The Oncology Nurse September/October 2014

SEPTEMBER/OCTOBER 2014

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GENETIC COUNSELING

CANCER CENTER PROFILE

The Nurse Navigation and the Cancer Survivorship Programs at the Trinity CancerCare Center

The staff of the Nurse Navigation and Cancer Survivorship programs at Trinity CancerCare Center (left to right): Carrie Lewis, RN, BSN, OCN, Navigator; Pamela Pearson, RN, MSN, FNP-C, AOCNP, Survivorship Program; Carol Mohagen, BSW, LSW, Navigation; and Jenene Kittleson, RN, MSN, OCN, CBCN, Navigator.

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ounded in 1922, Trinity Health was organized by the immigrants who settled Northwest North Dakota. Under the auspices of the newly formed Trinity Hospital Association, ground was broken to build a 30-bed hospital. Over the ensuing decades, Trinity expanded its facilities and increased the quality and scope of care. Trinity Health is now recognized as the region’s leading healthcare provider. As a nonprofit, fully integrated healthcare system, the network of more than 200 healthcare providers, hospitals, nursing homes, clinics, and other facilities serves an estimated 12,000 outpatients and 130,000 inpatients Continued on page 22 each year.

CONFERENCE NEWS

Highlights of the 2014 Annual Meeting of the American Society of Clinical Oncology Alice Goodman

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his year, the American Society of Clinical Oncology (ASCO) celebrates the 50th anniversary of its founding. ASCO’s 2014 annual meeting acknowledged the society’s role in the advances made against cancer and presented the latest research and educational information about prevention, detection, and treatment of cancer. This year’s meeting was well attended and provided a wealth of learning opportunities. Below are some

VOL 7, NO 5

What Is PALB2?

Cristi Radford, MS, CGC, Invitae Tuya Pal, MD, FABMG, Moffitt Cancer Center

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ou may have heard about this gene on the radio or in a news article lately. What’s all the fuss about?

On August 7, 2014, the New England Journal of Medicine (NEJM) published an article discussing breast cancer risk in families with mutations in PALB2.1 Although this is a recent article, the increased risk of breast cancer in individuals with a mutation in PALB2 has been known for a few years. Similar to many inherited genes that result in an increased cancer risk, testing routinely

Continued on page 8

THE WHOLE PATIENT

The Psychosocial Effects of Chemotherapy-Induced Alopecia Meg Barbor

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ontroversies in treatmentinduced alopecia and hair adverse events were brought to the attention of the medical community in a presentation by Mario Lacouture, MD, at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology 2014 annual meeting.

The controversies lie in the prevention and treatment of alopecia. “Hair adverse

events are frequent with anticancer therapies,” said Lacouture, a dermatologist at Memorial Sloan Kettering Cancer Center in New York City, specializing in conditions that result from cancer treatments.

“Patient counseling is critical so that doctors can make recommendations and assess the impact of these events on quality of life.”

In alopecia due to cytotoxic chemoContinued on page 22

INSIDE BREAST CANCER

highlights of the many ASCO presentations. These news briefs touch upon the harmful effects of obesity and the beneficial effects of weight loss on parameters of body composition and sex hormones, preservation of fertility in premenopausal breast cancer survivors, and a study that shows that loratadine is not effective in treating pegfilgrastim-induced bone pain.

for these genes was cost and time prohibitive prior to the availability of next-generation sequencing. This was particularly the case for PALB2, as these mutations were believed to be rare and their associated cancer risks were unclear.

PALB2 is a gene located on chromosome 16. It stands for “partner and localizer of BRCA2.” The name reflects initial findings that it encodes a protein involved in the BRCA2-related pathway.

However, subsequent studies have demonstrated it also interacts with BRCA1 and

Gap in Lymphedema Awareness. . . 3 Less May Be “More” With Zoledronic Acid. . . . . . . . . . . . . . . . 19 THE WHOLE PATIENT. . . . . . . . . .

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Sexuality Should Be Addressed With Cancer Patients SIDE EFFECTS MANAGEMENT. .

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Vaginal DHEA May Improve Sexual Function in Women With Breast/ Gynecologic Cancer

Continued on page 8 ©2014 Green Hill Healthcare Communications, LLC

BOOK REVIEW. . . . . . . . . . . . . . . .

19

The Myeloma Survival Guide: Essential Advice for Patients and Their Loved Ones THROUGH THE EYES OF AN ADVOCATE . . . . . . . . . . . . . . .

Pelvic Exam Not Needed for All Women?

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Start with TREANDA® (bendamustine HCI) for Injection for established front-line CLL therapy

TREANDA is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL). Efficacy relative to first-line therapies other than chlorambucil has not been established.

Important Safety Information Contraindication: TREANDA is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine.

Myelosuppression: TREANDA caused severe myelosuppression (Grade 3-4) in 98% of patients in the two NHL studies. Three patients (2%) died from myelosuppression-related adverse reactions. If myelosuppression occurs, monitor leukocytes, platelets, hemoglobin (Hgb), and neutrophils frequently. Myelosuppression may require dose delays and/or subsequent dose reductions if recovery to the recommended values has not occurred by the first day of the next scheduled cycle.

Infections: Infection, including pneumonia, sepsis, septic shock, and death have occurred. Patients with myelosuppression following treatment with TREANDA are more susceptible to infections.

Anaphylaxis and Infusion Reactions: Infusion reactions to TREANDA have occurred commonly in clinical trials. Symptoms include fever, chills, pruritus, and rash. In rare instances severe anaphylactic and anaphylactoid reactions have occurred, particularly in the second and subsequent cycles of therapy. Monitor clinically and discontinue drug for severe (Grade 3-4) reactions. Ask patients about symptoms suggestive of infusion reactions after their first cycle of therapy. Consider measures to prevent severe reactions, including antihistamines, antipyretics, and corticosteroids in subsequent cycles in patients who have experienced Grade 1 or 2 infusion reactions.

Tumor Lysis Syndrome: Tumor lysis syndrome associated with TREANDA treatment has occurred. The onset tends to be within the first treatment cycle of TREANDA and, without intervention, may lead to acute renal failure and death. Preventive measures include vigorous hydration and close monitoring of blood chemistry, particularly potassium and uric acid levels. There may be an increased risk of severe skin toxicity when TREANDA and allopurinol are administered concomitantly.

Skin Reactions: Skin reactions have been reported with TREANDA treatment and include rash, toxic skin reactions, and bullous exanthema. In a study of TREANDA (90 mg/m2) in combination with rituximab, one case of toxic epidermal necrolysis (TEN) occurred. TEN has been reported for rituximab. Cases of Stevens-Johnson syndrome (SJS) and TEN, some fatal, have been reported when TREANDA was administered concomitantly with allopurinol and other medications known to cause these syndromes. Where skin reactions occur, they may be progressive and increase in severity with further treatment. Monitor patients with skin reactions closely. If skin reactions are severe or progressive, withhold or discontinue TREANDA. Other Malignancies: There are reports of pre-malignant and malignant diseases that have developed in patients who have been treated with TREANDA, including myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia, and bronchial carcinoma. The association with TREANDA therapy has not been determined.

Extravasation Injury: TREANDA extravasations have been reported in postmarketing resulting in hospitalizations from erythema, marked swelling, and pain. Ensure good venous access prior to starting TREANDA infusion and monitor the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of TREANDA. Embryo-fetal Toxicity: TREANDA can cause fetal harm when administered to a pregnant woman. Women should be advised to avoid becoming pregnant while using TREANDA. Most Common Adverse Reactions: The most common non-hematologic adverse reactions for CLL (frequency ≥15%) are pyrexia, nausea, and vomiting. The most common hematologic abnormalities (frequency ≥15%) are anemia, thrombocytopenia, neutropenia, lymphopenia, and leukopenia.

Please see accompanying brief summary of Full Prescribing Information on following pages.

Learn more at TREANDAHCP.com. ©2013 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd. All rights reserved. TRE-40251 October 2013.

BREAST CANCER

Gap in Lymphedema Awareness Alice Goodman

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small study indicates that many patients with breast cancer are not informed about lymphedema as a possible treatment-related side effect and do not know how to

recognize its symptoms. Although this is a small study, the findings come from an academically affiliated cancer center and suggest that oncologists and nurses should be more proactive

about educating patients about the possibility of lymphedema and how to manage it. The study was presented as a poster at the 2014 American Association of Nurse Practitioners

Brief Summary of Prescribing Information for Chronic Lymphocytic Leukemia 1 INDICATIONS AND USAGE TREANDA® is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL). Efficacy relative to first line therapies other than chlorambucil has not been established.

2 DOSAGE AND ADMINISTRATION 2.1 Dosing Instructions for CLL Recommended Dosage: The recommended dose is 100 mg/m2 administered intravenously over 30 minutes on Days 1 and 2 of a 28-day cycle, up to 6 cycles.

Dose Delays, Dose Modifications and Reinitiation of Therapy for CLL: TREANDA administration should be delayed in the event of Grade 4 hematologic toxicity or clinically significant ≥ Grade 2 non-hematologic toxicity.

Once non-hematologic toxicity has recovered to ≤ Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) ≥ 1 x 109/L, platelets ≥ 75 x 109/L], TREANDA can be reinitiated at the discretion of the treating physician. In addition, dose reduction may be warranted. [See Warnings and Precautions (5.1)] Dose modifications for hematologic toxicity: for Grade 3 or greater toxicity, reduce the dose to 50 mg/m2 on Days 1 and 2 of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 25 mg/m2 on Days 1 and 2 of each cycle. Dose modifications for non-hematologic toxicity: for clinically significant Grade 3 or greater toxicity, reduce the dose to 50 mg/m2 on Days 1 and 2 of each cycle. Dose re-escalation in subsequent cycles may be considered at the discretion of the treating physician.

2.3 Reconstitution/Preparation for Intravenous Administration Aseptically reconstitute each TREANDA vial as follows: • 25 mg TREANDA vial: Add 5 mL of only Sterile Water for Injection, USP. • 100 mg TREANDA vial: Add 20 mL of only Sterile Water for Injection, USP. Shake well to yield a clear, colorless to a pale yellow solution with a bendamustine HCl concentration of 5 mg/mL. The lyophilized powder should completely dissolve in 5 minutes. If particulate matter is observed, the reconstituted product should not be used. Aseptically withdraw the volume needed for the required dose (based on 5 mg/mL concentration) and immediately transfer to a 500 mL infusion bag of 0.9% Sodium Chloride Injection, USP (normal saline). As an alternative to 0.9% Sodium Chloride Injection, USP (normal saline), a 500 mL infusion bag of 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, may be considered. The resulting final concentration of bendamustine HCl in the infusion bag should be within 0.2–0.6 mg/mL. The reconstituted solution must be transferred to the infusion bag within 30 minutes of reconstitution.

After transferring, thoroughly mix the contents of the infusion bag. The admixture should be a clear and colorless to slightly yellow solution. Use Sterile Water for Injection, USP, for reconstitution and then either 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, for dilution, as outlined above. No other diluents have been shown to be compatible. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Any unused solution should be discarded according to institutional procedures for antineoplastics.

2.4 Admixture Stability TREANDA contains no antimicrobial preservative. The admixture should be prepared as close as possible to the time of patient administration. Once diluted with either 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, the final admixture is stable for 24 hours when stored refrigerated (2-8°C or 36-47°F) or for 3 hours when stored at room temperature (15-30°C or 59-86°F) and room light.

Administration of TREANDA must be completed within this period.

3 DOSAGE FORMS AND STRENGTHS TREANDA for Injection single-use vial containing either 25 mg or 100 mg of bendamustine HCl as white to off-white lyophilized powder.

4 CONTRAINDICATIONS TREANDA is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine. [See Warnings and Precautions (5.3)] 5 WARNINGS AND PRECAUTIONS 5.1 Myelosuppression TREANDA caused severe myelosuppression (Grade 3-4) in 98% of patients in the two NHL studies. Three patients (2%) died from myelosuppressionrelated adverse reactions; one each from neutropenic sepsis, diffuse alveolar hemorrhage with Grade 3 thrombocytopenia, and pneumonia from an opportunistic infection (CMV). In the event of treatment-related myelosuppression, monitor leukocytes, platelets, hemoglobin (Hgb), and neutrophils frequently. In the clinical trials, blood counts were monitored every week initially. Hematologic nadirs were observed predominantly in the third week of therapy. Myelosuppression may require dose delays and/or subsequent dose reductions if recovery to the recommended values has not occurred by the first day of the next scheduled cycle. Prior to the initiation of the next cycle of therapy, the ANC should be ≥ 1 x 109/L and the platelet count should be ≥ 75 x 109/L. [See Dosage and Administration (2.1)]

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National Conference in Nashville, Tennessee.

“Most of my patients don’t recognize the symptoms of lymphedema.

Continued on page 4

5.2 Infections Infection, including pneumonia, sepsis, septic shock, and death have occurred in adult and pediatric patients in clinical trials and in postmarketing reports.

Patients with myelosuppression following treatment with TREANDA are more susceptible to infections. Advise patients with myelosuppression following TREANDA treatment to contact a physician if they have symptoms or signs of infection.

5.3 Anaphylaxis and Infusion Reactions Infusion reactions to TREANDA have occurred commonly in clinical trials.

Symptoms include fever, chills, pruritus and rash. In rare instances severe anaphylactic and anaphylactoid reactions have occurred, particularly in the second and subsequent cycles of therapy. Monitor clinically and discontinue drug for severe reactions. Ask patients about symptoms suggestive of infusion reactions after their first cycle of therapy. Patients who experience Grade 3 or worse allergic-type reactions should not be rechallenged.

Consider measures to prevent severe reactions, including antihistamines, antipyretics and corticosteroids in subsequent cycles in patients who have experienced Grade 1 or 2 infusion reactions. Discontinue TREANDA for patients with Grade 4 infusion reactions. Consider discontinuation for Grade 3 infusion reactions as clinically appropriate considering individual benefits, risks, and supportive care.

5.4 Tumor Lysis Syndrome Tumor lysis syndrome associated with TREANDA treatment has occurred in patients in clinical trials and in postmarketing reports. The onset tends to be within the first treatment cycle of TREANDA and, without intervention, may lead to acute renal failure and death. Preventive measures include vigorous hydration and close monitoring of blood chemistry, particularly potassium and uric acid levels. Allopurinol has also been used during the beginning of TREANDA therapy. However, there may be an increased risk of severe skin toxicity when TREANDA and allopurinol are administered concomitantly [see Warnings and Precautions (5.5)].

5.5 Skin Reactions Skin reactions have been reported with TREANDA treatment in clinical trials and postmarketing safety reports, including rash, toxic skin reactions and bullous exanthema. Some events occurred when TREANDA was given in combination with other anticancer agents. In a study of TREANDA (90 mg/m2) in combination with rituximab, one case of toxic epidermal necrolysis (TEN) occurred. TEN has been reported for rituximab (see rituximab package insert). Cases of Stevens-Johnson syndrome (SJS) and TEN, some fatal, have been reported when TREANDA was administered concomitantly with allopurinol and other medications known to cause these syndromes. The relationship to TREANDA cannot be determined. Where skin reactions occur, they may be progressive and increase in severity with further treatment.

Monitor patients with skin reactions closely. If skin reactions are severe or progressive, withhold or discontinue TREANDA. 5.6 Other Malignancies There are reports of pre-malignant and malignant diseases that have developed in patients who have been treated with TREANDA, including myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia and bronchial carcinoma. The association with TREANDA therapy has not been determined.

5.7 Extravasation Injury TREANDA extravasations have been reported in postmarketing resulting in hospitalizations from erythema, marked swelling, and pain. Assure good venous access prior to starting TREANDA infusion and monitor the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of TREANDA. 5.8 Embryo-fetal toxicity TREANDA can cause fetal harm when administered to a pregnant woman.

Single intraperitoneal doses of bendamustine in mice and rats administered during organogenesis caused an increase in resorptions, skeletal and visceral malformations, and decreased fetal body weights.

6 ADVERSE REACTIONS The following serious adverse reactions have been associated with TREANDA in clinical trials and are discussed in greater detail in other sections [See Warnings and Precautions] of the label: Myelosuppression (5.1); Infections (5.2); Infusion Reactions and Anaphylaxis (5.3); Tumor Lysis Syndrome (5.4); Skin Reactions (5.5); Other Malignancies (5.6). The data described below reflect exposure to TREANDA in 153 patients who participated in an actively-controlled trial for the treatment of CLL. 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.

