Immunocal Children Cancer Page 11

A B S T R A C T S

Poster Abstracts

First Annual Chicago Supportive Oncology Conference Chicago, Illinois October 6–8, 2005

Pain

SATIVEX

Mean NRS pain score 5.68 (ITT, Baseline) Change in NRS pain –1.37 score (ITTb) Change in NRS pain –1.41 score (per protocolb) Change in NRS pain –1.55 score (completed patientsb)

Abstract PA-1

Cannabis-Based Medicines in the Treatment of Cancer Pain: A Randomized, DoubleBlind, Parallel Group, Placebo-Controlled, Comparative Study of the Efficacy, Safety, and Tolerability of Sativex and Tetranabinex in Patients With Cancer-Related Pain Jeremy R. Johnson1, Stephen Wright2 1 Severn Hospice, Bicton Heath, Shrewsbury, United Kingdom; 2 GW Pharma Ltd, Salisbury, United Kingdom BACKGROUND: This study compared the efficacy and tolerability of two cannabis-based medicines with placebo in the relief of cancer pain. METHODS: Patients with cancer pain not wholly alleviated with strong opioid treatment were treated for a period of 14–21 days in addition to their ongoing strong opioid analgesic. Patients self-titrated their study medication: each 100 µL oromucosal spray of Sativex delivered 2.7 mg delta-9tetrahydrocannabinol (THC) and 2.5 mg of cannabidiol (CBD). Each 100 µL spray of Tetranabinex (a high THC content extract) delivered 2.7 mg THC. The primary outcome was the change from baseline in numerical rating scale (NRS) pain score at the end of 14–21 days of treatment. Secondary endpoints were Brief Pain Inventory Short Form, quality of life (European Organization for Research and Treatment of Cancer Qualityof-Life Questionnaire C-30), and 0–10 NRS scores for sleep disturbance, nausea, memory, appetite, and concentration. RESULTS: In all, 177 patients were randomized (n = 60 [Sativex], n = 58 [Tetranabinex], n = 59 [placebo]). The NRS pain score results appear in the table. There were no significant differences in the usage of escape medication (number of days on which escape was used [intent-to-treat]: Sativex vs placebo, P = 0.91; Tetranabinex vs placebo, P = 0.41). There were no statistically significant differences in the secondary endpoints in favor of Sativex or Tetranabinex, although there was evidence of small, but statistically significant, reductions in concentration and appetite for Sativex (concentration: P = J Support Oncol 2005;3(suppl 3):XX–XX

© 2005 Elsevier Inc. All rights reserved.

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TETRANABINEX

PLACEBO

P VALUEa

5.77

6.05

–1.01

–0.69

0.0142

–0.94

–0.59

0.0047

–1.18

–0.71

0.0090

P value for comparison of Sativex versus placebo; banalysis of covariance NRS = numerical rating scale; ITT = intent to treat a

0.02 [Wilcoxon]; appetite: P = 0.02 [ANCOVA]) and a similar trend for Tetranabinex. Both medicines were well tolerated. CONCLUSIONS: A combination of CBD and THC appeared to be more effective than THC alone. Further studies with a cannabis-based medicine are indicated.

Abstract PA-2

Assessment of Pain, Other Symptoms, Performance Status and Quality of Life in Children With Non-Hodgkin’s Lymphoma (NHL) Eleonora Mess, 2Wojciech Leppert, 1Adriana Borodzicz-Cedro, Krzysztof Szmyd Palliative Care Nursing Department, Public Health Faculty, Medical Academy, Wrocław, Poland1; Department of Palliative Medicine, Poznan University of Medical Sciences, Poznan, Poland2; Department of Paediatric Bone Marrow Transplantation, Oncology and Hematology, Wrocław Medical University, Wrocław, Poland3 1 3

BACKGROUND: To evaluate the incidence of pain and other symptoms, performance status, and global quality of life (QOL) in children diagnosed with NHL. METHODS: The study was performed in 25 children (10 boys and 15 girls, aged 9–16 years) diagnosed with NHL. The trial lasted from December 2004 until June 2005. Patients answered questionnaires; interviews were conducted with children and their parents. Pain was assessed with a visual analogue scale with colors from 0 = no pain (brightest color) to 9 = unbearable pain (darkest color)

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and subsequently was classified into three groups: weak pain intensity (0–3), moderate (4–6), or strong (7–9). Another 28 symptoms were assessed using the Rotterdam Symptom Checklist (RSC). Performance status was assessed by the Karnofsky scale (0%–100%). Global QOL was assessed by a questionnaire. RESULTS: Pain intensity assessment: weak (72%), moderate (20%), and strong (8%). The most frequent symptoms reported were fatigue (68%), loss of energy and weakness (56%), abdominal pain (52%), oral lesions (52%), irritation (48%), and worrying (48%). Karnofsky performance status: 20% (n = 3), 50% (n = 2), 60% (n = 9), 70% (n = 2), 80% (n = 2), 90% (n = 2), and 100% (n = 5). Global QOL: very good (16%), good (40%), rather good (20%), average (16%), rather poor (4%), and very poor (4%). CONCLUSIONS: Weak and moderate pain correlated well with the number of children with rather good, good, or very good global QOL. Strong pain in 2 children correlated with the 2 children reporting rather poor or very poor global QOL. The number of children (n = 22) reporting performance status as either moderate (50%–60%) or good (70%–100%) correlated with the percentage of children with very good, good, and rather good QOL (n =19; 76%).

Abstract PA-3

Evaluation and Treatment Recommendations for Taxane-Induced Peripheral Neuropathy in Women with Breast Cancer Meredith Wampler1,2, Ernest Rosenbaum1, Christine Miaskowski3 1 University of California, San Francisco; 2Graduate Program in Physical Therapy, San Francisco State University; 3Department of Physiological Nursing, University of California, San Francisco BACKGROUND: A major problem in cancer treatment is the development of chemotherapy-induced peripheral neuropathy (CIPN). Identifying feasible and valid measures of peripheral neuropathy will lead to practical solutions for the symptoms and functional limitations associated with CIPN. This study reviewed the clinical assessment and explored the treatment of CIPN. METHODS: A pilot study at the University of California, San Francisco Comprehensive Cancer Center evaluated 20 women with breast cancer who were taking taxane chemotherapy. Measures included several measures of CIPN, postural control (balance), physical performance, pain, and quality of life. RESULTS: The most significant findings in this study were 1) 70% of the women experienced pain, yet only 45% were taking pain medications; 2) the most intense qualities of the pain were numbness, tingling, unpleasantness, and aching; 3) impairments in balance and physical performance were significant; and 4) the modified total neuropathy score correlated with measures of quality of life, balance, and physical performance. CONCLUSIONS: Peripheral neuropathy is a common side effect of taxane chemotherapy and frequently is not properly evaluated. A majority of patients in this study were found to have occult, painful sensory neuropathies as well as impairments

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in postural control and physical mobility. Future studies to develop interventions to help patients with CIPN are planned. Some of these recommendations have included: use of adaptive equipment such as button hooks and elastic laces, referral to physical therapy for balance and mobility assessment and training, and management of neuropathic pain. These problems can be addressed appropriately by multidisciplinary approaches.

