been reported. The majority of these reactions occurred upon initial exposure.

However, in rare cases, allergic reactions, including anaphylaxis, recurred within days after discontinuing anti-allergic treatment.

In a placebo-controlled trial, bone pain occurred at a higher incidence in Neulasta®-treated patients as compared to placebotreated patients (31% vs. 26%). The most common adverse events reported in either placebo- or active-controlled trials were consistent with the underlying cancer diagnosis and its treatment with chemotherapy, with the exception of bone pain.

Consequences of febrile neutropenia, such as hospitalization, may impact patient care ■ In a prospective registry study (N = 2,692), febrile neutropenia affected more than 1 in 10 patients overall (10.7%) in the first 3 cycles of chemotherapy in select tumor types.1

First- and subsequent-cycle Neulasta® achieved significant results in patients receiving moderate-risk* regimens: ■ 94% reduction in febrile neutropenia vs. placebo (17% vs. 1%).2,3 ■ 93% reduction in febrile neutropenia–related hospitalization vs. placebo (14% vs. 1%).2,3 *Regimens associated with ≥ 17% risk of febrile neutropenia.

Please refer to brief summary of Neulasta® Prescribing Information. © 2009 Amgen. All rights reserved. MC45637 03-09 Class I www.neulasta.com

Start with support

—DB

www.TheOncologyNurse.com

February 2010 I VOL 3, NO 1

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Conference News ONS IOL

Diastolic Blood Pressure... Continued from page 9 sorafenib-refractory renal cell carcinoma, advanced thyroid cancer, advanced non– small-cell lung cancer, and metastatic melanoma were included in this analysis.

All patients were older than 18 years of age and had a baseline blood pressure of ≤140/90 mm Hg. A twice-daily dose of 5-mg axitinib was given to the patients in 28-day cycles, and blood pressure was measured at each clinic visit.

Retrospectively, the investigators cate-

gorized the patients into two groups: those with at least one dBP measurement of ≥90 mm Hg during treatment (n = 130; 67% male) and those who never went above that threshold (n = 100; 63% male). Median age for both groups was 60 years.

The primary outcomes were overall survival, progression-free survival, objective response rate, and adverse events (AEs).

Results from the pooled analysis

showed that the ≥90-mm Hg group had significantly longer median overall survival (30.1 months vs 10.2 months, P <.001) and a significantly better objective response rate (43.9% vs 12.0%, P <.001) compared with the <90-mm Hg group, respectively.

Although it wasn’t statistically significant, median progression-free survival was also longer for the patients in the ≥90-mm Hg group than for those in the other group (13.1 months vs 5.8

References: 1. Crawford J, et al. J Natl Compr Canc Netw. 2008;6:109-118. 2. Vogel C, et al. J Clin Oncol. 2005;23:1178-1184. 3. Neulasta® (pegfilgrastim) Prescribing Information. Thousand Oaks, Calif: Amgen.

Start with support BRIEF SUMMARY OF PRESCRIBING INFORMATION INDICATIONS AND USAGE Neulasta is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

CONTRAINDICATIONS Neulasta is contraindicated in patients with known hypersensitivity to E coli-derived proteins‚ pegfilgrastim‚ Filgrastim, or any other component of the product.

WARNINGS General The safety and efficacy of Neulasta for peripheral blood progenitor cell (PBPC) mobilization has not been evaluated in adequate and well-controlled studies.

Neulasta should not be used for PBPC mobilization.

Splenic Rupture SPLENIC RUPTURE, INCLUDING FATAL CASES, HAS BEEN REPORTED FOLLOWING THE ADMINISTRATION OF NEULASTA AND ITS PARENT COMPOUND, FILGRASTIM. PATIENTS RECEIVING NEULASTA WHO REPORT LEFT UPPER ABDOMINAL AND/OR SHOULDER TIP PAIN SHOULD BE EVALUATED FOR AN ENLARGED SPLEEN OR SPLENIC RUPTURE. Acute Respiratory Distress Syndrome (ARDS) Acute respiratory distress syndrome (ARDS) has been reported in patients receiving Neulasta, and is postulated to be secondary to an influx of neutrophils to sites of inflammation in the lungs. Patients receiving Neulasta who develop fever, lung infiltrates, or respiratory distress should be evaluated for the possibility of ARDS. In the event that ARDS occurs, Neulasta should be discontinued and/or withheld until resolution of ARDS and patients should receive appropriate medical management for this condition.

Allergic Reactions Allergic reactions to Neulasta, including anaphylaxis, skin rash, urticaria, and erythema/flushing have been reported in postmarketing experience. The majority of reported events occurred upon initial exposure. In some cases, symptoms recurred with rechallenge, suggesting a causal relationship. In rare cases, allergic reactions including anaphylaxis, recurred within days after initial anti-allergic treatment was discontinued. If a serious allergic reaction occurs, appropriate therapy should be administered, with close patient follow-up over several days. Neulasta should be permanently discontinued in patients with serious allergic reactions.

Sickle Cell Disorders Severe sickle cell crises have been associated with the use of Neulasta in patients with sickle cell disorders. Severe sickle cell crises, in some cases resulting in death, have also been associated with Filgrastim, the parent compound of pegfilgrastim. Only physicians qualified by specialized training or experience in the treatment of patients with sickle cell disorders should prescribe Neulasta for such patients, and only after careful consideration of the potential risks and benefits.

PRECAUTIONS General Use With Chemotherapy and/or Radiation Therapy Neulasta should not be administered in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy (see DOSAGE AND ADMINISTRATION) because of the potential for an increase in sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy.

The use of Neulasta has not been studied in patients receiving chemotherapy associated with delayed myelosuppression (eg, nitrosoureas, mitomycin C).

The administration of Neulasta concomitantly with 5-fluorouracil or other antimetabolites has not been evaluated in patients. Administration of pegfilgrastim at 0, 1, and 3 days before 5-fluorouracil resulted in increased mortality in mice; administration of pegfilgrastim 24 hours after 5-fluorouracil did not adversely affect survival.

The use of Neulasta has not been studied in patients receiving radiation therapy.

Potential Effect on Malignant Cells Pegfilgrastim is a growth factor that primarily stimulates neutrophils and neutrophil precursors; however, the G-CSF receptor through which pegfilgrastim and Filgrastim act has been found on tumor cell lines, including some myeloid, T-lymphoid, lung, head and neck, and bladder tumor cell lines. The possibility that pegfilgrastim can act as a growth factor for any tumor type cannot be excluded. Use of Neulasta in myeloid malignancies and myelodysplasia (MDS) has not been studied. In a randomized study comparing the effects of the parent compound of Neulasta, Filgrastim, to placebo in patients undergoing remission induction and consolidation chemotherapy for acute myeloid leukemia, important differences in remission rate between the two arms were excluded. Disease-free survival and overall survival were comparable; however, the study was not designed to detect important differences in these endpoints.* Information for Patients Patients should be informed of the possible side effects of Neulasta and be instructed to report them to the prescribing physician. Patients should be informed of the signs and symptoms of allergic drug reactions and be advised of appropriate actions. Patients should be counseled on the importance of compliance with their Neulasta treatment, including regular monitoring of blood counts.

If it is determined that a patient or caregiver can safely and effectively administer Neulasta (pegfilgrastim) at home, appropriate instruction on the proper use of Neulasta (pegfilgrastim) should be provided for patients and their caregivers, including careful review of the “Information for Patients and Caregivers” insert.

Patients and caregivers should be cautioned against the reuse of needles, syringes, or drug product, and be thoroughly instructed in their proper disposal.

A puncture-resistant container for the disposal of used syringes and needles should be available.

Laboratory Monitoring To assess a patient’s hematologic status and ability to tolerate myelosuppressive chemotherapy, a complete blood count and platelet count should be obtained before chemotherapy is administered. Regular monitoring of hematocrit value and platelet count is recommended.

Drug Interaction No formal drug interaction studies between Neulasta and other drugs have been performed. Drugs such as lithium may potentiate the release of neutrophils;

10

February 2010 I VOL 3, NO 1

patients receiving lithium and Neulasta should have more frequent monitoring of neutrophil counts.

Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results.

Carcinogenesis, Mutagenesis, and Impairment of Fertility No mutagenesis studies were conducted with pegfilgrastim. The carcinogenic potential of pegfilgrastim has not been evaluated in long-term animal studies.

In a toxicity study of 6 months duration in rats given once weekly subcutaneous injections of up to 1000 mcg/kg of pegfilgrastim (approximately 23-fold higher than the recommended human dose), no precancerous or cancerous lesions were noted.

When administered once weekly via subcutaneous injections to male and female rats at doses up to 1000 mcg/kg prior to, and during mating, reproductive performance, fertility, and sperm assessment parameters were not affected.

Pregnancy Category C Pegfilgrastim has been shown to have adverse effects in pregnant rabbits when administered subcutaneously every other day during gestation at doses as low as 50 mcg/kg/dose (approximately 4-fold higher than the recommended human dose). Decreased maternal food consumption, accompanied by a decreased maternal body weight gain and decreased fetal body weights were observed at 50 to 1000 mcg/kg/dose. Pegfilgrastim doses of 200 and 250 mcg/kg/dose resulted in an increased incidence of abortions. Increased post-implantation loss due to early resorptions was observed at doses of 200 to 1000 mcg/kg/dose, and decreased numbers of live rabbit fetuses were observed at pegfilgrastim doses of 200 to 1000 mcg/kg/dose, given every other day.

Subcutaneous injections of pegfilgrastim of up to 1000 mcg/kg/dose every other day during the period of organogenesis in rats were not associated with an embryotoxic or fetotoxic outcome. However, an increased incidence (compared to historical controls) of wavy ribs was observed in rat fetuses at 1000 mcg/kg/dose every other day. Very low levels (< 0.5%) of pegfilgrastim crossed the placenta when administered subcutaneously to pregnant rats every other day during gestation.

Once weekly subcutaneous injections of pegfilgrastim to female rats from day 6 of gestation through day 18 of lactation at doses up to 1000 mcg/kg/dose did not result in any adverse maternal effects. There were no deleterious effects on the growth and development of the offspring and no adverse effects were found upon assessment of fertility indices.

There are no adequate and well-controlled studies in pregnant women. Neulasta 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 pegfilgrastim is excreted in human milk. Because many drugs are excreted in human milk‚ caution should be exercised when Neulasta is administered to a nursing woman.

Pediatric Use The safety and pharmacokinetics of Neulasta were studied in 37 pediatric patients with sarcoma. The mean (± Standard Deviation) systemic exposure (AUC 0-inf) of Neulasta after subcutaneous administration at 100 mcg/kg was 22.0 (±13.1) mcg·hr/mL in the 6–11 years age group (n = 10), 29.3 (±23.2) mcg·hr/mL in the 12–21 years age group (n = 13) and 47.9 (±22.5) mcg·hr/mL in the youngest age group (0–5 years, n = 11).

The terminal elimination half-lives of the corresponding age groups were 20.2 (±11.3) hours, 21.2 (±16.0) hours and 30.1 (±38.2) hours, respectively. The most common adverse reaction was bone pain.

The 6 mg fixed dose single-use syringe formulation should not be used in infants, children, and smaller adolescents weighing less than 45 kg.

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

ADVERSE REACTIONS (See WARNINGS, Splenic Rupture, Acute Respiratory Distress Syndrome (ARDS), Allergic Reactions, and Sickle Cell Disorders.)

Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of Neulasta cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to Neulasta use and for approximating rates.

The data described below reflect exposure to Neulasta in 932 patients.

Neulasta was studied in placebo- and active-controlled trials (n = 467, and n = 465, respectively). The population encompassed an age range of 21 to 88 years. Ninety-two percent of patients were female. The ethnicity of the patients was as follows: 75% Caucasian, 18% Hispanic, 5% Black, and 1% Asian.

Patients with solid tumors (breast [n = 823], lung and thoracic tumors [n = 53]) or lymphoma (n = 56) received Neulasta after nonmyeloablative cytotoxic chemotherapy. Most patients received a single 100 mcg/kg (n = 259) or a single 6 mg (n = 546) dose per chemotherapy cycle over 4 cycles.

In the placebo-controlled trial, bone pain occurred at a higher incidence in Neulasta-treated patients as compared to placebo-treated patients. The incidence of other commonly reported adverse events were similar in the Neulasta- and placebo-treated patients, and were consistent with the underlying cancer diagnosis and its treatment with chemotherapy. The data in Table 1 reflect those adverse events occurring in at least 10% of patients treated with Neulasta in the placebo-controlled study.

Table 1. Adverse Events Occurring in ≥ 10%a of Patients in the Placebo-Controlled Study Event Alopecia Bone Painb Diarrhea Pyrexia (not including febrile neutropenia) Myalgia Headache Arthralgia Vomiting Asthenia Peripheral Edema Constipation

Neulasta (n = 467) 48% 31% 29%

Placebo (n = 461) 47% 26% 28%

23%

22%

21% 16% 16% 13% 13% 12% 10%

18% 14% 13% 11% 11% 10% 6%

a

Events occurring in ≥ 10% of Neulasta-treated patients and at a higher incidence as compared to placebo-treated patients Bone pain is limited to the specified adverse event term “bone pain”

b

In the active controlled studies, common adverse events occurred at similar rates and severities in both treatment arms (Neulasta, n = 465; Filgrastim, n = 331).

These adverse experiences occurred at rates between 72% and 15% and included: nausea, fatigue, alopecia, diarrhea, vomiting, constipation, fever, anorexia, skeletal pain, headache, taste perversion, dyspepsia, myalgia, insomnia, abdominal pain, arthralgia, generalized weakness, peripheral edema, dizziness, granulocytopenia, stomatitis, mucositis, and neutropenic fever.

Bone Pain The analysis of bone pain described below is based on a composite analysis using multiple, related, adverse event terms.

In the placebo-controlled study, the incidence of bone pain was 57% in Neulasta-treated patients compared to 50% in placebo-treated patients.

Bone pain was generally reported to be of mild-to-moderate severity.

Among patients experiencing bone pain, approximately 37% of Neulasta-and 31% of placebo-treated patients utilized non-narcotic analgesics and 10% of Neulasta- and 9% of placebo-treated patients utilized narcotic analgesics.

In the active-controlled studies, the use of non-narcotic and narcotic analgesics in association with bone pain was similar between Neulasta-and Filgrastimtreated patients. No patient withdrew from study due to bone pain.

Laboratory Abnormalities In clinical studies, leukocytosis (WBC counts > 100 x 109/L) was observed in less than 1% of 932 patients with nonmyeloid malignancies receiving Neulasta. Leukocytosis was not associated with any adverse effects.

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

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

Cytopenias resulting from a neutralizing antibody response to exogenous growth factors have been reported on rare occasions in patients treated with other recombinant growth factors. There is a theoretical possibility that an antibody directed against pegfilgrastim may cross-react with endogenous G-CSF, resulting in immune-mediated neutropenia. This has not been observed in clinical studies of Neulasta.

Postmarketing Experience The following adverse reactions have been identified during postapproval of Neulasta. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• splenic rupture (see WARNINGS: Splenic Rupture) • acute respiratory distress syndrome (ARDS) (see WARNINGS: Acute Respiratory Distress Syndrome) • allergic reactions (including anaphylaxis, skin rash, urticaria, erythema/flushing) (see WARNINGS: Allergic Reactions) • sickle cell crisis (see WARNINGS: Sickle Cell Disorders) • injection site pain • Sweet’s syndrome (acute febrile dermatosis) OVERDOSAGE The maximum amount of Neulasta that can be safely administered in single or multiple doses has not been determined. Single subcutaneous doses of 300 mcg/kg have been administered to 8 healthy volunteers and 3 patients with non-small cell lung cancer without serious adverse effects. These patients experienced a mean maximum ANC of 55 x 109/L, with a corresponding mean maximum WBC of 67 x 109/L. The absolute maximum ANC observed was 96 x 109/L with a corresponding absolute maximum WBC observed of 120 x 109/L. The duration of leukocytosis ranged from 6 to 13 days. Leukapheresis should be considered in the management of symptomatic individuals.

DOSAGE AND ADMINISTRATION The recommended dosage of Neulasta is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle. Neulasta should not be administered in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy (see PRECAUTIONS).

The 6 mg fixed-dose formulation should not be used in infants, children, and smaller adolescents weighing less than 45 kg.

No dosing adjustment is necessary for renal dysfunction.

Neulasta should be visually inspected for discoloration and particulate matter before administration. Neulasta should not be administered if discoloration or particulates are observed.

Rx Only This product, its production, and/or its use may be covered by one or more US Patents, including US Patent Nos. 5,824,784; 4,810,643; 4,999,291; 5,582,823; 5,580,755, as well as other patents or patents pending.

REFERENCE *Heil G, Hoelzer D, Sanz MA, et al. A randomized, double-blind, placebocontrolled, phase III study of Filgrastim in remission induction and consolidation therapy for adults with de novo Acute Myeloid Leukemia.

Blood. 1997;90:4710-4718. v.10 Issue Date: 11/2008

Manufactured by: Amgen Manufacturing, Limited, a subsidiary of Amgen Inc. One Amgen Center Drive Thousand Oaks, CA 91320-1799 © 2002–2009 Amgen Inc. All rights reserved.

MC45288

months, respectively; P = .107).

“Basically, we saw a tripling in overall survival and a more than doubling in progression-free survival in the [≥90mm Hg] group, which were inspiring results,” said Bair.

AEs were similar in the two groups, except for fatigue and hand-foot syndrome, which were more frequent for patients in the ≥90-mm Hg group.

“These findings may have clinical implications with respect to drug dosing, treatment monitoring, patient education, and future research,” Bair said.

“They also can potentially enhance the ability of nurses to recognize [dBP] response as a potential biomarker of treatment effect, leading to better patient compliance.”

A new, prospective phase 2 study is currently enrolling patients to further assess the association between blood pressure and efficacy of first-line axitinib therapy, focusing on patients with metastatic renal cell carcinoma.

“If we can show these same benefits in a prospective trial, I think [dBP] response measurement can become a very powerful, very simple tool. It’s easy, noninvasive, can be done right at the bedside, and it’s almost immediate. It’s still early yet in the field, but I think results of the new trial have the potential to significantly impact nursing care of cancer patients receiving axitinib,” Bair concluded.

This study was funded by Pfizer Oncology. ● —DB

Congratulations to Karen HamiltonSandles, RN, Pearland, Texas Winner of the iPod drawing held at The Oncology Nurse booth. Karen is a clinical oncology liaison at OSI Pharmaceuticals.

www.TheOncologyNurse.com

TON_Feb2010_FINAL_TON 2/2/10 11:37 AM Page 11

Conference News

Virtual Classroom Fosters Collaborative Relationships across the Country

O

ncology nursing students across eight states experienced numerous collaborative and learning opportunities while taking part in a novel virtual classroom academic program, according to a presentation by participants.

The information was presented by Darryl Somayaji, MSN, RN, CCRC, from Roswell Park Cancer Institute in Buffalo, New York, and Lanell Bellury, RN, MN, OCN, from Saint Josephâ&#x20AC;&#x2122;s Hospital of Atlanta in Georgia, at the eventâ&#x20AC;&#x201D;with fellow â&#x20AC;&#x153;virtual classmateâ&#x20AC;?

Rebecca Donohue, NP, AOCN, APNG, from Acadiana Medical Oncology in Lafayette, Louisiana, joining via webcam. â&#x20AC;&#x153;Technological advances must be embraced by advanced practice nurses,â&#x20AC;? said Somayaji. â&#x20AC;&#x153;Innovation, networking, and advanced educational opportunities are all extremely important.â&#x20AC;?