6.1 Clinical Trials Experience in CLL The data described below reflect exposure to TREANDA in 153 patients with CLL studied in an active-controlled, randomized trial.The population was 45-77 years of age, 63% male, 100% white, and were treatment naïve.

All patients started the study at a dose of 100 mg/m2 intravenously over 30 minutes on Days 1 and 2 every 28 days. Adverse reactions were reported according to NCI CTC v.2.0. Non-hematologic adverse reactions (any grade) in the TREANDA group that occurred with a frequency greater than 15% were pyrexia (24%), nausea (20%), and vomiting (16%). Other adverse

SEPTEMBER/OCTOBER 2014 I VOL 7, NO 5 3 Job Number: 20418

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BREAST CANCER

Gap in Lymphedema Awareness Either surgeons are not telling them about it, or the patient is not listening,” said Dorothy Pierce, RN, MSN, a nurse practitioner in radiation oncology at the Rutgers Cancer Institute of New Jersey/Robert Wood Johnson University Hospital in New Brunswick.

The cross-sectional survey was con-

ducted in 24 patients slated for radiation post surgery and lymph node dissection. Data were collected from April to June 2013. More than 50% of the participants were between the ages of 40 and 49 years. Most were white, and 75% had finished high school or had attended college. Of the patients,

reactions seen frequently in one or more studies included asthenia, fatigue, malaise, and weakness; dry mouth; somnolence; cough; constipation; headache; mucosal inflammation and stomatitis. Worsening hypertension was reported in 4 patients treated with TREANDA in the CLL trial and in none treated with chlorambucil. Three of these 4 adverse reactions were described as a hypertensive crisis and were managed with oral medications and resolved. The most frequent adverse reactions leading to study withdrawal for patients receiving TREANDA were hypersensitivity (2%) and pyrexia (1%). Table 1 contains the treatment emergent adverse reactions, regardless of attribution, that were reported in ≥ 5% of patients in either treatment group in the randomized CLL clinical study.

Table 1: Non-Hematologic Adverse Reactions Occurring in Randomized CLL Clinical Study in at Least 5% of Patients Number (%) of patients TREANDA (N=153) System organ class Preferred term Total number of patients with at least 1 adverse reaction Gastrointestinal disorders Nausea Vomiting Diarrhea General disorders and administration site conditions Pyrexia Fatigue Asthenia Chills Immune system disorders Hypersensitivity Infections and infestations Nasopharyngitis Infection Herpes Simplex Investigations Weight decreased Metabolism and nutrition disorders Hyperuricemia Respiratory, thoracic and mediastinal disorders Cough Skin and subcutaneous tissue disorders Rash Pruritus

Chlorambucil (N=143)

All Grades

Grade 3/4

All Grades

Grade 3/4

121 (79)

52 (34)

96 (67)

25 (17)

31 (20) 24 (16) 14 (9)

1 (<1) 1 (<1) 2 (1)

21 (15) 9 (6) 5 (3)

1 (<1) 0 0

36 (24) 14 (9) 13 (8) 9 (6)

6 (4) 2 (1) 0 0

8 (6) 8 (6) 6 (4) 1 (<1)

2 (1) 0 0 0

7 (5)

2 (1)

3 (2)

0

10 (7) 9 (6) 5 (3)

0 3 (2) 0

12 (8) 1 (<1) 7 (5)

0 1 (<1) 0

11 (7)

0

5 (3)

0

11 (7)

3 (2)

2 (1)

0

6 (4)

1 (<1)

7 (5)

1 (<1)

12 (8) 8 (5)

4 (3) 0

7 (5) 2 (1)

3 (2) 0

The Grade 3 and 4 hematology laboratory test values by treatment group in the randomized CLL clinical study are described in Table 2. These findings confirm the myelosuppressive effects seen in patients treated with TREANDA. Red blood cell transfusions were administered to 20% of patients receiving TREANDA compared with 6% of patients receiving chlorambucil.

Table 2: Incidence of Hematology Laboratory Abnormalities in Patients Who Received TREANDA or Chlorambucil in the Randomized CLL Clinical Study TREANDA N=150

Chlorambucil N=141

Laboratory Abnormality

All Grades n (%)

Grade 3/4 n (%)

All Grades n (%)

Grade 3/4 n (%)

Hemoglobin Decreased

134 (89)

20 (13)

115 (82)

12 (9)

Platelets Decreased

116 (77)

16 (11)

110 (78)

14 (10)

Leukocytes Decreased

92 (61)

42 (28)

26 (18)

4 (3)

Lymphocytes Decreased

102 (68)

70 (47)

27 (19)

6 (4)

Neutrophils Decreased

113 (75)

65 (43)

86 (61)

30 (21)

Continued from page 3

63% had a lumpectomy and 50% had 1 or more involved lymph nodes removed; 71% underwent adjuvant chemotherapy.

Notably, of all 24 participants surveyed, 79% experienced lymphedema symptoms and 71% incorrectly assumed that the symptoms they had

In the CLL trial, 34% of patients had bilirubin elevations, some without associated significant elevations in AST and ALT. Grade 3 or 4 increased bilirubin occurred in 3% of patients. Increases in AST and ALT of Grade 3 or 4 were limited to 1% and 3% of patients, respectively. Patients treated with TREANDA may also have changes in their creatinine levels. If abnormalities are detected, monitoring of these parameters should be continued to ensure that further deterioration does not occur.

6.3 Postmarketing Experience The following adverse reactions have been identified during post-approval use of TREANDA. 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: anaphylaxis; and injection or infusion site reactions including phlebitis, pruritus, irritation, pain, and swelling; pneumocystis jiroveci pneumonia and pneumonitis. Skin reactions including SJS and TEN have occurred when TREANDA was administered concomitantly with allopurinol and other medications known to cause these syndromes. [See Warnings and Precautions (5.5)] 10 OVERDOSAGE The intravenous LD50 of bendamustine HCl is 240 mg/m2 in the mouse and rat. Toxicities included sedation, tremor, ataxia, convulsions and respiratory distress. Across all clinical experience, the reported maximum single dose received was 280 mg/m2. Three of four patients treated at this dose showed ECG changes considered dose-limiting at 7 and 21 days post-dosing. These changes included QT prolongation (one patient), sinus tachycardia (one patient), ST and T wave deviations (two patients), and left anterior fascicular block (one patient). Cardiac enzymes and ejection fractions remained normal in all patients. No specific antidote for TREANDA overdose is known.

Management of overdosage should include general supportive measures, including monitoring of hematologic parameters and ECGs. 15 REFERENCES 1. OSHA Hazardous Drugs. OSHA. [Accessed on June 19, 2013, from http://www.osha.gov/SLTC/hazardousdrugs/index.html] 16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 Safe Handling and Disposal As with other potentially toxic anticancer agents, care should be exercised in the handling and preparation of solutions prepared from TREANDA. The use of gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage. If a solution of TREANDA contacts the skin, wash the skin immediately and thoroughly with soap and water. If TREANDA contacts the mucous membranes, flush thoroughly with water. TREANDA is an antineoplastic product. Follow special handling and disposal procedures1.

16.2 How Supplied TREANDA (bendamustine hydrochloride) for Injection is supplied in individual cartons as follows: NDC 63459-390-08 TREANDA (bendamustine hydrochloride) for Injection, 25 mg in 8 mL amber single-use vial and NDC 63459-391-20 TREANDA (bendamustine hydrochloride) for Injection, 100 mg in 20 mL amber single-use vial.

16.3 Storage TREANDA may be stored up to 25°C (77°F) with excursions permitted up to 30°C (86°F) (see USP Controlled Room Temperature). Retain in original package until time of use to protect from light.

Of all 24 participants surveyed, 79% experienced lymphedema symptoms and 71% incorrectly assumed that the symptoms they had of heaviness, firmness, and tightness in the affected arm were “normal.” of heaviness, firmness, and tightness in the affected arm were “normal,” Pierce explained.

Sixteen of the women said they had received no information about lymphedema from their doctors or nurses and they did not know what it was.

Of the 8 women who were informed about lymphedema, 5 said their radiation oncologist told them about it, 1 received information from a nurse, 1 heard about it from a medical oncologist, and 1 was told by a physical therapist.

Nine women had a mastectomy with 2 to 14 lymph nodes removed, and all of them developed symptoms of lymphedema. Among the 15 women who had a lumpectomy with 1 to 7 lymph nodes removed, 10 reported at least 1 symptom associated with lymphedema.

Ten women reported arm tenderness, 9 reported swelling of the arm, 6 reported arm numbness, and 5 reported impaired movement in the shoulders and fingers of the affected arm.

More than half of the patients with lymphedema symptoms did nothing for it. The other women used a variety of approaches: discussed it with their healthcare providers, had massage therapy, or slept with the elbow of the affected limb raised. l

Distributed By: Teva Pharmaceuticals USA, Inc. North Wales, PA 19454 TREANDA is a trademark of Cephalon, Inc. or its affiliates. ©2008-2013 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd or its affiliates.

All rights reserved.

(Label Code: 00016287.06)

Reference Pierce DN. Lymphedema knowledge and symptoms in breast cancer patients receiving radiation therapy.

Poster presented at: 2014 American Association of Nurse Practitioners National Conference; June 17-22, 2014; Nashville, TN.

8/2013 TRE-40156 This brief summary is based on TRE-008 TREANDA full Prescribing Information.

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EDITORIAL BOARD EDITOR-IN-CHIEF

Beth Faiman,

PhD(c), MSN, APRNBC, AOCN Cleveland Clinic Taussig Cancer Institute Cleveland, OH

Cassandra J. Hammond, RN, MSN, CRNP

Avid Education Partners, LLC Sharpsburg, MD

Catherine Bishop,

Shannon Hazen,

Johns Hopkins Kimmel Cancer Center/Sibley Infusion Washington, DC

Charlotte, NC

DNP, NP, AOCNP

Deena Damsky Dell, RN-BC, MSN,

RN, BSN, OCN

Taline Khoukaz, MSN, ACNP-C

Fox Chase Cancer Center Philadelphia, PA

Wendye DiSalvo,

Sandra E. Kurtin,

DNP, APRN, AOCN Genentech New London, NH

PhD, RN, AOCN

RN, DNS

Northern Michigan University Independent Oncology & Palliative Care Consultant Marquette, MI

Jayshree Shah, RN, APN-C, AOCNP, MSN

Pharmacy John F. Aforismo,

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

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

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

AOCN, LNC

Rita Wickham,

Melinda G. Oberleitner,

RN, MS, AOCN, ANP-C

Gary Shelton,

DNP(c), MSN, NP, ANP-BC, AOCNP

BSc Pharm, RPh, FASCP RJ Health Systems International, LLC Wethersfield, CT

Nutrition Karen Connelly, RD, CSO

NYU Clinical Cancer Center New York, NY

Somerset Medical Center Somerville, NJ

Lori Stover, RN,

Patient Advocacy Peg Ford

BSN

Ovarian Cancer Alliance of San Diego San Diego, CA

Arizona Cancer Center Tucson, AZ

Western Pennsylvania Cancer Institute Pittsburgh, PA

Denice Economou,

Ann McNeill,

Joseph D. Tariman,

City of Hope National Medical Center Duarte, CA

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Constance Engelking, RN,

Kena C. Miller,

Jacqueline Marie Toia, RN, MS,

Genetic Counseling Cristi Radford,

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

Millennium Pharmaceuticals, Inc Boston, MA

Northwestern University Myeloma Program Chicago, IL

DNP

MS, CGC

Patricia Molinelli,

Pamela Hallquist Viale, RN, MS,

RN, MN, CNS, AOCN

MS, CNS, OCN

Amy Ford, RN,

BSN, OCN Quintiles Dallas, TX

RN, MSN, APN

RN, MSN, ARNP-BC

MS, RN, APN-C, AOCNS

Somerset Medical Center Somerville, NJ

PhD, ANP-BC

Social Work Carolyn Messner, DSW, LCSW-R, BCD, OSW-C

DePaul University Chicago, IL

CancerCare New York, NY

CS, ANP, AOCN Saratoga, CA

Invitae Atlanta, GA

Managed Care and Pharmaceutical Management Burt Zweigenhaft, BS

Onco360/OncoMed New York, NY

Sharon S. Gentry, RN, MSN, AOCN, CBCN

Novant Health: Derrick L. Davis Cancer Center Winston-Salem, NC

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Ellen A. Neylon, MSN, FNP-BC, CCRP, OCN

Columbia University Medical Center Center for Lymphoid Malignancies New York, NY

Connie Visovsky,

PhD, RN, ACNP-BC University of South Florida College of Nursing Tampa, FL

Isabell Castellano, RN

Bristol-Myers Squibb Childrenâ&#x20AC;&#x2122;s Hospital Robert Wood Johnson University Hospital New Brunswick, NJ

Jeanne Westphal, RN Meeker Memorial Hospital Litchfield, MN

SEPTEMBER/OCTOBER 2014 I VOL 7, NO 5

5

FROM THE EDITOR PUBLISHING STAFF Senior Vice President, Sales & Marketing Philip Pawelko ppawelko@the-lynx-group.com Group Director, Sales & Marketing

John W. Hennessy jhennessy2@the-lynx-group.com Vice President/Director of Sales & Marketing Joe Chanley jchanley@the-lynx-group.com Publisher Russell Hennessy rhennessy@the-lynx-group.com Director, Client Services Dave Dempsey ddempsey@the-lynx-group.com Editorial Director Kristin Siyahian ksiyahian@the-lynx-group.com Managing Editor Kristen Olafson kolafson@the-lynx-group.com Copy Editors Jessica Cheng Mollie Friedman Peggy Roeske

T

his issue of The Oncology Nurse-APN/PA (TON), continues our coverage of the news from the recent Oncology Nursing Society (ONS) 39th Annual Congress and the 2014 Annual Meeting of the American Society of Clinical Oncology (ASCO).

At ONS, Anne Katz, RN, PhD, a clinical nurse specialist at CancerCare Manitoba, discussed how cancer and its treatments Beth Faiman, PhD(c), can affect a patient’s sexuality.

MSN, APRN-BC, AOCN Editor-in-Chief She notes that sexuality is an important part of a patient’s quality of life, but that studies show that this issue is rarely brought up with patients. Katz says that the interval between cancer diagnosis and treatment initiation presents an opportunity for nurses to assess how patients view their current sex life and how important sexuality is to them, and to prepare patients about what to expect.

Production Manager Cara Nicolini

READER POLL

THE LYNX GROUP President/CEO Brian Tyburski Chief Operating Officer Pam Rattananont Ferris Vice President of Finance Andrea Kelly

Do you talk to your patients about hair loss from chemotherapy?

Human Resources Jennine Leale Associate Director, Content Strategy & Development John Welz Director, Quality Control Barbara Marino Quality Control Assistant Theresa Salerno Director, Production & Manufacturing Alaina Pede Director, Creative & Design Robyn Jacobs Creative & Design Assistant Lora LaRocca Director, Digital Media Anthony Romano Web Content Managers David Maldonado Anthony Trevean Digital Programmer Michael Amundsen Meeting & Events Planner Linda Sangenito

This is a subject we should all be prepared to discuss with our patients. Katz gives us some guidelines on how to best approach this subject.

Our continuing ASCO coverage includes highlights of a few of the many presentations from the meeting.

We also present coverage from the recent annual meeting of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology.

Mario Lacouture, MD, discussed treatment-induced alopecia and hair adverse events. Lacouture notes that patients are often very overwhelmed by hair loss and that some patients consider it the most traumatic effect of chemotherapy—47% of breast cancer patients surveyed said this, with 8% of these patients saying they would reject chemotherapy because of alopecia alone.

Alopecia is the topic of our new reader poll. See below for information about going online to our website, www.TheOncologyNurse.com, to answer the question and provide your comments. While on the TON website, be sure to review the content and tell us what you like and don’t like. We appreciate your feedback and look forward to hearing from you. l

o Yes

o No

©iStockphoto.com/myrrha

A

t the recent annual meeting of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology, Mario Lacouture, MD, presented information about alopecia. He noted that “hair adverse events are frequent with anticancer therapies.” Patients often have a dramatic reaction to alopecia, and the psychosocial

ramifications must not be underestimated. According to 47% of patients with breast cancer surveyed, alopecia was the most traumatic effect of chemotherapy. Given how many patients—men and women—react to hair loss, is this a topic you discuss with patients? If so, how and when do you bring it up? Do patients express their concerns to you?

Go to www.TheOncologyNurse.com to answer the question and add your comments.