Anemia/Fatigue Abstract PA-4

Patient-Reported Fatigue in Three Sunitinib Malate (SU11248) Phase II Trials for the Treatment of Advanced Renal Cell Carcinoma, Gastrointestinal Stromal Tumor, and Neuroendocrine Tumor Jennifer L. Beaumont1, David Cella1, Jim Z. Li2, Xin Huang2, Paul Bycott2, Charles Baum2 and the SU11248 GIST, RCC, and NET study teams 1 Center on Outcomes, Research and Education (CORE), Evanston Northwestern Healthcare, Evanston, Illinois; 2Pfizer Inc., San Diego, California B ACKGROUND : Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor with both antiangiogenic and direct antitumor activities. This analysis describes patientreported fatigue data from three phase II trials of sunitinib for the treatment of metastatic renal cell carcinoma (RCC), malignant gastrointestinal stromal tumor (GIST), and advanced unresectable neuroendocrine tumor (NET). Clinical results from these trials have been reported elsewhere. Fatigue was further assessed after phase I trials had shown this to be a dose-limiting toxicity. METHODS: Sunitinib was administered once daily in repeated cycles of 4 weeks on treatment, 2 weeks off. Patient-reported fatigue was assessed weekly using the Functional Assessment of Chronic Illness Therapy-Fatigue (Fatigue) scale (scores: 0–52, higher scores = less fatigue) in the first 4 cycles (6 months). We report data from 63 patients in the RCC trial, 55 in the GIST trial, and 102 in the ongoing NET trial (n = 220). RESULTS: Baseline mean Fatigue scores of RCC, GIST and NET patients were 40.4, 37.6, and 39.8, respectively, all lower (ie, reflecting more fatigue) than the general US population’s average of 43.6. Baseline fatigue correlated with baseline ECOG performance scores in all trials: patients with a better performance score reported less fatigue. During the first 4 cycles of therapy, the mean fatigue changes from baseline scores ± SD in each trial were –2.2 ± 7.8 (RCC), 2.2 ± 8.8 (GIST) and –1.8 ± 8.1 (NET), all smaller than the established minimally important difference of 3 points for the Fatigue scale. The changes from baseline scores did not differ with response to therapy in the 3 trials. Within treatment cycles, the mean scores decreased slightly (reflecting more fatigue) during the 4 weeks

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Poster Abstracts

on treatment and increased (reflecting less fatigue) during the 2 weeks off treatment. This pattern generally was consistent in all 4 cycles and for all 3 trials. CONCLUSIONS: Patient-reported outcome data indicate that sunitinib did not cause a significant clinically meaningful change in patient-reported fatigue in these 3 trials. However, within treatment cycles, patients reported slightly more fatigue while on treatment and less fatigue while off treatment.

Abstract PA-5

Communication Regarding ChemotherapyInduced Anemia and Related Fatigue: Recommendations From an Observational Linguistic Study D. Blum, D. Cella, B. Davidson, H. Hamilton, L. Nail, R. Waltzman BACKGROUND: Many instruments exist for determining the impact of chemotherapy-induced anemia and related fatigue on patient quality of life, but few studies analyze how healthcare providers actually discuss anemia and fatigue with patients. METHODS: Letters of invitation were mailed to over 1,000 community-based oncologists; of these, 15 met the criteria and agreed to participate in this research. Thirty-six patients undergoing chemotherapy were videorecorded during regularly scheduled visits. Post-visit interviews were conducted separately with patients and physicians and/or allied health professionals. Interviews were transcribed and analyzed using sociolinguistic techniques. RESULTS: In all, 52% of visits were spent discussing side effects and symptoms; 31% on hematologic issues (anemia and related fatigue, blood counts, growth factors, etc). However, most discussions of fatigue/anemia lacked specificity and the time reference necessary to determine impact on patients’ lives. For example, the word “normal” or a surrogate was used in 67% of visits, but without clarity to its reference (ie, without reference to “normal symptom for someone with cancer,” “normal side effect for chemotherapy,” etc). Physician inquiries regarding fatigue also tended to be too brief to elicit patients’ chief concerns. On average, less than one question/visit relating to fatigue/anemia was asked of the patient. No fatigueassessment instrument was used or referenced, in whole or in part, in any visit. CONCLUSIONS: Chemotherapy-induced anemia and related fatigue were discussed, but not with the specificity required to understand impact on quality-of-life. Communitybased oncologists are encouraged to modify their vocabulary (eg, use “expected” in lieu of “normal”) and consider incorporating a simple instrument to improve communication.

Abstract PA-6

The Effectiveness of Darbepoetin Alfa Administered Every 3 Weeks on Clinical Outcomes in Elderly Patients With Chemotherapy-Induced Anemia Ralph Boccia1, Peter Silberstein2, Simon Tchekmedyian3, Dianne Tomita4, Greg Rossi4, and Greg Otterson5 on behalf of the Aranesp Synchronicity (20030206) Study Group 1 Center for Cancer and Blood Disorders, Bethesda, Maryland; 2 Creighton University, Omaha, Nebraska; 3Pacific Shores Medical Group, Huntington Beach, California; 4Amgen Inc., Thousand Oaks, California; 5Ohio State University, Columbus, Ohio BACKGROUND: Chemotherapy-induced anemia (CIA) is common in patients receiving chemotherapy with adverse effects on clinical outcomes and quality of life. METHODS: We present an exploratory analysis from a large, multicenter, open-label, 16-week study of the effectiveness of every-3-week (Q3W) darbepoetin alfa 300 µg in cancer patients with CIA. RESULTS: Results are presented for elderly (≥ 65 years [mean 73.7 years; n = 724]) and younger (< 65 years [mean 52.1 years; n = 769]) patients. Most patients were female (52% and 69%, respectively). The most frequent cancer type varied: gastrointestinal (27%) in elderly and breast cancer (41%) in younger patients. Mean (SD) baseline hemoglobin levels were identical (10.1 [0.7] g/dL in both groups). Similar percentages of patients in each group had a baseline hemoglobin level < 10 and ≥ 10 g/dL (31% and ~60%, respectively). A high percentage of patients (95% CL) achieved target hemoglobin (11–13 g/dL): 79% (76, 82) in both groups, with 73% of patients in each group subsequently maintaining these levels. Red blood cell transfusion requirements were reduced from months 1 to 4: 11% to 3% in elderly and 12% to 4% in younger patients. Mean (95% CL) change in Functional Assessment of Cancer TherapyFatigue scores (baseline to week 16) differed by age: 2.9 (1.7, 4.0) in elderly, and 6.4 (5.3, 7.6) in younger patients. The safety profile was as expected for this patient population. CONCLUSIONS: Darbepoetin alfa Q3W appears to be well tolerated and effective for treating CIA in both elderly and younger patients. However, elderly patients experienced less improvement in quality of life scores than younger patients.

Abstract PA-7

Status of Anemia Management in Community Oncology Barry Fortner, Ling Zhu, Lee S. Schwartzberg Accelerated Community Oncology Research Network, Memphis, Tennessee BACKGROUND: Despite available treatments and management guidelines for chemotherapy-induced anemia, evidence suggests a significant portion of patients continue to go untreated or inadequately treated. This study is a pilot project aimed at describing the status of anemia management in relation to

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published guidelines and standards. METHODS: For each clinic, two chart samples of 25 chronologically consecutive cancer patients presenting to community oncology clinics on July 1, 2004, and September 1, 2004, were abstracted for quality parameters relating to the target visit. RESULTS: Results are from 977 patients (20 clinics) receiving chemotherapy. Patients were 60% female; mean (SD) age of 62 (13) years; 78% Caucasian; 42% on Medicare; heterogeneous on cancer, stage, and chemotherapy; presenting for visits involving a range of services (lab 70%, physician 51%, nurse 48%, chemotherapy 63%, erythropoietic therapy [either epoetin alfa or darbepoetin alfa] 21%, growth factor 11%). Mean (SD) hemoglobin (Hgb) was 11.8 (1.6) g/dL. Fifty-two percent (n = 506) of patients were receiving an erythropoietic agent, of which 11% were receiving iron supplementation (2% IV). Five percent of patients (n = 49) had received a red blood cell transfusion in the 4 weeks prior. Hemoglobin level by anemia severity, use of erythropoietin by anemia severity, description of anemia course, erythropoietin type and schedule, erythropoietin initiation by hemoglobin level severity, and rate of fatigue severity assessment by type of visit were analyzed. CONCLUSIONS: Anemia was a frequent problem for patients receiving chemotherapy. These data will be important to collect on an ongoing basis to establish and maximize clinical outcomes in actual clinical practice.