This virtual classroom was set up and delivered online through the University of Utah College of Nursing PhD Distance Program. Under the direction of Kathi Mooney, PhD, RN, FAAAN, AOCN, professor of nursing at the University of Utah and past president of the Oncology Nursing Society, nine female students (considered a cohort) enrolled in the program, which started in 2006. â&#x20AC;&#x153;Dr Mooney came up with this idea of an oncology-focused program,â&#x20AC;? Somayaji said. â&#x20AC;&#x153;It was set up to address the shortage of PhD-prepared cancer nurse scientists and nursing faculty within a hightech learning environment.â&#x20AC;?

Some of the challenges faced while creating this community included coordinating logistics and technical needs of students from four different time zones, at the same time as coordinating the universityâ&#x20AC;&#x2122;s administrative needs.

The students used interactive IP videoconferencing to access the live classroom several times per week from their home or workplace. In addition, both faculty and students could use the videoconferencing tool to discuss other issues among themselves during nonclassroom hours. â&#x20AC;&#x153;Weâ&#x20AC;&#x2122;re able to get great interaction this way since you can actually see everyoneâ&#x20AC;&#x2122;s faces, which is something you donâ&#x20AC;&#x2122;t get in a traditional classroom,â&#x20AC;? Bellury said. She explained that during the class, live shots of all the cohort members are shown onscreen along with the professor.

Although the setup was new, it had the same requirements as an onsite class, including a core curriculum and classroom access open to other students and staff members.

www.TheOncologyNurse.com

For face time, the online students meet 2 weeks per year in Salt Lake City and once per year at a research conference. So far, there have been no dropouts.

The presenters reported that the program benefits have been many, including

the establishment of ongoing professional relationships among classmates in various roles and settings, such as private practice, hospice, communitybased and university healthcare systems, and cancer centers. â&#x20AC;&#x153;There is no PhD program around

the rural area where I am in Louisiana,â&#x20AC;? Donohue said. â&#x20AC;&#x153;Itâ&#x20AC;&#x2122;s been great to pilot test my dissertation survey to the other cohort members and get instant feedback and a lot of help.â&#x20AC;?

When asked about possible difficulContinued on page 36

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Pain Management Addressing Concerns about Opioid Use for Cancer Pain Continued from cover At what point should use of opioids be considered in patients with cancer pain?

According to the World Health Organization’s pain ladder, when a patient has moderate-to-severe pain it makes sense to introduce an opioid.

That correlates to patient-rated pain, using a 0 to 10 scale, of 4 and above.

Also, when patients have milder pain, we might start very low doses of an opioid. This would apply in patients who may not be candidates for a nonopioid because of adverse effects or because their pain would not necessarily be responsive to adjuvant analgesics.

What assessments should be done before introduction of opioids?

It’s critical that we do a comprehensive pain history, which includes a pain assessment. The pain rating is a small piece of that assessment. We also want to know where all the pain sites are and the quality of the pain, because these factors help in selection of pharmacologic and nonpharmacologic interventions. We determine if the pain is constant, intermittent, or both, and we look at aggravating and alleviating factors. The combined data along with a physical examination and, in some cases, computed tomography scans, xrays, or other tests help clarify the underlying etiology of the pain. If we know the etiology, we can do a better job of identifying pharmacologic and nonpharmacologic therapies, and, in some cases, anticancer therapies that might be helpful. For example, someone with back pain who has a malignancy may have back pain because of an unrelated herniated disc. But a person who has back pain due to vertebral body metastases might benefit from radiotherapy or, in some cases, vertebroplasty or kyphoplasty. By knowing the underlying cause of the pain, we can be much more precise in our management.

Are there medical conditions that are contraindications to use of opioids?

We do want to know about related medical history and diseases, but these are not generally a contraindication for opioid therapy. These conditions are more likely to be contraindications for nonsteroidal anti-inflammatory drugs (NSAIDs). If the patient has chronic renal disease, for instance, then you wouldn’t choose an NSAID. If the patient has liver failure or chronic liver disease, you wouldn’t want to use anything containing acetaminophen. If the patient has narrow-angle glaucoma, you would be very cautious about using certain tricyclic antidepressants.

If the patient is taking a particular chemotherapeutic or hormonal agent,

12

February 2010 I VOL 3, NO 1

you wouldn’t want to use a drug that interferes with the action of that agent; for example, you wouldn’t want to use duloxetine in a person who is taking tamoxifen because it might interfere with the metabolism of tamoxifen. It’s critical that we have a sense of each patient’s current medical diseases and medical history as well as his or her current medication list.

use psychostimulants such as methylphenidate. Nausea also can occur, often early in the course of opioid use in people who are opioid-naïve. We typically have them take an antiemetic around the clock for the first day or two, and then we can wean down the antinausea drug. Most patients become tolerant of the nauseating effect of the opioid by that time.

We also want to know where all the pain sites are and the quality of the pain, because these factors help in selection of pharmacologic and nonpharmacologic interventions.

In addition, we like to take a thorough psychosocial history, which includes asking patients about their current and past use of cigarettes, alcohol use, and recreational drug use. Recently, we’ve begun asking people about the history of addictive diseases in firstorder family members. A history of addictive diseases in any of their family members will make it more challenging in terms of prescribing opioids, but it isn’t a contraindication. We also like to ask patients about the things that give them strength, such as family, work, their religious affiliation, or spiritual belief. Often, we can use those to help devise nonpharmacologic approaches to help patients with cancer cope with chronic pain and their other symptoms.

How can constipation and other common side effects of opioids be prevented or managed?

The best strategy is to prevent the constipation, but the measures that are generally useful in preventing constipation are not particularly helpful when it’s opioid-induced constipation.

We generally encourage patients to take a laxative in combination with a softener. Most patients need to take these agents regularly, so it requires a lot of education. When it has been more than 2 days since their last bowel movement, we become more aggressive and prescribe tablets, liquids, suppositories, or enemas, depending on the patients’ preference and whether they have any contraindications.

What about other common side effects?

Cognitive blunting is probably the second most problematic side effect that patients describe. We help people to understand that during the first day or two of opioid therapy they are likely to be sedated, but that for many people sedation dissipates over time. For some, however, it persists, and we will

Other side effects include itching and urinary retention, but for most people, these tend to go away over time. We might switch to a different opioid if they occur. Some of these adverse effects are more common in a postoperative setting or with spinal drug delivery.

Are there any special considerations in treating pain in the elderly?

The elderly tend to have some borderline renal dysfunction, so NSAIDs are dangerous in a certain population of the elderly. In an older cancer patient with cachexia, the patient isn’t eating well, which further exacerbates the adverse effects associated with acetaminophen. There is a sense that acetaminophen is safe in lower doses, and yet people who are in a wasting syndrome should not take acetaminophen. So in the elders, it is safest to use opioids. The biggest issue we have found is the need to start very slowly and increase the dose very gradually.

Over time, the patients end up at a similar dose to what might be used for a middle-aged person; it just takes longer to get there.

Probably the biggest challenge we face when working with an older patient who has cancer is caregiver issues, such as remembering when to take medication.

A caregiver can remind the patient to take a pain medication, but if the patient doesn’t have that kind of encouragement or support, he or she may not get good pain relief.

In addition, obtaining schedule II opioids is very difficult. The neighborhood pharmacy may not have that medication, and getting to another pharmacy may be difficult. Again, it comes down to having caregiver support.

Are there issues concerning reimbursement for opioids for cancer pain?

It has gotten very complicated. Even for patients who have insurance, many insurance companies place caps on the

numbers of tablets that a patient may obtain, not just for opioids but on any drug/compound used for pain control.

For example, a lot of insurance companies have issued refusals for pregabalin, which is newer and slightly more expensive than gabapentin. The insurance companies want the patient to first fail on gabapentin before obtaining pregabalin even though pregabalin has better bioavailability and is easier to titrate. Another example is lidocaine patches. There is very little if any systemic uptake of the drug. So for patients who are having side effects to some of the oral agents, this is a useful addition to their treatment regimen, but some insurance companies are refusing to pay for these unless the patient has postherpetic neuropathy.

In addition, I have found lately that some insurance companies have placed a maximum on how many oxycodone tablets they will pay for.

Different insurance companies will allow only a limited number of tablets of oxycodone in any given dose, but they’ll allow a patient to order 90 tablets of the 60-mg dose, 90 tablets of the 40-mg dose, and 90 tablets of the 20-mg dose. This becomes very confusing for the patient. What’s happening for professionals is we are spending an enormous amount of time on the telephone and filling out paperwork for prior authorization when the insurance companies refuse to pay.

What role can nurses play in overcoming barriers to use of opioids for cancer pain?

Nurses need to be aware of the barriers, the patient’s fears in particular because nurses are exquisitely trained to address these fears with their patients and often have the most intimate relationships with their patients.

They have the insight to be aware of what might be serving as an obstacle to good pain control.

Studies have demonstrated that patients don’t want to talk about symptoms with their oncologist, because they are afraid to distract the oncologist from the cancer care and are concerned that if they report symptoms they won’t be a candidate for clinical trials. Through their skills and education, nurses can address these concerns with patients and family members. Pain management really needs to be directed not just to the patient but also to the family. You could have done the best education for the patient, but if the spouse is very anxious about opioids, he or she will send messages to the patient to withhold the drug. ●

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TON_Feb2010_FINAL_TON 2/5/10 10:30 AM Page 14

CONTINUING EDUCATION EDITORIAL BOARD

PROGRAM TON1 • RELEASE DATE: FEBRUARY 15, 2010 • EXPIRATION DATE: FEBRUARY 15, 2011

Pamela Hallquist Viale, RN, MS, CS, ANP, AOCNP

ESTIMATED TIME TO COMPLETE: 1.0 HOUR

Oncology Nurse Practitioner and Consultant Saratoga, CA 95970

Cancer Treatment–related Bone Loss and Osteoporosis: A Concern for Women with Breast Cancer

Assistant Clinical Professor Dept of Physiological Nursing University of California San Francisco Box 0610 San Francisco, CA 94143

Rita Wickham, PhD, RN, AOCN Assistant Professor Rush University College of Nursing 600 S. Paulina Street Armour Academic Center Suite 1080 Chicago, IL 60612

PLANNING COMMITTEE Gloria Mui Medical Director Veritas Institute for Medical Education, Inc. 611 Route 46 West Hasbrouck Heights, NJ 07604 Julie Ann Tagliareni CME Director Veritas Institute for Medical Education, Inc. 611 Route 46 West Hasbrouck Heights, NJ 07604 Anne L. Finger President Veritas Institute for Medical Education, Inc. 611 Route 46 West Hasbrouck Heights, NJ 07604 Dawn Lagrosa Associate Editor Green Hill Healthcare Communications, LLC 241 Forsgate Drvie Monroe Twp, NJ 08831 Karen Rosenberg Editorial Director Green Hill Healthcare Communications, LLC 241 Forsgate Drvie Monroe Twp, NJ 08831

By Rita Wickham, PhD, RN, AOCN Rush University College of Nursing, Oncology and Palliative Care Consultant, Chicago, Illinois STATEMENT OF NEED

As women treated for breast cancer are living longer, their bone health is a major concern. Healthcare providers should be able to identify risk factors for bone loss to determine who may benefit from current management options.

TARGET AUDIENCE

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

After completing this activity, the reader should be better able to: • Explain normal bone physiology and the effects of cancer therapies on bone health • Identify risk factors for bone loss • Discuss current recommendations for pharmacologic and nonpharmacologic interventions to prevent and treat bone loss in patients with cancer

B

reast cancer is a disease of women: only 1% of cases occur in men. Risk for breast cancer increases with age, and 95% of new cases are diagnosed in women aged 40 years or older.1 The median age at diagnosis is 61 years,1 so half of all cases occur in younger women—who may be premenopausal. Women are more likely than men to develop osteoporosis, because they have smaller bones with proportionally less bone volume and density. In addition, women with breast cancer may be at high risk for cancer treatment–induced bone loss (CTIBL), leading to low bone mass (formerly called osteopenia) or osteoporosis.1 The effects of CTIBL can occur independently of bone

metastases and pathologic fractures.

Because women treated for localized or metastatic breast cancer are living longer, their bone health is a major concern.

Healthcare providers must have an understanding of normal bone turnover, patientand treatment-related risk factors for bone loss, measurement of bone mineral density (BMD), and implications for clinical practice.

Patients at risk for bone loss should be identified early so that care interventions can be planned to decrease risks for osteoporosis, maintain or restore normal BMD, sustain functional independence, and prevent potentially fatal low-impact (fragility) fractures.

Normal bone turnover Bones are stiff, flexible, lightweight, and strong to aid in body movement, support and protect vital organs, produce blood cells, and serve as rapid stores for body minerals. Sixty percent of bone is mineralized as calcium hydroxyapatite in a collagen matrix. There are two types of bone: the outer compact (or cortical) bone that makes up most of the long bones (femur, tibia, humerus) and pelvis, as well as the outer covering of flat bones (ileum, vertebrae, ribs), and the inner trabecular (cancellous or spongy) bone found near the ends of the long bones and within flat bones.2 Bone turnover continues over a lifetime to maintain strength and integrity, and all bone undergoes remodeling depending on the forces placed on it. Only a small portion of total bone is remodeled at a given time; areas of greatest stress—vertebral bodies, femoral head and hip, and long bones—are the sites of most frequent remodeling. Turnover is greater in trabecular than in compact bone.

CONTINUING NURSING EDUCATION ACCREDITATION AND CONTACT HOURS STATEMENT

Veritas Institute for Medical Education, Inc. approved by the California Board of Registered Nursing, Provider #13986 for 1.0 Contact Hours.

METHOD OF PARTICIPATION

1. Read the article in its entirety 2. Log on to www.TheOncologyNurse.com 3. Click on “CE Credits” 4. Click on “Click here to complete the posttest and obtain a CE certificate online” 5. Register to participate 6. Enter program number TON1 7. Complete and submit the CE posttest and CE Activity Evaluation and Request for Credit Form online 8. Print your Statement of Completion This activity is provided free of charge to participants.

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February 2010 I VOL 3, NO 1

Bone homeostasis is tightly regulated and, in general, bone resorption and bone synthesis are coupled. During childhood and after fractures, more bone is synthesized than resorbed, but in young adults, bone resorbed equals bone made. After about age 30 to 35 years, slightly less bone is formed, and gradual bone density loss continues into old age.

This uncoupling in bone turnover increases dramatically in women during menopause because of the sudden loss of estrogen. This pronounced uncoupling wanes after 5 to 10 years, and bone loss in postmenopausal women and men older than 55 years is equivalent (about 0.5%-1% per year).3,4 There are three types of bone cells: osteocytes, osteoclasts, and osteoblasts. Osteocytes are the functional bone cells, osteoclasts (c for bone consuming) break down bone, and osteoblasts (b for bone building) synthesize new bone cells and differentiate into osteocytes. Each bone cell influences the activity of the other cell types, which are also influenced by hormones, cytokines, and local growth factors, as well as the central and peripheral nervous system.5,6 For example, osteoclasts and osteoblasts of women and men express estrogen receptors and androgen receptors. Estrogen is more important and may prevent bone loss by regulating cytokine production, maintaining coupled bone turnover, and suppressing the rate of turnover.3 Loss of estrogen increases and intensifies osteoclast activity and may impair osteoblast activity, thereby uncoupling bone homeostasis with more bone resorbed than formed and decreasing bone mass.7,8 Bone remodeling occurs over 3 to 6 months in phases of initiation, transition, and termi-

FINANCIAL DISCLOSURES

Veritas Institute for Medical Education, Inc. is required to disclose to the activity audience the relevant financial relationships of the planners and faculty involved in the development of CE content. An individual has a relevant financial relationship if he or she has a financial relationship in any amount occurring in the last 12 months with a commercial interest whose products or services are discussed in the CE activity content over which the individual has control. In addition, all faculty are expected to openly disclose any unlabeled/unapproved/investigational uses of drugs or devices discussed in this activity. Disclosures are as follows: • Pamela Hallquist Viale, RN, MS, CS, ANP, AOCNP, is a paid speaker for Novartis.

• Rita Wickham, PhD, RN, AOCN, has nothing to disclose.

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

DISCLAIMER

The opinions expressed in this activity are those of the presenters and do not necessarily reflect the opinions or recommendation of Veritas Institute for Medical Education, Inc. Copyright © 2010 Veritas Institute for Medical Education, Inc. All rights reserved.

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www.TheOncologyNurse.com nation. Initiation begins when microcracks in bone, loss of mechanical loading (as caused by prolonged inactivity), or altered hormones or cytokines cause monocytes to gather and differentiate into preosteoclasts. These subsequently fuse into large, multinucleated osteoclasts that have powerful proteases to demineralize and resorb damaged bone. Resorption lasts about 3 weeks.7,9 During transition (or reversal), osteoclasts stimulate local mesenchymal stem cells to differentiate into preosteoblasts and then osteoblasts, at which point osteoclasts undergo apoptosis and stop resorbing bone. During termination (or formation), osteoblasts begin to form new bone.

Layering of osteoblasts continues until the resorbed cavity fills in over 3 to 4 months. Osteoblasts ultimately flatten and differentiate into osteocytes and become encased in hydroxyapatite. New bone is not as mineralized (or strong) as older bone.

Risk factors for BMD loss Bone strength depends on BMD and bone quality (mineralization, hydroxyapatite matrix, altered repair, and microdamage).3 Only BMD can be measured, and evaluation of BMD is recommended in individuals at high risk for osteoporosis and low-intensity fractures. These fractures can result from a fall from a height no more than the person’s standing height or occur spontaneously with coughing, sneezing, or abrupt movement.10 Aging inevitably leads to bone loss, so elderly women and men have less bone strength than young adults. Some risk factors for osteoporosis, such as genetic predisposition and early menopause (<45 years of age) are unchangeable; however, other factors, including

Tamoxifen, a SERM, is an estrogen antagonist on bone and increases bone loss in premenopausal women, but is an agonist on bone and spares bone in postmenopausal women. sedentary lifestyle, low calcium and vitamin D intake, cigarette smoking, and alcohol intake, can be changed.10,11 Bone architecture is altered with bone loss, and osteoporotic compact bone is thin and brittle, whereas cancellous bone loses many trabeculae; both loss of trabeculae and compact bone greatly weaken bone.12 Cancer medications that can cause CTIBL, autologous bone marrow/stemcell transplantation, and multiple myeloma are all high-risk factors for patients with cancer. Chronic corticos-

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Table 1. T-scores and BMD Category

Definition

T-score

Normal

• BMD within 1 SD of young normal adult

–1.0 and above

Low bone mass (osteopenia)

• BMD between 1 and 2.5 SDs below that of young normal adult

Between –1.0 and –2.5

Osteoporosis

• BMD is 2.5 SD or more below that of young normal adult

Below –2.5

Severe osteoporosis

• BMD is 2.5 SD or more below that of young normal adult • Has had ≥1 low-impact (fragility) fracture

Below –2.5

BMD indicates bone mineral density; SD, standard deviation.

Source: Reference 11.

Table 2. ASCO Recommendations for Patients with Nonmetastatic Breast Cancer DXA Hip ± Spine

Management

Monitoring

Not recommended

Lifestyle advice; calcium and vitamin D

Annual history for risk status

T-score: –1.0 and above Recommended

Lifestyle advice; calcium and vitamin D

Annual BMD

T-score: –1.0 to –2.5

Lifestyle advice; calcium and vitamin D

Annual BMD

Lifestyle advice; calcium and vitamin D; begin bisphosphonate or raloxifenea

Annual BMD

Low risk High risk

Recommended

T-score: –2.5 and below Recommended

Raloxifene, a selective estrogen-receptor modulator, is not recommended in patients who have taken tamoxifen.