Senior Project Manager Jini Gopalaswamy Project Manager Deanna Martinez Project Coordinator Mike Kodada IT Specialist Carlton Hurdle Executive Administrator Rachael Baranoski Office Coordinator Robert Sorensen

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The Oncology Nurse-APN/PA®, ISSN 1944-9798 (print); ISSN 1944-9801 (online) is published 6 times a year by Green Hill Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. Telephone: 732.656.7935. Fax: 732.656.7938. Copyright ©2014 by Green Hill Health­care Com­munications, LLC. All rights reserved. The Oncology Nurse-APN/PA® logo is a registered trademark of Green Hill Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the Publisher. Printed in the United States of America.

EDITORIAL CORRESPONDENCE should be addressed to EDITORIAL DIRECTOR, The Oncology Nurse-APN/PA®, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. E-mail: editorial@greenhillhc.com. YEARLY SUBSCRIPTION RATES: United States and possessions: individuals, $105.00; institutions, $135.00; single issues, $17.00. Orders will be billed at individual rate until proof of status is confirmed. Prices are subject to change without notice. Correspondence regarding permission to reprint all or part of any article published in this journal should be addressed to REPRINT PERMISSIONS DEPARTMENT, Green Hill Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. The ideas and opinions expressed in The Oncology Nurse-APN/PA® do not necessarily reflect those of the Editorial Board, the Editorial Director, or the Publisher. Publication of an advertisement or other product mentioned in The Oncology Nurse-APN/PA® should not be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturer with questions about the features or limitations of the products mentioned. Neither the Editorial Board nor the Publisher assumes any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this periodical. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosage, the method and duration of administration, or contraindications.

It is the responsibility of the treating physician or other healthcare professional, relying on independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Every effort has been made to check generic and trade names, and to verify dosages. The ultimate responsibility, however, lies with the prescribing physician. Please convey any errors to the Editorial Director.

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Kyprolis® (carfilzomib) for Injection

Now Has a Permanent J Code: J9047

Takes Flight

For more information Visit KYPROLIS.com/HCP

Onyx, Onyx Pharmaceuticals, Onyx Pharmaceuticals logo, Kyprolis and Kyprolis logo are all trademarks of Onyx Pharmaceuticals, Inc. www.TheOncologyNurse.com

©2013 Onyx Pharmaceuticals, Inc., South San Francisco, CA SEPTEMBER/OCTOBER 1112-CARF-436R1 2014 December 2013 I VOL 7, NO 5 7

GENETIC COUNSELING

What Is PALB2?

RAD51.2 Similar to other genes in the BRCA2 pathway, biallelic inactivation of PALB2 (ie, mutation in both copies of the gene) results in Fanconi anemia, whereas a heterozygous germline mutation (ie, mutation in one copy of the gene) increases an individual’s risk for cancer.

The first PALB2 truncating mutations in familial breast cancer families were identified in 2007,3,4 and mutations have been identified in individuals of various descents, including African American, Australian, Chinese, Finnish, FrenchCanadian, German, Italian, Polish, Russian, South African, and Spanish.5-16 Most studies have focused on mutations found in familial and early-onset breast cancer cases in which mutation prevalence has ranged from 0.4% to 3.4%17 and risk of breast cancer has ranged from 2- to 4-fold.3,8 An association with pancreatic cancer has also been observed in both men and women, but risk estimates are poorly defined.18,19 With the exception of a few particular mutations in PALB2, previous studies have primarily provided risk in terms of relative risk. It is important to recall that “fold” is usually a measure of relative risk—it is the ratio of the probabilities of 2 absolute risks. For example, a 2-fold risk may imply that a group with the PALB2 mutation has twice as great a chance of developing breast cancer as the group without the mutation in the popula-

Continued from cover

tion studied.20 How often does a woman present to genetic counseling inquiring about relative risk? The typical question is a variation of: “What is my chance of developing breast cancer and/or a second breast cancer?” This question is one of absolute risk. The NEJM article is the first article to broadly address the absolute risk of breast cancer conferred by PALB2 mutations. The researchers behind this article found that the risk of breast cancer for PALB2 female mutation carriers by age 70 ranges from 33% to 58%, depending on family history, and provide a table depicting breast cancer risk by age and family history.1 When age 80 is used as lifetime risk, the range is 41% to 67%.

Furthermore, this same article estimated the risk of breast cancer in men with PALB2 mutations at just over 8-fold.

The availability of absolute risk data for PALB2 provides useful information for genetic counseling. For one, the upper risk range of PALB2 overlaps with the risk range of the well-described gene BRCA2.

Thus, it is reasonable to consider PALB2 testing whenever BRCA2 testing is indicated. Additionally, the lower risk range to age 70 is at the risk level for which guidelines suggest annual surveillance via breast magnetic resonance imaging (MRI). Therefore, even in the absence of extensive family history, a female with a PALB2 mutation may be a candidate for breast MRI.21 However, as with any genetic counseling session, other factors,

Cristi Radford, MS, CGC

Tuya Pal, MD, FABMG

such as mutation-specific information, must be taken into account when presenting risk and management options.

There are data suggesting that certain mutations in PALB2 may have a more aggressive phenotype and lower associated survival.22 For women with these particular mutations, it may be important to consider risk-reducing mastectomies if these findings are confirmed.

Additionally, the penetrance of certain mutations may be higher. For example, in 2010, an Australian study reported that a mutation in PALB2 conferred a breast cancer risk of 91% to age 70.6 PALB2 mutations may also have therapeutic significance, as it has been demonstrated that PALB2-deficient cells are sensitive to PARP inhibitors.23 All of these findings could have an impact on a PALB2 carrier’s surveillance and management options. However, to translate these findings into clinical practice, prospective studies of PALB2 mutation carriers are needed to refine the clinical pheno-

type and determine optimal cancer risk management and treatment options to improve patient outcomes.

Take-Home Messages • Depending on family history, women with a PALB2 mutation have a 41% to 67% risk of breast cancer to age 80.

There is also an 8-fold risk of breast cancer in men as well as a reported association with pancreatic cancer in both men and women.

• Although previous studies suggest mutations in PALB2 are rare, the mutation prevalence remains unclear; regardless, this new article suggests that the impact to individuals carrying a PALB2 mutation is high. Identifying PALB2 carriers may lead to tailored surveillance and medical management.

• As the lifetime breast cancer risk for PALB2 carriers overlaps BRCA2, it is reasonable to consider testing for PALB2 mutations when BRCA2 testing is offered or in individuals who

CONFERENCE NEWS: ASCO Continued from cover

Exemestane Plus Ovarian Suppression a Valid Option in Premenopausal Early Breast Cancer The aromatase inhibitor exemestane was superior to tamoxifen when combined with ovarian function suppression (OFS) in preventing recurrence in premenopausal women with hormone-sensitive breast cancers. These were the findings of a joint analysis of 2 important phase 3 clinical trials, TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial), that were presented at the American Society of Clinical Oncology 2014 annual meeting and published simultaneously in the New England Journal of Medicine.1,2 Lead author, Olivia Pagani, MD, explained that up until now exemestane has been used only in postmenopausal women. “This analysis demonstrates that an aromatase inhibitor is effective adjuvant therapy for premenopausal women when combined with ovarian suppression. Exemestane [plus OFS] is a valid alternative to tamoxifen [plus OFS] in young women with hormone-sensitive disease. It is a new adjuvant treatment option that reduces recurrence in this setting,” she stated. Pagani is clinical direcContinued on page 11

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SEPTEMBER/OCTOBER 2014 I VOL 7, NO 5

“This analysis demonstrates that an aromatase inhibitor is effective adjuvant therapy for premenopausal women when combined with ovarian suppression.”

Olivia Pagani, MD

Photo by © ASCO/Silas Crews 2014.

www.TheOncologyNurse.com

GENETIC COUNSELING

previously tested negative for BRCA mutations.

• It is important to conduct large-scale prospective studies of PALB2 carriers to further define cancer risks and optimize cancer risk management and treatment options. l

Drs Steven Narod, Kelly Metcalfe, and Tuya Pal, together with the ICARE study team, are in the process of recruiting 500 PALB2 mutation carriers to determine breast cancer characteristics and outcomes. Only through these types of research efforts will we be able to learn more about this important gene and figure out how to help those with mutations. Please contact us through our website (inheritedcancer.net), email (ICARE@inheritedcancer.net), or phone (813-745-6446) if you have a patient with a PALB2 mutation who may be interested in participating in this effort.

References

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1. Antoniou AC, Casadei S, Heikkinen T, et al. Breastcancer risk in families with mutations in PALB2. N Engl J Med. 2014;371(6):497-506.

2. Zhang F, Ma J, Wu J, et al. PALB2 links BRCA1 and BRCA2 in the DNA-damage response. Curr Biol.

2009;19(6):524-529.

3. Rahman N, Seal S, Thompson D, et al. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet. 2007;39(2):165167.

4. Foulkes WD, Ghadirian P, Akbari MR, et al.

Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French-Canadian women. Breast Cancer Res. 2007;9(6):R83.

5. Ding YC, Steele L, Chu LH, et al. Germline mutations in PALB2 in African-American breast cancer cases. Breast Cancer Res Treat. 2011;126(1):227-230.

6. Southey MC, Teo ZL, Dowty JG, et al; kConFab for the Breast Cancer Family Registry. A PALB2 mutation associated with high risk of breast cancer. Breast Cancer Res. 2010;12(6):R109.

7. Cao AY, Huang J, Hu Z, et al. The prevalence of PALB2 germline mutations in BRCA1/BRCA2 negative Chinese women with early onset breast cancer or affected relatives. Breast Cancer Res Treat.

2009;114(3):457-462.

8. Erkko H, Xia B, Nikkilä J, et al. A recurrent mutation in PALB2 in Finnish cancer families. Nature.

2007;446(7133):316-319.

9. Kuusisto KM, Bebel A, Vihinen M, et al. Screening for BRCA1, BRCA2, CHEK2, PALB2, BRIP1, RAD50, and CDH1 mutations in high-risk Finnish BRCA1/2-founder mutation-negative breast and/ or ovarian cancer individuals. Breast Cancer Res. 2011;13(1):R20.

10. Pern F, Bogdanova N, Schürmann P, et al. Mutation analysis of BRCA1, BRCA2, PALB2 and BRD7 in a hospital-based series of German patients with triple-negative breast cancer. PLoS One. 2012;7(10):e47993.

11. Ghadirian P, Robidoux A, Zhang P, et al. The contribution of founder mutations to early-onset breast cancer in French-Canadian women. Clin Genet.

2009;76(5):421-426.

12. Bogdanova N, Sokolenko AP, Iyevleva AG, et al. PALB2 mutations in German and Russian patients with bilateral breast cancer. Breast Cancer Res Treat.

2011;126(2):545-550.

13. Balia C, Sensi E, Lombardi G, et al. PALB2: a novel inactivating mutation in a Italian breast cancer family.

Fam Cancer. 2010;9(4):531-536.

14. Dansonka-Mieszkowska A, Kluska A, Moes J, et al.

A novel germline PALB2 deletion in Polish breast and ovarian cancer patients. BMC Med Genet. 2010;11:20.

15. Sluiter M, Mew S, van Rensburg EJ. PALB2 sequence variants in young South African breast cancer patients. Fam Cancer. 2009;8(4):347-353.

16. García MJ, Fernández V, Osorio A, et al. Analysis of FANCB and FANCN/PALB2 fanconi anemia genes in BRCA1/2-negative Spanish breast cancer families.

Breast Cancer Res Treat. 2009;113(3):545-551.

17. National Cancer Institute. Genetics of Breast and Ovarian Cancer PDQ. http://www.cancer. gov/cancertopics/pdq/genetics/breast-and-ovarian/ HealthProfessional/page3#Section_1322. Modified July 11, 2014. Accessed August 25, 2014.

18. Tischkowitz MD, Sabbaghian N, Hamel N, et al. Analysis of the gene coding for the BRCA2interacting protein PALB2 in familial and sporadic pancreatic cancer. Gastroenterology. 2009;137(3):11831186.

19. Jones S, Hruban RH, Kamiyama M, et al. Exomic sequencing identified PALB2 as a pancreatic cancer susceptibility gene. Science. 2009;324(5924):217.

20. Radford C. Inherited cancer risk statistics: absolute risk versus relative risk. The Oncology Nurse-APN/PA. 2012;5(11):1, 28.

21. Murphy CD, Lee JM, Drohan B, et al. The American Cancer Society guidelines for breast screening with magnetic resonance imaging: an argument for genetic testing. Cancer. 2008;113(11):3116-3120.

22. Heikkinen T, Kärkkäinen H, Aaltonen K, et al. The breast cancer susceptibility mutation PALB2 1592delT is associated with an aggressive tumor phenotype. Clin Cancer Res. 2009;15(9):3214-3222.

23. Buisson R, Dion-Côté AM, Coulombe Y, et al. Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination. Nat Struct Mol Biol. 2010;17(10):12471254.

SEPTEMBER/OCTOBER 2014 I VOL 7, NO 5

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Now enrolling: MURANO study Investigating the Selective BCL-2 Inhibitor GDC-0199/ABT-199 in Chronic Lymphocytic Leukemia GDC-0199/ABT-199 is an investigational agent that has not been approved by regulatory agencies.

A Phase III Study of GDC-0199/ABT-199 Plus Rituximab Compared With Bendamustine Plus Rituximab in Patients With Relapsed or Resistant Chronic Lymphocytic Leukemia (CLL)

GDC-0199/ABT-199 + rituximab

Phase III Relapsed or resistant CLL (N=370)

GDC-0199/ABT-199 continued for 2 years or until disease progression

Bendamustine + rituximab Randomize Primary Endpoint

Secondary Endpoints

• Investigator-assessed progression-free survival, defined as time from randomization until disease progression or death from any cause

• Overall response rate • Incidence of adverse events

Key Inclusion Criteria

Key Exclusion Criteria

• Adult patients ≥18 years of age • Diagnosis of CLL per diagnostic criteria and relapsed or refractory CLL per the iwCLL guidelines • Previously treated with 1-3 lines of therapy (eg, completed ≥2 treatment cycles per therapy), including ≥1 standard chemotherapy-containing regimen • Previously treated with bendamustine, only if duration of response was ≥24 months • ECOG performance status of 0-1 • Adequate bone marrow function • Adequate renal and hepatic function

• Transformation of CLL to aggressive non-Hodgkin lymphoma or CNS involvement by CLL • Undergone an allogenic stem-cell transplant • A history of significant renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease • Hepatitis B, hepatitis C, or known HIV-positive • Receiving warfarin treatment • Received an anti-CLL monoclonal antibody within 8 weeks prior to the first dose of study drug • Received any anticancer or investigational therapy within 14 days prior to the first dose of study drug or has not recovered from previous therapy • Received CYP3A4 inhibitors (such as fluconazole, ketoconazole and clarithromycin) or inducers (such as rifampin, carbamezapine, phenytoin, St John’s Wort) within 7 days prior to the first dose of GDC-0199/ABT-199 • Prior GDC-0199/ABT-199 treatment

To learn more about this study, please visit www.ClinicalTrials.gov (NCT02005471, GO28667) or call the Trial Information Support Line at 1-888-662-6728.

GDC-0199/ABT-199 is being codeveloped by AbbVie and Genentech, a member of the Roche Group.

© 2014 Genentech USA, Inc. All rights reserved. BIO0002506000 Printed in USA.

Reference: ClinicalTrials.gov, as of 5/2014.

A2396579

CONFERENCE NEWS: ASCO Continued from page 8

Exemestane Plus Ovarian Suppression a Valid Option in Premenopausal Early Breast Cancer tor of the Breast Unit at the Oncology Institute of Southern Switzerland in Bellinzona.

OFS is used more frequently in Europe than in the United States to achieve low estrogen levels in patients with hormone-sensitive breast cancer.

Tamoxifen is considered the standard of care in this setting, and adjuvant chemotherapy is sometimes used depending on the judgment of the oncologist and patient preference.

Both SOFT and TEXT compared 5 years of tamoxifen plus OFS versus 5 years of exemestane plus OFS. SOFT was a 3-arm trial comparing both of those treatment approaches versus tamoxifen alone; results of the tamoxifen-alone arm have not yet been analyzed, so it is currently not possible to determine if tamoxifen alone is superior, equal, or inferior to hormonal therapy plus OFS. The joint analysis of SOFT and TEXT included 4690 patients from both trials enrolled in the OFScontaining arms.

Chemotherapy was given at the discretion of the treating physician, and

42.6% did not receive chemotherapy.

About 28% of the women who did not get chemotherapy had tumors larger than 2 cm and some positive nodes. In a separate interview, Pagani said that the study suggests that exemestane plus OFS could replace chemotherapy in some patients.