Emesis Abstract PA-8

Enhanced Pharmacokinetic Profile of Ondansetron Oral Spray Greg Berk1, Arkady Rubin2, Gavin Choy1 1 Hana Biosciences, Inc., South San Francisco, California; 2 NovaDel Pharma, Inc., Flemington, New Jersey BACKGROUND: Ondansetron, a potent, highly selective, competitive antagonist of 5-HT3 receptors, is the active ingredient of Zofran, the most broadly prescribed antiemetic. Ondansetron is approved for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy or radiotherapy and for the prevention of postoperative nausea and vomiting. It is currently available in tablet, orally disintegrating tablet, oral solution, and intravenous formulations. We report the development of ondansetron oral spray, a multidose oral spray dosage form of ondansetron that may offer certain advantages over the currently available formulations. METHODS: This oral spray achieves therapeutic drug levels by delivering small droplets of concentrated drug solutions over the oral mucosa, which has a rich blood supply and has been found to be permeable for the purpose of drug delivery. The pharmacokinetic profile of 8 mg of ondansetron oral spray was compared with an 8-mg Zofran tablet in a pilot pharmacokinetic study conducted in 9 healthy adult male volunteers. RESULTS: Although the mean maximum plasma concentration and bioavailability as measured by the area under the curve for the spray did not exceed that of

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the tablet during the 12-hour observation period, the time to achievement of measurable drug concentration was about 20 minutes shorter for the 8-mg ondansetron oral spray versus 8mg Zofran tablet. Also, at 20 minutes post dose, the oral spray formulation significantly increased the total amount of drug delivered and the mean ondansetron plasma concentration relative to the conventional oral tablet. CONCLUSIONS: Ondansetron oral spray was safe and well tolerated.

Abstract PA-9

Post-Marketing Surveillance Data Demonstrate a Favorable Safety Profile of Palonosetron for Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Clinical Practice Michael T. Cullen, Jr.1, Mary M. McGuiggan1, Mario Bertazzoli2 1 MGI Pharma Inc., Bloomington, Minnesota; 2Helsinn Healthcare SA, Lugano, Switzerland BACKGROUND: Palonosetron hydrochloride (Aloxi) is a selective serotonin subtype 3 (5-HT3) receptor antagonist differentiated from other 5-HT3 receptor antagonists by its high receptor binding affinity and extended plasma half-life (~40 hours). Palonosetron injection 0.25 mg is indicated in the United States (US) for the prevention of acute and delayed nausea and vomiting associated with moderately emetogenic chemotherapy and the prevention of acute nausea and vomiting associated with highly emetogenic chemotherapy. The safety profile of palonosetron demonstrated in the pivotal trials was similar to other 5-HT3 receptor antagonists. Headache and constipation are the most frequently reported adverse reactions in this class. Since the product has been launched, over 1.8 million vials of Aloxi have been distributed. METHODS: An extensive postmarketing surveillance (PMS) review was completed to evaluate Aloxi’s safety profile in the post marketing exposed patient population for the reporting period from September 2003 up to and including April 24, 2005. All spontaneous adverse events reported, including any adverse events from ongoing clinical trials, were collected and processed in the Helsinn Global Safety Database (ARGUS by Relsys Incorporated, US). RESULTS: PMS data from September 2003–April 2005 included 88 case reports. Of these 88 spontaneous adverse event reports, 14 (16%) were considered serious, and 74 (84%) were considered nonserious. The most frequently reported adverse events included headache (n = 16), hypersensitivity reactions (n = 8), and injection site reactions (n = 11). No instance of QT interval prolongation and one nonserious case of constipation were reported. In addition, only 22 cases of lack of efficacy were reported (0.0012%). With over 1.8 million doses distributed, these spontaneous PMS data showed a favorable safety profile with very few cases reported (n = 88, 0.0049%). CONCLUSIONS: With over 1.8 million doses administered, PMS data confirmed a favorable safety profile for palonosetron in clinical practice.

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Poster Abstracts

Abstract PA-10

Control of Chemotherapy-Induced Nausea Remains Suboptimal Despite Widespread Use of Multiple-Day Ondansetron, Dolasetron, or Granisetron Antiemetic Therapy Jane Hickok, Gary Morrow, Joseph A. Roscoe University of Rochester Cancer Center, Rochester, New York BACKGROUND: Despite improvement in control of vomiting with short-acting 5-HT3 receptor antagonists, nausea continues to be a significant problem for patients receiving chemotherapy. Short-acting 5-HT3 receptor antagonists appear to be prescribed widely on the days following chemotherapy for patients receiving moderately emetogenic chemotherapy (MEC), despite high-level evidence that they are not very effective for control of delayed nausea. METHODS: In total, 2,068 nurses were surveyed at the 2005 Oncology Nursing Society 30th Annual Congress regarding perceptions of antiemetic prescribing in their clinical practices. For comparison, nausea incidence rates for days 2 and 3 also were reported from a recently completed randomized clinical trial in which 226 patients received dexamethasone on day 1 and a shortacting 5-HT3 receptor antagonist on days 1–3 following MEC that included doxorubicin. RESULTS: The survey data demonstrated that 77% of practices routinely prescribe oral 5-HT3 receptor antagonists after day 1 of chemotherapy to prevent delayed nausea and vomiting. Results from the clinical trial showed that the rate of delayed nausea in patients receiving a short-acting oral 5-HT3 on days 2 and 3 was almost 80%. CONCLUSIONS: For patients receiving doxorubicin-based chemotherapy, daily administration of short-acting 5-HT3 receptor antagonists on days 2 and 3 did not control nausea in the vast majority of patients. It is unclear why this practice pattern continues when better agents may be available to control this potentially debilitating side effect of common chemotherapy.

hyoscine derivatives (second step); and finally levomepromazine and octreotide (third step). METHODS: Clinical assessment of 420 patients with advanced cancer that suffered from chronic nausea and/or vomiting induced by different causes, including 95 patients diagnosed with inoperable bowel obstruction. The intensity of symptoms was assessed by verbal scale, from 0 (lack of NV) to 3 (strong NV). Symptoms were assessed three times: 1) beginning of care, 2) during symptomatic treatment, and 3) the last week of life. Treatment was beneficial if there was a decrease from strongor-moderate to mild-or-none NV, maintenance of mild NV, or complete disappearance of symptoms. Treatment was a failure when there was an increase in NV or when moderate or strong NV was maintained. RESULTS: In all patients, beneficial effects were seen in patients from beginning of care to symptomatic treatment (n = 344; 82%) and from the treatment period to the last week of life (n = 357; 85%). In patients with inoperable bowel obstruction, beneficial effects were seen in patients from beginning of care to symptomatic treatment (n = 56; 59%), and from the treatment period to the last week of life (n = 49; 51%). CONCLUSIONS: Treatment of NV according to the proposed three-step antiemetic ladder was beneficial in over 80% treated patients. However, in over 15% of patients with gastrointestinal obstruction, control of NV was unsatisfactory, indicating a need for more intensive treatment and more effective therapy methods in this group of patients.