ASCO indicates American Society of Clinical Oncology; BMD, bone mineral density; DXA, dual-energy x-ray absorptiometry.

Source: Reference 15.

a

teroid treatment (eg, 5 mg prednisone per day for ≥3 months) can also induce bone loss and osteoporosis.

Chemotherapy and hormones may indirectly cause bone loss by leading to loss of estrogen. Ovarian damage and premature menopause occur in 63% to 96% of premenopausal women within 1 year after adjuvant chemotherapy that includes cyclophosphamide, and older women receiving higher cumulative doses are at greatest risk for bone loss.7 More than two thirds of breast cancers are estrogen receptor–positive, and hormones—particularly selective estrogen-receptor modulators (SERMs) and aromatase inhibitors (AIs) that are given to treat or prevent breast cancer by inducing menopause or further reducing estrogen levels—also affect bone remodeling.13 Tamoxifen, a SERM, is an estrogen antagonist on bone and increases bone loss in premenopausal women, but is an agonist on bone and spares bone in postmenopausal women.7,14 AIs block the action of aromatase, the enzyme that converts adrenally produced androgens into estrogen in postmenopausal women. Anastrozole, letrozole, and exemestane increase bone loss and frac-

ture rates, but this effect is reversible shortly after the AI is stopped. It is not known, however, whether lost bone is regained or over what period. Similarly, a gonadotropin-releasing hormone agent such as goserelin dramatically decreases circulating estrogen, as does oophorectomy or sudden menopause.

Detection and management of osteoporosis It is critical to identify patients at risk for bone loss because osteoporosis is asymptomatic until a fracture occurs.

The best single test for BMD is central dual-energy x-ray absorptiometry (DXA or DEX), which provides two-dimensional views of the hip and spine, or total body bone.7,10 DXA results, reported as T-scores, represent the differences in standard deviations (SDs) in the patient’s BMD and a standard comparison group of young adult women. BMD may be normal, low bone mass (osteopenia), osteoporosis, or severe osteoporosis (Table 1).11 Fracture risk is inversely correlated with BMD and increases by 1.6 to 2.2 times for each fall in T-score SD.15 In 2003, the American Society of Clinical Oncology published updated guidelines for management of bone

health in women with breast cancer (Table 2). The guidelines stress the importance of early detection and therapy for osteoporosis.16 Management involves both nondrug and pharmacologic therapies.10-12 First, healthcare providers must identify at-risk patients who may benefit from lifestyle changes that can decrease bone loss. For example, current recommendations from the National Osteoporosis Foundation for daily intake of calcium and vitamin D are 1200 mg/day and 800 IU/day to 1000 IU/day, respectively, and many individuals will need supplements to attain these levels.11 Supplemental calcium should not exceed 1500 mg/day (in divided doses), however, because of risks for kidney stones and cardiovascular problems.

Patients should also be counseled on strategies to stop smoking and limit alcohol intake, and the benefits of regular weight-bearing exercise (walking or jogging, stair climbing, Tai-Chi) and muscle-strengthening exercise (weight training, resistive exercises), which may decrease the risk of falls and modestly increase BMD, should be emphasized.11 Raloxifene, estrogen (not used in patients with breast cancer), calcitonin, Continued on page 16

February 2010 I VOL 3, NO 1

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CONTINUING EDUCATION Continued from page 15

Cancer Treatment–related Bone Loss and Osteoporosis...

CASE REPORT

M

T was diagnosed with stage IIB breast cancer at age 42 years. After lumpectomy and axillary node dissection, she underwent chemotherapy (followed by radiotherapy). She received four cycles of intravenous (IV) doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 (AC) every 3 weeks, followed by four cycles of IV paclitaxel 175 mg/m2 every 3 weeks.

Her menstrual periods stopped after her second cycle of AC and never resumed.

At her 18-month follow-up, MT reported vaginal dryness and discomfort with intercourse. She told her advanced practice nurse about an article she had read regarding osteoporosis and wondered about her risk, because of her chemotherapy-induced menopause and her mother’s osteoporosis, which resulted in a hip fracture at age

72 years. Her other risk factors included a history of cigarette smoking (down to six to seven cigarettes/day from one pack/day at diagnosis) and relative thinness (5’6” tall, 119 lb). MT underwent a baseline dual-energy xray absorptiometry (DXA) scan, and her T-scores were –2.4 (spine) and –2.0 (hip).

MT’s diagnosis was low bone mass, but the oncologist decided MT should start bisphosphonate therapy to prevent further bone mineral density loss. MT was already taking a daily vitamin containing vitamin D 400 IU and calcium 600 mg, so the nurse advised her to take an additional 600 mg of calcium each evening. MT’s creatinine clearance was 110 mL/min and her serum calcium level was 8.6 mg/dL. She was given IV zoledronic acid over 30

minutes. The plan is to repeat DXA and zoledronic acid in 1 year.

Three days after receiving zoledronic acid, MT phoned the nurse and reported “jerky” muscles, cramps in her legs, and tingling in her fingers and toes. She returned for laboratory tests, which showed the following: serum calcium, 7.5 mg/dL, and serum vitamin D (calcidiol), 15 ng/mL. She was given IV vitamin D 50,000 U and instructed to increase her supplemental vitamin D to 1000 U/day. Laboratory tests will be repeated in 2 days, and IV vitamin D treatment repeated if her calcidiol is <30 ng/mL.

ng/mL are considered normal, and deficiency impairs absorption of dietary calcium and parathyroid hormone metabolism.1 Internists would likely check calcidiol before starting a bisphosphonate for osteoporosis, but oncologists less commonly do so.2 Bisphosphonate administration in the face of vitamin D deficiency can cause calamitous hypocalcemia (neuromuscular irritability evidenced by tetany [positive Chvostek’s or Trousseau’s sign], confusion, cardiac arrhythmia, seizures) and worsen secondary hyperparathyroidism, low bone mass, and the risk for fracture.

References

Discussion Vitamin D deficiency is common in the United States because of sun avoidance and few dietary sources.

Calcidiol levels of 32 ng/mL to 100

1. Heaney RP. Vitamin D endocrine physiology. J Bone Miner Res. 2007;22(suppl 2):V25-V27.

2. Wang-Gillam A, Miles DA, Hutchins LF. Evaluation of vitamin D deficiency in breast cancer patients on bisphosphonates. Oncologist. 2008;13:821-827.

COMMENTARY

A Nurse’s Perspective Pamela Hallquist Viale, RN, MS, CS, ANP, AOCNP Oncology Nurse Practitioner and Consultant, Saratoga, California

B

reast cancer is estimated to be the most common malignancy diagnosed in women for the year 2009, and to be the second leading cause of death, affecting approximately 40,170 women.1 Endocrine therapy is an integral part of the treatment for women with breast cancer, and the first endocrine agent, tamoxifen, was found to reduce the rate of breast cancer recurrence significantly, thus cementing its role in the therapy of women with estrogen receptor/progesterone receptor (ER/PR)-positive cancer. Aromatase inhibitor (AI) agents have since attained a prominent role in the armamentarium of agents approved in ER/PR-positive breast cancer, and are now considered to be superior to tamoxifen for hormonally responsive breast cancer in patients who are postmenopausal.

Although tamoxifen has a protective effect against bone loss, the potent effect of AIs on reduction of estrogen levels has a negative effect on bone loss, with women experiencing higher fractures and bone loss with AI therapy.2 Therefore, women with breast cancer on AI therapy are at increased risk for bone loss and osteoporosis related to their endocrine therapy.

Nonpharmacologic strategies to prevent bone loss include physical activity, weight and strength training, and

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February 2010 I VOL 3, NO 1

other types of exercise, including stretching.3 Ingestion of calcium and vitamin D is essential to help maintain bone mass; lifestyle changes, such as cessation of smoking or excessive alcohol use, are also important.3 Pharmacologic strategies include agents, such as bisphosphonates. These agents are inhibitors of osteoclastmediated osteolysis and can be effective treatment for osteoporosis; the nitrogen-containing bisphosphonates are considered the treatment of choice for bone loss associated with AI therapy (ibandronate, alendronate, risedronate, and zoledronic acid).2,4 In addition, zoledronic acid has shown significant benefit in premenopausal women in several studies.5,6 Treatment with bisphosphonates is not without risks. Although the agents are generally well-tolerated, oral therapies require the patient to stay upright for 30 minutes or more to avoid gastrointestinal side effects.7 In addition, although rare, osteonecrosis of the jaws (ONJ) has been linked to patients taking bisphosphonate therapy, although it is more common with intravenously administered agents versus oral and in patients receiving the agents for metastatic disease versus osteoporosis.8,9 A recent retrospective analysis of 4019 patients treated with intravenous bisphosphonates between 1996 and

2004 identified a 1.2% incidence of ONJ in patients with breast cancer compared with a 2.4% incidence in patients with multiple myeloma.9 All cases were for patients receiving the agents for metastatic disease compared with an indication for osteoporosis.

Nonetheless, ONJ is generally considered a condition in which exposed, nonhealing bone, with or without pain, persists; often ONJ is linked to other risk factors, such as previous dental extractions.9 Oncology nurses should inquire about dental health prior to treatment with bisphosphonate therapy in patients on AIs, and patients should be encouraged to report any signs or symptoms of ONJ as early as possible for appropriate intervention.

Intravenous bisphosphonates are dosed according to renal function, with baseline creatinine clearance and subsequent serum creatinine measurement important parts of patient assessment. In addition, supplementation with vitamin D and calcium are important to prevent depletion of these minerals.7 Oncology nurses play a crucial role in assisting patients with breast cancer who are prescribed AI therapy.

Understanding the increased risk for osteoporosis and possible treatment strategies are crucial in managing this patient population.

References 1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225-249.

2. Hadji P. Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis. Crit Rev Oncol Hematol. 2008;69:73-82.

3. Delaney MF. Strategies for the prevention and treatment of osteoporosis during early postmenopause. Am J Obstet Gynecol. 2006; 194(2 suppl):S12-S23.

4. Bauss F, Schimmer RC. Ibandronate: the first once-monthly oral bisphosphonate for treatment of postmenopausal osteoporosis. Ther Clin Risk Manag. 2006;2:3-18.

5. Gnant MFX, Mlineritsch B, LuschinEbengreuth G, et al; for the Austrian Breast and Colorectal Cancer Study Group.

Zoledronic acid prevents cancer treatmentinduced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2007; 25:820-828.

6. Gnant M, Hausmaninger H, Samonigg H, et al. Changes in bone mineral density caused by anastrozole or tamoxifen in combination with goserelin (± zoledronate) as adjuvant treatment for hormone receptor-positive premenopausal breast cancer: results of a randomized multicenter trial. Breast Cancer Res Treat. 2002;76(suppl 1):Abstract 12.

7. Yamamoto DS, Viale PH. Update on identifying and managing osteoporosis in women with breast cancer. Clin J Oncol Nurs.

2009;13:E18-E29.

8. Gomez Font R, Martinez Garcia ML, Olmos Martinez JM. Osteochemonecrosis of the jaws due to bisphosphonate treatments.

Update. Med Oral Patol Oral Cir Bucal.

2008;13:E318-E324.

9. Hoff AO, Toth BB, Altundag K, et al.

Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res. 2008;23:826-836.

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TON_Feb2010_FINAL_TON 2/4/10 9:53 AM Page 17

www.TheOncologyNurse.com Table 3. Agents that Might Be Used in Patients with Breast Cancer and Osteoporosis Class/Agent

Indications Prevention

Bisphosphonates Alendronate (Fosamax, Fosamax D)

Postmenopausal osteoporosis

Dosing Treatment

Tablet: 5 mg/day or 35 mg/week

Tablet or liquid: 10 mg/day or 70 mg/week

Comments

Take upon rising in AM with 8 oz water, empty stomach; do not eat or drink and stay upright for 30 minutes

Tablet: 70 mg/week with 2800 IU or 5600 IU of vitamin D Ibandronate (Boniva)

Postmenopausal osteoporosis

Tablet: 2.5 mg/day or 150 mg/month

Tablet: 2.5 mg/day or 150 mg/month IV: 3 mg every 3 months

Take upon rising in AM with 8 oz water, empty stomach; do not eat or drink and stay upright for 60 minutes

Risedronate (Actonel, Actonel with calcium)

Postmenopausal osteoporosis; increase bone mass in men with osteoporosis; prevent, treat osteoporosis in men and women starting or taking glucocorticoid

Tablet: 5 mg/day or 35 mg/week or 75 mg on two consecutive days or 150 mg once a month

Take upon rising in AM with 8 oz water, empty stomach; do not eat or drink and stay upright for 30 minutes

Zoledronic acid (Reclast)

Postmenopausal osteoporosis

IV: 5 mg once a year

Administer over at least 15 minutes

Women at least 5 years postmenopausal

Single daily intranasal spray 200 IU

Alternate nares

Postmenopausal women at high risk for fracture

Daily subcutaneous injection: 20 μg

Contraindicated: patients receiving skeleton or bone radiotherapy to metastases, history of skeletal malignancy, hypercalcemia

Calcitonin Salmon calcitonin (Miacalcin, Fortical) Parathyroid hormone PTH (1-34) Teriparatide (Forteo)

IV indicates intravenous.

Sources: References 10 and 11.

parathryroid hormone, and some bisphosphonates have US Food and Drug Administration approval to treat postmenopausal osteoporosis (Table 3).10,11 Bisphosphonates, which suppress osteoclast activity to slow bone resorption, are the most commonly used agents in patients with cancer. An evidence-based review of bisphosphonates for CTIBL in breast cancer patients confirmed that clodronate, ibandronate, pamidronate, risedronate, and zoledronic acid have protective effects against bone loss secondary to chemotherapy-induced menopause, ovarian ablation with goserelin, or treatment with an AI.13 When using pamidronate and zoledronic acid, it is important to remember that the doses used to treat osteoporosis are lower than those commonly used for hypercalcemia. It is also important to assess vitamin D levels in patients who are prescribed a bisphosphonate for osteoporosis, because vitamin D insufficiency, which is common in patients with cancer, can worsen hypocalcemia and lead to secondary hyperparathyroidism, low bone mass, and fractures.17 Patients with low vitamin D levels thus

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require instruction about vitamin D supplementation during bisphosphonate therapy. To take an oral bisphosphonate, patients must be able to take it with tap water on an empty stomach and to sit or stand for 30 minutes after taking it because of the potential for reflux, esophageal irritation, and gastritis. Some oral bisphosphonates are given weekly or monthly to simplify administration, but adherence is problematic, and up to 50% of patients stop taking oral agents after less than 1 year.18 Ibandronate and zoledronic acid can be administered intravenously. This may enhance adherence but can also cause acute flulike symptoms, which can be alleviated by acetaminophen.

Conclusion Osteoporosis is likely to become an increasingly important issue in survivorship care plans for patients with breast cancer. Early identification of patients at risk—particularly as they age—and counseling about maintaining healthy weight, regular exercise, calcium and vitamin D intake, moderate alcohol use, and avoidance of smoking are essential for prevent-

ing this complication. Some patients will also require pharmacologic management of CTIBL, which will require nurses, pharmacists, and others caring for these patients to maintain up-to-date knowledge about current recommended therapies to teach patients about drug benefits and burdens and aid patient adherence. ● References 1. Breast Cancer Facts and Figures 2007-2008.

Atlanta, GA: American Cancer Society; 2008.

2. Datta HK, Ng WF, Walker JA, et al. The cell biology of bone metabolism. J Clin Pathol.

2008;61:577-587.

3. Almeida M, Han L, Martin-Millan M, et al.

Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids.

J Biol Chem. 2007;282:27285-27297.

4. Lønning PE. Endocrine therapy and bone loss in breast cancer: time to close in the RANK(L)? J Clin Oncol. 2008;26:4859-4861.

5. Borovecki F, Pecina-Slaus N, Vukicevic S. Biological mechanisms of bone and cartilage remodeling—genomic perspective. Int Orthop.

2007;31:799-805.

6. Elefteriou F. Regulation of bone remodeling by the central and peripheral nervous system. Arch Biochem Biophys. 2008;473:231-236.

7. Michaud LB, Goodin S. Cancer-treatment-induced bone loss, part 1. Am J Health Syst Pharm.

2006;63:419-430.

8. Zallone A. Direct and indirect estrogen actions on osteoblasts and osteoclasts. Ann N Y Acad Sci. 2006;1068:173-179.

9. Matsuo K, Irie N. Osteoclast-osteoblast communication. Arch Biochem Biophys. 2008;473:201-209.

10. Institute for Clinical Systems Improvement.

Health Care Guideline: Diagnosis and Treatment of Osteoporosis. September 2008. www.icsi.org/ osteoporosis/diagnosis_and_treatment_of_osteo porosis__3.html. Accessed November 20, 2009.

11. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. 2008. http://nof.org/professionals/NOF_ clinicians_guide.pdf. Accessed November 20, 2009.

12. Turner Biomechanics Laboratory. Osteoporosis/ biomechanics. 2005. www.engr.iupui.edu/~tur nerch/biomech.htm. Accessed November 20, 2009.

13. Saad F, Adachi JD, Brown JP, et al. Cancer treatment-induced bone loss in breast and prostate cancer. J Clin Oncol. 2008;26:5465-5476.

14. Bjarnason NH, Hitz M, Jorgensen NR, Vestergaard P. Adverse bone effects during pharmacological breast cancer therapy. Acta Oncol. 2008; 47:747-754.

15. Johnell O, Kanis JA, Oden A, et al. Predictive value of BMD for hip and other fractures. J Bone Miner Res. 2005;20:1185-1194.

16. Hillner BE, Ingle JN, Chlebowski RT, et al.

American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer.

J Clin Oncol. 2003;21:4042-4057.

17. Wang-Gillam A, Miles DA, Hutchins LF. Evaluation of vitamin D deficiency in breast cancer patients on bisphosphonates. Oncologist.

2008;13:821-827.

18. Boonen S, Vanderschueren D, Venken K, et al.

Recent developments in the management of postmenopausal osteoporosis with bisphosphonates: enhanced efficacy by enhanced compliance. J Intern Med. 2008;264:315-332.

February 2010 I VOL 3, NO 1

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Nursing School Profile University of Louisiana, Lafayette... Continued from cover country, has been recognized with state and national awards. In this interview, Melinda G. Oberleitner, RN, DNS, APRN, CNS, associate dean and oncology clinical nurse specialist, Theresa Frederick, RN, MSN, APRN, nursing faculty, Rebecca Donohue, MSN, FNPBC, AOCN, APNG, oncology nurse practitioner, and Beth Harris, RN, MSN, ACNS-BC, nursing faculty discuss the nursing curriculum as well as the trends in oncology nursing.

Does the University of Louisiana at Lafayette have nursing programs at both the bachelor’s and master’s levels?

Melinda Oberleitner (MO): We have one of the largest undergraduate nursing programs in the country. We have about 1500 undergraduates; we had record enrollment for the fall term.

The master’s program is part of a three-

we have about 300 graduate students.

At the master’s level, we offer the nurse practitioner track in adult health and adult psychiatric/mental health nursing as well as clinical nurse specialist tracks in those areas. We also have nursing education and nursing leadership and administration tracks.

We don’t offer a specific track in oncology, but graduate students can plan their clinical practicum experiences to be in the oncology specialty.

Beth Harris (BH): I was awarded my degree in 1996, and at the time, I was working as a breast cancer clinician. They allowed me to tailor my clinical experience to my own particular interests.

Rebecca Donohue (RD): As an undergraduate, I took the oncology elective and was able to go with my preceptor and experience the oncology floor. As a graduate student, I was

“In the past, we would only have given chemotherapy in the office, but today we do everything except for blood transfusion.”