“Our study suggests that for hormonesensitive tumors, go for exemestane and OFS and you can avoid chemotherapy,” Pagani stated.

At a median follow-up of 68 months, 5-year disease-free survival was 91.1% with exemestane plus OFS versus 87.3% in the tamoxifen plus OFS group (P < .001). The 5-year rate of freedom from breast cancer was 92.8% in the exemestane-treated patients compared with 88% in those who received tamoxifen (P < .001). Among patients who did not receive chemotherapy and were treated with exemestane plus OFS, 97.6% of those in the TEXT population and 97.5% of those in the SOFT population were free of breast cancer at 5 years.

The 5-year rate of freedom from recurrence at a distant site was 93.8%

The 5-year rate of freedom from recurrence at a distant site was 93.8% in the exemestane plus OFS group compared with 92% in the tamoxifen plus OFS group.

in the exemestane plus OFS group compared with 92% in the tamoxifen plus OFS group. At 5 years, overall survival was 95.9% in the exemestane group and 96.9% in the tamoxifen group. However, it is premature to determine survival, Pagani said.

Side effects of both drugs were as expected. Adverse events that were more frequent with exemestane includ-

ed fractures, musculoskeletal symptoms, vaginal dryness, decreased libido, and dyspareunia; those more frequently reported with tamoxifen included thromboembolic events, hot flushes, night sweats, and urinary incontinence.

Gynecologic cancers were reported in 7 exemestane-treated patients and in 9 patients in the tamoxifen group; endometrial cancers occurred in 2 and 5 patients, respectively. About 30% of patients in both arms experienced grade 3 or 4 adverse events.

Experts said that they were awaiting results of the tamoxifen-alone arm of the TEXT trial to see whether these findings would be practice changing. l References

1. Pagani O, Regan MM, Walley B, et al. Randomized comparison of adjuvant aromatase inhibitor (AI) with exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): joint analysis of IBCSG TEXT and SOFT trials. Presented at: 50th Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2014; Chicago, IL. Abstract LBA1.

2. Pagani O, Regan MM, Walley BA, et al; the TEXT and SOFT Investigators and the International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer.

N Engl J Med. 2014;371(2):107-118.

Goserelin Preserves Ovarian Function in Premenopausal Women With Breast Cancer The addition of goserelin to chemotherapy was shown to preserve ovarian function, fertility, and the ability to have a successful pregnancy in premenopausal women with hormone receptor–negative (HR–) early breast cancer, according to results of the Prevention of Early Menopause Study (POEMS), an international Intergroup trial coordinated by the Southwest Oncology Group. The study was presented as a late-breaking oral abstract during the American Society of Clinical Oncology 2014 annual meeting.

“This is the first demonstration of fertility prospects and more successful pregnancies in women with breast cancer. Premenopausal women with HR– breast cancer should be offered this option,” stated lead author Halle Moore, MD, of the Cleveland Clinic in Ohio.

Goserelin and other luteinizing hormone-releasing hormone (LHRH) analogs shut down ovarian function and put patients in a postmenopausal state.

The goal of using this drug is to protect the ovaries during chemotherapy.

Ovarian failure was the primary end point of the study and was defined as amenorrhea for the prior 6 months and postmenopausal levels of follicle-stimulating hormone (FSH). The investigators also assessed disease-free survival (DFS) and overall survival (OS).

The study, which was conducted from February 2004 to May 2011, randomized 257 premenopausal women (median age, 38 years) with stage I-IIIA HR– breast cancer to treatment with cyclophos-

www.TheOncologyNurse.com

phamide-containing chemotherapy (standard arm) or the same chemotherapy plus goserelin given as monthly injections starting 1 week before chemotherapy.

More than 90% got anthracycline-containing chemotherapy, and cancer stage distribution was similar in the 2 arms. Endocrine toxicity was twice as high in the goserelin arm compared with chemotherapy and included hot flashes, mood swings, dry vagina, and headache.

At 2 years, ovarian failure occurred in 22% of the chemotherapy arm versus 8% of the goserelin arm (P = .04). Regardless of stratification factors, goserelin achieved a lower rate of ovarian failure.

The 2-year rate of ovarian dysfunction was also significantly lower in the goserelin arm: 33% with standard chemotherapy versus 14% with goserelin (P = .03). Goserelin did not increase the risk of any complications or terminations of pregnancy compared with chemotherapy alone.

Eighteen patients in the standard chemotherapy arm and 25 in the goserelin arm tried to become pregnant. Women in the goserelin arm were about 2.5 times more likely to conceive. Successful pregnancies were reported in 12 patients (11%) in the standard chemotherapy arm and 22 (21%) in the goserelin arm. Live births were reported in 8 patients in the standard chemotherapy arm (7%, 12 babies) and 15 patients in the goserelin arm (15%, 18 babies; P = .03). Goserelin did not increase the risk of any complications or terminations of pregnancy compared with chemotherapy alone.

Unexpectedly, goserelin also improved DFS and OS. The 4-year DFS rate was 78% in the standard chemotherapy arm and 89% in the goserelin arm (P = .04), and 4-year OS was 82% versus 92%, respectively (P = .06).

The study had some limitations, however, including missing data for 38% of patients, but Moore said this is the largest randomized study of LHRH agonist use for ovarian protection in HR– breast cancer, and it is the most informative study reporting pregnancy outcomes with an LHRH analog during chemotherapy. l

Halle Moore, MD

Photo by © ASCO/Scott Morgan 2014.

Reference

Moore HCF, Unger JM, Phillips K-A, et al. Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: an international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance). Presented at: 50th Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2014; Chicago, IL. Abstract LBA505.

Continued on page 12

SEPTEMBER/OCTOBER 2014 I VOL 7, NO 5

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CONFERENCE NEWS: ASCO Continued from page 11

Benefits of Weight Loss in Breast Cancer Two studies explored the beneficial effects of exercise and weight loss, one study in healthy women and another in breast cancer survivors.

The first study, SHAPE-2,1 found that active postmenopausal women (those who exercised and restricted their calories) had up to a 25% risk reduction in breast cancer compared with inactive women.

Both exercise plus diet and diet alone achieved the same magnitude of weight loss, but the exercise group had more robust effects on body composition and physical fitness.

Lead investigator was Anne Maria May, PhD, of the Julius Center for Health Sciences and Primary Care at the University Medical Center Utrecht in the Netherlands.

SHAPE-2 enrolled 243 inactive, overweight, nonsmoking women from the Netherlands. After a 4- to 6-week run-in period during which participants followed a standardized diet, participants were randomly assigned to a diet group (n=97), an exercise plus some caloric restriction group (n=98), or a stable-weight control group (n=48). The study period was 16 weeks.

The diet intervention entailed caloric reduction of 500 kcal per day. The exercise intervention consisted of 4 hours of moderate to vigorous resistance and endurance exercise per week plus reduced caloric intake by 250 kcal per day. The goal of both interventions was a weight loss of 5 kg to 6 kg; control participants were instructed to maintain their body weight.

The primary outcome measure of this study was change in serum levels of sex hormones at 16 weeks. Both intervention groups had similar demographic characteristics, with a mean age of 60 years and mean body mass index of 29 kg/m2.

Both interventions met the primary end point for weight loss compared to controls (P < .001), while the weight remained stable in the control arm.

The exercise intervention group also achieved significant reductions in serum estradiol, free estradiol, and serum testosterone compared with controls (only free estradiol was lower in the diet group), and both intervention groups showed an increase in sex hormone–binding glob-

(LEAN) study,2 presented by Melinda Irwin, PhD, MPH, of Yale University in New Haven, Connecticut, explored the effects of weight loss on inflammatory and metabolic biomarkers in breast cancer survivors.

The LEAN study enrolled 100 overweight or obese breast cancer patients: 33 were assigned to usual care and were given American Institute for Cancer Research (AICR) nutrition and activity brochures as well as a 30-minute weightloss counseling session at 6 months; 67 women were assigned to receive eleven 30-minute weight-loss counseling sessions (either in person or by telephone) over 6 months. The goal of the intervention was

Both exercise plus diet and diet alone achieved the same magnitude of weight loss, but the exercise group had more robust effects on body composition and physical fitness.

ulin compared with controls (P < .025).

When findings were adjusted for the percentage change in body fat, however, the effects were attenuated or eliminated.

Patients who exercised showed significantly greater changes compared with the diet group for body weight, body fat, lean mass preservation, and physical fitness as measured by peak VO2 levels (all, P < .001).

The Lifestyle, Exercise, and Nutrition

10% weight loss, 150 minutes of physical activity per week, and 10,000 steps per day.

Fifty-two women (78%) completed the weight-loss counseling intervention compared with 29 women (88%) in the usualcare group. Participants were a mean age of 59 years and were overweight, physically inactive, highly educated, and postmenopausal, with a mean time since diagnosis of 2.8 years. Most women

were non-Hispanic white, had stage I-II breast cancer, and were taking hormone therapy.

Women in the intervention group (whether counseled by phone or in person) lost significantly more weight than those in the usual-care group (6% weight loss vs 2% weight loss, respectively).

Irwin said the women were motivated to lose weight and that is why they entered the study. It seems that motivation helped prevent weight gain, even in the usual-care group, she noted.

The telephone and in-person counseling groups were combined for analysis of effects on biomarkers. The diet groups achieved a 30% decrease in C-reactive protein, a marker of inflammation, versus 1% in the usual-care group; they also had greater decreases in insulin, glucose, leptin, and TNF-alpha and increases in adiponectin, IL-6, and IGF-1 compared to those receiving usual care.

The more weight loss the better, in this study. Women who lost more than 5% of body weight had more beneficial changes in these factors than women who lost less than 5% of body weight. l

References

1. May AM, van Gemert W, Peeters P, et al. Effects of equivalent weight loss, with or without exercise, on sex hormones related to breast cancer risk in postmenopausal women: the SHAPE-2 trial. Presented at: 50th Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2014; Chicago, IL. Abstract 1504.

2. Loftfield E, Harrigan M, Li F, et al. Effect of weight loss intervention on inflammatory and metabolic markers in breast cancer survivors: the lifestyle, exercise, and nutrition (LEAN) study. Presented at: 50th Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2014; Chicago, IL. Abstract 1505.

Loratadine and Bone Pain Pegfilgrastim, which mobilizes white blood cells that fight infection, is indicated by the US Food and Drug Administration for the treatment of cancer patients with nonmyeloid malignancies who are receiving anticancer drugs that are associated with clinically significant febrile neutropenia.1 Although pegfilgrastim is a highly effective drug, about half of the patients who receive it experience moderate to severe bone pain that can interfere with quality of life and compromise adherence to treatment.2 “The mechanism of this bone pain is unclear,” said Joanna Schwartz, PharmD, BCOP, of Albany College of Pharmacy and Health Sciences in Colchester, Vermont, one of the authors of a phase 2 pilot study of loratadine for the prevention of pegfilgrastim-induced bone pain (PIP). Lead author was Julia Moukharskaya, MD, of the University of Vermont College of Medicine in Burlington.

Schwartz noted that granulocyte colony-stimulating factor (G-CSF)–induced bone marrow expansion of white blood cell precursors has been associated with histamine release and possibly pain.

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SEPTEMBER/OCTOBER 2014 I VOL 7, NO 5

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen have not been highly effective in studies of treatment of PIP. Based on anecdotal evidence, the investigators postulated that the antihistamine loratadine could be an effective treatment for PIP. Disappointingly, loratadine failed to have an impact in this phase 2 pilot study.

The prospective, randomized, placebo-controlled trial enrolled 227 patients undergoing pegfilgrastim treatment who were observed for the development of clinically significant PIP, which was defined as a score of 5 or higher on the Brief Pain Inventory instrument, with a 2-point or greater increase from baseline after an initial dose of pegfilgrastim. Of these, 65 patients developed PIP and were eligible for randomization, with 45 of them going on to be randomized to loratadine 10 mg or placebo daily for 7 days, initiated on day 1 of pegfilgrastim administration.

Twenty patients dropped out of the study because they did not receive further pegfilgrastim, leaving

25 for evaluation (13 in the loratadine group and 12 in the placebo group). Patients randomized to loratadine achieved 59% improvement in PIP from baseline compared with 54.5% for placebo, which was not significantly different.

Results remained the same after data were adjusted for use of rescue analgesics, including NSAIDs and non-NSAIDs. “This proves the value of confirming pilot studies. Based on this study, loratadine should not be used to treat PIP. However, a prophylactic study with loratadine versus naproxen use starting the day prior to pegfilgrastim is ongoing, and may guide a future role for this agent in the treatment of PIP,” Schwartz said. l References

1. Neulasta [package insert]. Thousand Oaks, CA: Amgen Inc; February 2014.

2. Moukharskaya J, Abrams DM, Khan FB, et al. Randomized phase II pilot study of loratadine for the prevention of bone pain caused by pegfilgrastim. Presented at: 50th Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2014; Chicago, IL. Abstract 9628.

www.TheOncologyNurse.com

NOTEWORTHY NUMBERS

Breast Cancer Awareness National Breast Cancer Awareness Month (NBCAM) originated in October 1985 when the American Cancer Society (ACS) partnered with the pharmaceutical division of Imperial Chemical Industries, now part of AstraZeneca, to sponsor a weeklong event. Today, the ACS is only one of many public and private organizations that help sponsor NBCAM programs in the United States, and Breast Cancer Awareness Month is now observed worldwide to help support awareness, early detection, and treatment.

•T he first Susan G. Komen Race for the Cure was held in Dallas, Texas, in 1983 with 800 participants.

By 2002, races were being held in more than 100 US cities and 2 foreign countries, with more than 1.3

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Belgium, Georgia, Germany, Greece, Italy, and Tanzania. Recognizing that breast cancer is a global disease that requires local solutions based on differences in cultures, healthcare systems, and economic conditions, International Komen Race for the Cure events are unique in each country.1 •S ome aspects of the US approach to breast cancer have had global influence. The first support program for breast cancer patients, Reach to Recovery, was founded in 1952 by Terese Lasser, became an official program of the ACS in 1969, and was adopted in Europe in 1974.2 Traditionally, physicians in Poland opposed patient involvement, but Zbigniew Wronkowski, MD, and Krystyna Mika, PhD, at the Centre of Oncology in Warsaw started a small (only 3 women!) support group focused on rehabilitation.

Not until the mid 1990s, however, did Polish physicians begin to accept the patient-to-patient support model.2 Breast cancer survivors became known as “Amazons,” and in 1993, the Polish Federation of Breast Cancer Support Groups— Amazons was organized. By 2010 there were more than 200 Amazon groups with over 15,000 members.3

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million participants. In 2014, plans include over 150 races worldwide.

Events are planned for the Bahamas,

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• I n Australia, the Pink Lady icon is a symbol for breast cancer awareness.

Last October, Breast Cancer Network Australia organized the presentation of a Tribute Field of Women, for which 15,000 Pink Lady silhouettes, representing the estimated 15,000 Australian women who would be diagnosed with breast cancer in 2013, were placed in Bennelong Lawn in the Royal Botanic Gardens, near the Sydney Opera House.4 • I n 1992, Evelyn H. Lauder, then Senior Corporate Vice President, launched the Estée Lauder Companies Breast Cancer Awareness (BCA) Campaign.

In 2000, the “Global Landmarks Illumination Initiative” was created. Since then, historic landmarks around the world have been illuminated with pink lights annually in October. In 2010, the BCA Campaign illuminated 38 global sites, including the Taj Mahal, the Tokyo Tower, the Hotel Majestic in France, and the Empire State Building in New York City.5

WEST COAST REGIONAL MEETING WEST COAST REGIONAL MEETING May 18-20, 2015 May 18-20, 2015

Motif Seattle Hotel • Seattle, Washington Motif Seattle Hotel • Seattle, Washington

AONNonline.org/regionals/west-coast AONNonline.org/regionals/west-coast AONN2015WCAsize100214 AONN2015WCAsize100214

www.TheOncologyNurse.com

Sources 1. http://ww5.komen.org/AboutUs/GlobalReach.html.

2. http://pinkribbonblues.org/resources/beyond-aware ness-workbook/background/support-groups/.

3. http://www.reachtorecoveryinternational.org/bloom/.

4. http://www.bcna.org.au/news/2013-09/october-breastcancer-awareness-month.

5. http://www.elcompanies.com/Pages/The-LauderFamily.aspx.

SEPTEMBER/OCTOBER 2014 I VOL 7, NO 5

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THE WHOLE PATIENT

Sexuality Should Be Addressed With Cancer Patients Alice Goodman

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ancer and its treatments affect sexuality, but this is not typically discussed with patients.