Abstract PA-12

Improving the Functional Status of Patients With Cancer by More Effectively Preventing Chemotherapy-Induced Nausea and Vomiting (CINV): A Comparison of Palonosetron (PALO) vs Ondansetron (OND) or Dolasetron (DOL) Carl de Moor, 2Regina S. Cunningham Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts1; The Cancer Institute of New Jersey, New Brunswick2 1

Abstract PA-11

The Use of the Three-Step Antiemetic Ladder in the Treatment of Chronic Nausea and Vomiting and in the Course of Inoperable Bowel Obstruction in Patients With Advanced Cancer Wojciech Leppert, 2Sławomir Paweł Wozniak, 1Jacek Łuczak Department of Palliative Medicine, Poznan University of Medical Sciences, Poznan, Poland1; Palliative Care Department, Down Silesian Oncology Centre, Wrocław, Poland2 1

BACKGROUND: Nausea and vomiting (NV) are frequent symptoms in patients with advanced cancer. We submit results of using the three-step antiemetic ladder concerning treatment of chronic NV in patients with and without inoperable gastrointestinal obstruction. For patients with inoperable bowel obstruction, we propose metoclopramide and dexamethasone (first step); followed by haloperidol, dimenhydrinate, promethazine, and

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BACKGROUND: More effective prevention of CINV at treatment initiation can improve the functional status of patients with cancer and reduce consumption of caregiver resources. In two pooled, phase III, randomized trials (n = 754), PALO 0.25 mg demonstrated superior prevention of CINV compared with OND 32 mg or DOL 100 mg in patients receiving moderately emetogenic chemotherapy (MEC). METHODS: The Functional Living Index-Emesis (FLIE) instrument assessed the impact of CINV on daily life activities in the first 24 hours (acute) and on days 2–4 (delayed) after chemotherapy. The FLIE is a validated, patient-reported instrument with 9 questions in two domains (nausea and emesis), with responses scored on a 100-mm, 7point visual analog scale (VAS) anchored by “none/not at all” (7) and “a great deal” (1). Higher VAS scores indicated less impact on functioning, and “No impact on daily life” (NIDL) was defined as an average score > 6. RESULTS: Significantly

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PALO

NIDL (% Patients) Nausea 66.9a Emesis 79.1 Total 72.8a Mean FLIE Scores Nausea 81.6a Emesis 87.1a Total 84.4a

ACUTE OND/DOL

P VALUE

57.2 72.6 63.6

0.006 0.077 0.006

64.8a 79.4a 70.4a

53.7 71.3 58.8

0.001 0.005 0.001

76.2 83.0 79.5

0.011 0.037 0.014

81.7a 89.6a 85.6a

74.9 84.6 79.7

0.001 0.003 0.001

PALO

DELAYED OND/DOL P VALUE

and overall (0–120 hr) no emesis and complete response (CR: no emesis, no rescue) rates. RESULTS: See table. CONCLUSIONS: In challenging emetogenic situations such as with AC or HEC, PALO provides better overall protection from emesis than a first-generation agent. Research supported by MGI Pharma, Inc. and Helsinn Healthcare, SA. AC PALO OND OR DOL (n = 131) (n = 132) P VALUE

a

PALO superior to OND/DOL; Mean scores adjusted for age, gender, alcohol, and prior chemotherapy experience and regimen. NIDL = no impact on daily life; FLIE = Functional Living Index-Emesis

more PALO-treated patients reported NIDL and had higher FLIE scores. A further evaluation of the FLIE scores by quartile revealed the greatest differences to be in patients with the most interference in daily functioning (see table). CONCLUSIONS: These FLIE analyses suggest that improved control of CINV with PALO allows more patients to maintain their functional status after MEC. This more effective antiemetic should result in improved patient quality of life and should ease management for oncology care providers.

Abstract PA-13

Single-Dose Palonosetron is Superior to Single-Dose Ondansetron or Dolasetron in Preventing Emesis in Patients Receiving Highly Emetogenic Chemotherapy (HEC) or Anthracycline-Cyclophosphamide (AC)-Based Chemotherapy for Breast Cancer Hope S. Rugo1, Steven M. Grunberg2 1 University of California San Francisco Comprehensive Cancer Center, San Francisco; 2University of Vermont, Burlington BACKGROUND: Acute chemotherapy-induced emesis is the greatest predictor for emesis in the subsequent days or cycles. Palonosetron 0.25 mg (PALO), has demonstrated superior, prolonged efficacy versus first-generation agents in patients receiving a variety of emetogenic chemotherapy agents. Emesis resulting from AC-based chemotherapy and highly emetogenic agents like cisplatin is difficult to manage and results in decreased quality of life for many patients. Acute antiemetic protection with PALO could improve the overall management of these challenging chemotherapeutic situations. METHODS: Efficacy of single-dose PALO versus single-dose ondansetron 32 mg (OND) or dolasetron 100 mg (DOL) was evaluated in the subset of women with breast cancer receiving their first cycle of AC chemotherapy in two multicenter, doubleblind, randomized, controlled trials. Efficacy of PALO + dexamethasone (DEX) versus OND + DEX was evaluated in patients receiving HEC in a third trial. Patients received PALO or OND/DOL (± DEX) prior to chemotherapy, with no followup antiemetics. Efficacy measurements included acute (0–24 hr)

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No emesis (% patients) Acute 73%a 50% Overall 57%a 31% CR (% patients) Acute 63%a 47% Overall 47%a 24%

HEC PALO + DEX OND + DEX (n = 150) (n = 147) P VALUE

< 0.001 < 0.001

75%a 53%a

59% 0.003 33% < 0.001

0.013 0.001

65% 41%a

55% 25%

0.125 0.005

PALO superior to OND/DOL. AC = anthracycline-cyclophosphamide; HEC = highly emetogenic chemotherapy; CR = complete response a

Abstract PA-14

Cost Comparison of Palonosetron to ShortActing Serotonin Receptor Antagonists (SRAs) for the Prevention of Acute and Delayed Chemotherapy-Induced Nausea and Vomiting (CINV) Lee S. Schwartzberg1, Gordon J. Vanscoy2 1 The West Clinic, Memphis, Tennessee; 2University Pharmacotherapy Associates, LLC, Monroeville, Pennsylvania BACKGROUND: Palonosetron (PALO) offers improved acute and prolonged CINV control versus short-acting SRAs and can provide a cost-effective alternative for patients, medical practitioners and payers. Efficacy of PALO and analysis of both upfront and downstream costs are considerations in an overall economic model from a payer perspective. METHODS: Complete response (CR, no emesis, no rescue) rates for ondansetron, dolasetron or granisetron (OND/DOL/GRAN) given on day 1, with SRA follow-up for the delayed period (days 2–5), were compared with CR rates for day 1 PALO (with no follow-up) from literature. An economic model comparison was made between patients receiving 1-day PALO versus 3-day OND (IV Day 1, twice daily oral follow-up) therapy. Total costs were estimated as total antiemetic costs plus total medical and pharmacy costs associated with extreme CINV events for 6 months. Drug acquisition costs were based on average wholesale price (AWP) discounted at 20% for Day 1 intravenous drug and wholesale acquisition cost (WAC) for oral follow-up therapy. It was assumed that 4% of PALO- and 11% of first-generation 5-HT3 receptor antagonist-treated patients would experience an extreme event, per published literature. Estimated direct medical (including pharmacy) costs associated with these events were included in the model (Shih et al, J Clin Oncol 2005, Abstract 6053). RESULTS: PALO results in 18%–19%

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Poster Abstracts

higher acute and delayed CR rates than OND/DOL/GRAN (P < 0.01). A net savings of $1.0M for every 1,000 patients could be obtained when using 1-day PALO instead of 3-day OND therapy. The net savings ranged from $0.9M to $1.1M for every 1,000 patients regardless of the first-generation SRA chosen. CONCLUSIONS: The use of PALO instead of short-acting SRAs not only provided patients with improved CINV control, but reduced the overall costs to payers of managing these distressing side effects, also impacting practices and society.