—Rebecca Donohue, MSN, FNP-BC, AOCN, APNG

university consortium that offers the MSN degree. Our other two consortium partners are McNeese State University in Lake Charles and Southeastern Louisiana University in Hammond. The three universities come together to offer a unified curriculum, which leads to the MSN degree. Between the three universities,

encouraged to participate in different specialty clinic experiences.

Do you notice a trend among current nursing students to specialize in certain areas just as medical students are doing?

MO: The trend is rather than working on just a general medical/sur-

Left side: first row: Merrit Thomas, Sabrina Breaux, Taylor Leblanc, Allie Laville, Amber Trahan. 2nd row: Megan Troha, Bria Vidos, Jessica Bain, Allie Lacomb.

Right side: first row: Beth Harris, Manivahn Homratsamy, Shonrieka Thomas, Hannah Moore, Jessica Phillips. 2nd row: James Hoffpauir, Dominique Smith, Ashley Payne.

18

February 2010 I VOL 3, NO 1

“With so much information on the Internet, patients need to know what’s reliable, what isn’t reliable, and what applies to their particular situation.”

—Melinda G. Oberleitner, RN, DNS, APRN, CNS

gical unit, most students want to work on a unit with a specific clinical identity. Those of us who are in oncology tend to steer some of our students who seem to have affinity for that area into that specialty. Other students want to work in the critical care area, and others are interested in the maternal/child health area.

Have you noticed any effects from the economy on nursing students, perhaps more men going into the field or more people with previous experience in other fields?

MO: We have an accelerated-option degree program in which we have people with a previous degree in another field come into the nursing program at the undergraduate level and then progress through the program in an accelerated fashion. We have always had a high percentage of male students and minority students. So we track above the national average for enrollment of male students and minority students.

We find that more people are going on to graduate school. The trend we’re seeing is that they are doing it at a younger age and that they are going right from the bachelor’s to the master’s degree program.

so today, with so many options available to patients for treatment. And with so much information on the Internet, patients need to know what’s reliable, what isn’t reliable, and what applies to their particular situation. Education is absolutely critical for the nursing staff as well as for patients and family.

Communication is one of our major competencies at both the undergraduate and graduate levels along with the responsibility as a professional to remain educated and the responsibility for educating the patient. Large areas of our curriculum are devoted to excellence in those competencies.

What are some of the honors the college has received over the years?

MO: We were recognized as a Center of Excellence in Nursing Education by the National League of Nursing from 2005 to 2008. We were one of only eight colleges of nursing in the country to receive that designation. The college was also honored with the 2009 Nightingale Nursing School of the Year award by the Louisiana State Nurses Association and the Louisiana Nurses Foundation.

We are also well known for having one of the most technologically advanced How are career opportusimulation facilities. We nities for recent graduates? were one of the first colleges Are they having any trouof nursing in the country to ble getting jobs? establish a simulated materMO: Not in our area, nal-child/neonatal simulaalthough we do hear that is tion laboratory. In addihappening across the country. tion, we have taken a The dean and I met with our leading role in the South Theresa Frederick, major clinical affiliates over in offering faculty develRN, MSN, APRN the summer and talked about opment opportunities for employment prospects for our nursing faculty. Faculty students; all of them said they are in from many programs have toured our growth phases. A report by Louisiana simulation laboratories and received Works, which is part of our Department assistance from our faculty in establishof Labor, shows that nursing is the top ing their own. employment prospect in our state.

Although our program is extremely large, it is a high-quality program. We Melinda, since you have been an don’t just rest on our laurel of size; oncology nurse for quite a while, have we want to produce a quality practitionyou noticed any different trends in er, at either the graduate or undergradunursing or in the opportunities and ate level. We have a 25-year history of a challenges for nurses today?

98% first-time pass rate on the National MO: Patient education has always Council Licensure Examination. been crucial in oncology and even more Continued on page 19

www.TheOncologyNurse.com

TON_Feb2010_FINAL_TON 2/4/10 12:06 PM Page 19

Genitourinary Cancers The Changing Kidney Cancer Treatment Landscape... Continued from cover Northwestern University, Chicago.

“Physical, functional, social, and emotional factors should be taken into consideration while assessing the general well-being of RCC patients.”

He said that because oncology nurses have their fingers on the pulse of patients’ needs, they are ideally suited for assessing PROs. Cella, a clinical psychologist specializing in cancer care, said medical interventions largely focus on symptom relief and the maintenance of physical functioning. Pain and emotional stress can be equally important, however, and that is where oncology nurses are now playing an ever more critical role.

Many RCC patients who are treated for metastatic disease experience problems with physical, social, and mental functioning. They may experience sleeping problems, lack of appetite, nausea, vomiting, and shortness of breath. Cella said oncology nurses can play a pivotal role in formally assessing these issues.

“Symptom patterns are vital and can signal tumor responses and disease progression,” Cella said. “It is very important to measure symptoms and the patients’ quality of life as they go through treatment. You need to measure these things, and there need to be standards.”

At his institution, Cella and his colleagues use a 15-statement type of evaluation that asks questions such as, “Do you lack energy?” Using this tool and similar ones that are available, it may be possible for nurses to know when treatment regimens are failing or need to be adjusted.

“The treatment options are unprecedented, and there has never been a better outlook,” said Cella in an interview with The Oncology Nurse. “Nurses and pharmacists have an ever-increasing role in helping with oral medication compliance needs. Managing side effects and adjusting doses when necessary are some of the new roles that go beyond the old infusion times. There are daily medicine requirements, and the patients may have concerns arising between visits.”

New agents require new management New oral agents are changing how RCC patients are managed and the role of the oncology nurse. These new agents work through different mechanisms of actions, and each comes with its own side effect profile. Furthermore, these side effects may manifest differently in individual patients.

“Doctors may treat the disease, but it is the nurse who is the one who sees the patients, and it is critically important that oncology nurses know the side effects of each agent and how to manage each of the side effects,” said William Bro, the CEO of the Kidney Cancer Association.

He said today RCC is very much like diabetes. Both conditions can be manageable, chronic illnesses that can impair a person’s quality of life. With proper management, however, both illnesses can be controlled while maintaining a high quality of life.

“We have entered into a whole new era in kidney cancer. People think they

are cured or not cured, but it would be nutrition plans, and physical therapy. better if they looked at it like it was a He noted that nurses can play a key chronic condition that is managed like role in helping with referrals for diabetes. Today, no one these types of services. thinks of diabetes as a deadly “Many people don’t realdisease, but that was not the ize all the resources that case decades ago. That is the are available,” Bro said. point where we are now Another issue that nurses headed,” Bro said. “Oral may need to discuss with agents are a tremendous new their patients is alternative convenience. They are intherapies they may be takherently better for everying. Vitamin use is another one. We are moving into area of concern. Some canthe area of personalized cer patients may be taking David Cella, PhD medicine, and so there megadoses of vitamins in needs to be an expertise the hope that it will help and a familiarity by the nurse.” with their disease. Studies suggest, howBro said it is important that nurses ever, that taking megadoses of vitamin A address three areas of well-being that or vitamin E may not be in the patients’ may be impacting the lives of patients best interest. In addition, megadoses of with RCC. The three areas are emotion- vitamin C can be hard on a remaining al, physical, and practical. Emotional kidney and cause the formation of kidissues may include isolation and depres- ney stones in patients with RCC, most of sion. Physical issues may involve symp- whom have had a nephrectomy and toms, medication side effects, and func- have only one functioning kidney. tioning. Practical issues may involve In just the past few years, PRO assessemployment, financial problems, and ments have grown in credibility and, end-of-life care.

Cella said, in the area of kidney cancer it, He noted that it is not uncommon for is an assesment that may make a dramatRCC patients to isolate themselves, and ic difference in terms of morbidity and this can often lead to depression, and mortality. “when this happens, the support system “What patients say has a way of defincan quickly disintegrate.” He said this ing the clinical landscape,” said Cella. “It common problem is one that nurses can can be the most important factor in how detect and manage. someone does and whether they survive.

Bro added that it is important to Patients need to be brought into the address all forms of care aimed at sup- clinical picture more.” ● porting quality of life. This may encompass therapy, support groups, patient Part 1 of this report appeared in the education, palliative care, developing November/December 2009 issue.

University of Louisiana, Lafayette... Continued from page 18 Do your students have an opportunity to gain experience in the community?

Theresa Frederick: In my oncology elective, I encourage the students to join the Oncology Nursing Society (ONS) and to subscribe to the ONS e-newsletter for students. We also started an oncampus chapter of Colleges Against Cancer, which has become a universitywide program. Colleges Against Cancer is a part of the American Cancer Society focused on fund-raising and awareness.

BH: I teach the palliative care elective at the university, and I had the opportunity to bring our students to our state prison. One of the things that we talk about in our electives is the barriers to the delivery of care, and prisoners are a vulnerable population. The Louisiana State Penitentiary has a model prison hospice. With the help of an instructional teaching grant, I had the opportunity to bring the students there to meet with the patients. It was a very powerful experience for them. ●

www.TheOncologyNurse.com

Beth Harris and students on their way to Louisiana State Penitentiary.

February 2010 I VOL 3, NO 1

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Conference News ASH 2009 The following articles are based on reports at the 51st Annual Meeting and Exposition of the American Society of Hematology (ASH), held in New Orleans, December 5-9, 2009.

Nilotinib: First-line Treatment Option for Chronic-phase CML?

By Wayne Kuznar

I

n the first head-to-head comparison of targeted oral tyrosine kinase inhibitors as initial treatment for early-stage chronic myeloid leukemia (CML), molecular and cytogenetic remissions were more common with nilotinib compared with imatinib, the previous standard for treating earlystage CML, said Giuseppe Saglio, MD. The finding could elevate nilotinib to first-line treatment in early CML. Currently, nilotinib is approved for the treatment of patients with Philadelphia chromosome–positive (Ph+) CML in the chronic and accelerated phases who are resistant to prior therapy.

“The superior efficacy and favorable tolerability profile of nilotinib compared with imatinib suggests that nilotinib may become the standard of care in newly diagnosed CML,” said Saglio, University of Turin, Italy, and lead investigator of the comparison.

In the open-label study, 846 patients with newly diagnosed Ph+ CML in chronic phase were randomized to either 400 mg of imatinib once daily or 300 mg or 400 mg of nilotinib twice daily. Follow-up lasted about 5 years.

At 12 months, the rates of major molecular response (the primary end point of the study) were 44% with 300 mg nilotinib, 43% with 400 mg of nilo-

tinib, and 22% with 400 mg of imatinib.

The median time to a major molecular response was faster by about 2.5 months in the nilotinib groups compared with the imatinib group.

Saglio noted that molecular monitoring is the most sensitive measure of CML disease burden. “Major molecular response is associated with an extremely low rate of disease progression,” he said. Of the patients who experienced progression of disease in this study, none achieved a major molecular response, he said.

Complete cytogenetic responses at 12 months were also significantly better in the nilotinib recipients: 80% with nilotinib 300 mg; 78% with nilotinib 400 mg; and 65% with imatinib 400 mg.

Rates of progression to accelerated phase or blast crisis were 3.9% in the imatinib group compared with less than 0.7% and 0.4% in the patients treated with 300 mg and 400 mg of nilotinib, respectively.

According to Bayard L. Powell, MD, chief, Section of Hematology and Oncology at Wake Forest University, Winston-Salem, North Carolina, the difference between nilotinib and imatinib in rates of progression to accelerated phase or blast crisis is the most meaningful finding of the study, “because

people who go into accelerated phase or blast phase don’t really have the opportunity for second-line therapy.”

Nilotinib was superior to imatinib on efficacy end points across all risk groups of patients based on their Sokal score (a risk index based on six criteria).

Seven percent to 11% of patients in each group discontinued their study drug because of adverse events or abnormalities in laboratory values, with no significant differences between groups. Four percent of patients in the imatinib group discontinued because of treatment failure, 4% discontinued because of disease progression, and 2% because of suboptimal response. Edema and weight gain occurred more often with imatinib therapy. Grade 3 or 4 toxicities were rare in any group.

In commenting on the study, Rick Van Etten, MD, PhD, director of the Tufts Medical Center Cancer Center, Boston, agreed that the finding “could be used to argue for nilotinib as firstline therapy.”

More potent agents lead to impressive complete cytogenetic responses Additional studies of nilotinib and dasatinib, another oral tyrosine kinase

inhibitor that is several times as potent as imatinib, show favorable efficacy on major molecular response in patients with newly diagnosed CML. Both sets of data were reported by Jorges E. Cortes, MD, professor and deputy chair, Department of Leukemia, Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, Houston.

The two studies he presented were identical in the nature of their design. In the open-label, single-agent trials, the efficacy of either nilotinib, 400 mg twice daily, or dasatinib, 100 mg/day (given as either 50 mg twice daily or 100 mg once daily), was investigated as first-line therapy in chronic-phase CML. In the nilotinib study, 32 (63%) of 51 patients who were followed for at least 3 months achieved a complete molecular response and 98% achieved a complete cytogenetic response.

In the dasatinib study, major molecular response was achieved in 70% and a complete cytogenetic response was achieved in 98% of the 50 patients who were followed for at least 3 months.

Cortes noted that the cytogenetic response rates with nilotinib and dasatinib in these studies compare favorably with that observed in imatinibtreated patients. ●

Rituximab Improves Overall Survival in Previously Untreated CLL Patients

A

dding rituximab to fludarabine and cyclophosphamide chemotherapy improves overall survival (OS) in patients with advanced, symptomatic chronic lymphocytic leukemia (CLL) compared with chemotherapy alone, according to a study by German researchers.

In a randomized study, 87.2% of patients with previously untreated CLL who received rituximab plus chemotherapy were alive after follow-up of more than 3 years compared with 82.5% who received chemotherapy alone, said Michael Hallek, MD, University of Cologne, Germany, lead investigator.

This marks the first time that an induction therapy has been shown to improve survival in a randomized trial in patients with advanced CLL, he said.

Rituximab binds to the CD20 antigen on the surface of normal and malignant B cells. It recruits the body’s natural

20

February 2010 I VOL 3, NO 1

defenses to attack and kill the marked B cells. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B cells to regenerate after treatment and return to normal levels within several months.

“This is the first randomized trial to demonstrate that the choice of first-line therapy improves the natural course of CLL,” said Hallek. “The results support the recommendation to use fludarabine, cyclophosphamide, and rituximab as standard therapy in physically fit patients with CLL.” He presented the second analysis of a study conducted in 191 study sites across 11 countries, in which 817 patients with untreated active CLL who were physically fit were randomized to treatment with either chemotherapy (fludarabine and cyclophosphamide) alone or rituximab plus chemotherapy, and followed for a median of 37.7 months.

The first analysis showed that patients receiving rituximab in combination with chemotherapy as first-line treatment lived an average of 40 months without cancer progression, compared with an average of 32 months for patients receiving chemotherapy alone.

The primary end point of the study was progression-free survival (PFS).

Patients who received rituximab plus chemotherapy had a median PFS of 51.8 months, compared with 32.8 months for those who received chemotherapy alone. The median survival has not yet been reached.

At 3 years, PFS was achieved by 64.9% of patients in the rituximab/ chemotherapy arm versus 44.7% of those in the chemotherapy alone arm.

OS was superior in the patients with Binet stage A or B who received rituximab, but not Binet stage C. Hallek explained that treatment intensity

may not have been sufficient to demonstrate a significant survival benefit in Binet stage C patients because of their higher tumor load.

A complete response (CR) was observed in 44.1% of rituximab/chemotherapy recipients compared with 21.8% of patients receiving chemotherapy alone. Patients who achieved CR had better OS than those without CR. Safety was consistent with previous studies of rituximab. The most common adverse events that occurred more often in the rituximab/chemotherapy arm included blood and lymphatic system disorders, infections, and neoplasms.

Grade 3 or greater events that occurred more often in the rituximab/chemotherapy arm were hematologic toxicity, neutropenia, and leukocytopenia. ● —WK Conference News continued on page 23

www.TheOncologyNurse.com

TON_Feb2010_FINAL_TON 2/4/10 10:47 AM Page 21

NE NEW W LLOWER OWER P PRICE RICE OP OPTION TION No Now w Available Available

Totect T ottect® (dexrazoxane (dexrazoxane for for injec injection) tion) eatment of is indicated treatment indicated for for the tr extravasation extravasation rresulting esulting from from IV anthracycline anthracycline chemotherapy. chemotherapy.

First and only FDA approved treatment for anthracycline extravasation.

Supp Supplied as a convenient and accessible complete three day emergency treatment kit, ld be proactively stocked on-site and infused as soon as possible e and a which should within 6 hours of an anthracycline extravasation.

Demonstrates 98% overall efficacy based on two biopsy-confirmed clinical trails1,2 in preventing the need for: o Surgical debridement, plastic surgery and related healthcare costs o Postponement of a patient’s chemotherapy treatments o Rehabilitation, follow-up and avoidance of long-term consequences

See accompanyying brief ssummarryy for further information

For For more more information, information, call 866-478-8274 or visit our w website ebsite at at www.totect.com prescribing information w ww.totect.com for for full pr escribing inf ormation Visit V isit our exhibit exhi at the ONS National onal Confer Conference C onference in SSan an Antonio, Antonio o, April April 30 - May 2, 2009

1

2

Mouridsen HT et al. Treatment of anthracycline extravasation with savene (dexrazoxane).

Results from two prospective clinical multicentre studies. Ann Oncol 2007; 18:546-550.

Totect® package insert. ©

2009 TopooTarget USA. All rights reserved. TOT0077/02-09 TOT0077/02-09 SA Totect and its logo mark are registered trademarks of TopoTTarget USA, Inc., Rockaway, NJ, USA.

To T o or order der Totect®, Totect®, contact contact one of our authorized authorized distribut distributors: ors: ASD Healthcare Cardinal Specialty McKesson/OTN Oncology Supply (800) 746-6273 (866) 677-4844 (800) 482-6700 (800) 633-7555

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TON_Feb2010_FINAL_TON 2/2/10 11:37 AM Page 22

Totect® – Brief prescribing information Please refer to the package insert for full prescribing information. Each Totect carton contains 10 vials of Totect® (dexrazoxane for injection) 500 mg and 10 vials of 50 mL diluent. Indication: Treatment of extravasation resulting from IV anthracycline chemotherapy. Dosage and administration: Administration of Totect should begin as soon as possible and within 6 hours following the anthracycline extravasation. Totect should be given as an intravenous (IV) infusion once daily for 3 consecutive days. The dose of Totect is based on the patient’s body surface area: day one, 1000 mg/m2; day two, 1000 mg/m2; day three, 500 mg/m2. For patients with a body surface area of > 2 m2, a dose of 2000 mg should be given on days 1 and 2, and a dose of 1000 mg should be given on day 3. The Totect dose should be reduced 50% for patients with creatinine clearance values of <40 mL/minute. Cooling procedures such as ice packs should be removed from the affected area at least 15 minutes prior to Totect administration. Totect (dexrazoxane for injection) must be reconstituted with diluent, supplied in the carton. The patient’s Totect dose is diluted in 0.9% 1000 mL NaCl prior to administration. Contraindications: None known.