Patients with cancer are often not forthcoming about sexuality, and nurses and other healthcare practitioners may not be comfortable raising the issue.

“A few simple questions [about sexuality] can improve the quality of life of our patients. You need to ask,” said Anne Katz, RN, PhD, clinical nurse specialist at CancerCare Manitoba in Winnipeg, Canada.

Speaking to an audience at the Oncology Nursing Society (ONS) 39th Annual Congress, Katz cited studies showing that younger nurses and those with less experience tended to be more uncomfortable with raising sexuality as an issue, while nurses who work in outpatient settings tend to be more comfortable and identified fewer barriers; nurses knew that their patients wanted to talk about this, but they were reluctant to do so; and 45% of cancer patients had never discussed sexuality with a healthcare provider.1

4. Fear of embarrassing self 5. Fear of offending patient 6. Denial of responsibility (the oncologist thinks it is the nurse’s duty, the nurse thinks it is the social worker’s duty, etc) 7. Institutional issues 8. Lack of awareness of guidelines even though ONS and American Society of Clinical Oncology (ASCO) state that discussions about sexuality are an important part of patient care.

“Some providers medicalize their interactions with patients by hiding behind their white coats. They may not bring up sexuality because it is not a life-and-death issue, and they may want to avoid this topic,” Katz noted.

The interval between cancer diagnosis and treatment initiation is an opportunity to prepare patients about what to expect in terms of impact on sexuality. During this interval, nurses can assess how patients view their current sex life and how important sexuality is to them. Unfortunately, studies suggest that most of the time the issue is never brought up.

“A few simple questions [about sexuality] can improve the quality of life of our patients. You need to ask.”

Anne Katz, RN, PhD

For nurses, barriers to communication included: 1. Lack of knowledge and lack of confidence 2. Avoidance of sexual assessment and intervention 3. Conservative attitudes

“We can start with anticipatory guidance, because pretreatment is a teachable moment. Keep this in mind. Their sex lives are not going to get better after treatment,” she said.

Several models for assessment of sexual health exist, including the

EX-PLISSIT model2 and the adapted version of the “5 A’s” originally designed to help smoking cessation3: Advise, Ask, Assess, Assist, and Arrange.

The interval between cancer diagnosis and treatment initiation is an opportunity to prepare patients about what to expect in terms of impact on sexuality.

Katz gave the following advice to the audience: Raise the issue of sexuality by explaining to the patient that you are concerned about quality of life and sexuality. Reassure patients that there are appropriate resources for them, and educate them about the sexual side effects of treatment. Always record your assessment and intervention in the patient’s chart.

Specific sexual challenges for patients with cancer include communication, arousal, and desire (libido), Katz continued.

“Communication lies at the root of all our relationships. Sexuality may not be discussed often by couples, and single survivors may not be open to disclosing a cancer history to people they are dating. Most couples get into a cycle of behavior about sex—what we call ‘sexual scripts.’ Cancer treatment takes away the reliability and the usual ‘sexual script,’ that is—the repetition of their sexual behavior,” she explained.

Couples whose coping styles are more rigid may be unable to be creative and

flexible emotionally and intellectually, so they have a hard time creating new ways of being sexual with each other.

“Cancer takes away spontaneity and requires couples to do things differently,” she explained.

If couples do not communicate about sex, the message is that the subject is taboo, she noted. “In some way, sexuality is where death and dying was 20 years ago.”

Desire is a complex phenomenon, especially in today’s society, where most people have very busy lives with little time for desire to surface. When it does, it may be fleeting. Even though desire is partly dependent on hormones, replacing hormones may not induce desire, especially for women, she said.

“If they ever find a pill to increase desire in women, it will be the best-selling drug ever! Problems with desire are related to assumptions about sexual response cycles. For some people, desire won’t happen spontaneously,” Katz told listeners.

Arousal is less complex, especially for men. Arousal is anatomical, physiological, and psychological. Cancer treatments can affect patients’ arousal.

The focus of pharmacologic interventions has been the blood vessels and nerves related to arousal.

Katz emphasized the need for open discussions with patients and including sexuality as part of those discussions.

This will go a long way toward preparing them for the sexual side effects of treatment and approaches that can help. l References

1. Katz A. Sexuality and cancer for the frontline nurse.

Presented at: Oncology Nursing Society 39th Annual Congress; May 1-4, 2014; Anaheim, CA. 2. Taylor B, Davis S. Using the extended PLISSIT model to address sexual healthcare needs. Nurs Stand.

2006;21(11):35-40.

3. Sanchez Varela V, Zhou ES, Bober SL. Management of sexual problems in cancer patients and survivors. Curr Probl Cancer. 2013;37(6):319-352.

HAVE YOU EVER WANTED TO WRITE AN ARTICLE FOR TON ?

We’re interested in articles about the everyday issues that affect nurses—everything from chemotherapy safe handling to supportive care for patients to challenging cases.

Contact editorial@greenhillhc.com for information.

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SIDE CANCER EFFECTS CENTER MANAGEMENT PROFILE

Vaginal DHEA May Improve Sexual Function in Women With Breast/Gynecologic Cancer Meg Barbor

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aginal dehydroepiandrosterone (DHEA) may improve sexual function, without negative systemic effects, in women with breast and gynecologic cancer with vaginal and sexual-related complaints.

Breast and gynecologic cancer patients can experience a range of symptoms associated with sexual dysfunction, among them vaginal dryness and dyspareunia. According to findings presented by Debra Barton, RN, PhD, AOCN, at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology 2014 annual meeting, effective treatment is needed for female sexual dysfunction associated with breast and gynecologic cancer, and vaginal DHEA has proven beneficial.

inal complaints present for no less than 2 months. This analysis of secondary physiological end points examined the impact of vaginal DHEA on vaginal health, hormone concentrations, bone turnover, and sexual function.

A total of 464 women were accrued from 82 sites; 21 withdrew prior to randomization and 2 could not classify worst symptom. The remaining women Table

small,” added Barton.

This study provided evidence of some systemic absorption of DHEA accompanied by hormone changes, although these changes were small and concentrations for all hormones still stayed in the lower normal ranges.

Based on the bone biomarker data, there was no indication of extravaginal effects of the DHEA. The adverse and

Results of FSFI Questionnairea

FSFI Subscale

No DHEA, mean

3.25-mg DHEA, mean

Desire

.2

.3

.5b

Arousal

.4

.7b

1.0b

1.1

1.3

3.0b

Orgasm

.7

.8

1.0

Satisfaction

.5

.9

1.1b

Pain

1.0

1.4b

2.0b

Overall total

3.8

5.5

7.1b

Lubrication

Current Interventions The vagina is highly regulated by estrogen. “When estrogen is depleted it leads to changes in vaginal tissues, resulting in a vagina that is dry, uncomfortable, and susceptible to infections,” said Barton, professor and the Mary Lou Willard French Endowed Chair in Oncology at the University of Michigan School of Nursing in Ann Arbor.

The focus of treatment for vaginal symptoms is local, noted Barton.

Current evidence-based interventions include lubricants, which are used solely for the purpose of reducing friction during intercourse, and vaginal moisturizers, which are used several times a week and for the purpose of hydrating vaginal tissue. Vaginal estrogen is the gold standard for treatment, but it is a last resort in women with cancer due to safety concerns. “There is a need for effective treatment without systemic estrogenic effects,” Barton said.

were randomized to study arms of 3.25 versus 6.5 mg of DHEA versus plain moisturizer (PM). DHEA was compounded into a bioadhesive vaginal moisturizer gel, which was designed to adhere to the vaginal wall. Women inserted the DHEA using a prefilled syringe nightly for 12 weeks, just before sleep and subsequent to any sexual activity. Laboratory tests, maturation index, and vaginal pH were evaluated at baseline and again at 12 weeks.

DHEA—A Possible Solution “One possible solution is DHEA,” said Barton. DHEA is a prohormone made by the adrenal gland. A prohormone has no known activity in and of itself but has to be converted, mostly in target tissue, to either estrogens or androgens. Previous work with DHEA has supported the hypothesis that when used vaginally it does not produce systemic effects.

Barton and her colleagues conducted a study on postmenopausal women with a history of breast/gynecologic cancer who had completed chemotherapy and radiation and had no evidence of disease. Women were eligible if they reported at least moderately severe vag-

Safety and Physiological Effects Blood samples were taken from the 147 women on each of the 3 study arms; a total of 47 women provided pre- and postvaginal tissue samples. Women in all arms experienced a decrease in pH, which is the desired direction, with a greater decrease in the DHEA arms.

While none in the control arm (who had levels >5 at baseline) achieved a pH 5, this lower level was achieved by 9% with DHEA 3.25 mg and 7% with DHEA 6.5 mg.

Vaginal cell maturation (no intermediate superficial cells vs some/any) was observed in 100% receiving DHEA 3.25 mg, 86% with DHEA 6.5 mg, and 64% with PM.

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Regarding systemic hormone concentrations, DHEA levels increased in each DHEA arm, significantly different from the PM group. However, while the increases were considered to be significant, these values at 12 weeks were not out of line with the normal range for women in that age group, Barton explained.

Bone biomarkers were essentially

6.5-mg DHEA, mean

Abbreviations: DHEA, dehydroepiandrosterone; FSFI, Female Sexual Function Index. a Higher numbers equal better function. b Statistically significant difference compared with no DHEA.

unchanged. “Based on our data, there is no evidence that vaginal DHEA was having effects on the bones,” she added. A lack of effect on bone markers indicates the absence of estrogenic activity.

DHEA—Did It Work?

In all arms, a significant reduction in the primary symptom was observed compared with baseline, with severity reduced by almost half, and there were no significant differences between the study arms.

“However, the 2 doses of DHEA did significantly improve sexual function, with the 6.5-mg dose improving every single subscale of sexual function except for orgasm,” Barton noted (Table).

Self-reported adverse effects included vaginal discharge, which was experienced by women in all 3 arms, as well as voice change experienced by women in the DHEA arms. “In concert possibly with the testosterone levels, we did see some evidence of androgenic side effects, with voice change being statistically different in the DHEA arms compared to moisturizer, although these differences are quite

physiological effects led to the hypothesis that vaginal DHEA is working through androgenic means at the site of the vagina, with only minor systemic androgenic effects.

Based on these data, Barton and her colleagues concluded that DHEA improved physiological vaginal health and overall female sexual function more than did PM alone. l

Previous work with DHEA has supported the hypothesis that when used vaginally it does not produce systemic effects.

Reference

Barton D, Sloan JA, Shuster LT, et al. Physiologic effects of vaginal dehydroepiandrosterone (DHEA): Alliance Trial N10C1. Presented at: 2014 Annual Meeting of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology; June 26-28, 2014; Miami, FL.

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For patients with bone metastases from solid tumors

Prevent bone complications longer In a prespecified integrated analysis of 3 pivotal trials (N = 5,723),

8.2

XGEVA® was proven to delay the median time to first bone complication by

months longer vs zoledronic acid1

XGEVA® is a convenient 120 mg subcutaneous injection administered once every 4 weeks.2

Bone complications, or skeletal-related events (SREs), are defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression.2,3 Median Time to First Bone Complication1 27.7

months

Data from a prespecified integrated analysis of three international, phase 3, double-blind, double-dummy, active-controlled trials comparing XGEVA® with zoledronic acid for the prevention of bone complications in patients with bone metastases from solid tumors or multiple myeloma.1

XGEVA VA® 120 mg Q4W (n = 2,862) VA

19.5

months

zoledronic acid 4 mg Q4W (n = 2,861) 1 YEAR

HR* = 0.83 (95% CI: 0.76-0.90)

2 YEARS

P < 0.001

†

IMPORTANT SAFETY INFORMATION Hypocalcemia • Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®. XGEVA® can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when XGEVA® is administered with other drugs that can also lower calcium levels. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.

• An increased risk of hypocalcemia has been observed in clinical trials of patients with increasing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis), and with inadequate/no calcium supplementation.

Monitor calcium levels and calcium and vitamin D intake.

Hypersensitivity • XGEVA® is contraindicated in patients with known clinically significant hypersensitivity to XGEVA®, including anaphylaxis that has been reported with use of XGEVA®.

Reactions may include hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue XGEVA® therapy permanently.

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*Hazard ratio (HR) is defined as the increase or decrease in likelihood of an event of interest (in this case a bone complication) for one group relative to that in a comparator group.

P value for superiority.

†

Drug Products with Same Active Ingredient • Patients receiving XGEVA® should not take Prolia® (denosumab).

Osteonecrosis of the Jaw • Osteonecrosis of the jaw (ONJ) can occur in patients receiving XGEVA®, manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials in patients with osseous metastasis, the incidence of ONJ was higher with longer duration of exposure.

• Perform an oral examination and appropriate preventive dentistry prior to the initiation of XGEVA® and periodically during XGEVA® therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with XGEVA®.

• Patients who are suspected of having or who develop ONJ while on XGEVA® should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.

Atypical Subtrochanteric and Diaphyseal Femoral Fracture • Atypical femoral fracture has been reported with XGEVA®.

These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution.

www.TheOncologyNurse.com

XGEVA® is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

XGEVA® is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.

• RANK Ligand (RANKL) is produced by bone cells in the skeleton and is a key mediator of bone resorption4 • RANKL production is increased at sites of bone metastases, and stimulates osteoclasts to destroy bone4 • XGEVA® acts precisely to bind RANKL and inhibits osteoclast formation, function, and survival2 • Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®2

Learn more at XGEVA.com

• Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. During XGEVA® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patient presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of XGEVA® therapy should be considered, pending a risk/benefit assessment, on an individual basis.

Embryo-Fetal Toxicity • XGEVA® can cause fetal harm when administered to a pregnant woman. Based on findings in animals, XGEVA® is expected to result in adverse reproductive effects.

©2014 Amgen Inc. All rights reserved. 04/14 80218-R1-V1

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• Advise females of reproductive potential to use highly effective contraception during therapy, and for at least 5 months after the last dose of XGEVA®. Apprise the patient of the potential hazard to a fetus if XGEVA® is used during pregnancy or if the patient becomes pregnant while patients are exposed to XGEVA®.

Adverse Reactions • The most common adverse reactions in patients receiving XGEVA® with bone metastasis from solid tumors were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction was dyspnea. The most common adverse reactions resulting in discontinuation were osteonecrosis and hypocalcemia.

Please see brief summary of Prescribing Information on the following page.

REFERENCES: 1. Lipton A, Fizazi K, Stopeck AT, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials.

Eur J Cancer. 2012;48:3082-3092. 2. XGEVA® (denosumab) prescribing information, Amgen. 3. Brodowicz T, O’Byrne K, Manegold C. Bone matters in lung cancer. Ann Oncol. 2012;23:2215-2222. 4. Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004;350:1655-1664.

www.XGEVA.com SEPTEMBER/OCTOBER 2014 I VOL 7, NO 5

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S:9.5”

Brief Summary: Consult package insert for complete Prescribing Information

Body System GASTROINTESTINAL Nausea Diarrhea GENERAL Fatigue/ Asthenia IN VESTIGATIONS Hypocalcemiab Hypophosphatemiab NEUROLOGICAL Headache RESPIRATORY Dyspnea Cough

Xgeva n = 2841 %

Zoledronic Acid n = 2836 %

31 20

32 19

45

46

18 32

9 20

13

14

21 15

18 15

Adverse reactions reported in at least 10% of patients receiving Xgeva in Trials 1, 2, and 3, and meeting one of the following criteria: • At least 1% greater incidence in Xgeva-treated patients, or • Between-group difference (either direction) of less than 1% and more than 5% greater incidence in patients treated with zoledronic acid compared to placebo (US Prescribing Information for zoledronic acid) b Laboratory-derived and below the central laboratory lower limit of normal [8.3 – 8.5 mg/dL (2.075 – 2.125 mmol/L) for calcium and 2.2 – 2.8 mg/dL (0.71 – 0.9 mmol/L) for phosphorus] Severe Mineral/Electrolyte Abnormalities • Severe hypocalcemia (corrected serum calcium less than 7 mg/dL or less than 1.75 mmol/L) occurred in 3.1% of patients treated with Xgeva and 1.3% of patients treated with zoledronic acid. Of patients who experienced severe hypocalcemia, 33% experienced 2 or more episodes of severe hypocalcemia and 16% experienced 3 or more episodes.

• Severe hypophosphatemia (serum phosphorus less than 2 mg/dL or less than 0.6 mmol/L) occurred in 15.4% of patients treated with Xgeva and 7.4% of patients treated with zoledronic acid.