Mucositis Abstract PA-15

Palifermin Is Safe and Well Tolerated in Patients With Hematologic Malignancies (HM) Undergoing High-Dose Chemoradiotherapy (HD-CRT) Followed By Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) B. Blazar1, D. Weisdorf1, T. DeFor1, A. Goldman1, S. Silver1, J.L.M. Ferrara2 University of Minnesota, Minneapolis1; University of Michigan, Ann Arbor2 BACKGROUND: Palifermin reduces the incidence and duration of severe oral mucositis (OM) in patients with HM receiving myelotoxic therapy requiring HSCT. In the allogeneic transplant setting, graft-versus-host disease (GVHD) is the limiting complication. Palifermin’s safety, tolerability, and effect on acute GVHD were evaluated in a phase 1 trial of HM patients requiring allo-HSCT. METHODS: Patients were randomized (1 placebo: 2 palifermin) to one of three sequential cohorts (stage 1, 2, or 3), receiving 3 doses of study drug before HSCT and 3, 6, or 9 doses post-HSCT. Safety evaluation included 100day and 1-year survival/relapse rates. Secondary endpoints included the incidence of OM. RESULTS: 100 patients were randomized to stage 1, 2, or 3. Twenty patients (2 placebo,18 palifermin) discontinued the study. Of these, 6 patients (2 placebo, 4 palifermin) experienced a total of 11 dose-limiting toxicities (DLTs). Discontinuations and DLTs were most common in patients who received at least 6 doses of study drug after engraftment (day 0). Eighteen patients (5 placebo, 13 palifermin) died prior to day 100, primarily due to HSCT complications. No significant differences in the time to absolute neutrophil count or platelet engraftment, or on survival, relapse rates, or acute GVHD were observed. Palifermin appeared to have a beneficial effect on OM. CONCLUSIONS: Palifermin is generally safe and well-tolerated in the allo-HSCT setting, did not have negative effects GVHD or survival rates, and appeared to have a beneficial effect on OM.

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Abstract PA-16

Oral Mucositis Incidence and Severity Reduced With AES-14: Results of a Phase III Pivotal Trial in Patients with Breast Cancer Douglas E. Peterson1, Robert G. Petit II2 1 University of Connecticut Health Center, Farmington; 2MGI Pharma Inc., Bloomington, Minnesota BACKGROUND: Oral mucositis (OM) is a common toxicity secondary to high-dose chemotherapy (CT) and can cause CT-dose limitation in patients. This randomized, double-blind, placebo controlled, phase III crossover study evaluated the efficacy and safety of L-glutamine administered via a proprietary oral drug delivery system (UpTec) in breast cancer patients receiving anthracycline-based CT regimens. The primary objective was to compare incidence and severity of moderate-severe (World Health Organization [WHO] grade ≥ 2) OM during AES-14 versus placebo treatment. METHODS: A total of 326 of 2,084 subjects developed WHO grade ≥ 2 OM during the screening CT cycle. These 326 subjects were randomized in a 1:1 ratio to receive AES-14 (n = 163) or placebo (n = 163), administered as a 5 mL dose three times a day during their next CT cycle (Treatment Cycle 1). Patients then received the alternate treatment during the next cycle of CT (Treatment Cycle 2). Efficacy was assessed by evaluation of the oral mucosa using WHO Toxicity Criteria and the Oral Mucositis Assessment Scale. Safety was assessed by adverse events, physical examination, and laboratory evaluations. RESULTS: Primary efficacy analysis focused on Treatment Cycle 1 data only, due to a significant carryover effect in Treatment Cycle 2. Incidence of WHO grade ≥ 2 OM was significantly reduced for AES-14 treated patients (38.7%) compared with placebo (49.7%; P = 0.026). Incidence of WHO grade ≥ 3 OM was significantly lower in AES-14 treated subjects (1%; 2/163) versus the placebo cohort (7%; 11/163; P = 0.0047). The carryover effect favored AES-14, whereby those who received AES-14 during Treatment Cycle 1 had a lower than expected rate of OM when they received placebo in Treatment Cycle 2. Incidence of study drug treatment-emergent adverse events was comparable in both cohorts. CONCLUSIONS: AES-14 significantly reduced incidence of clinically significant OM associated with anthracycline-based CT and could be administered safely. Study has been supported by Aesgen Inc. (until September 2004) and MGI Pharma Inc. (October 2004—present).

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2005 Chicago Supportive Oncology Conference

Abstract PA-17

No Difference on Long-Term Disease Outcomes Between Patients With Hematologic Malignancies (HM) Treated with Palifermin in the Autologous Hematopoietic Stem Cell Transplant (HSCT) Setting P. Stiff1, C. Emmanouilides2, U. Gayko3, Mon-Gy Chen3, R. Spielberger4 1 Cardinal Bernardin Cancer Center, Maywood, Illinois; 2UCLA Medical Center, Los Angeles, California; 3Amgen Inc, Thousand Oaks, California; 4City of Hope National Medical Center, Duarte, California BACKGROUND: Oral mucositis (OM), a debilitating side effect of myelotoxic chemoradiotherapy, is often associated with significant pain and increased risk of complications. Palifermin, shown to reduce the incidence and duration of severe OM in HM patients receiving myelotoxic therapy and HSCT, should not interfere with treatment outcomes, since the KGF receptor is absent in HM. We report the long-term disease outcomes of palifermin-treated patients. METHODS: Patients participating in 4 trials (phase I–III and pharmacokinetic/pharmacodynamic) and receiving one or more doses of investigational drug enrolled into an ongoing, long-term follow-up study evaluating survival, progression-free survival (PFS), and secondary malignancies. Patients were assessed at 6-month intervals during the first year and annually thereafter until death or loss to follow-up. The Kaplan-Meier (K-M) method provided estimates of the safety endpoints. Data reported here are as of August 2004. RESULTS: In all, 650 patients (408 palifermin, 242 placebo) participated in the parent trials; 538 patients enrolled in the long-term study. Median follow-up was similar (23.8 months palifermin; 23.1 months placebo), and the overall survival curves were superimposable (Figure). In each group 26% of patients died, with most of the deaths occurring within months 3–12 of randomization. PFS was similar, with 6% of patients in each group experiencing a secondary malignancy (the most common were myelodysplastic syndromes and acute lymphocytic leukemia/ acute myelogenous leukemia). Based on these data, overall survival, progression-free

survival, and secondary malignancy incidences were similar and not unexpected for this pt population. CONCLUSIONS: Palifermin use had no impact on long-term disease outcomes, including survival, in the HSCT setting.

Abstract PA-18

A Patient Self-Reported Daily Questionnaire Is a Feasible and Valid Tool in Oral Mucositis in Patients With Hematologic Malignancies Undergoing High-Dose Chemoradiotherapy (CRT) with HSCT Patrick J. Stiff1, William I. Bensinger2, Christos Emmanouilides3, Z. John Lu4, Alessandra Cesano4, Ricardo Spielberger5 1 Loyola University, Maywood, Illinois; 2Fred Hutchinson Cancer Research Center, Seattle, Washington; 3UCLA David Geffen School of Medicine, Los Angeles, California; 4Amgen, Inc., Thousand Oaks, California; 5City of Hope National Medical Center, Duarte, California Background: Oral mucositis (OM) is a frequent complication of CRT and often is rated as the most debilitating treatment-related side effect. In a pivotal phase 3 clinical trial of palifermin conducted in the HSCT setting, patients (placebo = 106, palifermin = 106) were asked to assess their OM severity and functional limitations (swallowing, eating, drinking, talking, sleeping) through a selfreported daily questionnaire (Oral Mucositis Daily Questionnaire [OMDQ]) while physicians used the World Health Organization (WHO) clinical scale for measuring OM severity (WHO-OM). The feasibility and validity of the OMDQ were evaluated and are reported here. METHODS: OMDQ feasibility was measured by daily compliance rate. Pearson correlation coefficients were computed to measure test-retest reliability, internal consistency reliability, and discrimination validity. RESULTS: The mean daily compliance rate for OMDQ completion over the entire study period was at least 84% in both treatment groups. The Pearson correlation coefficients ranged from 0.6–0.9, 0.5–0.8; and 0.3–0.6 for testretest reliability, internal consistency reliability, and discriminative WHO and OMDQ Scores