Warnings: Pregnancy Category D. Dexrazoxane was toxic to pregnant rats at doses of 2 mg/kg (1/80 the human dose on a mg/m2 basis) and embryotoxic and teratogenic at 8 mg/kg when given daily during the period of organogenesis. Teratogenic effects in the rat included imperforate anus, microphthalmia, and anophthalmia. In offspring allowed to develop to maturity, fertility was impaired in the male and female rats treated in utero during organogenesis at 8 mg/kg. In rabbits, doses of 5 mg/kg daily during the period of organogenesis caused maternal toxicity and doses of 20 mg/kg were embryotoxic and terato-

genic. Teratogenic effects in the rabbit included several skeletal malformations such as short tail, rib and thoracic malformations, and soft tissue variations including subcutaneous, eye and cardiac hemorrhagic areas, as well as agenesis of the gallbladder and of the intermediate lobe of the lung. There is no adequate information about the use of Totect in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Precautions: Totect is a cytotoxic drug. When administered to patients receiving anthracycline-containing cytotoxic therapy, additive cytotoxicity may occur. Treatment with Totect is associated with leukopenia, neutropenia, and thrombocytopenia. Reversible elevations of liver enzymes may occur. Blood counts and liver enzymes should be monitored. Greater exposure to dexrazoxane may occur in patients with compromised renal function.

The Totect dose should be reduced by 50% in patients with creatinine clearance values <40 mL/min.

Dimethyl sulfoxide (DMSO) should not be used in patients who are receiving dexrazoxane to treat anthracycline-induced extravasation. Women who have the potential to become pregnant should be advised that Totect might cause fetal harm. There are no known drug interactions. No carcinogenicity studies have been done with Totect in animals. The carcinogenic potential of dexrazoxane has not been investigated.

Long term dosing with razoxane (the racemic mixture of dexrazoxane, ICRF-187, and its enantiomer ICRF-186) is associated with the development of malignancies in rats and possibly in mice. Dexrazoxane was not mutagenic to bacteria in vitro (Ames assay), but caused significant chromosomal aberrations in mammalian cells in vitro. It also increased the formation of micronucleated polychromatic erythrocytes in

mice. Dexrazoxane is mutagenic and clastogenic. The possible adverse effects of Totect on the fertility of humans and experimental animals, male or female, have not been adequately studied. Testicular atrophy was seen with dexrazoxane administration at doses as low as 30 mg/kg weekly for 6 weeks in rats (about 1/5 the human dose on a mg/m2 basis) and as low as 20 mg/kg weekly for 13 weeks in dogs. The effect of dexrazoxane on labor and delivery in humans has not been studied. It is not known whether dexrazoxane or its metabolites are excreted in human milk.

Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from dexrazoxane, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. The safety and effectiveness of Totect in pediatric patients have not been established. No differences in safety or efficacy were observed between older and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older patients has been observed. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Adverse reactions: Adverse reactions of nausea/vomiting, diarrhea, stomatitis, bone marrow suppression (neutropenia, thrombocytopenia), altered liver function (increased AST/ALT), and infusion site burning have been observed. These adverse reactions have been reversible.

Answers for Cancer.

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TOT0077/02-09 ©2009 TopoTarget USA

Rx only Totect® is a registered trademark of TopoTarget A/S US Patent No. 6,727,253B2

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

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TON_Feb2010_FINAL_TON 2/4/10 9:54 AM Page 23

Conference News ASH 2009

Continued from page 20

Sustained Improvements in Quality of Life Observed with Bortezomib in Multiple Myeloma

By Caroline Helwick

T

he addition of bortezomib to a standard regimen for patients newly diagnosed with multiple myeloma resulted in sustained improvements in quality of life, compared with the standard two-drug regimen, according to long-term results from the landmark Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA) trial, which led to the approval of bortezomib for this indication.

“Since we are considering myeloma as a chronic disease, patients are living longer, and it is important to see we are improving their quality of life as well,” said Ravinder Dhawan, PhD, of Johnson & Johnson Pharmaceutical Services, Raritan, New Jersey.

In the phase 3 VISTA trial, 854 patients were randomized to treatment with melphalan and prednisone (MP) or MP plus bortezomib (VMP). The researchers found that VMP was superior to MP across all end points, including response rate, time-to-progression, and overall survival.

“The VISTA trial was extremely important. Two years ago, when the data were presented at ASH, there was a standing ovation. It was a transformational study for newly diagnosed

multiple myeloma,” he noted.

“We previously reported that achieving a complete response [CR] has a positive impact on health-related quality of life [HRQOL] at the fourth cycle after CR onset,” said Dhawan.

“This subanalysis evaluated the number of patients who experienced sustained HRQOL improvement after their best tumor response and the overall HRQOL impact in the VMP and MP arms—in other words, once you have a good response, is this response sustainable and is there a benefit in terms of quality of life?”

HRQOL improvements observed after best response achieved The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, an HRQOL questionnaire commonly used in multiple myeloma, was administered at screening, day 1 of each cycle during treatment, and every 8 weeks until progression. Sustained HRQOL improvement was defined as a change in an individual domain or function score of at least five points for two consecutive cycles after achieving a best response. At baseline, all EORTC QLQ-C30 domain and

function scores were similar between the two treatment arms.

At the time they achieved their best response, patients receiving bortezomib actually had lower HRQOL scores in six domains, indicating worse health status. These included physical, role, social, emotional, and cognitive

Statistically significant differences were shown for nausea/vomiting, appetite loss, and diarrhea, favoring bortezomib. “Improvement in appetite, for example, was observed in 36% of patients with good responses. And the improvements in nausea and diarrhea remained significant after adjustment

After achieving the best response, a higher percentage of patients in the VMP arm experienced sustained HRQOL improvements, versus those in the MP arm, in all of the 15 EORTC QLQ-C30 scores except for cognitive function. function, as well as global health status (although statistical significance was shown only for role function and social function). The VMP arm was numerically superior in nine domains at the time of best response.

But after achieving the best response, a higher percentage of patients in the VMP arm experienced sustained HRQOL improvements, versus those in the MP arm, in all of the 15 EORTC QLQ-C30 scores except for cognitive function, a domain that was essentially the same for each arm, Dhawan reported.

for baseline score, score at best response, and type of response,” he said. “A trend for higher rates of sustained HRQOL improvement after best response was also observed in many other domains for patients treated with VMP versus MP. “Although HRQOL decrements were often higher in the bortezomib arm at onset of best response, these data suggest that VMP patients experience substantial and durable HRQOL improvements after they achieve their best response,” he concluded. ●

Aprepitant Improves Emesis Control in Transplant Patients with No Adverse Effect on Clinical Outcomes

P

atients receiving the neurokinin 1 (NK1) antagonist aprepitant as part of a preparative regimen prior to stem-cell transplant had improved control of acute and delayed nausea and vomiting, and the drug did not interfere with antitumor efficacy, according to investigators from a prospective, randomized, double-blind, phase 3 trial.

“Everyone would have guessed that aprepitant would be effective as antiemesis, but we did not know whether it might negatively impact long-term survival,” explained Mary Fox-Geiman, PharmD, of the Department of Pharmacy at Loyola University, Maywood, Illinois. The study’s principal investigator was Patrick Stiff, MD, of Loyola’s College of Medicine.

Aprepitant is known to interact with cytochrome P450 isoenzymes involved in the bioactivation of highdose cyclophosphamide and may also interfere with etoposide pharmacoki-

www.TheOncologyNurse.com

netics. Its impact on long-term survival as well as regimen-associated toxicity after hematopoietic stem-cell transplantation is unknown, she explained.

“Once you increase the cyclophos-

73.3% of the aprepitant group never experienced a single episode of emesis during the study, versus 22.5% of the placebo group. phamide in these regimens, you saturate the enzymes that normally metabolize the drug, and these enzymes are the same ones that are inhibited by aprepitant,” she said, “so there is a theoretical possibility that aprepitant could inhibit the production of the active metabolites and thus decrease the effectiveness of the chemotherapy.”

This possibility had to be conveyed to potential trial enrollees as part of informed consent, and this made it difficult to recruit patients to the trial.

“We got 181 patients, but the study was begun in 2004 and we expected it to be completed within 15 months,” she said. “The study population is highly skewed in favor of men, as they were more likely to consent.”

As part of an ablative preparative regimen, patients scheduled for hematopoietic stem-cell transplant were randomized to placebo or aprepitant 125 mg orally on day 1, then 80 mg daily during the administration of chemotherapy and for 3 days after the regimen was completed. They all received oral ondansetron 8 mg every 8 hours plus intravenous dexamethasone daily during and for 1 day after the preparative regimen. Only as-needed lorazepam was permitted for nausea.

The aprepitant arm demonstrated a

significant improvement in complete response rate, the primary end point.

Complete responses (no emesis and no or mild nausea) were observed in 81.9% of patients taking aprepitant versus 65.8% receiving placebo, and 48.9% and 14.6%, respectively, met this end point for the entire study period, Fox-Geiman reported.

In addition, 73.3% of the aprepitant group never experienced a single episode of emesis during the study, versus 22.5% of the placebo group.

The greatest benefit was observed in the reduction of delayed vomiting, she emphasized.

Reassuringly, clinical outcomes were similar between the two groups, including days to engraftment (white blood cell or platelets), 30-day survival, progression-free survival, and overall survival, she reported. ● —CH

February 2010 I VOL 3, NO 1

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Psychosocial Issues

Interdisciplinary Approach Best for Addressing Emotional, Practical Issues Associated with Cancer An Interview with Carolyn Messner, DSW, MSW, LCSW-R, BCD

By Karen Rosenberg

C

arolyn Messner, DSW, MSW, LCSW-R, BCD, has been an oncology social worker for 30 years. She is currently director of education and training for CancerCare, professor at the Hunter College School of Social Work, and president of the Association of Oncology Social Work.

In this interview, Dr Messner identifies the most common emotional and practical issues experienced by patients with cancer, cancer survivors, their families, and caregivers and discusses how nurses and social workers can work together to provide support and counseling.

What are some of most common psychological and social problems you see in patients with cancer?

The most common problems are practical problems but there are also emotional and social issues associated with a diagnosis of cancer. Some practical questions that immediately spring to mind when a person is diagnosed are: • Where do I go for my care?

• Who’s going to pay for it?

• Who will take care of my children, or my spouse, or my elderly parents?

• Which treatment do I choose?

• How do I get information?

• How will I deal with the side effects?

Then there are concerns about sharing the news with family, friends, and coworkers, such as how many people to tell and how to tell them. Some people will tell everyone about their cancer, whereas others are very circumspect.

So the practical issues weave into the social and emotional ones.

What are some of the issues regarding employment?

Many people have to continue working full-time to maintain their health benefits, and for people who are in the workforce, there are a lot of issues around disclosure. There are workplace protections for people if they disclose or choose not to disclose.

The Americans with Disabilities Act and the Family Medical Leave Act offer protections, but they require that the person disclose to the human resource department or to his or her direct supervisor the reason some workplace accommodation is needed.

If one just begins to take time off without giving a reason, it could put their job in jeopardy.

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February 2010 I VOL 3, NO 1

“The best model is all of us working very closely together.

Social workers are trained to talk to people systemically about their concerns and the issues they confront.”

—Carolyn Messner, DSW, MSW, LCSW-R, BCD

There are social issues in the workplace too. Patients are often concerned about how their coworkers and supervisors will react if they disclose their illness and worry that they may view them as unable to do the job.

You’ve spoken about the practical issues. What are some of the emotions patients may experience?

Emotional concerns for a person newly diagnosed with cancer include: • How am I going to get through this?

• How am I going to help my family or my loved ones get through this?

• How do I deal with the different feelings that I might be having?

There are also spiritual issues, not necessarily in the traditional sense, such as: • Why is this happening to me?

• How does this interface with my belief system?

• How does this fit in with my plans about where my life was supposed to be going?

For different people, these reactions ocurr incrementally, that is, at different stages along the course of the disease.

The initial diagnosis is often very difficult because it comes as a shock and they need time to absorb it. Once they complete treatment, people begin to rebound and feel a bit more connected back to normalcy, but the whole phase of survivorship comes into play. At this stage, people begin to be concerned about possible recurrence of the disease.

Different types of cancer may have different effects on a patient’s quality of life and invoke different psychological reactions. For instance, someone with a difficult-to-treat type of cancer like pancreatic or liver cancer may have a different reaction from someone with early-stage breast cancer. Men and women and younger and older patients may react differently as well.

For younger patients, concerns about fertility can have a dramatic impact on their thinking about the future. It’s also difficult for older patients. Some patients have never felt old until they were diagnosed with cancer. And older patients’ perception of cancer may be based on the experience of family members or others who had cancer years ago before the newer, more effective treatments were available.

What is the role of nurses versus social workers in dealing with psychosocial issues and how can they best work together?

In my own experience, oncology nurses and oncology social workers work very well together. Many social workers are employed in the hospital or community cancer center setting but increasingly they are employed in physicians’ offices as well. Some patients prefer to talk to one person about their concerns, but others need as many people as possible to offer support. Oncology nurses in a physician practice who are administering the outpatient chemotherapy tend to get to know patients very well. If there is a social worker in that practice, he or she might run a support group and work with those patients as well. The oncology nurse may help with the medical aspects of the patient’s concerns, but they often also talk about the fatigue or other symptoms that carry over into the psychosocial realm because they impact one’s ability to work, to spend time with the children, or do household chores. The best model is all of us working very closely together. Social workers are trained to talk to people systemically about their concerns and the issues they confront.

There are many organizations like CancerCare throughout the country that use social work staff to run support

groups and online groups and spend a huge amount of time with patients talking about their concerns. These organizations may be a particularly useful resource in rural communities that do not have a lot of resources for patients.

In the world we live in today, interdisciplinary practice is the best for patients because we are working together and sharing. Cancer is a complicated disease, and it requires a team of healthcare professionals whose purpose is to help people. In other words, it’s up to all of us as health professionals to refer back and forth to each other so that we can direct patients to the people who can best help them.

None of us can do everything alone.

We have to do it as a team. We can’t take away the disease, but we can do something that enhances patients’ quality of life. ● Editor’s Note: Future articles in this series will address psychosocial issues associated with certain types of cancer, in different patient populations, effects of cancer on caregivers, work-related concerns, and other topics. Please send suggestions about topics and authors for this series to editorial@greenhillhc.com.

Coming in March • CE: Aspirin Therapy and

Survival in Colorectal Cancer • Anemia Management Using ESAs and IV Iron • Managing Chemotherapy Administration Competency • Conference News: Reports from ASH, SABCS, ASCO GI, ASCO GU • Psychosocial Issues in Patients with Cancer

www.TheOncologyNurse.com

TON_Feb2010_FINAL_TON 2/2/10 11:38 AM Page 25

STRONG. FROM THE START.

HELP ESTABLISH A SUCCESSFUL CINV PREVENTION STRATEGY FROM THE FIRST CYCLE When your patients experience acute chemotherapyinduced nausea and vomiting (CINV) during their first cycle of chemotherapy, they may have an increased risk of CINV on subsequent days and in subsequent cycles.1-3 ALOXI®: Starts strong to prevent CINV4 A single IV dose lasts up to 5 days after MEC4,5* Can be used with multiple-day chemotherapy regimens6† * Moderately emetogenic chemotherapy. † Based on sNDA approval in August 2007, the restriction on repeated dosing of ALOXI (palonosetron HCl) injection within a 7-day interval was removed.

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

Important Safety Information • ALOXI is contraindicated in patients known to have hypersensitivity to the drug or any of its components • Most commonly reported adverse reactions in chemotherapy-induced nausea and vomiting include headache (9%) and constipation (5%) Please see the following brief summary of prescribing information.

REFERENCES: 1. The Italian Group for Antiemetic Research. Dexamethasone alone or in combination with ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy. N Engl J Med. 2000;342:1554-1559. 2. Hickok JT, Roscoe JA, Morrow GR, et al. 5-hydroxytryptamine-receptor antagonists versus prochlorperazine for control of delayed nausea caused by doxorubicin: a URCC CCOP randomised controlled trial. Lancet Oncol. 2005;6:765-772. Epub September 13, 2005. 3. Cohen L, de Moor CA, Eisenburg P, Ming EE, Hu H. Chemotherapy-induced nausea and vomiting: incidence and impact on patient quality of life at community oncology settings. Support Care Cancer. 2007;15:497-503. Epub November 14, 2006. 4. Gralla R, Lichinitser M, Van der Vegt S, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol. 2003;14:1570-1577. 5. Eisenberg P, Figueroa-Vadillo J, Zamora R, et al. Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer. 2003;98:2473-2482. 6. ALOXI® (palonosetron HCl) injection full prescribing information.

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

Distributed and marketed by Eisai Inc. © 2009 Eisai Inc. All rights reserved. Printed in USA. AL447-A 08/09

www.ALOXI.com

TON_Feb2010_FINAL_TON 2/2/10 11:38 AM Page 26

Conference News SABCS 2009 The following article is based on a presentation at the 32nd Annual San Antonio Breast Cancer Symposium in San Antonio, Texas.

Anthracyclines May Not Be Necessary for HER2-positive Breast Cancer

By Caroline Helwick

D

ebate continues as to whether all patients with early human epidermal growth factor receptor

ALOXI® (palonosetron HCl) injection BRIEF SUMMARY OF PRESCRIBING INFORMATION INDICATIONS AND USAGE Chemotherapy-Induced Nausea and Vomiting ALOXI is indicated for: • Moderately emetogenic cancer chemotherapy – prevention of acute and delayed nausea and vomiting associated with initial and repeat courses • Highly emetogenic cancer chemotherapy – prevention of acute nausea and vomiting associated with initial and repeat courses DOSAGE AND ADMINISTRATION Recommended Dosing Chemotherapy-Induced Nausea and Vomiting Dosage for Adults - a single 0.25 mg I.V. dose administered over 30 seconds. Dosing should occur approximately 30 minutes before the start of chemotherapy.

Instructions for I.V. Administration ALOXI is supplied ready for intravenous injection.

ALOXI should not be mixed with other drugs. Flush the infusion line with normal saline before and after administration of ALOXI. Parenteral drug products should be inspected visually for particulate matter and discoloration before administration, whenever solution and container permit.

CONTRAINDICATIONS ALOXI is contraindicated in patients known to have hypersensitivity to the drug or any of its components. [see Adverse Reactions (6) in full prescribing information ] WARNINGS AND PRECAUTIONS Hypersensitivity Hypersensitivity reactions may occur in patients who have exhibited hypersensitivity to other 5-HT 3 receptor antagonists.

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

In clinical trials for the prevention of nausea and vomiting induced by moderately or highly emetogenic chemotherapy, 1374 adult patients received palonosetron.

Adverse reactions were similar in frequency and severity with ALOXI and ondansetron or dolasetron. Following is a listing of all adverse reactions reported by ≥ 2% of patients in these trials (Table 1).

Table 1: Adverse Reactions from ChemotherapyInduced Nausea and Vomiting Studies ≥ 2% in any Treatment Group ALOXI Ondansetron Dolasetron Event 0.25 mg 32 mg I.V. 100 mg I.V. (N=410) (N=633) (N=194) Headache 60 (9%) 34 (8%) 32 (16%) Constipation 29 (5%) 8 (2%) 12 (6%) Diarrhea 8 (1%) 7 (2%) 4 (2%) Dizziness 8 (1%) 9 (2%) 4 (2%) Fatigue 3 (< 1%) 4 (1%) 4 (2%) Abdominal Pain 1 (< 1%) 2 (< 1%) 3 (2%) Insomnia 1 (< 1%) 3 (1%) 3 (2%) In other studies, 2 subjects experienced severe constipation following a single palonosetron dose of approximately 0.75 mg, three times the recommended dose. One patient received a 10 mcg/kg oral dose in a postoperative nausea and vomiting study and one healthy subject received a 0.75 mg I.V. dose in a pharmacokinetic study.

In clinical trials, the following infrequently reported adverse reactions, assessed by investigators as treatment-related or causality unknown, occurred following administration of ALOXI to adult patients receiving concomitant cancer chemotherapy: Cardiovascular: 1%: non-sustained tachycardia, bradycardia, hypotension, < 1%: hypertension, myocardial ischemia, extrasystoles, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles and QT prolongation. In many cases, the relationship to ALOXI was unclear.