Osteonecrosis of the Jaw In the primary treatment phases of Trials 1, 2, and 3, ONJ was confirmed in 1.8% of patients in the Xgeva group (median exposure of 12.0 months; range 0.1 – 40.5) and 1.3% of patients in the zoledronic acid group. The trials in patients with breast (Trial 1) or prostate (Trial 3) cancer included an Xgeva open label extension treatment phase where patients were offered Xgeva 120 mg once every 4 weeks (median overall exposure of 14.9 months; range 0.1 – 67.2). The patient-year adjusted incidence of confirmed ONJ was 1.1% during the first year of treatment and 4.1% thereafter. The median time to ONJ was 20.6 months (range: 4 – 53).

Atypical Subtrochanteric and Diaphyseal Fracture Atypical femoral fracture has been reported with Xgeva.

Postmarketing Experience. Because postmarketing 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.

The following adverse reactions have been identified during post approval use of Xgeva: • Hypocalcemia: Severe symptomatic hypocalcemia, including fatal cases.

• Hypersensitivity, including anaphylactic reactions.

• Musculoskeletal pain, including severe musculoskeletal pain. Positive rechallenge has been reported.

Immunogenicity. As with all therapeutic proteins, there is potential for immunogenicity. Using an electrochemiluminescent bridging immunoassay, less than 1% (7/2758) of patients with osseous metastases treated with denosumab doses ranging from 30 – 180 mg every 4 weeks or every 12 weeks for up to 3 years tested positive for binding antibodies. No patient with positive binding antibodies tested positive for neutralizing antibodies as assessed using a chemiluminescent cell-based in vitro biological assay. There was no evidence of altered pharmacokinetic profile, toxicity profile, or clinical response associated with binding antibody development. The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of a positive antibody (including neutralizing antibody) test result 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 antibodies to denosumab with the incidence of antibodies to other products may be misleading.

DRUG INTERACTIONS: No formal drug-drug interaction trials have been conducted with Xgeva. In clinical trials in patients with breast cancer metastatic to bone, Xgeva was administered in combination with standard anticancer treatment. Serum denosumab concentrations at 1 and 3 months and reductions in the bone turnover marker uNTx/Cr (urinary N-terminal telopeptide corrected for creatinine) at 3 months were similar in patients with and without prior intravenous bisphosphonate therapy.

There was no evidence that various anticancer treatments affected denosumab systemic exposure and pharmacodynamic effect. Serum denosumab concentrations at 1 and 3 months were not altered by concomitant chemotherapy and/or hormone therapy. The median reduction in uNTx/Cr from baseline to month 3 was similar between patients receiving concomitant chemotherapy and/or hormone therapy.

USE IN SPECIFIC POPULATIONS: Pregnancy: Category D. Risk Summary: Xgeva can cause fetal harm when administered to a pregnant woman based on findings in animals. In utero denosumab exposure in cynomolgus monkeys resulted in increased fetal loss, stillbirths, and postnatal mortality, along with evidence of absent lymph nodes, abnormal bone growth and decreased neonatal growth. There are no adequate and well-controlled studies with Xgeva in pregnant women. Women should be advised not to become pregnant when taking Xgeva. 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. Women who become pregnant during Xgeva treatment are encouraged to enroll in Amgen’s Pregnancy Surveillance Program. Patients or their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll.

Clinical Considerations: The effects of Xgeva are likely to be greater during the second and third trimesters of pregnancy. Monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester. If the patient becomes pregnant during Xgeva therapy, consider the risks and benefits in continuing or discontinuing treatment with Xgeva. a

Animal Data: The effects of denosumab on prenatal development have been studied in both cynomolgus monkeys and genetically engineered mice in which RANK ligand (RANKL) expression was turned off by gene removal (a “knockout mouse”).

In cynomolgus monkeys dosed subcutaneously with denosumab throughout pregnancy at a pharmacologically active dose, there was increased fetal loss during gestation, stillbirths, and postnatal mortality. Other findings in offspring included absence of axillary, inguinal, mandibular, and mesenteric lymph nodes; abnormal bone growth, reduced bone strength, reduced hematopoiesis, dental dysplasia and tooth malalignment; and decreased neonatal growth. At birth out to one month of age, infants had measurable blood levels of denosumab (22-621% of maternal levels). Following a recovery period from birth out to 6 months of age, the effects on bone quality and strength returned to normal; there were no adverse effects on tooth eruption, though dental dysplasia was still apparent; axillary and inguinal lymph nodes remained absent, while mandibular and mesenteric lymph nodes were present, though small; and minimal to moderate mineralization in multiple tissues was seen in one recovery animal. There was no evidence of maternal harm prior to labor; adverse maternal effects occurred infrequently during labor.

Maternal mammary gland development was normal. There was no fetal NOAEL (no observable adverse effect level) established for this study because only one dose of 50 mg/kg was evaluated. In RANKL knockout mice, absence of RANKL (the target of denosumab) also caused fetal lymph node agenesis and led to postnatal impairment of dentition and bone growth. Pregnant RANKL knockout mice showed altered maturation of the maternal mammary gland, leading to impaired lactation.

Nursing Mothers. It is not known whether Xgeva is excreted into human milk.

Measurable concentrations of denosumab were present in the maternal milk of cynomolgus monkeys up to 1 month after the last dose of denosumab (≤ 0.5% milk:serum ratio). Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Xgeva, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Maternal exposure to Xgeva during pregnancy may impair mammary gland development and lactation based on animal studies in pregnant mice lacking the RANK/RANKL signaling pathway that have shown altered maturation of the maternal mammary gland, leading to impaired lactation postpartum. However, in cynomolgus monkeys treated with denosumab throughout pregnancy, maternal mammary gland development was normal, with no impaired lactation. Mammary gland histopathology at 6 months of age was normal in female offspring exposed to denosumab in utero; however, development and lactation have not been fully evaluated.

Pediatric Use. Xgeva is not recommended in pediatric patients. The safety and effectiveness of Xgeva in pediatric patients have not been established. Treatment with Xgeva may impair bone growth in children with open growth plates and may inhibit eruption of dentition. In neonatal rats, inhibition of RANKL (the target of Xgeva therapy) with a construct of osteoprotegerin bound to Fc (OPG-Fc) at doses ≤ 10 mg/kg was associated with inhibition of bone growth and tooth eruption.

Adolescent primates treated with denosumab at doses 5 and 25 times (10 and 50 mg/kg dose) higher than the recommended human dose of 120 mg administered once every 4 weeks, based on body weight (mg/kg), had abnormal growth plates, considered to be consistent with the pharmacological activity of denosumab.

Cynomolgus monkeys exposed in utero to denosumab exhibited bone abnormalities, reduced hematopoiesis, tooth malalignment, decreased neonatal growth, and an absence of axillary, inguinal, mandibular, and mesenteric lymph nodes. Some bone abnormalities recovered once exposure was ceased following birth; however, axillary and inguinal lymph nodes remained absent 6 months post-birth.

Geriatric Use. Of patients who received Xgeva in Trials 1, 2, and 3, 1260 (44%) were 65 years of age or older. No overall differences in safety or efficacy were observed between these patients and younger patients.

Renal Impairment. Two clinical trials were conducted in patients without cancer and with varying degrees of renal function. In one study, patients (N=55) with varying degrees of renal function (ranging from normal through end-stage renal disease requiring dialysis) received a single 60 mg subcutaneous dose of denosumab. In a second study, patients (N=32) with severe renal dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis) were given two 120 mg subcutaneous doses of denosumab. In both studies, greater risk of developing hypocalcemia was observed with increasing renal impairment, and with inadequate/no calcium supplementation. Hypocalcemia was mild to moderate in severity in 96% of patients.

Monitor calcium levels and, calcium and vitamin D intake.

Females and Males of Reproductive Potential. Contraception Females: Counsel patients on pregnancy planning and prevention. Advise females of reproductive potential to use highly effective contraception during therapy, and for at least 5 months after the last dose of Xgeva. Advise patients to contact their healthcare provider if they become pregnant, or a pregnancy is suspected, during treatment or within 5 months after the last dose of Xgeva. Males: The extent to which denosumab is present in seminal fluid is unknown. There is potential for fetal exposure to denosumab when a male treated with Xgeva has unprotected sexual intercourse with a pregnant partner. Advise males of this potential risk.

OVERDOSAGE: There is no experience with overdosage of Xgeva.

HOW SUPPLIED/STORAGE AND HANDLING: Xgeva is supplied in a singleuse vial. Store Xgeva in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton. Do not freeze. Once removed from the refrigerator, Xgeva must not be exposed to temperatures above 25°C/77°F or direct light and must be used within 14 days. Discard Xgeva if not used within the 14 days. Do not use Xgeva after the expiry date printed on the label. Protect Xgeva from direct light and heat. Avoid vigorous shaking of Xgeva.

PATIENT COUNSELING INFORMATION: Advise patients to contact a healthcare professional for any of the following: • Symptoms of a hypersensitivity reaction, including rash, urticaria, pruritus, lip swelling, shortness of breath, hypotension and respiratory tract edema • Symptoms of hypocalcemia, including paresthesias or muscle stiffness, twitching, spasms, or cramps • Symptoms of ONJ, including pain, numbness, swelling of or drainage from the jaw, mouth, or teeth • Persistent pain or slow healing of the mouth or jaw after dental surgery • Symptoms of atypical femoral fracture, including new or unusual thigh, hip, or groin pain • Pregnancy or nursing Advise patients of the need for: • Avoiding therapy with Xgeva if a serious allergic reaction occurred with prior Xgeva or Prolia therapy • Proper oral hygiene and routine dental care • Informing their dentist that they are receiving Xgeva • Avoiding invasive dental procedures during treatment with Xgeva • The use of highly effective contraception during and for at least 5 months after treatment with Xgeva for females of reproductive potential Advise patients that denosumab is also marketed as Prolia®. Patients should inform their healthcare provider if they are taking Prolia.

Amgen Manufacturing Limited, a subsidiary of Amgen Inc. One Amgen Center Drive Thousand Oaks, California 91320-1799 ©2010-2014 Amgen Inc. All rights reserved.

Printed in USA.

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INDICATIONS AND USAGE: Bone Metastasis from Solid Tumors. Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

Important Limitation of Use. Xgeva is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.

DOSAGE AND ADMINISTRATION: Recommended Dosage. The recommended dose of Xgeva is 120 mg administered as a subcutaneous injection every 4 weeks in the upper arm, upper thigh, or abdomen. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia.

Preparation and Administration. Visually inspect Xgeva for particulate matter and discoloration prior to administration. Xgeva is a clear, colorless to pale yellow solution that may contain trace amounts of translucent to white proteinaceous particles. Do not use if the solution is discolored or cloudy or if the solution contains many particles or foreign particulate matter. Prior to administration, Xgeva may be removed from the refrigerator and brought to room temperature (up to 25°C/77°F) by standing in the original container. This generally takes 15 to 30 minutes. Do not warm Xgeva in any other way. Use a 27-gauge needle to withdraw and inject the entire contents of the vial. Do not re-enter the vial. Discard vial after single-use or entry.

CONTRAINDICATIONS: Hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating therapy with Xgeva.

Hypersensitivity. Xgeva is contraindicated in patients with known clinically significant hypersensitivity to Xgeva.

WARNINGS AND PRECAUTIONS: Drug Products with Same Active Ingredient. Xgeva includes the same active ingredient (denosumab) found in Prolia. Patients receiving Xgeva should not take Prolia.

Hypersensitivity. Clinically significant hypersensitivity including anaphylaxis has been reported with use of Xgeva. Reactions may include hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue Xgeva therapy permanently.

Hypocalcemia. Xgeva can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Correct pre-existing hypocalcemia prior to Xgeva treatment. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when Xgeva is administered with other drugs that can also lower calcium levels. In the postmarketing setting, severe symptomatic hypocalcemia has been reported. Advise patients to contact a healthcare professional for symptoms of hypocalcemia. An increased risk of hypocalcemia has been observed in clinical trials of patients with increasing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis), and with inadequate/no calcium supplementation. Monitor calcium levels and calcium and vitamin D intake.

Osteonecrosis of the Jaw. Osteonecrosis of the jaw (ONJ) can occur in patients receiving Xgeva, manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion.

Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials, in patients with osseous metastasis, the incidence of ONJ was higher with longer duration of exposure (see Adverse Reactions). Seventy-nine percent of patients with ONJ had a history of tooth extraction, poor oral hygiene, or use of a dental appliance as a predisposing factor. Perform an oral examination and appropriate preventive dentistry prior to the initiation of Xgeva and periodically during Xgeva therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with Xgeva. Patients who are suspected of having or who develop ONJ while on Xgeva should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.

Atypical Subtrochanteric and Diaphyseal Femoral Fracture. Atypical femoral fracture has been reported with Xgeva. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution. Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. During Xgeva treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patient presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of Xgeva therapy should be considered, pending a risk/benefit assessment, on an individual basis.

EMBRYO-FETAL TOXICITY: Xgeva can cause fetal harm when administered to a pregnant woman. Based on findings in animals, Xgeva is expected to result in adverse reproductive effects. In utero denosumab exposure in cynomolgus monkeys resulted in increased fetal loss, stillbirths, and postnatal mortality, along with evidence of absent peripheral lymph nodes, abnormal bone growth, and decreased neonatal growth (see Use in Specific Populations). Advise females of reproductive potential to use highly effective contraception during therapy, and for at least 5 months after with the last dose of Xgeva. Apprise the patient of the potential hazard to a fetus if Xgeva is used during pregnancy or if the patient becomes pregnant while patients are exposed to Xgeva. Advise patients to contact their healthcare provider if they become pregnant or a pregnancy is suspected during this time.

ADVERSE REACTIONS: The following adverse reactions are discussed below and elsewhere in the labeling: • Hypocalcemia • Osteonecrosis of the Jaw The most common adverse reactions in patients receiving Xgeva (per-patient incidence greater than or equal to 25%) were fatigue/asthenia, hypophosphatemia, and nausea (see Table 1). The most common serious adverse reaction in patients receiving Xgeva was dyspnea. The most common adverse reactions resulting in discontinuation of Xgeva were osteonecrosis and hypocalcemia.

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 other clinical trials and may not reflect the rates observed in practice. The safety of Xgeva was evaluated in three randomized, double-blind, double-dummy trials in which a total of 2841 patients with bone metastasis from prostate cancer, breast cancer, or other solid tumors, or lytic bony lesions from multiple myeloma received at least one dose of Xgeva. In Trials 1, 2, and 3, patients were randomized to receive either 120 mg of Xgeva every 4 weeks as a subcutaneous injection or 4 mg (dose adjusted for reduced renal function) of zoledronic acid every 4 weeks by intravenous (IV) infusion. Entry criteria included serum calcium (corrected) from 8 to 11.5 mg/dL (2 to 2.9 mmol/L) and creatinine clearance 30 mL/min or greater. Patients who had received IV bisphosphonates were excluded, as were patients with prior history of ONJ or osteomyelitis of the

jaw, an active dental or jaw condition requiring oral surgery, non-healed dental/ oral surgery, or any planned invasive dental procedure. During the study, serum chemistries including calcium and phosphorus were monitored every 4 weeks.

Calcium and vitamin D supplementation was recommended but not required. The median duration of exposure to Xgeva was 12 months (range: 0.1 – 41) and median duration on-study was 13 months (range: 0.1 – 41). Of patients who received Xgeva, 46% were female. Eighty-five percent were White, 5% Hispanic/Latino, 6% Asian, and 3% Black. The median age was 63 years (range: 18 – 93). Seventy-five percent of patients who received Xgeva received concomitant chemotherapy.

Table 1. Per-patient Incidence of Selecteda Adverse Reactions of Any Severity (Trials 1, 2, and 3)

BOOK REVIEW

The Myeloma Survival Guide Essential Advice for Patients and Their Loved Ones Beth Faiman, PhD(c), MSN, APRN-BC, AOCN Multiple Myeloma Nurse Practitioner, Taussig Cancer Institute, Cleveland Clinic

I

magine you’ve been feeling more tired lately, but you think, who isn’t? You work long hours at the office and at home. The fatigue becomes worse. After a battery of blood tests, the practitioner tells you the results. The anemia is caused by excess protein in the blood and has damaged your bones. The diagnosis is multiple myeloma (MM).

What is multiple myeloma? What does this diagnosis mean to me and my family?