Kaplan-Meier Survival Curves for Palifermin and Placebo Patients

3.5 WHO mucositis grade, OMDQ score

Percent survival

100% 80% 60% 40% Palifermin (n = 241) Placebo (n = 409)

20% 0%

12

24

36 Study month

48

60

3.0

WHO grade

2.5

OMDQ score

2.0 1.5 1.0 0.5 0.0

–12 –8

–4

0

4

8 12 Study day

16

20

24

28

32

WHO = World Health Organization; OMDQ = Oral Mucositis Daily Questionnaire

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THE JOURNAL OF SUPPORTIVE ONCOLOGY

Poster Abstracts

validity, respectively. Figure 1 shows the distributions over time of the average daily scores from the OMDQ (mouth and throat soreness) and WHO-OM. Although the shapes of the distribution curves were similar, there was a significant temporal difference. Patients reported onset, peak, and resolution of oral pain earlier (1 to 3 days) than did their physicians, who were using the clinical assessments. CONCLUSIONS: A daily diary could be used as a valid alternative to clinical measurements of OM in clinical settings where the latter might be impractical.

Abstract PA-20

Neutropenia

BACKGROUND: We conducted a retrospective study comparing patterns of care and neutropenia-related complications among patients receiving pegfilgrastim in 2003 and patients receiving filgrastim in 2001. METHODS: Consecutive medical records (n = 829, filgrastim; n = 1922, pegfilgrastim) were abstracted for adult chemotherapy patients from a random sample of 99 US oncology practices, obtaining characteristics, treatment, and neutropenia-related complications data. RESULTS: The most common tumor types were breast (51%), lung (19%), and non-Hodgkin’s lymphoma (18%). There were no significant differences in age (mean, 58 and 60 years for pegfilgrastim and filgrastim, respectively) or prior neutropenia or febrile neutropenia (4% and 5%, respectively). Pegfilgrastim was initiated in cycle 1 in 62% of patients and used in cycle 2 by 84%. Filgrastim was initiated in cycle 1 in 54% of patients and used in cycle 2 by 78%. Growth factor was initiated within 72 hours of chemotherapy in 86% of cycles for pegfilgrastim patients but only 48% of cycles for filgrastim patients. Among patients receiving filgrastim in cycle 1, treatment was initiated > 10 days after chemotherapy in 49% of patients versus 6% of pegfilgrastim patients. Filgrastim patients experienced more neutropenia-related complications. CONCLUSIONS: Patients receiving pegfilgrastim were more likely to receive growth factor within 72 hours of chemotherapy and had a lower incidence of neutropenia-related complications compared with patients receiving filgrastim.

Abstract PA-19

Pegfilgrastim Use in Older Patients (> 60 Years) Maintains Dose Intensity of DoseDense Adjuvant Chemotherapy for EarlyStage Breast Cancer R.E. Birhiray, R.T. Schmidt, J. Powell, R.M. Harwood Hematology-Oncology of Indiana, PC, Indianapolis, Indiana BACKGROUND: Long-term survival in early-stage breast cancer (ESBC) correlates positively with > 85% relative dose intensity (RDI) and dose density of adjuvant chemotherapy (Bonnadonna,1995; Citron, 2003). A recent national survey reported that nearly 75% of patients receive < 85% RDI. Increased age and no first-cycle colony-stimulating factor have been identified as independent predictors for reduced RDI (Lyman, 2003). This retrospective case study evaluates pegfilgrastim use in the first and subsequent cycles to support dose-dense chemotherapy for breast cancer in patients > 60 years. METHODS: Patients > 60 years with ESBC treated over a 2-year period with dose-dense adjuvant chemotherapy (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2 weeks followed by paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 every 2 weeks) and pegfilgrastim (6 mg/cycle) were identified by chart review. RDI, treatment delays, neutropenic fevers, and other toxicities were assessed. RESULTS: Fifteen patients were evaluated. Median (range) age was 66 (60–78) years, and all patients had a performance status of 1. In total, 119 of 120 planned chemotherapy cycles were administered (one withheld due to peripheral neuropathy), and RDI was 94.8%. Dose delays occurred in 2 patients (1 pneumonia, 1 peripheral neuropathy). Four patients had four episodes of neutropenic fever over 119 cycles (3.4%). These patients subsequently received antibiotic prophylaxis without reoccurrence. Anemia (hemoglobin level < 11 g/dL) occurred in 12 patients, all requiring erythropoietin support. Other toxicities included nausea and vomiting, hand and foot syndrome (docetaxel), peripheral neuropathy, bone pain, facial cellulitis, mucositis, pneumonia, and headaches. CONCLUSIONS: In this small case study, patients > 60 years with ESBC were successfully administered dose-dense adjuvant chemotherapy with pegfilgrastim support.

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Patterns of Care and Incidence of Neutropenia-Related Complications During Chemotherapy and the Use of Pegfilgrastim and Filgrastim in Community Practice: Results of the ACCEPT Study Luis T. Campos1, Mitchell H. Folbe2, Veena Charu3, Jennifer Malin4, Beiying Ding4, Roger Dansey4 1 Oncology Consultants, P.A., Houston, Texas; 2Medical Oncology, Troy, Michigan; 3Pacific Cancer Medical Center, Inc., Anaheim, California; 4Amgen Inc., Thousand Oaks, California

NEUTROPENIA-RELATED PEGFILGRASTIM COMPLICATIONS (% [95% CL]) (n = 1,922)

FILGRASTIM (n = 829)

P VALUE

Febrile neutropenia Hospitalization for febrile neutropenia Anti-infective treatment for infection

6% (5, 7) 4% (3, 4)

10% (8, 12) 6% (4, 8)

0.0004 0.01

24% (22, 26)

32% (29, 35)

< 0.0001

CL = confidence limits

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Abstract PA-21

Pegfilgrastim in All Cycles Reduces Chemotherapy-Induced Neutropenia in Older Patients W. Ershler1, T. Pluard2, N. Angel3, S. Shahin4, J. Green4, R. Dansey4, L. Balducci5 1 Institute for Advanced Studies in Aging, Washington, DC; 2 Missouri Cancer Care PC, Saint Charles, Missouri; 3Oncology Center at Providence Park, Mobile, Alabama; 4Amgen Inc., Thousand Oaks, California; 5Moffitt Cancer Center and Research Institute, Tampa, Florida BACKGROUND: Chemotherapy-induced neutropenia is common in older patients. As a result, older patients often receive reduceddose chemotherapy, limiting effectiveness. This study evaluated first-cycle pegfilgrastim in reducing neutropenic complications of chemotherapy among older patients. METHODS: Patients ≥ 65 years old receiving chemotherapy for lung, breast, or ovarian cancer or non-Hodgkin’s lymphoma (NHL) were randomized to receive either pegfilgrastim 6 mg in all cycles or no pegfilgrastim in cycle 1 with subsequent use determined by physician. Results are presented only for solid tumors. RESULTS: In total, 686 patients were included in the primary analysis set, 343 per treatment group. Median age was 72 years (range, 65–88); 66% were female. The most commonly administered chemotherapies were carboplatin with paclitaxel (36%), etoposide (15%) or docetaxel (12%), and doxorubicin with cyclophosphamide (15%). In the physician discretion arm, 42% of patients received pegfilgrastim, most often due to grade 3/4 neutropenia in a previous cycle (62%). Overall incidence of febrile neutropenia (absolute neutrophil count < 1,000/µL and temperature ≥ 38°C) was significantly lower for patients receiving pegfilgrastim in all cycles (4%) than for those receiving no pegfilgrastim in cycle 1 (10%; P = 0.0014). Patients receiving pegfilgrastim in all cycles had a lower incidence of grade 3/4 neutropenia (30% vs 80%), chemotherapy dose reduction (7% vs 14%), hospitalization for neutropenia-related events (5% vs 9%), anti-infective use (12% vs 29%), and serious adverse events (26% vs 35%) compared with patients in the other group. CONCLUSIONS: Pegfilgrastim used from the first chemotherapy cycle onward offered patients advantages in terms of reducing neutropenic complications, thus improving clinical outcomes.