Dermatological: < 1%: allergic dermatitis, rash.

Hearing and Vision: < 1%: motion sickness, tinnitus, eye irritation and amblyopia.

Gastrointestinal System: 1%: diarrhea, < 1%: dyspepsia, abdominal pain, dry mouth, hiccups and flatulence.

26

February 2010 I VOL 3, NO 1

type 2 (HER2)-positive breast cancer need an anthracycline with trastuzumab.

Updated data from the Breast Cancer General: 1%: weakness, < 1%: fatigue, fever, hot flash, flu-like syndrome.

Liver: < 1%: transient, asymptomatic increases in AST and/or ALT and bilirubin. These changes occurred predominantly in patients receiving highly emetogenic chemotherapy.

Metabolic: 1%: hyperkalemia, < 1%: electrolyte fluctuations, hyperglycemia, metabolic acidosis, glycosuria, appetite decrease, anorexia.

Musculoskeletal: < 1%: arthralgia.

Nervous System: 1%: dizziness, < 1%: somnolence, insomnia, hypersomnia, paresthesia.

Psychiatric: 1%: anxiety, < 1%: euphoric mood.

Urinary System: < 1%: urinary retention.

Vascular: < 1%: vein discoloration, vein distention.

Postmarketing Experience The following adverse reactions have been identified during postapproval use of ALOXI. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Very rare cases (<1/10,000) of hypersensitivity reactions and injection site reactions (burning, induration, discomfort and pain) were reported from postmarketing experience of ALOXI 0.25 mg in the prevention of chemotherapy-induced nausea and vomiting.

DRUG INTERACTIONS Palonosetron is eliminated from the body through both renal excretion and metabolic pathways with the latter mediated via multiple CYP enzymes. Further in vitro studies indicated that palonosetron is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4/5 (CYP2C19 was not investigated) nor does it induce the activity of CYP1A2, CYP2D6, or CYP3A4/5. Therefore, the potential for clinically significant drug interactions with palonosetron appears to be low.

Coadministration of 0.25 mg I.V. palonosetron and 20 mg I.V. dexamethasone in healthy subjects revealed no pharmacokinetic drug-interactions between palonosetron and dexamethasone.

In an interaction study in healthy subjects where palonosetron 0.25 mg (I.V. bolus) was administered on day 1 and oral aprepitant for 3 days (125 mg/80 mg/80 mg), the pharmacokinetics of palonosetron were not significantly altered (AUC: no change, Cmax: 15% increase).

A study in healthy volunteers involving single-dose I.V. palonosetron (0.75 mg) and steady state oral metoclopramide (10 mg four times daily) demonstrated no significant pharmacokinetic interaction.

In controlled clinical trials, ALOXI injection has been safely administered with corticosteroids, analgesics, antiemetics/antinauseants, antispasmodics and anticholinergic agents.

Palonosetron did not inhibit the antitumor activity of the five chemotherapeutic agents tested (cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C) in murine tumor models.

USE IN SPECIFIC POPULATIONS Pregnancy Teratogenic Effects: Category B Teratology studies have been performed in rats at oral doses up to 60 mg/kg/day (1894 times the recommended human intravenous dose based on body surface area) and rabbits at oral doses up to 60 mg/ kg/day (3789 times the recommended human intravenous dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to palonosetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, palonosetron should be used during pregnancy only if clearly needed.

Labor and Delivery Palonosetron has not been administered to patients undergoing labor and delivery, so its effects on the mother or child are unknown.

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

International Research Group (BCIRG)006 trial suggest that eliminating the anthracycline will have comparable effiPediatric Use Safety and effectiveness in patients below the age of 18 years have not been established.

Geriatric Use Population pharmacokinetics analysis did not reveal any differences in palonosetron pharmacokinetics between cancer patients ≥ 65 years of age and younger patients (18 to 64 years). Of the 1374 adult cancer patients in clinical studies of palonosetron, 316 (23%) were ≥ 65 years old, while 71 (5%) were ≥ 75 years old. No overall differences in safety or effectiveness were observed between these subjects and the younger subjects, but greater sensitivity in some older individuals cannot be ruled out. No dose adjustment or special monitoring are required for geriatric patients.

Of the 1520 adult patients in ALOXI PONV clinical studies, 73 (5%) were ≥65 years old. No overall differences in safety were observed between older and younger subjects in these studies, though the possibility of heightened sensitivity in some older individuals cannot be excluded. No differences in efficacy were observed in geriatric patients for the CINV indication and none are expected for geriatric PONV patients. However, ALOXI efficacy in geriatric patients has not been adequately evaluated.

Renal Impairment Mild to moderate renal impairment does not significantly affect palonosetron pharmacokinetic parameters. Total systemic exposure increased by approximately 28% in severe renal impairment relative to healthy subjects.

Dosage adjustment is not necessary in patients with any degree of renal impairment.

Hepatic Impairment Hepatic impairment does not significantly affect total body clearance of palonosetron compared to the healthy subjects. Dosage adjustment is not necessary in patients with any degree of hepatic impairment.

Race Intravenous palonosetron pharmacokinetics was characterized in twenty-four healthy Japanese subjects over the dose range of 3 – 90 mcg/kg. Total body clearance was 25% higher in Japanese subjects compared to Whites, however, no dose adjustment is required. The pharmacokinetics of palonosetron in Blacks has not been adequately characterized.

OVERDOSAGE There is no known antidote to ALOXI. Overdose should be managed with supportive care.

Fifty adult cancer patients were administered palonosetron at a dose of 90 mcg/kg (equivalent to 6 mg fixed dose) as part of a dose ranging study. This is approximately 25 times the recommended dose of 0.25 mg. This dose group had a similar incidence of adverse events compared to the other dose groups and no dose response effects were observed.

Dialysis studies have not been performed, however, due to the large volume of distribution, dialysis is unlikely to be an effective treatment for palonosetron overdose. A single intravenous dose of palonosetron at 30 mg/kg (947 and 474 times the human dose for rats and mice, respectively, based on body surface area) was lethal to rats and mice. The major signs of toxicity were convulsions, gasping, pallor, cyanosis and collapse.

PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling (17.2) in full prescribing information Instructions for Patients • Patients should be advised to report to their physician all of their medical conditions, any pain, redness, or swelling in and around the infusion site [see Adverse Reactions (6) in full prescribing information].

• Patients should be instructed to read the patient insert.

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

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

Distributed and marketed by Eisai Inc., Woodcliff Lake, NJ 07677. © 2009 Eisai Inc. All rights reserved. Printed in USA. AL449 08/09

cacy and be less toxic.

Dennis Slamon, MD, PhD, of the University of California, Los Angeles, announced that a nonanthracyclinebased regimen with trastuzumab was not associated with significantly more breast cancer recurrences or deaths at 5.5 years, and no subgroup demonstrated special benefit from the anthracycline-based regimen. Furthermore, by eliminating the anthracycline, risk of heart failure and leukemia was significantly reduced, he said.

“We should no longer think that the high-risk patient needs anthracyclinebased chemotherapy,” Slamon commented at a press briefing. “The data do not support that.”

The trial included 3222 HER2-positive patients who were randomized to one of three arms: standard anthracycline-based therapy with doxorubicin, cyclophosphamide, and docetaxel (AC-T), the same regimen plus trastuzumab (AC-TH) or the nonanthracycline regimen of docetaxel and carboplatin plus trastuzumab (TCH).

Findings from the third planned analysis, based on 65-month follow-up, led to the following main conclusions: • Trastuzumab provides a similar and significant advantage for both disease-free survival (DFS) and overall survival (OS) when used with either anthracycline-based chemotherapy (AC-TH) or a nonanthracycline regimen (TCH), in both low-risk and high-risk patients.

• The acute and chronic toxicity profiles of TCH are better than those seen with the AC-TH regimen in almost all parameters measured.

• There is no statistical advantage of AC-TH over TCH, but there is a 29-event numerical advantage in DFS events with AC-TH. • This numerical advantage comes at a cost: increases in congestive heart failure and leukemias, all in patients receiving AC as part of the treatment.

DFS at 65 months was 84% with AC-TH compared with 81% for TCH and 75% for AC-T. With the AC-T regimen as the reference (control), AC-TH reduced risk by 36%, whereas TCH reduced risk by 25%. These differences were less robust at this time point than at the first analysis, when risk was reduced by 51% and 49%, respectively.

OS was 92% with AC-TH, 91% with TCH, and 87% with TCH, with Continued on page 34

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TON_Feb2010_FINAL_TON 2/2/10 12:37 PM Page 27

Presents the Third Annual Curriculum for

CONSIDERATIONS IN MULTIPLE MYELOMA A Newsletter Series for Cancer Care Professionals Center of Excellence Media, along with Editor-in-Chief Sagar Lonial, MD, of Emory University, are pleased to offer your multidisciplinary cancer team this series of newsletters focusing on the challenges of treating patients with multiple myeloma.

SAGAR LONIAL, MD Associate Professor of Hematology and Oncology Emory University School of Medicine

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PARTICIPATE TODAY at www.COEXM.com For complete learning objectives and accreditation information, please refer to each activity.

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

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TON_Feb2010_FINAL_TON 2/2/10 11:38 AM Page 28

CALLING ALL NURSE SAVE THE DATE September 17-19, 2010

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TON_Feb2010_FINAL_TON 2/2/10 11:38 AM Page 29

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NURSING CAREERS Rose Virani receives ONS Making a Difference Award

CANCER CENTER PROFILE University of Pittsburgh Medical Center Cancer Centers and Cancer Institute provide high-quality care

page 14

page 30

NOVEMBER/DECEMBER 2009 â&#x20AC;˘ VOL. 2, NO. 7

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REMS for Opioids: What Will They Mean for Oncology Nurses and Patients?

An interview with Leslie Greenberg, RN, MSN, OCN

O

n May 27, 2009, the US Food and Drug Administration (FDA) heard testimony on its proposed Opioid Analgesic and Risk Evaluation & Mitigation Strategies (REMS). In this interview, Leslie Greenberg, RN, MSN, OCN, health policy manager for the Oncology Nursing Society (ONS), discusses her testi-

mony and the possible implications of REMS for opioids for oncology nurses and their patients.

What are REMS and what type of drugs are they used for?

REMS stands for Risk Evaluation and Mitigation Strategies. In September 2007, the Food and Drug

Administration Amendments Act gave the FDA expanded authority, including the ability to require companies to submit REMS when deemed necessary to ensure that a productâ&#x20AC;&#x2122;s benefits outweigh its risks.

REMS are a step between issuing a warning letter and pulling a drug off the market. The FDA wanted to Continued on page 17

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Fertility Preservation before Cancer Treatment: Too Little, Too Late?

The Changing Kidney Cancer Treatment Landscape.

Part 1. New Opportunities, New Challenges

ORLANDOâ&#x20AC;&#x201D;Cancer patients who wish to preserve their fertility after treatment may be getting shortchanged, according to a study presented at the 2009 annual meeting of the American Society of Clinical Oncology (ASCO) that found oncologists to be less than proactive.

Surveys of cancer patients show that loss of fertility is an immense concern, one that often does not surface until treatment has been completed and options for

SEATTLEâ&#x20AC;&#x201D;Advances in the detection and treatment of cancer in recent years bring new hope for patients, but they also challenge the medical community to keep up with rapid changes in the landscape. One very dramatic example is the quiet and slow revolution that has taken place with kidney cancer.

Renal cell carcinoma (RCC), the most common type

Continued on page 18

Continued on page 9

Treatment Options for Chemotherapy-induced Nausea and Vomiting Increasing

COST-EFFECTIVENESS RESEARCH New technology Based on research by David C. Miller, MD, MPH

page 24

page 8

BY 1'.)-' +'--26,45 7,'-)%$3/%$.4%$(4%$'/1%$'0(/1 ONCOLOGY NURSE PRACTITIONER AND CONSULTANT, SARATOGA,NOVEMBER/DECEMBER CALIFORNIA, AND ASSISTANT CLINICAL PROFESSOR, UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

2009 â&#x20AC;˘ VOL. 2, NO. 6

he treatment of patients receiving chemotherapy has become vastly more complex in the past 25 years, particularly with the introduction of many new chemotherapy and targeted therapy agents.

Supportive care for patients receiving these treatments includes the management of chemotherapy-induced nausea and vomiting (CINV) and, although considerable advances have been made in the management of this side effect, some patients still rank CINV as one of

T Re Mu .42 od ltip 983 a g >> le My 188= y fo iste >! eloma16 Con r Y r 29 84> side ou 4? ;64 rati r 7 <<4: ons www.jomcc.com !29 ;4: in 7 54;!

Continued on page 11

COMPLIMENTARY CE CREDIT AT WWW.THEONCOLOGYNURSE.COM PROGRAM #09CE040

College of Nursing Continuing Nursing Education

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PAGE 20

www.theoncologynurse.com to ensure uninterrupted FREE delivery of The Oncology Nurse

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The Workforce Shortage and the Use of Non-physician Practitioners

Chemotherapy-induced Peripheral Neuropathy: Prevention and Treatment

YOU COULD BE HOLDING YOUR LAST ISSUE! Douglas W. Blayney, MD Register online at Š 2009 Green Hill Healthcare Communications, LLC

BREAST CANCER Weekly paclitaxel as effective, less toxic than docetaxel/capecitabine Based on a study by Aman U. Buzdar, MD

T

Photo courtesy of American Society of Clinical Oncology.

NAVIGATING PATIENTS ACROSS THE CONTINUUM OF CANCER CARE

ffective tobacco control strategies, improved hormonal and chemotherapy treatments, and targeted therapies have all contributed to impressively declining cancer death rates in the United States. â&#x20AC;&#x153;We have a good news story to tell,â&#x20AC;? stated the president of the American Society of Clinical Oncology (ASCO), Douglas W. Blayney, MD, medical director of the Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor. He warned, how-

ever, that continued momentum toward reduced mortality in the United States is not guaranteed and is, in fact, threatened by contrary workforce trends. The solution, Blayney said at the third annual Onmark National Payor/Provider Forum, is the wider use of â&#x20AC;&#x153;physician extenders.â&#x20AC;?

Physicians less productive; population aging Younger oncologists are less productive Continued on page 13

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Cost, Noncompliance Bitter Pills to Swallow in the Age of Oral Chemotherapy

Colorectal Cancer Screening Cost-effective: Fecal DNA Promising

A

s more oral cancer therapies are introduced into practice, adherence to therapy is likely to play a larger role in outcomes, said Angela DeMichele, MD, associate professor of medicine and epidemiology at the University of Pennsylvania, Abramson Cancer Center, Philadelphia, Pennsylvania.

Drug cost is one major barrier to adherence, she said, potentially leading to drug-taking behaviors that can

C

olorectal cancer (CRC) is the second most common solid tumor in the United States, accounting for nearly 150,000 new cases annually and 50,000 deaths. Robert Mayer, MD, Stephen B. Kay Family Professor of Medicine, Harvard Medical School, and Dana-Farber Cancer Institute, Boston, chaired the update on CRC screening at the annual meeting of the American Society of Clinical Oncology, emphasizing

Continued on page 16

Oncology at an Inflection Point An interview with Bruce A. Cutter, MD

W

ith declining reimbursement for oncology drugs, regulatory changes, and other pressures on oncology practice, oncologists in community cancer practices are having to find new ways to provide quality care for their patients and control costs. In this interview, Bruce A. Cutter, MD, discusses challenges facing oncology Bruce A. Cutter, MD practices and suggests innovative approaches that can help them adapt to change and potentially lead to better outcomes for their patients. Dr Cutter is past president and currently a chairperson of the quality and the pharmacy and therapeutics committees of Cancer Care Northwest, Seattle, Washington.

Continued on page 8

MULTIDISCIPLINARY TUMOR BOARD CASE STUDY Treating a Second Breast Cancer John F. Turner, MD Victor L. Randolph, MD Sonia Y. Newton, MD Billy Jo Day, RN, BSN

Continued on page 17

Mayur A. Patel, MD Poonam Srivastava, MD Ashok Kumar, MD

Page 10

ONCOLOGY DRUG CODES Medications Used for the Treatment of Leukemias Page 18 Š 2009 Green Hill Healthcare Communications, LLC

www.AONNonline. org

TON_Feb2010_FINAL_TON 2/2/10 3:23 PM Page 30

ONCOLOGY DRUG CODES Supplied by: RJ Health Systems

Medications Used for the Treatment of Cervical Cancer Cervical cancer forms in tissues of the cervix (the organ connecting the uterus and vagina).

It is usually a slow-growing cancer that may not have symptoms but can be found with regular Pap tests. Cervical cancer is almost always caused by human papillomavirus (HPV) infection. The following sections will assist healthcare professionals and payers by providing appropriate coding, billing, and reimbursement information associated with the management of cervical cancer.

In the November/December issue, the Oncology Drug Codes for the Medications Used for the Treatment of Leukemias inadvertently did not note which agents are FDA-approved or included in the NCCN Drugs & Biologics Compendium for off-label use. The complete codes can be viewed at www.theoncologynurse.com.

Associated ICD-9-CM Codes Used for Cervical Cancer

The following sections include: • Associated ICD-9-CM codes used for the classification of cervical cancer • Drugs that have been FDA-approved in the treatment of cervical cancer. Please note: if a check mark appears in the FDA column it will NOT appear in the Compendia section even if a drug is included in the NCCN (National Comprehensive Cancer Network) Drugs & Biologics Compendium • Drugs included in the NCCN Drugs & Biologics Compendium for off-label use in cervical cancer. NCCN is recognized by CMS (Centers for Medicare & Medicaid Services) as a referencing source • Corresponding HCPCS/CPT Codes and Code Descriptions • Current Code Price (AWP-based pricing) • Most recent ASP plus 6% (Medicare allowable) • Possible CPT Administration Codes for each medication

generic (Brand) name

HCPCS code: code description

bevacizumab (Avastin) bleomycin (Blenoxane) carboplatin (Paraplatin) cisplatin (Platinol AQ) cisplatin (Platinol AQ) docetaxel (Taxotere) doxorubicin HCl liposome (Doxil)

J9035: injection, bevacizumab, 10 mg J9040: injection, bleomycin sulfate, 15 units J9045: injection, carboplatin, 50 mg J9060: cisplatin, powder or solution, per 10 mg J9062: cisplatin, 50 mg J9171: injection, docetaxel, 1 mg J9001: injection, doxorubicin hydrochloride, all lipid formulations, 10 mg J9178: injection, epirubicin HCl, 2 mg

epirubicin (Ellence)

180 Malignant neoplasm of cervix uteri Includes: invasive malignancy [carcinoma] Excludes: carcinoma in situ (233.1) 180.0 Endocervix Cervical canal, not otherwise specified Endocervical canal Endocervical gland 180.1 Exocervix 180.8 Other specified sites of cervix Cervical stump Squamocolumnar junction of cervix Malignant neoplasm of contiguous or overlapping sites of cervix uteri whose point of origin cannot be determined 180.9 Cervix uteri, unspecified 233 Carcinoma in situ of breast and genitourinary system 233.1 Cervix uteri Adenocarcinoma in situ of cervix Cervical intraepithelial glandular neoplasia, > grade III < Cervical intraepithelial neoplasia III [CIN III] Severe dysplasia of cervix Excludes: cervical intraepithelial neoplasia II [CIN II] (622.12) cytologic evidence of malignancy without histologic confirmation (795.06) high-grade squamous intraepithelial lesion (HGSIL) (795.04) moderate dysplasia of cervix (622.12)

FDAapproved for cervical cancer

NCCN Drugs & Biologics Compendium off-label use for cervical cancer

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

Medicare allowable (ASP + 6%), effective 1/10/10-3/31/10

CPT administration codes

$66.99

$57.46

96413, 96415

$45.30

$28.47

96401, 96409

$85.10

$4.84

96409, 96413, 96415

$4.33

$2.08

96409, 96413, 96415

$21.66

$10.41

96409, 96413, 96415

$23.23

$17.62

96413

$559.32

$471.38

96413

$8.16

$2.65

✓ ✓ ✓ ✓ ✓ ✓

✓ 96409, 96413

✓ Continued on page 32

30

February 2010 I VOL 3, NO 1

www.TheOncologyNurse.com

TON_Feb2010_FINAL_TON 2/5/10 2:36 PM Page 31

Metastatic Colorectal Cancer: Sound Strategies for Selecting First-Line Therapies

LOG ON TODAY TO PARTICIPATE www.coexm.com/ace01.asp FACULTY

Release Date: November 25, 2009 Expiration Date: November 24, 2010

Neal P. Christiansen, MD Assistant Professor of Medicine Medical University of South Carolina Division of Hematology/Oncology Charleston, South Carolina

TARGET AUDIENCE This activity is intended for hematologists, oncologists, oncology nurses, oncology/specialty pharmacists, and others who are involved with the care of patients with metastatic colorectal cancer (mCRC).