Multiple myeloma is a cancer of the bone marrow plasma cells. Malignant plasma cells secrete clones of normal immunoglobulins that produce cytokines and attack the organs. Hallmarks of the cancer include hypercalcemia, anemia, renal insufficiency, and bone lesions.1 In 2014, approximately 24,000 patients will receive an MM diagnosis. As of 2011, an estimated 83,000 patients in the United States were living with this cancer.2 Although MM is largely incurable, overall survival has dramatically increased to 8 to 10 years, owing to the advent of newer thera-

pies.3,4 There is currently no standard of care for treatment of MM at diagnosis; thus, clinical trial participation is encouraged.

Given the chronic nature of MM, upon diagnosis patients and their caregivers immediately become concerned about the short- and long-term physical, financial, social, and societal issues.

Informed and proactive patients will strive to learn about the best treatment options, adverse effect management strategies, and what questions to ask.

Support groups, patient care organizations, and hospitals themselves provide resources. But until now, there has been no single source of information written by someone with firsthand knowledge of living with this cancer.

To fill this gap, a patient and caregiver have offered their unique perspectives by cowriting The Myeloma Survival Guide, in concert with Their Best Advice Foundation.5 Their intimate knowledge of living with cancer allowed the authors to highlight the common health and psychosocial concerns the patient experiences as well as

the resources to address them.

I had the opportunity to read the book, which is chock-full of resources to deal with common issues and answers frequently asked questions.

The reader navigates the “forest full of trees” that is living with MM and experiences “new normal” ways of life. Key areas highlighted include the aforementioned financial, social, and psychological issues, and all are appropriately addressed. This book is a practical guide for all patients and caregivers as they steer through the rapidly changing landscape of the myeloma diagnosis and treatment process.

The Myeloma Survival Guide is pragmatic and relevant. As nurses, APNs, and PAs, we strive to understand what the patient and family are going through. But only those who have dealt firsthand with the diagnosis can truly understand what it means to live with this disease. I highly recommend this book for patients and caregivers who would like to learn more about MM and the resources available. Feel free to go to www.tbafoundation.org

and share this information with your patients! l Visit http://www.demoshealth.com/ store/ to receive a 20% discount on The Myeloma Survival Guide.

During the checkout process, enter the discount code SSTON20. This code will allow purchasers to receive the 20% discount and free shipping for orders placed within the continental United States. The discount expires December 31, 2014.

References

1. Palumbo A, Rajkumar SV, San Miguel JF, et al.

International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol.

2014;32(6):587-600.

2. Howlander N, Noone AM, Krapcho M, et al (eds).

SEER Cancer Statistics Review (CSR) 1975-2011. http://seer.cancer.gov/csr/1975_2011/. Updated August 27, 2014. Accessed August 28, 2014.

3. Kurtin S, Faiman B. The changing landscape of multiple myeloma: implications for oncology nurses. Clin J Oncol Nurs. 2013;17(suppl):7-11.

4. Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients.

Leukemia. 2014;28(5):1122-1128.

5. Tamkin J, Visel D. The Myeloma Survival Guide. New York, NY: Demos Health; 2014.

BREAST CANCER

Less May Be “More” With Zoledronic Acid Caroline Helwick

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n breast cancer patients with bone metastasis, less frequent infusion of zoledronic acid was as effective as the standard monthly dose, the randomized OPTIMIZE-2 study showed.

“We found that less frequent treatment may reduce the risk of serious side effects, with the additional benefits of reduced inconvenience to the patient and less cost,” said Gabriel N. Hortobagyi, MD, Professor of Medicine at the University of Texas MD Anderson Cancer Center, Houston, at the American Society of Clinical Oncology (ASCO) 2014 annual meeting.

Zoledronic acid 4 mg given every 3 months was as effective as infusions given every 3 to 4 weeks, which is the schedule approved by the US Food and Drug Administration.

OPTIMIZE-2 compared the schedules in 403 women with breast cancer and bone metastases who had received at least 9 doses of an intravenous bisphosphonate (either zoledronic acid or pamidronate) before enrolling in the study.

The rate of skeletal-related events was 22% in the monthly group and 23.2% in the every-12week group, indicating that less frequent dosing is not inferior. Other efficacy measures, such as time to first skeletal-related event and change from

www.TheOncologyNurse.com

Gabriel N. Hortobagyi, MD

Photo by © ASCO/Scott Morgan 2014.

baseline in bone turnover markers, were also similar between the arms, and safety profiles were similar as well.

ASCO press briefing moderator Patricia Ganz, MD, a supportive care specialist from the University

of California Los Angeles, commented, “It’s not necessary for women to come in every 4 weeks.”

The data are important because there are no evidence-based guidelines for the optimal treatment schedule after 1 year of treatment.

Importantly, less frequent dosing seemed to ameliorate some of the safety concerns for bisphosphonates as a class. Like all agents in the class, “zoledronic acid has some safety concerns,” said Hortobagyi, indicating osteonecrosis of the jaw (ONJ), long-bone fractures (ie, atypical femoral fractures), and chronic kidney function impairment.

The less frequent dosing in this study was associated with fewer cases of ONJ (0 vs 2) and lower rates of renal impairment (7.9% vs 9.6%) compared with monthly dosing. No patients experienced longbone fractures.

Since the study size was, in Hortobagyi’s terms, “relatively modest” and there were some “design limitations,” he said the findings should be “interpreted with caution.” l Reference

Hortobagyi GN, Lipton A, Chew HK, et al. Efficacy and safety of continued zoledronic acid every 4 weeks versus every 12 weeks in women with bone metastases from breast cancer: results of the OPTIMIZE-2 trial.

Presented at: 50th Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2014; Chicago, IL. Abstract LBA9500.

SEPTEMBER/OCTOBER 2014 I VOL 7, NO 5

19

THROUGH THE EYES OF AN ADVOCATE

Pelvic Exam Not Needed for All Women?

Peg Ford

Peg Ford

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ecently, the American College of Physicians (ACP) released a statement on its website with the headline “American College of Physicians recommends against screening pelvic examination in adult, asymptomatic, average risk, non-pregnant women.” After a systematic review of previously published research from 1946 to January 2014 apparently showed that when it comes to the manual pelvic exam, the risks outweigh the benefits, the ACP published new clinical practice guidelines in the Annals of Internal Medicine. Coauthor Linda Humphrey, MD, FACP, stated “Routine pelvic examination has not been shown to benefit asymptomatic, average risk, non-pregnant women.

It rarely detects important disease and does not reduce mortality and is associated with discomfort for many women, false positive and negative examinations, and extra cost.” The ACP further indicated that “the pelvic exam is appropriate for women with symptoms such as vaginal discharge, abnormal bleeding, pain, urinary problems, or sexual dysfunction.”1 The ACP statement was reported on the internet under the headline “Pelvic exam not needed for all women: US doctors’ group,”2 creating a buzz in the ovarian cancer patient community. I and many others are aware of a number of survivors whose ovarian cancer either was discovered or became an issue for further testing with CT scan or transvaginal ultrasound based on the results of a pelvic/rectal examination even without any subtle suggestive symptoms.

Without a screening test for the early detection of ovarian cancer, the pelvic/ rectal exam is the only procedure we presently have to assist in diagnosing this most lethal gynecologic cancer at an early stage. Currently, the overall 5-year survival rate for ovarian cancer is dismal—only 44%—as most women

20

are diagnosed at stage III or IV after the cancer has metastasized, and most will face recurrences, eventually succumbing to this disease; however, the overall 5-year survival rate increases to over 90% if the cancer is detected early at stage I disease!3 Some women are aware, but, unfortunately, at the present time most are not aware that they are at a higher risk due to family medical history or other factors. My concern is that this ACP statement will encourage women to make the decision to pass on this important component of the annual gynecologic checkup. It seems the term “average risk” can often be misinterpreted. The ovarian cancer patient community would prefer to see a clarification as to what the term “average risk” means for the general public. We would also welcome assistance to increase awareness by listing the accepted common symptoms and risk factors for ovarian cancer to ensure that forgoing the pelvic exam does not become the sweeping norm for all women. Symptoms listed in the ACP statement that can be related to ovarian cancer in particular include pain, urinary problems, abnormal bleeding (most often for uterine cancer but can be a symptom for some subtypes of ovarian cancer), and sexual dysfunction1; other generally accepted symptoms include bloating, difficulty eating, or feeling full quickly.4 With all the increased emphasis on genetic mutations and family medical history, it is known that a woman with a family medical history of ovarian, uterine, or colon cancer or personal history of breast cancer is at an increased lifetime risk for ovarian cancer. The BRCA1 and BRCA2 genetic mutations are being publicized and addressed more often, and researchers are working diligently to identify other genetic mutations in the fight against this deadly disease.

On June 30, 2014, the American College of Obstetricians and Gynecologists (ACOG) issued an opinion5 in regard to the ACP’s statement: The American College of Obstetricians and Gynecologists (The College) has reviewed the recommendations from the American College of Physicians about annual pelvic examinations and continues to stand by its guidelines, which complement those released recently by the ACP. The College’s guidelines, which were detailed in this year’s Committee Opinion on the Well-Woman Visit, acknowledge that no current scientific evidence supports or refutes an annual pelvic exam for an asymptomatic, low-risk patient,

SEPTEMBER/OCTOBER 2014 I VOL 7, NO 5

instead suggesting that the decision about whether to perform a pelvic examination be a shared decision between health care provider and patient, based on her own individual needs, requests and preferences....While not evidence-based, the use of pelvic exams is supported by the clinical experiences of gynecologists treating their patients. Pelvic examinations also allow gynecologists to explain a patient’s anatomy, reassure her of normalcy, and answer her specific questions, thus establishing open communication between patient and physician.

The ovarian cancer patient community would prefer to see a clarification as to what the term “average risk” means for the general public.

In addition, the ACOG Committee Opinion #477, March 2011, The Role of the Obstetrician-Gynecologist in the Early Detection of Epithelial Ovarian Cancer,6 states: Women with persistent and progressive symptoms, such as an increase in bloating, pelvic or abdominal pain, or difficulty eating or feeling full quickly, should be evaluated, with ovarian cancer being included in the differential diagnosis. Evaluation of the symptomatic patient includes physical examination and may include transvaginal ultrasonography and measurement of levels of the serum tumor marker CA 125. Patients suspected of having ovarian cancer should be managed by a gynecologic surgeon, such as a gynecologic oncologist, who is trained to perform comprehensive surgical staging and cytoreductive (debulking) surgery.

Currently, it appears that the best way to detect ovarian cancer is for both the patient and her clinician to have a high index of suspicion of the diagnosis in symptomatic women. This requires education of both as to the symptoms commonly associated with ovarian cancer [author underlined]. Persistent and progressive symptoms such as an increase in bloating, pelvic or abdominal pain, or difficulty eating or feeling full quickly, should be evaluated, with ovarian cancer being included in the differential diagnosis.

In evaluating these symptoms, physicians should perform a physical examination, including a pelvic examination.

A rectovaginal examination may provide additional information. Imaging studies,

especially transvaginal ultrasonography, may be helpful in recognizing increased ovarian size or morphologic changes associated with ovarian cancer.

For this article, I also contacted a highly respected gynecologic oncologist, Robert A. Burger, MD, Director of Clinical Research and Fellowship Program in Gynecologic Oncology and Professor of Obstetrics and Gynecology at the Hospital of the University of Pennsylvania for a comment. He stated, “In my opinion, the diagnosis of ovarian cancer can be greatly facilitated by proper physical assessment, including combined rectal-vaginalabdominal examination.”

The outreach programs of my organization, Ovarian Cancer Alliance of San Diego (www.ocaofsd.org), are designed with the goal of increasing awareness among both the medical community and general public as to the symptoms and risk factors of ovarian cancer in order to promote the early detection of this disease. We strongly support ACOG’s Committee Opinion and recommendation that the performance of a pelvic examination be discussed and a shared decision reached between healthcare provider and patient, based on the patient’s individual needs, requests, and preferences. We are committed to our efforts, as well as to those of other organizations across the country, to empower women to be informed and involved in their healthcare. We also encourage all healthcare providers to think of ovarian cancer first, not last, in their differential diagnosis to save more women’s lives.

Because I am a firm believer in evidence-based medicine, I would also advocate for a clinical trial to be designed and/or a systematic review to be conducted that would focus on patients with ovarian cancer to ascertain the benefit of pelvic and/or rectal examinations in the diagnosis of ovarian cancer, with an emphasis on possible early detection. l Sources

1. American College of Physicians. www.acponline.org/ pressroom/screening_pelvic_exam.htm?hp.

2. Kerry Sheridan. Yahoo: AFP News. http://news. yahoo.com/pelvic-exam-not-needed-women-us-doctorsgroup-214342665.html.

3. American Cancer Society. www.cancer.org/cancer/ ovariancancer/detailedguide/ovarian-cancer-survivalrates.

4. Centers for Disease Control and Prevention. www. cdc.gov/cancer/ovarian/basic_info/symptoms.htm.

5. American Congress of Obstetricians and Gynecologists. www.acog.org/About-ACOG/News-Room/ Statements-and-Advisories/2014/ACOG-PracticeAdvisory-on-Annual-Pelvic-Examination-Recom mendations.

6. American Congress of Obstetricians and Gynecologists. www.acog.org/Resources-And-Publications/ Committee-Opinions/Committee-on-GynecologicPractice/The-Role-of-the-Obstetrician-Gynecologistin-the-Early-Detection-of-Epithelial-Ovarian-Cancer.

www.TheOncologyNurse.com

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3RD ANNUAL

eO seri Vie nc es w olo on the gy lin Nu e a rse t .co m

ONQUERING THE C CANCER CARE Third in a series

CONTINUUM

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A 5-part series Impact of Nonadherence to Cancer Therapy CONQUERING THE FIRST ISSUE IN THE 2014 SERIES THIRD ANNUAL

Associate Professor, Virginia Commonwealth University CANCER CARE The publishers of The Oncology CONTINUUM Nurse-APN/PA, The Oncology term oral medication regimens range from to 80%, he predominant scenario for systemic treatment o17% C nq ue with an average around 50%. A common assumption ring th of cancerand has traditionally involved administraPharmacist, Personalized e anceber I anticancer C tion of intravenous chemotherapy by highly that adherence to oral agents would Car Medicine in Oncology are proudhigher, due to the severity of the disease, C ohas trained personnel who closely monitored the patient. n been tinuu e m ethe When these procedures took place in an proven untrue. Studies indicate h t to present our 3rd annual Conquerg n i r e u q n rates fori cancer oadherence oncologist’s office or in a hospital infutherapy are C e has r a ing the Cancer Care Continuum r e sion center, extensive education of the 15% toc97%.

Nonadherence C n a CCbeenOassociated onquering M UC Uworse patient and family was possible. More with outcomes series.

NTIN the Lea Ann Hansen, PharmD, BCOP

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Changing the Image of Palliative Good Manufacturing ProcessCare

2-4

Lillie D. Shockney, RN, BS, MAS

vention and relief of suffering by means of early identiam enthusiastic about this 6-part series titled Confication and impeccable assessment and treatment of Continuum Each edition of quering the Cancer Care Continuum. pain and other problems, physical, psychosocial, and CCCC will address an important topic in oncology spiritual.” (http://www.who.int/cancer/ management and offer expert stakeES RI SE palliative/en/). holder commentaries. Topics will 2014 E TH IN UE care, pain manageFor too long, however, the image of include: palliative D ISS THIR palliative care has been tied exclusively ment, hospice care, comprehensive AL AN NU IR D to end-of-life care and focused solely on treatment TH planning, survivorship care, ™ pain control. and the role of biosimilars in supportThe articles that follow provide a ive care. In this issue, we address pal- Lillie D. Shock ney, RN clear understanding of the intent of liative care. , BS, MA S palliative care today, with the primary Palliation in cancer care is a topic goal of ending its identification solely that commonly makes people (medical FOUR TH ISSUE as cancer care provided for the dying. providers as well as patients) uncomIN THE 20 14 SERIES Instead, palliative care should be assofortable. I recently had the opportunity Lillie D. Shockney, RN, TH IR D AN ciated with quality-of-life care for all to speak with members of our palliative BS, MAS ™ N UA L cancer patients and survivors, no matcare team at Johns Hopkins and learned ter what their clinical outcome. that the word “palliative” comes from the word “palliare,” Your cancer patients may not tell you about the side which means to disguise or cloak. Centuries ago, this word effects of treatment they are experiencing or about their was used for the drapes that covered a casket. Although discomfort due to their cancer diagnosis or its treatment. we continue to drape coffins—most memorably with the In many cases they may simply assume that the discomflag—the drape is no longer referred to by this term. fort “comes with the disease.” However, with the imThe World Health Organization modified its origprovements in medicine and the power of science, it inal definition of palliative care as follows: “Palliative doesn’t have to anymore. Do not wait for your patients care is an approach that improves the quality of life to initiate a discussion about their symptoms; be proacof patients and their families facing the problems astive and initiate this discussion at the time you are plansociated MAS with life-threatening illness, through the preBS, RN, ey,

Introduc tion to O ncology Pain Ma nagem ent

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NEXT ISSUE

Cancer Care

nts recently, however, an increasingly comin a number ofCritdisease and with ort to Patie ical Suppstates g ct infe Sid in oveidEf Pr es e: nc ar C va e d A FIFTH IS Hospic ement SUEhigher mon situation involves the use of one or increased physician visits, g milies IN THE 2hosFa M dna ana 14 SERIE C0O NST I N U U ™ TH IR D A N Nstays, more oral medications and self-adminpitalization rates, longer hospital UAL M I disease worsening, and increased Personalized istered subcutaneous therapies in the mor-Treatment Pla nning home environment. The direct respontality.6 Approximately one-third to T sibility for drug acquisition and admintwo-thirds of all medication-related istration is shifting to the patients and hospitalizations are due to medication ™ their social support network, if availnonadherence—at a cost of $100 bilP Peersdoia Lea Ann Hansen, na tric 7P lize daTrtie able. At the present time, more than 20 lion annually.