Abstract PA-22

Impact of First and Subsequent Cycle Pegfilgrastim on Neutropenic Events in Patients Receiving Myelosuppressive Chemotherapy: Preliminary Results of FIRST, a Prospective Community-Based Study Howard Ozer1, Beiying Ding2, Roger Dansey2 1 University of Oklahoma Cancer Center, Oklahoma City; 2 Amgen Inc., Thousand Oaks, California BACKGROUND: Most alterations to chemotherapy dose and schedule

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are due to neutropenic events, mostly occurring in cycle 1. The ANC Registry documented cycle 1 febrile neutropenia rates of 8% in patients receiving chemotherapy with community colonystimulating factor support. This community-based study in cancer patients receiving myelosuppressive chemotherapy evaluates the impact of first-and-subsequent cycle pegfilgrastim on neutropenic events. METHODS: This open-label, single-arm study enrolled 2,252 adult patients (319 sites) with cancers other than leukemia or myelodysplastic syndrome patients, including patients with major comorbid illnesses not generally eligible for clinical trials. Patients received pegfilgrastim 6 mg about 24 hours post chemotherapy in each cycle. Endpoints include neutropenic complications and chemotherapy dose reductions and delays. Point estimates (95% confidence limits (CL]) are provided. RESULTS: First-cycle data from 874 patients (201 sites) are available. In all, 76% of patients were women, and most had breast cancer (51%). The mean (SD) age was 58.6 (12.9), 48% of patients had early-stage (I–II) disease, 21% received prior chemotherapy, 15% received prior radiotherapy, and 26% had significant comorbidities. See table for neutropeniarelated events. Serious adverse events were consistent with those observed in patients receiving myelosuppressive chemotherapy. CONCLUSIONS: Community-practice patients receiving firstand-subsequent cycle pegfilgrastim and myelosuppressive chemotherapy experienced few neutropenic complications and alterations in chemotherapy dose and schedule. NEUTROPENIA-RELATED EVENTS

Cycle 1 febrile neutropenia Cycle 1 neutropenia-related IV antibiotics use Cycle 1 neutropenic hospitalizations Cycle 2 reported dose reductions (all reasons) Neutropenia-related dose reductions Cycle 2 reported dose delays (all reasons) Neutropenia-related dose delays

INCIDENCE (95% CL) (n=874)

2% 2% 2% 6% 2% 5% < 1%

(1%, 4%) (1%, 3%) (1%, 3%) (5%, 8%) (1%, 3%) (4%, 7%) (0%, 1%)

Abstract PA-23

Neutropenia and Anxiety in Advanced NonSmall Cell Lung Cancer (NSCLC) Patients: Initial Report of a Randomized, Controlled, Pilot Trial Using Pegfilgrastim to Reduce Neutropenia Complications F. Smith1, L. Wagner2, M. Kandahari3, S. Shahin3, J. Malin3, R. Dansey3, J. Crawford4 1 Sibley Memorial Hospital, Washington, DC; 2Northwestern University, Feinberg School of Medicine, Chicago, Illinois; 3 Fairfax Hospital Cancer Center, Fairfax, Virginia; 3Amgen, Thousand Oaks, California; 4Duke University Medical Center, Durham, North Carolina BACKGROUND: Potential chemotherapy side effects may adversely impact patients’ physical, social, and mental well-being (eg, anxiety). This study evaluated the association between

THE JOURNAL OF SUPPORTIVE ONCOLOGY

Poster Abstracts

chemotherapy-induced neutropenia and quality-of-life changes using the Hospital Anxiety and Depression Scale (HADS) and other measures. METHODS: Stage IIIB/IV NSCLC patients receiving carboplatin AUC 5/6 with paclitaxel 175–225 mg/m2 or docetaxel 75 mg/m2 randomized to first-and-subsequent-cycle pegfilgrastim or no pegfilgrastim in cycle 1 with subsequent cycle use according to physician discretion. Complete blood counts and HADS were administered on day 1 of cycles 1 to 3, and at expected cycle 1 and 2 ANC nadir. Endpoints included neutropenia incidence and change in HADS-anxiety (HADS-A) subscale (ranging from 0 [not anxious] to 21 [most anxious]). RESULTS: In all, 149 patients were treated, mean (SD) age 65.0 (11.4), 60% male, 52% carboplatin-paclitaxel. Grade 3/4 neutropenia incidence (95% CL) in cycles 1 and 2 was 5% (2%, 13%) for patients receiving first-and-subsequent-cycle pegfilgrastim and 43% (31%, 55%) for patients receiving physician-discretion pegfilgrastim. Over 70% of patients completed all HADS-A items at each timepoint. Exploratory analyses of HADS-A change scores from baseline to end of cycle 1 and 2 are presented in the table. CONCLUSIONS: Neutropenia was markedly reduced, and initial analysis suggested anxiety may have been reduced for patients receiving first-andsubsequent-cycle pegfilgrastim. FIRST-CYCLE PEGFILGRASTIM

PHYSICIAN DISCRETION

Mean (95% CL) HADS-A 7.15 (5.88, 8.42) 7.02 (6.05, 7.98) cycle 1 baseline n = 59 n = 65 HADS-A mean change (95% CL) from cycle 1 baseline to end of: Cycle 1 –1.69 (–2.81, –0.58) –0.40 (–1.17, 0.37) n = 59 n = 65 Cycle 2 –1.65 (–2.88, –0.43) –0.34 (–1.32, 0.64) n = 55 n = 50 HADS = Hospital Anxiety and Depression Scale; CL = confidence limits

Involuntary Weight Loss Abstract PA-24

Cost-Utility Analysis: Oxandrolone Versus No Treatment for Cancer-Related Weight Loss Hind T. Hatoum , A. Simon Pickard 1 Hind T. Hatoum & Company, Chicago, Illinois; 2University of Illinois, College of Pharmacy, Chicago 1,2

2

BACKGROUND: Cancer-related involuntary weight loss (IWL) adversely impacts cancer outcomes and quality of life (QOL). Studies have demonstrated oxandrolone to be effective, resulting in improved weight and QOL scores and associated cost savings. We performed a cost-utility analysis of oxandrolone treatment versus no treatment in cancer-related IWL from a payer perspective. METHODS: Data from an open-label trial of oxandrolone 10 mg twice daily in cancer patients were used. Direct medical care costs were derived from predicted hospitalization and discharge to long term care based on body mass index (BMI) change. Incremental cost-effectiveness using quality adjusted

VOLUME 3, NUMBER 5, SUPPLEMENT 3

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life-years was calculated by transforming QOL data (Functional Assessment of Cancer Therapy-General [FACT-G]) responses to utilities using an algorithm derived from cancer patients. RESULTS: Based on 67 patients with complete FACT-G and BMI at baseline and 2 months, oxandrolone resulted in a net cost savings of $895 per patient and an improvement in the FACT-G based mean utility score of 0.034 ± 0.09 (P = 0.008) versus no treatment. CONCLUSIONS: Oxandrolone was a dominant strategy resulting in cost savings and gains in health-related QOL after more than 2 months versus no treatment. Sensitivity analysis resulted in an incremental cost-utility ratio for oxandrolone of $3,427 per quality adjusted life month within 2 months of treatment, becoming a dominant strategy from 3 months onwards, with net cost savings averaging $606 per patient per month.