STATEMENT OF NEED Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer death in the United States. Approximately 149,000 new cases are diagnosed each year. At the time of presentation, about 20% of patients with CRC will have metastatic disease. Cure at this stage is rarely possible, although some patients whose metastases are limited (especially if to the liver or lung) may be “cured” by surgical means. For most sufferers of mCRC, however, treatment is palliative, offering prolonged survival, improvement in symptoms, and enhanced quality of life.

EDUCATIONAL OBJECTIVES On completion of this activity, participants should be able to: • Evaluate and assess current findings in the management of mCRC • Identify current first-line therapies, both chemotherapeutic and biologic agents, and practices in mCRC • Tailor a therapeutic regimen to meet the needs of the individual patient with mCRC • Employ select strategies to minimize exposure to ineffective therapies and their toxicities

INSTRUCTIONS To receive a statement of credit, you must: • Review the content of the activity • Successfully complete the post-test (70% or higher) • Complete the evaluation at the end of the activity Your statement of credit will be issued immediately upon successful completion of the post-test and submission of the evaluation

ACCREDITATION STATEMENT 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 the University of California, Irvine School of Medicine (UCI) and Center of Excellence Media, LLC. The University of California, Irvine School of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT The University of California, Irvine School of Medicine designates this educational activity for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. This activity is complimentary.

FACULTY INFORMATION AND DISCLOSURES Dr Christiansen has received consultancy fees from sanofi-aventis and Genentech.

Off-label use of cetuximab (in patients in whom irinotecan has not failed) and bevacizumab (continuing after first-line therapy) will be discussed in this presentation.

Conflict resolution: This presentation has been peer reviewed for evidence base and fair balance.

GENERAL DISCLOSURE STATEMENT It is the policy of the University of California, Irvine School of Medicine and the University of California CME Consortium to ensure balance, independence, objectivity, and scientific rigor in all CME activities. Full disclosure of conflict resolution will be made in writing via handout materials or syllabus.

Bonnie Carroll, Director, CME, UC Irvine School of Medicine, has no financial or other relationship to products or devices with commercial interests related to the content of this CME/CE activity.

Center of Excellence Media, LLC: The planners and managers have nothing to disclose related to the content of this activity.

Erica Johansson, RN, Astute CE, LLC, has nothing to disclose related to the content of this activity.

Dr. Randall F. Holcombe, University of California, Irvine School of Medicine, peer-reviewed the content for evidence base and fair balance. Dr Holcombe has no real or apparent conflicts of interest related to this activity.

Conflict resolution: This presentation has been peer reviewed for evidence base and fair balance.

This activity is in compliance with California Assembly Bill 1195, which requires continuing medical education components to include curriculum in the subjects of cultural and linguistic competency. For specific information regarding Bill 1195 and definitions of cultural and linguistic competency, please visit the CME web site at http://www.cme.uci.edu.

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

In collaboration with

TON_Feb2010_FINAL_TON 2/2/10 3:26 PM Page 32

ONCOLOGY DRUG CODES Supplied by: RJ Health Systems Continued from page 30

generic (Brand) name

HCPCS code: code description

fluorouracil (Adrucil) gemcitabine (Gemzar) ifosfamide (Ifex) irinotecan (Camptosar) mesna (Mesnex) mitomycin (Mutamycin) mitomycin (Mutamycin) mitomycin (Mutamycin) paclitaxel (Taxol, Onxol) pemetrexed (Alimta) topotecan (Hycamtin) vinorelbine (Navelbine)

J9190: injection, fluorouracil, 500 mg J9201: injection, gemcitabine hydrochloride, 200 mg J9208: injection, ifosfamide, 1 gram J9206: injection, irinotecan, 20 mg J9209: injection, mesna, 200 mg J9280: mitomycin, 5 mg J9290: mitomycin, 20 mg J9291: mitomycin, 40 mg J9265: injection, paclitaxel, 30 mg J9305: injection, pemetrexed, 10 mg J9350: injection, topotecan, 4 mg J9390: injection, vinorelbine tartrate, per 10 mg

FDAapproved for cervical cancer

NCCN Drugs & Biologics Compendium off-label use for cervical cancer

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

Medicare allowable (ASP + 6%), effective 1/10/10-3/31/10

CPT administration codes

$3.30

$1.60

96409

$169.46

$144.93

96413

$56.40

$30.08

96413, 96415

$84.71

$6.94

96413, 96415

$10.44

$4.64

96409

$67.20

$17.15

96409

$218.40

$68.60

96409

$300.00

$137.19

96409

$17.70

$9.43

$59.25

$50.59

96409

$1264.99

$1031.91

96413

$42.60

$11.59

96409

✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ 96413, 96415

✓ ✓ ✓

✓

References • HCPCS Level II Expert 2009 • CPT 2010; 2009 • ICD-9-CM for Professionals Volumes 1 & 2; 2010 • The Drug Reimbursement Coding and Pricing Guide, Vol 7, No 1; RJ Health Systems International LLC; 1st Quarter 2010 • FDA-approved indication (from products’ prescribing information) • NCCN Drugs & Biologics Compendium; 2010; National Cancer Institute; www.ReimbursementCodes.com powered by RJ Health Systems International, LLC, Wethersfield, Connecticut • CMS-Medicare allowable 1st Quarter 2010 (effective dates 1/1/10-3/31/10).

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

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

2010 UPDATES OF THE HEALTHCARE COMMON PROCEDURE CODING SYSTEM (HCPCS)

This information was supplied by:

Effective: January 1, 2010 New C9257: injection, bevacizumab, 0.25 mg (Avastin) J9155: injection, degarelix, 1 mg (Firmagon) J9171: injection, docetaxel, 1 mg (Taxotere) J9328: injection, temozolomide, 1 mg (Temodar) Deleted Q2024: injection, bevacizumab, 0.25 mg (code deleted effective 1/1/10; see C9257 and J9035) J9170: injection, docetaxel, 20 mg (code deleted effective 1/1/10; see J9171) C9253: injection, temozolomide, 1 mg (code deleted effective 1/1/10; see J9328)

32

February 2010 I VOL 3, NO 1

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

www.TheOncologyNurse.com

TON_Feb2010_FINAL_TON 2/2/10 11:38 AM Page 33

CONTINUING EDUCATION CREDITS

Current activities at www.COEXM.com include:

TON_Feb2010_FINAL_TON 2/4/10 12:09 PM Page 34

Books and Media

Woman Cancer Sex

By Anne Katz, RN, PhD Hygeia Media, an imprint of the Oncology Nursing Society, Pittsburgh, PA; ONS Publishing Division; 2009.

Reviewed by Lyssa Friedman, RN, MPA, OCN

in a heterosexist healthcare system.

Although Katz seems culturally literate, the book is less so. A woman in her 20s and two in their 60s are mentioned, yet of the women discussed the average age is 44, and there is no socioeconomic, ethnic, or apparent racial diversity.

A sexuality counselor, Katz reviews sexual anatomy and the female sexual response cycle, then presents issues such as altered body image, loss of desire, and problems with arousal and painful sex.

the context of our religious, cultural, and ethnic beliefs and practices.” Indeed, in “Lesbians with Cancer,” Jen’s radiation oncology nurse, counseling her about breast skin changes, assumes Jen’s sexual partner is her husband. Discussing Jen’s reluctance to “come out,” Katz communicates the challenges lesbians may face

out partners are equally concerned about sexual changes. In addition, transgendered women with their unique hormonal influences warrant attention.

This safe, conservative approach does a disservice to what could be a revolutionary book.

Kudos to Dr. Katz for discussing subjects many oncology nurses find challenging. This type of handbook is a great start for the frontline nurse, yet nurses need complete and unbiased information. This reader hopes that the first revision will correct the book’s current omissions. ● @Copyright iStockphotos.com/Amanda Rohde

S

ex and sexuality are important aspects of life…whether we express that with a partner or alone, frequently or infrequently, proudly or with conflicting feelings,” writes Anne Katz, RN, PhD, in Woman Cancer Sex. So begins a sensitive look at cancer, sex, and sexuality, that should be required reading for oncology nurses in primary care.

A sexuality counselor, Katz reviews sexual anatomy and the female sexual response cycle, then presents issues such as altered body image, loss of desire, and problems with arousal and painful sex.

Each is explored from three different perspectives: a personalized case study, commentary defining the case’s clinical components, and “take-away points,” which offer professional guidance when counseling a patient.

Katz takes on painful subjects. In “Sexuality and Terminal Illness,” Caryl has advanced ovarian cancer and is receiving hospice care at home. One evening she beckons her husband.

“Wanna fool around? One last time?” A

gentle encounter follows, which Caryl proclaims “the best sex I ever had.” She dies 2 days later.

In the Introduction, Katz promotes sensitivity to diversity. “Our sexual orientation…is an intrinsic part of our sexuality,” she writes. “All of this occurs in

The only case study depicting a lesbian addresses not a sexual issue universal to all women, such as fertility or problems with orgasm, but examines lesbian identity from a sociologic perspective. In each case, women are married or partnered and sexuality is discussed in the relationship context, yet women with-

Did You Know?

Nurses are the most trusted professionals in the United States, according to a recent Gallup survey. A total of 83% of survey respondents rated nurses as having “high or very high” ethical standards. Pharmacists and physicians ranked numbers two and three with 66% and 65%, respectively, of respondents giving them the highest rating.

SABCS 2009

Anthracyclines May Not Be... Continued from page 26 risk reduced by 37% and 23%, respectively, he reported.

Anthracycline-based therapy was expected to benefit the high-risk patients the most, Slamon added; however, even in patients with four or more positive

to the 35% of patients whose tumors coamplify the topoisomerase II alpha (TOP2A) gene, a close genetic neighbor of HER2. Slamon advocated the nonanthracycline regimen for patients regardless of TOP2A status,

“At this point, when we see an HER2-positive patient, we have elected to treat those patients with a nonanthracyclinecontaining regimen to get close to equivalent efficacy but considerably better safety.”

—Dennis Slamon, MD, PhD

lymph nodes, the two trastuzumab regimens resulted in identical DFS outcomes.

BCIRG-006 also demonstrated that incremental benefit conferred by AC in HER2-positive patients is restricted

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February 2010 I VOL 3, NO 1

to “avoid the long-term and lifealtering toxicities seen with anthracycline-based regimens.”

He emphasized the toxicity of the AC-TH regimen, which led to 21 cases

of congestive heart failure, compared with four cases in the TCH arm.

Additionally, 194 patients had sustained reductions in left ventricular ejection fraction, compared with 97 with TCH, and eight versus zero developed leukemia.

“The acute and chronic toxicity profiles of TCH are better than those seen with the AC-TH regimen in almost all parameters measured,” he told the press.

“At this point, when we see an HER2-positive patient, we have elected to treat those patients with a nonanthracycline-containing regimen to get close to equivalent efficacy but considerably better safety, in particular, not for the acute toxicity but more important for the life-changing toxicities,” he said.

Questions remain Eric Winer, MD, of Dana-Farber Cancer Center, Boston, however, is not convinced that anthracyclines can

be safely eliminated. He told The Oncology Nurse, “Ultimately, the most important thing is survival. The differences shown between the arms in the trial are not statistically significant [versus each other], and the two arms were, in fact, never intended to be compared with each other, and the study is therefore not powered to show equivalence between anthracyclineand nonanthracycline-based regimens,” he said.

“I don’t have a problem with using TCH to avoid cardiac problems. It is an acceptable regimen, but I am not of the view that it should be a preferred regimen,” he said. “There are some patients for whom TCH might be appropriate, based on the need to avoid the side effects. But in someone at low risk for developing cardiac problems, I think one has to think long and hard before opting for a regimen that might be slightly less effective. And I think we must be very cautious before adopting new standards.” ●

www.TheOncologyNurse.com

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TON_Feb2010_FINAL_TON 2/4/10 9:55 AM Page 36

Nursing Life @Copyright iStockphotos.com/Gary Novosel

Nursing Excellence Award Honors Oncology Nurse Who Goes Above and Beyond the Call of Duty

By John Schieszer

Spaghetti Squash Bruschetta

W

inter meals can be colorful and refreshing when you take advantage of such vegetables as spaghetti squash.

Winter squash come in many different varieties, such as butternut, acorn, Hubbard, turban, pumpkin, and spaghetti squash. These vegetables are an excellent source of beta-carotene and a good source of vitamin C, potassium, dietary fiber, folate, omega-3 fatty acids, and B vitamins. Winter squash is harvested late into the fall and has a storage life of up to 6 months. Spaghetti squash can be used as a side dish or as the main meal, as in the featured recipe.

Ingredients 1 large spaghetti squash, baked and removed from skin 4 garlic cloves, sliced ½ cup basil, chiffonaded

C

arrie Daly, MS, RN, APN, skin-care and mouth-care protocols for AOCN, is a nurse who has a patients receiving radiation therapy. very rich life because of her job.

“I have been a nurse 29 years and an She has worked tirelessly over a num- oncology nurse for 25 years. I worried I ber of years to help hundreds of cancer would lose my empathy over the years patients and survivors. for the patients, but I haven’t. My famiDaly was the recipient of the 2009 ly was worried I had picked the wrong American Society for Radiation type of nursing because I cry at movies Oncology (ASTRO) Nurse Excellence and I am very sensitive. However, I Award. This award is given to think that has helped a registered nurse who goes me to relate to the above and beyond the normal patients. Patients know standards of nursing practice. when you are sincere “To be an oncology nurse, and when you are not,” you have to be a good listener to Daly said. deal with death and dying. You Daly is a member of treat the entire body from head the hospital’s Cancer to toe in terms of the symptoms.

Survivors’ Day commitYou can help spiritually, medtee and helps organize ically, socially, and you can have an annual event that an intimate and close relation- Carrie Daly, MS, RN, has gone from 50 people APN, AOCN ship with the patient and the to more than 400 peofamily. Patients feel that you ple, in part, because of benefit them so much, but I feel I get so Daly’s involvement. For the past 23 much from my patients,” Daly told The years, Daly has been a volunteer at One Oncology Nurse.

Step at a Time’s summer camp for chilDaly is an oncology nurse manager dren with cancer. She is also an active and advanced practice nurse at Rush volunteer for Gilda’s Club Chicago and University Medical Center in Chicago. has volunteered at Saint Joseph Hospital She has developed site-specific educa- in Chicago at a biweekly support group tional materials for patients receiving for women. radiation therapy and implemented “One of the big things that I do is

treat my patients and their families the way I would like to be treated. Some people think being a cancer nurse is depressing, but in reality, it is just the opposite because it is fulfilling to help people, and not everyone dies from cancer. Vast numbers are living today, and a diagnosis of cancer is not what it used to be. It is not a death sentence,” said Daly.

“Carrie’s dedication and compassionate care toward her patients during their treatments and throughout the cancer journey is the definition of nurse excellence in radiation oncology,” said Vanna Dest, MSW, APRN, chair of ASTRO’s Nursing Committee. “I am honored to be able to recognize her with this award.”

“I think being an oncology nurse takes a special type of person, and nurses in this field do it because they have a passion,” Dest said in an interview with The Oncology Nurse. “Helping cancer patients through their treatments can be a very difficult journey, but I think Carrie is someone who helps each patient through each facet of the journey. There are physical and emotional challenges that patients and their families encounter, and she is able to recognize and assess those needs and implement interventions that can help.” ●

3 tomatoes, diced small ½ onion, diced small

ONS IOL

¼ cup olive oil

Virtual Classroom... Continued from page 11

½ teaspoon salt ¼ cup shredded Asiago cheese

Directions

ties, including the fact that setting up a clinical project usually involves a lot of collaboration, Somayaji said that was easily worked out. “I’m in New

York and my oncology nurse chair is in Portland. And we have one-on-one time on camera through Skype or email a lot and it’s all worked really

• Heat pan and add olive oil.

• Add garlic and onions and sauté until soft.

• Add tomatoes, basil, spaghetti squash, and salt.

• Heat all ingredients thoroughly.

• Finish with shredded Asiago cheese.

Nutritional Information Yield: five 1-cup servings

Each serving provides: 70 calories, 2.5 g saturated fat, 1 g saturated fat, 5 mg cholesterol, 300 mg sodium, 10 g total carbohydrate, 1 g dietary fiber, 2 g sugars, 3 g protein.

Recipe courtesy of Peter Pascale, CCC Executive Chef, Somerville, New Jersey.

Darryl Somayaji and Lanell Bellury in person and Rebecca Donohue on the computer discuss their PhD program.

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February 2010 I VOL 3, NO 1

well.” She reported that usually committee members at the students’ respective centers are available to help or mentor in person, if needed.

“And I will defend in person.”

In fact, the program has been deemed so successful, that all nursing PhD programs at the university now include this format option.

“This is the way of the future for research,” according to Bellury. “It’s become normal to communicate via email, text, webcams, etc. With so many nursing researchers looking for multisite and multidisciplinary work, this is the technology that can make all that happen. I may not have embarked on my PhD if I hadn’t had this technology.”

The university is currently enrolling a new cohort of students to start this program in the fall semester of 2010.

“Anyone interested can apply now,” Bellury said. ● —DB

www.TheOncologyNurse.com

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International News

Reports from International Meetings and Researchers

By Jill Stein

Palliative Care for Children with Cancer Is Suboptimal MELBOURNE, AUSTRALIA—Healthcare workers need to pay more attention to children with cancer to better manage common end-of-life symptoms, a group from the Children’s Cancer Center at the Royal Children’s Hospital advised.

John A. Heath, PhD, FRACP, clinical associate professor at the hospital, and his coworkers analyzed responses to questionnaires completed by 89 parents of children who had died of cancer roughly 5 years earlier.

Their findings showed that 84% of parents of these children maintained that their child had suffered “a lot” or “a great deal” from at least one symptom in their last month of life. These symptoms included pain (46%), fatigue (43%), and poor appetite (30%).

The study also found that current treatments for these symptoms were often inadequate. In fact, fewer than half of all symptoms were successfully treated using presently available treatments. The symptoms that were the most difficult to treat were fatigue, poor appetite, constipation, and diarrhea.

In Australia, children represent the majority of those who receive end-of-life care, the authors wrote in their article.

The study was published in the January 2010 issue of The Medical Journal of Australia.

Drivers Should Wear Gloves to Cut Skin Cancer Risk WELLINGTON, NEW ZEALAND— The Cancer Society of New Zealand is recommending that drivers wear gloves to avoid developing skin cancer.