The purpose of this area ntm t Cea ntre PharmD, BCOP Planning oral medications are FDA approved for ticle is to describe general concepts the first-line treatment of cancer (Table 1). In addition, regarding patient adherence and the research related to a number of other oral agents are used for tumors that adherence to cancer treatment. The incidence, risk fachave relapsed or are refractory to initial treatment. Actors, and consequences of this problem will be reviewed. cording to the National Comprehensive Cancer NetThe last article in this series will subsequently examine work, approximately 25% of all compounds in the the best practices for maximizing adherence and clinical oncology research and development pipeline are adminoutcomes.

1 istered orally, so the trend is likely to continue.

With this shift in responsibility comes the increased Definitions and Measures of Adherence possibility that anticancer medications may not be adAdherence was defined by the World Health Organministered correctly, especially for regimens that require ization in 2003 as the “extent to which a person’s berepeated dosing. Overall estimates of adherence to longhavior, taking medication, following a diet, and/or

Upcoming topics include: • Good Manufacturing Process

• Access to Quality Care

• Advances in Side Effect Management

• Impact of the Affordable Care Act in Cancer Care • Pediatric Patient Care

ckn Lillie D. Sho

Conquering t Cancer Carehe

edition of you the next © 2014 Green Hill Healthcare Communications, LLC e to bring to t is my privileg Continuum Cancer Care options, Conquering the ses specifically on hospice Hope focu read. to nt orta issue, which imp to be vitally eve beli be I will one is Lillie D. Sho s addressed here s of ckney, RN, fully, concept BS, MAS and better way adopted as newterminally ill cancer supporting our r families. thei and an ents ing pati years ago gett He ral seve ll . reca I Bill a man named rnet and e-mail from via the Inte had found me ing that his young stat can wrote to me astatic breast r, met had y, wife, Mar her live progressed to cer that had n. She was and now brai sleeping lungs, bone, ital and hosp the in y fused at currentl was awake, con d still more than she “ha weight, but times, losing chemotherapy until g ivin doctor been rece wrote that the yesterday.” He for the last t him this n care of her who had take come and mee s. He said asked him to t step 4 years had talk about nex to room for a while her would linger ng place, morning in Lillie ist olog D. onc Sh the taki oc e kney wer, RN that usually ussions thatS , MA said e types of disc tor, BS whenever thes was very brief. The doc he but this time

situation. The goal of the team is optima l medical There are som e considerati cally been abse ons that hav e histori nt but can no orilonger remain so. Patients want to know about the pro s and cons of treatment, risks and ben n efits, what their quality of life will be while on treatment as well as after treatment is completed. An d there is a new wrinkle in the trea tment plannin g process – what will this treatme nt cost? Wil patients hav l e to pay out of pocket for their treatme nt? Is the cost of treat-ment worth the clinical outcomes to be achieve d? No patient s want to leave their family in dee p debt, and although we have entered an exciting situation. era of persona lized medicin The goal e, the cost of the tea of these new therapy ou dru compared with m is optim tcomes. al medical treatments we havgs is incredibly high to in the There are e been accusto past. Even prio some cons med r treatment been dauntin iderations cally been regimens hav g from a cost that have absent but e perspective.

Eve his e wan can no lon i- ts to mak ger remainthe ryontor e sure that the want to kn so.righ Pattie trea patient gets tment at the nts ow about the way right time and Now pros.an of treatmen clin in the icia d righ ns must realize t t, risks and treatment’scons that treatme bene , whsake is never their quali nt for wise and not at ty of life wi Thofits tful dec the mission isions about ll be ughile treatment . treatment patient on as well as aft and wh er treatmen s, oncologists, pharmacolo are a must, completed gists, palliati t is . And the ve re is a kle

CONTI

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he fourth issue of Co nquering the Continuum Cancer Ca series addre re sses Treatm ning Throu ent Plangh the Ca Following ncer Care are 2 key Continuum articles to the role of . provide ins the clinic ight into al pharmaco gist as a me lomber of th e multidis plinary tea cim working co lla to render recommend boratively ations ab treatment out planning ndd 1 GHC106-3.i options. Go are the da ne ys, or they should be, oncology spe when cialists me rely passed – either on on paper or ele ctronically prescription new wrinin the treatm – ins ent plann by the pharm tructions to be filled – what wi ll this treatm ing process acologist or ent cost? W These ind pharmacist. patients ha ividuals, ill ve to pa y out of po experts in managem their treatm cket for drug ent, intera ent? Is the ction, and cost of tre mization, are ment worth optiatintegral to th e cli nic the oncolog care team. al outcome to be achiev y You will s ed? No pa soon read tients want learn why. leave their Lillie D. Sh and ockney, to family in RN, deep debt, although we And speak BS, MAS and ing of the have enter team, it is ed an excit that the pa era of perso critically im ing tient, and nalized me portant certai dicine, the cases, be co of these ne cost compared nsidered me n family members in w drugs is with treatm incredibly some mbers of the ning team. ents we ha hig to We should h tre in atm th ve been acc e past. Ev ent plannot be doing we must be en prior tre ustomed been daun things to a doing thing atment reg ting from patient; s with a pa patients, of imens have a cost persp tient. Thou course, are Ev ery ect on ive e gh the wa . not experts many have the right tre nts to make sure tha on oncolog desperately t the patie y care, atment at tried to be sort by tur nt gets the right tim way. Now ning to the come expe e and in the clinicians rts of a Internet an for themselv must realize d trying to right tre es what tre atm en determine t’s sake is that treatm atment wo never wise ent for uld be best Thoughtfu and not th for their l decision e mission. s about tre and patient atm s, oncolog ent are a ists, pharm must, acologists, © 2014 Gr palliative een Hill He althcare Co mmunicatio ns, LLC

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CANCER CENTER PROFILE

The Nurse Navigation…

The Trinity CancerCare Center, located in Minot, North Dakota, is part of Trinity Health. In line with the requirements for American College of Surgeons (ACS) certification as a comprehensive cancer center, Trinity has instituted both a Nurse Navigation Program and a Cancer Survivorship Program. The Oncology Nurse-APN/PA spoke with Jenene Kittleson, RN, MSN, OCN, CBCN, about the Nurse Navigation Program, and Pamela Pearson, RN, MSN, FNP-C, AOCNP about the Cancer Survivorship Program.

How did the navigation and survivorship programs get started?

Jenene Kittleson (JK): We started the Nurse Navigation Program for breast can-

Continued from cover

cer patients, funded by a Helmsley Grant.

The program blossomed into a navigation program for all new cancer consults at our center.

Now I see all new cancer consults, and I focus on patient barriers, including fear of the unknown and transportation, among others. I make sure that patients understand their treatment plan and that we have involved all the resources they will need, including a dietitian, pastoral care, exercise rehabilitation, affordable housing while being treated, and discounts on gasoline.

We also provide a distress screening as part of the ACS criteria, and our social worker follows up and identifies other resources that may be necessary in light of the levels of distress that are found.

Pamela Pearson (PP): Our Cancer Survivorship Program grew out of the Nurse Navigation Program and is only a few months old. My goal is to assess patients within 1 month of chemotherapy and/or radiation for domains such as physical, social, emotional, functional, sexual, body image, and stress. Upon completion of their treatment, a summary care plan is provided. This also includes long-term side effects to be aware of, for the patients and their primary care provider (PCP).

Depending on what the assessment shows, we develop a plan of care that will best help the patients make the trajectory through their treatment. The Survivorship Program offers complementary alternative medicine, including massage and yoga, acupuncture, healthy

lifestyle maintenance, and any needed referrals. We offer the following services at no charge, and these are provided by volunteers: yoga, pastoral care, social services, “Look Good, Feel Better,” and cancer rehabilitation exercise.

How many patients will be able to participate in these programs?

JK and PP: An estimated 400 to 500 patients per year.

What kind of feedback do you get from patients?

PP: In the 3 months that the Survivorship Program has been offered, the feedback so far has been very good. This is a new concept for most patients, and we find that most want to participate.

THE WHOLE PATIENT

The Psychosocial Effects… therapy, there is a reduction in the number of cells that make hair, resulting in hair loss; inhibited growth; weak, brittle, and constricted hair shafts subject to breakage; and a reduction in diameter of the hair shaft.

Typically, people who lose a lot of hair lose it very fast; people who lose hair slowly have a longer recovery.

“This may be important for counseling of patients as well as for understanding the mechanisms of toxicity,” Lacouture said.

The Psychosocial Implications The psychosocial ramifications of chemotherapy-induced alopecia must not be underestimated. Alopecia is the most traumatic effect of chemotherapy, according to 47% of breast cancer patients surveyed, 8% of whom said they would reject chemotherapy because of alopecia alone. Some women report that losing a breast due to a mastectomy would be less traumatic than losing all of their hair, Lacouture noted.

Additionally, there is a gender difference in terms of the psychosocial impact of hair loss. Women are much more concerned about scalp alopecia, whereas men tend to be more concerned about body alopecia.

Children undergoing cytotoxic chemotherapy tend to suffer social isolation as a result of alopecia, while people older than 60 years tend to be more affected by its psychosocial impact. Additionally, there is the issue of stigma; everyone knows the patient is receiving chemotherapy, which results in a feeling of loss of privacy.

The relative impact of alopecia depends on tumor type and stage. It is the second most important toxicity in breast and lung cancers, whereas it is not even in the top 10 in gastrointestinal cancers or stage 4 disease.

Chemotherapy-induced alopecia is graded by the Common Terminology Criteria for Adverse Events, but other grading systems have been implemented in the past few years, primarily led by Elise Olsen, MD, at Duke University Medical Center in Durham, North Carolina, one of the world’s leading hair experts. She has devised a grading system in which a person has to lose more than 50% of his or her hair in order for other people to notice. “This is reassuring to patients,” said

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Lacouture. “It also helps us to understand the severity of hair loss.”

There is a lesser severity of alopecia with the use of targeted therapies. It is important to keep in mind, though, that patients exposed to epidermal growth factor receptor (EGFR) inhibitors develop a myriad of skin toxicities and infections. Therefore, alopecia is not only a mechanism-based effect; it can also be a consequence of infection. Patients can present with alopecia that is actually an infection on the scalp, Lacouture explained.

“The problem with this and what makes patients very upset,” he said, “is that once these patients have an infection on the scalp, it leads to a scar. And when there is a scar on the scalp the hair is never going to grow back there again. This is a very undertreated problem.”

Patients on EGFR inhibitors who develop crust on their scalp should have the areas cultured; these patients are likely to have an infection that will need oral antibiotics, Lacouture advised.

Persistent Alopecia and Its Consequences “I’ve never seen patients as upset as those on cytotoxic agents whose hair never fully grows back, because these people were never told that this could happen,” said Lacouture.

The incidence of persistent alopecia is unknown, but one group significantly affected is children who receive chemotherapy. In an analysis of over 40,000 patients from the Childhood Cancer Survivor Study, about 40% of children experienced persistent hair loss, which led to a higher risk of depression and anxiety when they became adults. “This is important for us to know since childhood cancer survivors are living longer and longer,” stated Lacouture.

“I favor the term ‘persistent’ because that connotes that there is something that can be done. If you see a patient and you tell them they have ‘permanent’ chemotherapy-induced alopecia, that means there is probably nothing that can be done. I don’t think we know yet that there is nothing that can be done, and

the histology does not support the notion that there is nothing that can be done,” he said.

It is important to evaluate chemotherapy-induced alopecia at baseline and again every 3 months with standardized photos, trichoscopies, and, in some cases when inflammation or infection is suspected, with scalp biopsies. This allows for careful quantification, as patients who rely on memory can be very disappointed by their hair regrowth.

Monitoring, Treatment, and Counseling—What Can Be Done?

Lacouture and his colleagues have found that for EGFR inhibitor–induced toxicities and the prevention and management of alopecia, over-the-counter minoxidil is effective for regrowth of eyebrows, as is prescription bimatoprost for eyelashes. Camouflaging hair powders, thickeners, and wigs are also recommended.

In observational and autopsy studies, scalp cooling has been shown to be safe and cost-effective for alopecia prevention. According to some studies, in patients who develop complete alopecia, shaving the head is less traumatic than seeing clumps of hair falling out. Additionally, in anecdotal studies, about 65% of patients report changes in density, color, or structure of their hair after it has been lost and recovered. It is important to keep this in mind when counseling patients prior to the start of chemotherapy, Lacouture advised.

Chemotherapy-induced alopecia reminds patients of their disease, negatively affects social interactions, and can lead to decreased self-esteem, sexuality, and sensuality. Therefore, patient counseling is critical.

“Women ask frequently, ‘Am I going to lose my eyebrows and my eyelashes? ’ ” added Lacouture. “The best answer we have for them is ‘Maybe.’ We want to have numbers.” l Reference

Lacouture ME. Controversies in chemotherapy and endocrine agent-induced alopecia [meet the expert]. Presented at: 2014 Annual Meeting of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology; June 26-28, 2014; Miami, FL.

www.TheOncologyNurse.com

CANCER CENTER PROFILE

JK: We have had good feedback from surveys. We would actually like to have some negative feedback so we know what areas need to be improved.

How do you think these programs improve quality of care at Trinity

CancerCare?

PP: The programs help us fulfill the ACS requirements for accreditation as a comprehensive cancer care center. This also helps us to provide a comprehensive holistic approach to living with or beating cancer.

What are some challenges you have faced?

PP and JK: The biggest challenge has been integrating these programs into cancer care work flow. Bringing change into an area always requires understanding and education.

Pamela Pearson, RN, MSN, FNP-C, AOCNP (left); Jenene Kittleson, RN, MSN, OCN, CBCN (right)

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The Academy of Oncology Nurse & Patient Navigators (AONN+) invites you to share your story of how cancer has affected you or a loved one. These stories will serve as a forum to build awareness and be a source of inspiration and reassurance to others. Select stories will be featured on the AONN+ website and in future issues of the Journal of Oncology Navigation & Survivorship®.

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JK: When navigation was fairly new, a lot of physicians did not understand what a nurse navigator does. My role extends beyond case management; I follow a patient from diagnosis and into the whole trajectory of treatment.

PP: The beauty of our program is that patients come back for a recheck after chemotherapy and/or radiation, and we start there to make sure they are comfortable with moving on to a PCP. Eventually with survivorship we connect with the PCP and provide all the patient records to eliminate gaps in care. Patients can request another meeting with us if they want to.

What are your rewards?

PP and JK: The biggest reward is getting patients to view themselves from a holistic perspective and feel confident moving forward in their new life after cancer. They are not just cancer patients, but full human beings. It can be particularly gratifying to help head and neck cancer patients who have so many side effects that can compromise quality of life.

If you had the funds, what services would you like to add to the Nurse Navigation and Cancer Survivorship programs?

JK: I would like to improve our patient library. We participate in free colorectal cancer screening programs for the area we serve, which includes a large population of Native Americans. This group presents with more advanced breast cancers at younger ages. I would like to have funding to provide education to the general public and promote the need for screening to Native Americans.

PP: My “wish list” includes adding more integrative services to the Survivorship Program, including stress management, resiliency training, counseling services for sexual dysfunction and other problems, and acupuncture. l

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