Closed car windows do not protect hands that are on the driving wheel against ultraviolet radiation, the charity said in a statement. In fact, standard glass windows block only 37% of ultraviolet-A radiation.

Ultraviolet radiation is known to increase the risk of malignant melanoma and other skin cancers.

The drivers with the greatest risk are those who are exposed to the sun through side windows on long trips or frequent trips, a charity spokesman said.

Wine Drinkers Should Consider Lower-alcohol Wine to Decrease Cancer Risk LONDON, UK—Individuals who drink a large glass (250 mL) of wine every day may significantly reduce their risk of cancer by substituting a lower-alcohol alternative, a UK charity said in a news release.

Persons who regularly consume a 250-mL glass of wine every day with an

www.TheOncologyNurse.com

alcohol content of 14% can lower their odds of developing bowel cancer by 7% by switching to a 10% wine, according to the World Cancer Research Fund.

Spokeswoman Dr Rachel Thompson was quick to emphasize that the charity is

not advocating drinking wine but instead is just being realistic. “From a cancer prevention point of view, it is best not to drink at all,” she said. “But we have to be realistic, and the fact is that many people in the United Kingdom enjoy a drink

RITUXAN® (Rituximab) Brief summary—Please consult full prescribing information. postmarketing reports, the mean time to documented gastrointestinal perforation was 6 (range 1–77) days in patients with NHL. Perform a thorough diagnostic evaluation and WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), institute appropriate treatment for complaints of abdominal pain, especially early in the SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL course of Rituxan therapy. [See Adverse Reactions.] Immunization The safety of LEUKOENCEPHALOPATHY (PML) immunization with live viral vaccines following Rituxan therapy has not been studied and Infusion Reactions: Rituxan administration can result in serious, including vaccination with live virus vaccines is not recommended. Laboratory Monitoring fatal infusion reactions. Deaths within 24 hours of Rituxan infusion have Because Rituxan binds to all CD20-positive B lymphocytes (malignant and nonoccurred. Approximately 80% of fatal infusion reactions occurred in malignant), obtain complete blood counts (CBC) and platelet counts at regular intervals association with the first infusion. Carefully monitor patients during during Rituxan therapy and more frequently in patients who develop cytopenias [see infusions. Discontinue Rituxan infusion and provide medical treatment for Adverse Reactions]. The duration of cytopenias caused by Rituxan can extend months Grade 3 or 4 infusion reactions [see Warnings and Precautions, Adverse beyond the treatment period. ADVERSE REACTIONS The most common adverse Reactions]. Tumor Lysis Syndrome (TLS): Acute renal failure requiring dialysis with instances of fatal outcome can occur in the setting of TLS reactions of Rituxan (incidence ≥25%) observed in patients with NHL are infusion following treatment of non-Hodgkin’s lymphoma (NHL) patients with Rituxan reactions, fever, chills, infection, asthenia, and lymphopenia. The most important serious [see Warnings and Precautions, Adverse Reactions]. Severe Mucocutaneous adverse reactions of Rituxan are infusion reactions, tumor lysis syndrome, Reactions: Severe, including fatal, mucocutaneous reactions can occur in mucocutaneous toxicities, hepatitis B reactivation with fulminant hepatitis, PML, other patients receiving Rituxan [see Warnings and Precautions, Adverse viral infections, cardiac arrhythmias, renal toxicity, and bowel obstruction and perforation.

Reactions]. Progressive Multifocal Leukoencephalopathy (PML): JC virus Clinical Trials Experience Non-Hodgkin’s Lymphoma Because clinical trials are infection resulting in PML and death can occur in patients receiving Rituxan 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 [see Warnings and Precautions, Adverse Reactions]. drug and may not reflect the rates observed in practice. The data described below reflect INDICATIONS AND USAGE Non-Hodgkin’s Lymphoma (NHL) Rituxan® (rituximab) is exposure to Rituxan in 1606 patients, with exposures ranging from a single infusion up indicated for the treatment of patients with: Relapsed or refractory, low-grade or to 6–8 months. Rituxan was studied in both single-agent and active-controlled trials (n = follicular, CD20-positive, B-cell NHL as a single agent; Previously untreated follicular, 356 and n = 1250). These data were obtained in adults with low-grade, follicular, or CD20-positive, B-cell NHL in combination with CVP chemotherapy; Non–progressing DLBCL NHL. Most patients received Rituxan as an infusion of 375 mg/m2 per infusion, (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after given as a single agent weekly for up to 8 doses, in combination with chemotherapy for first-line CVP chemotherapy; Previously untreated diffuse large B-cell, CD20-positive up to 8 doses, or following chemotherapy for up to 16 doses. Infusion Reactions In the NHL in combination with CHOP or other anthracycline-based chemotherapy regimens. majority of patients with NHL, infusion reactions consisting of fever, chills/rigors, nausea, WARNINGS AND PRECAUTIONS Infusion Reactions Rituxan can cause severe, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, including fatal, infusion reactions. Severe reactions typically occurred during the first myalgia, dizziness, or hypertension occurred during the first Rituxan infusion. Infusion infusion with time to onset of 30–120 minutes. Rituxan-induced infusion reactions and reactions typically occurred within 30 to 120 minutes of beginning the first infusion and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, resolved with slowing or interruption of the Rituxan infusion and with supportive care pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, (diphenhydramine, acetaminophen, and intravenous saline). The incidence of infusion ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death. Premedicate reactions was highest during the first infusion (77%) and decreased with each patients with an antihistamine and acetaminophen prior to dosing. Institute medical subsequent infusion. [See Boxed Warning, Warnings and Precautions.] Infections management (e.g. glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion Serious infections (NCI CTCAE Grade 3 or 4), including sepsis, occurred in less than reactions as needed. Depending on the severity of the infusion reaction and the required 5% of patients with NHL in the single-arm studies. The overall incidence of infections interventions, consider resumption of the infusion at a minimum 50% reduction in rate was 31% (bacterial 19%, viral 10%, unknown 6%, and fungal 1%). [See Warnings and after symptoms have resolved. Closely monitor the following patients: those with pre- Precautions.] In randomized, controlled studies where Rituxan was administered existing cardiac or pulmonary conditions, those who experienced prior cardiopulmonary following chemotherapy for the treatment of follicular or low-grade NHL, the rate of adverse reactions, and those with high numbers of circulating malignant cells (≥25,000/ infection was higher among patients who received Rituxan. In diffuse large B-cell mm3). [See Boxed Warning, Warnings and Precautions, Adverse Reactions.] Tumor lymphoma patients, viral infections occurred more frequently in those who received Lysis Syndrome (TLS) Rapid reduction in tumor volume followed by acute renal failure, Rituxan. Cytopenias and hypogammaglobulinemia In patients with NHL receiving hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia, can occur within rituximab monotherapy, NCI-CTC Grade 3 and 4 cytopenias were reported in 48% of 12–24 hours after the first infusion. Fatal TLS cases have occurred after administration patients. These included lymphopenia (40%), neutropenia (6%), leukopenia (4%), of Rituxan. A high number of circulating malignant cells (≥25,000/mm3) or high tumor burden anemia (3%), and thrombocytopenia (2%). The median duration of lymphopenia was confers a greater risk of TLS after rituximab. Consider prophylaxis for TLS in patients at 14 days (range, 1–588 days) and of neutropenia was 13 days (range, 2–116 days). A high risk. Correct electrolyte abnormalities, monitor renal function and fluid balance, and single occurrence of transient aplastic anemia (pure red cell aplasia) and two occurrences administer supportive care, including dialysis as indicated. [See Boxed Warning.] of hemolytic anemia following Rituxan therapy occurred during the single-arm studies. In Severe Mucocutaneous Reactions Mucocutaneous reactions, some with fatal studies of monotherapy, Rituxan-induced B-cell depletion occurred in 70% to 80% of outcome, can occur in patients treated with Rituxan. These reactions include patients with NHL. Decreased IgM and IgG serum levels occurred in 14% of these paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, patients. Single-Agent Rituxan Adverse reactions in Table 1 occurred in 356 patients vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of these reactions with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL treated in has varied from 1–13 weeks following Rituxan exposure. Discontinue Rituxan in patients single-arm studies of Rituxan administered as a single agent. Most patients received Rituxan who experience a severe mucocutaneous reaction. The safety of readministration of 375 mg/m2 weekly for 4 doses.

Rituxan to patients with severe mucocutaneous reactions has not been determined. [See Table 1 Boxed Warning, Adverse Reactions.] Progressive Multifocal Leukoencephalopathy Incidence of Adverse Events in ≥5% of Patients with Relapsed or Refractory, Low-Grade (PML) JC virus infection resulting in PML and death can occur in Rituxan-treated or Follicular NHL, Receiving Single-agent Rituxan (N = 356)a,b patients with hematologic malignancies or with autoimmune diseases. The majority of All Grades (%) Grade 3 and 4 (%) All Grades (%) Grade 3 and 4 (%) patients with hematologic malignancies diagnosed with PML received Rituxan in Any Adverse Events 99 57 38 4 Respiratory System as a Whole 86 10 Increased Cough 13 1 combination with chemotherapy or as part of a hematopoietic stem cell transplant. The BodyFever 53 1 Rhinitis 12 1 Chills 33 3 Bronchospasm 8 1 patients with autoimmune diseases had prior or concurrent immunosuppressive therapy.

Infection 31 4 Dyspnea 7 1 Most cases of PML were diagnosed within 12 months of their last infusion of Rituxan.

Asthenia 26 1 Sinusitis 6 0 Headache 19 1 Metabolic and Nutritional Consider the diagnosis of PML in any patient presenting with new-onset neurologic 14 1 38 3 Abdominal Pain Disorders Pain 12 1 Angioedema 11 1 manifestations. Discontinue Rituxan and consider discontinuation or reduction of any 10 1 9 1 Back Pain Hyperglycemia concomitant chemotherapy or immunosuppressive therapy in patients who develop Throat Irritation 9 0 Peripheral Edema 8 0 5 0 7 0 LDH Increase PML. [See Boxed Warning, Adverse Reactions.] Hepatitis B Virus (HBV) Reactivation HemeFlushing and Lymphatic System 67 48 Digestive System 37 2 Lymphopenia 48 40 Nausea 23 1 Hepatitis B virus (HBV) reactivation with fulminant hepatitis, hepatic failure, and death Leukopenia 14 4 Diarrhea 10 1 can occur in patients with hematologic malignancies treated with Rituxan. The median Neutropenia 14 6 Vomiting 10 1 Thrombocytopenia 12 2 Nervous System 32 1 time to the diagnosis of hepatitis was approximately 4 months after the initiation of Anemia 8 3 Dizziness 10 1 44 2 5 1 Anxiety Rituxan and approximately one month after the last dose. Screen patients at high risk of Skin and Appendages Night Sweats 15 1 Musculoskeletal System 26 3 HBV infection before initiation of Rituxan. Closely monitor carriers of hepatitis B for 15 1 10 1 Rash Myalgia Pruritus 14 1 Arthralgia 10 1 clinical and laboratory signs of active HBV infection for several months following Rituxan Urticaria 8 1 Cardiovascular System 25 3 therapy. Discontinue Rituxan and any concomitant chemotherapy in patients who Hypotension 10 1 Hypertension 6 1 develop viral hepatitis, and institute appropriate treatment including antiviral therapy. a b Insufficient data exist regarding the safety of resuming Rituxan in patients who develop Adverse reactions observed up to 12 months following Rituxan. Adverse reactions graded for severity by hepatitis subsequent to HBV reactivation. [See Adverse Reactions.] Infections Rituxan is NCI-CTC criteria. not recommended for treatment of patients with severe active infections. The following In these single-arm Rituxan studies, bronchiolitis obliterans occurred during and up to additional serious viral infections, either new, reactivated, or exacerbated, have been 6 months after Rituxan infusion. Rituxan in Combination With Chemotherapy identified in clinical studies or postmarketing reports. The majority of patients received Adverse reactions information below is based on 1250 patients who received Rituxan in Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell combination with chemotherapy or following chemotherapy. Rituxan in Combination transplant. These viral infections included cytomegalovirus, herpes simplex virus, With Chemotherapy for Low-Grade NHL In Study 4, patients in the R-CVP arm parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis C. In some cases, experienced a higher incidence of infusional toxicity and neutropenia compared to the viral infections occurred as late as one year following discontinuation of Rituxan and patients in the CVP arm. The following adverse reactions occurred more frequently have resulted in death. [See Adverse Reactions.] Cardiovascular Discontinue infusions (≥5%) in patients receiving R-CVP compared to CVP alone: rash (17% vs. 5%), cough for serious or life-threatening cardiac arrhythmias. Perform cardiac monitoring during (15% vs. 6%), flushing (14% vs. 3%), rigors (10% vs. 2%), pruritus (10% vs. 1%), and after all infusions of Rituxan for patients who develop clinically significant arrhythmias, neutropenia (8% vs. 3%), and chest tightness (7% vs. 1%). In Study 5, the following or who have a history of arrhythmia or angina. [See Adverse Reactions.] Renal Severe, adverse reactions were reported more frequently (≥5%) in patients receiving Rituxan including fatal, renal toxicity can occur after Rituxan administration in patients with following CVP compared to patients who received no further therapy: fatigue (39% vs. hematologic malignancies. Renal toxicity has occurred in patients with high numbers of 14%), anemia (35% vs. 20%), peripheral sensory neuropathy (30% vs. 18%), infections circulating malignant cells (≥25,000/mm3) or high tumor burden who experience tumor (19% vs. 9%), pulmonary toxicity (18% vs. 10%), hepato-biliary toxicity (17% vs. 7%), lysis syndrome and in patients with NHL administered concomitant cisplatin therapy rash and/or pruritus (17% vs. 5%), arthralgia (12% vs. 3%), and weight gain (11% vs. during clinical trials. The combination of cisplatin and Rituxan is not an approved 4%). Neutropenia was the only Grade 3 or 4 adverse reaction that occurred more treatment regimen. Use extreme caution if this non-approved combination is used in frequently (≥2%) in the Rituxan arm compared with those who received no further clinical trials and monitor closely for signs of renal failure. Consider discontinuation of therapy (4% vs. 1%). Rituxan in Combination With Chemotherapy for DLBCL In Rituxan for patients with a rising serum creatinine or oliguria. Bowel Obstruction and Studies 6 and 7, the following adverse reactions, regardless of severity, were reported Perforation Abdominal pain, bowel obstruction and perforation, in some cases leading more frequently (≥5%) in patients age ≥60 years receiving R-CHOP as compared to to death, can occur in patients receiving Rituxan in combination with chemotherapy. In CHOP alone: pyrexia (56% vs. 46%), lung disorder (31% vs. 24%), cardiac disorder

and see it as part of their social life.”

The release noted that switching to lower-strength alcohol may also decrease the risk of cancer of the breast, liver, esophagus, mouth, pharynx, and larynx to the same degree as bowel cancer. ●

(29% vs. 21%), and chills (13% vs. 4%). Detailed safety data collection in these studies was primarily limited to Grade 3 and 4 adverse reactions and serious adverse reactions.

In Study 7, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R-CHOP vs. 1.0% for CHOP). The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs. 7%) and lung disorder (6% vs. 3%). Other Grade 3 or 4 adverse reactions occurring more frequently among patients receiving R-CHOP were viral infection (Study 7), neutropenia (Studies 7 and 8), and anemia (Study 8). Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Rituxan with the incidence of antibodies to other products may be misleading. Using an ELISA assay, anti-human anti-chimeric antibody (HACA) was detected in 4 of 356 (1.1%) patients with low-grade or follicular NHL receiving singleagent Rituxan. Three of the four patients had an objective clinical response. The clinical relevance of HACA formation in Rituxan-treated patients is unclear. Postmarketing Experience The following adverse reactions have been identified during post-approval use of Rituxan in hematologic malignancies. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to Rituxan. Hematologic: prolonged pancytopenia, marrow hypoplasia, and late-onset neutropenia, hyperviscosity syndrome in Waldenstrom’s macroglobulinemia. Cardiac: fatal cardiac failure. Immune/Autoimmune Events: uveitis, optic neuritis, systemic vasculitis, pleuritis, lupus-like syndrome, serum sickness, polyarticular arthritis, and vasculitis with rash. Infection: viral infections, including progressive multifocal leukoencephalopathy (PML), increase in fatal infections in HIV-associated lymphoma, and a reported increased incidence of Grade 3 and 4 infections in patients with previously treated lymphoma without known HIV infection.

Neoplasia: disease progression of Kaposi’s sarcoma. Skin: severe mucocutaneous reactions. Gastrointestinal: bowel obstruction and perforation. Pulmonary: fatal bronchiolitis obliterans and pneumonitis (including interstitial pneumonitis).

DRUG INTERACTIONS Formal drug interaction studies have not been performed with Rituxan. USE IN SPECIFIC POPULATIONS Pregnancy Category C: There are no adequate and well-controlled studies of rituximab in pregnant women. Postmarketing data indicate that B-cell lymphocytopenia generally lasting less than six months can occur in infants exposed to rituximab in-utero. Rituximab was detected postnatally in the serum of infants exposed in-utero. Non-Hodgkin’s lymphoma is a serious condition that requires treatment. Rituximab should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Reproduction studies in cynomolgus monkeys at maternal exposures similar to human therapeutic exposures showed no evidence of teratogenic effects. However, B-cell lymphoid tissue was reduced in the offspring of treated dams. The B-cell counts returned to normal levels, and immunologic function was restored within 6 months of birth. Nursing Mothers It is not known whether Rituxan is secreted into human milk. However, Rituxan is secreted in the milk of lactating cynomolgus monkeys, and IgG is excreted in human milk. Published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts. The unknown risks to the infant from oral ingestion of Rituxan should be weighed against the known benefits of 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 frequently among elderly patients. Serious pulmonary adverse reactions were also more common among the elderly, including pneumonia and pneumonitis. Low-Grade or Follicular Non-Hodgkin’s Lymphoma Clinical studies of Rituxan in low-grade or follicular, CD20-positive, B-cell NHL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. OVERDOSAGE There has been no experience with overdosage in human clinical trials. Single doses of up to 500 mg/m2 have been given in dose-escalation clinical trials. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term animal studies have been performed to establish the carcinogenic or mutagenic potential of Rituxan, or to determine potential effects on fertility in males or females. PATIENT COUNSELING INFORMATION Patients should be provided the Rituxan Medication Guide and provided an opportunity to read prior to each treatment session. Because caution should be exercised in administering Rituxan to patients with active infections, it is important that the patient’s overall health be assessed at each visit and the risks of Rituxan therapy and any questions resulting from the patient’s reading of the Medication Guide be discussed.

Rituxan is detectable in serum for up to six months following completion of therapy.

Individuals of childbearing potential should use effective contraception during treatment and for 12 months after Rituxan therapy.

Revised 10/2009 (4851501) Jointly Marketed by: Biogen Idec Inc. 5200 Research Place San Diego, CA 92122 Genentech USA, Inc. 1 DNA Way South San Francisco, CA 94080-4990 ©2009 Biogen Idec Inc. and Genentech, Inc. 7140918 November 2009

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Across approved NHL indications

DRIVING PATIENT OUTCOMES IN NHL Supporting your central role in patient care

BOXED WARNINGS and Additional Important Safety Information

Indications 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 Weekly ×4

Weekly ×8

Bulky disease

Retreatment

Previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy Non-progressing (including stable disease), low-grade, CD20-positive B-cell NHL, as a single agent, after first-line CVP chemotherapy Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens

©2009 Genentech USA, Inc., and Biogen Idec Inc. All rights reserved.

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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.

For additional safety information, please see following page for brief summary of prescribing information, including BOXED WARNINGS and Medication Guide.

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

December 2009