Abstract PA-25

A Pilot Limited Institutional Study to Evaluate the Safety and Tolerability of Immunocal, a Nutraceutical Cysteine Delivery Agent in the Management of Wasting in High-Risk Childhood Cancer Patients Steven J. Melnick1, Paul Rogers2, Nancy Sacks3, Thomas A. Kwyer4, Jacqueline Halton5, Eric Sandler6, Enrique Escalon7, Elena J. Ladas8 1 Department of Pathology and Laboratories, Miami Children’s Hospital. Miami, Florida; 2Division of Paediatric Haematology/ Oncology & Bone Marrow Transplantation, C&W Hospital and University of BC, Vancouver, British Columbia, Canada; 3 Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; 4Division of Otolaryngology, Department of Surgery, Medical University of Ohio, Toledo, 5 Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada; 6Nemours Children’s Clinic-Jacksonville Hematology/ Oncology; Jacksonville, Florida; 7Division of Hematology/ Oncology, Miami Children’s Hospital, Miami, Florida; 8 Integrative Therapies Program for Children with Cancer, Columbia University, New York, New York B ACKGROUND : This pilot study, conducted through the Nutrition subcommittee of the Children’s Oncology Group (COG), evaluated the safety and tolerability of Immunocal, an undenatured whey-protein derivative that provides glutathione precursors. Depletion of reduced glutathione (GSH) in various organs including the immune system is a common finding in cachexia, reduced immune function, and poor wound healing, which are among the serious consequences cancer patients endure due to their disease and/or therapy. The study was a 90-day, two-dose evaluation of Immunocal (0.5 g/kg vs 1.0 g/kg) added to the standard institutional nutritional regimen. METHODS: Twelve patients with high-risk solid tumors were enrolled from three institutions. Clinical and biochemical data were assessed at baseline and on days 45 and 90. RESULTS: Immunocal was successfully administered by one or more of three routes (oral, gastric tube, and nasogastric tube) and was

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2005 Chicago Supportive Oncology Conference

generally well tolerated. Compliance ranged from 55%–100% (7 patients with > 88%). All but 2 patients gained weight ranging from 7.3%–26.9% from the prestudy weight. Though not statistically significant, GSH levels increased in 83% of patients, whereas oxidized glutathione levels decreased in 83%. Other observations include the amelioration of severe mucositis in 2 patients and abatement of nausea and vomiting in 2 patients. CONCLUSIONS: The findings indicated Immunocal could be given safely and was well tolerated in the majority of pediatric cancer patients. The results are being used to establish end-points for a double-blind placebo controlled trial to be submitted to the COG scientific committee to evaluate of the efficacy of Immunocal in high-risk cancer patients.

Abstract PA-26

Psychosocial and Dietary Management of Anorexia by Patients with Advanced Cancer Jeremy E. Shragge1,2, Kärin Olson2, Wendy Wismer1, Vickie Baracos3 1 Department of Agricultural, Food and Nutritional Sciences, 2 International Institute for Qualitative Methodology, and 3 Department of Oncology, University of Alberta, Edmonton, Alberta, Canada. BACKGROUND: Anorexia (loss of appetite) figures prominently in the numerous stresses and losses that cancer patients face near the end of life. Malnutrition attendant to anorexia may undermine tolerance to treatment, strain patient-family relationships, and hasten patient death. The primary objective of this qualitative study was the creation of a theoretic framework that would integrate the strategies used by patients to manage the dietary and psychosocial consequences of anorexia. METHODS: Grounded Theory methodology was employed to guide and analyze tape-recorded, open-ended interviews with anorectic patients with advanced cancer (n = 9). RESULTS: We discovered that preparation and consumption of meals lost most of their pleasurable qualities for patients. In addition, patients craved specific foods rarely, experienced little spontaneous food ideation, and suffered varying degrees of early satiety. The unconscious impetus to eat (hunger) was greatly diminished if not totally lost. Whereas anorexia was not in itself necessarily distressful to patients, its logical, long-term consequences (ie, weakness and starvation) were. “Establishing control” over both the impetus to eat and the maintenance of adequate caloric intake emerged as the core category. Despite appetite loss, patients would often attempt food by resolving that they “had to eat” in order to survive. When the conscious impetus to eat (“I have to eat”) was overridden by the compelling desire to avoid nausea and emesis (“I just can’t eat”), patients often were left feeling conflicted and frustrated. In some instances, however, patients were content with small meals that did not precipitate distressing physical symptoms. C ONCLUSIONS : Nutritional interventions developed to ameliorate the consequences of

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anorexia must a) compensate for the loss of the unconscious impetus to eat and b) acknowledge that patients physically capable of oral intake can nevertheless experience an absolute inability to eat.

Quality Care Abstract PA-27

Psychosocial Outcomes of Prostate Cancer Survivors on Androgen-Deprivation Therapy Sylvie Aubin Department of Psychiatry and Behavioral Medicine, University of Washington, Seattle B ACKGROUND : Prostate cancer is the most common solid tumor in men. Following primary therapy, more than 20% of men experience a biochemical relapse. Androgen-deprivation therapy (ADT) is commonly used to treat biochemical relapse but significantly affects quality of life (QOL). Research has investigated the physical effects of ADT extensively, yet minimal studies examine psychosocial effects of ADT. This study evaluated the impact of intermittent use of ADT on QOL domains of physical stamina/vitality and sexual function. Participants (n = 32) with biochemical relapse and no evidence of metastases were treated with leuprolide and flutamide on an intermittent basis of 9 months of followed by an “off” period. METHODS: Self-report questionnaires included the Southwest Oncology Group Intermittent Androgen Suppression Quality of Life Questionnaire administered prior to ADT and after 9 months of treatment. RESULTS: The median age was 66 years (range, 51–71). Results showed significant pre- to post-ADT decrease in physical stamina/vitality. Men reported feeling more worn out and tired. In addition, results showed an increase in the number of men reporting a lack of sexual activities, decreased sexual desire, and worsening of their overall sexual function. CONCLUSIONS: Significant results stressed the importance of assessing changes in stamina, fatigue, and sexuality of men treated with ADT. Results also suggested the need to assess non-functional aspects of sexuality, such as intimacy, to determine if it also is negatively impacted by ADT. The study results improved our knowledge of the effects of ADT on QOL and may help design interventions to address side effects.

THE JOURNAL OF SUPPORTIVE ONCOLOGY

Poster Abstracts

Abstract PA-28

The Use and Delivery of Emergency Drug Kits (EDKs) at the Birmingham VA Medical Center: A Multidisciplinary Quality Improvement Project Using the Plan-Do-Study-Act (PDSA) Cycle Joseph T. Chan1,2, Heather D. Au1, J. Andrew Carr1, James T. Coleman1, Debra Cook-Rice1,and Frank Amos Bailey1,2 1 Birmingham VA Medical Center, Birmingham, Alabama; 2 University of Alabama at Birmingham Center for Palliative Care, Birmingham BACKGROUND: The Birmingham VA Medical Center’s Palliative Care Service provides an emergency drug kit (EDK) to veterans enrolled in hospice to alleviate anticipated terminal symptoms. The EDK contains lorazepam, morphine sulfate, promethazine, scopolamine, furosemide, haloperidol and gatifloxacin. Prescription adherence to an EDK including morphine sulfate and the complete delivery of the EDK have not been consistent, which is a barrier to symptom control at the end of life. We evaluated the effectiveness of a multidisciplinary intervention based on the following outcome measures: (a) provider adherence to an EDK prescription; (b) inclusion of morphine sulfate, and (c) complete delivery of the EDK. METHODS: This is a pre-post intervention trial based on a Plan-Do-Study-Act (PDSA) cycle. The intervention involved strategies from medical, information technology, nursing, and pharmacy disciplines. Before- and afterimplementation outcome measures data were abstracted from the medical records of deceased veterans enrolled in hospice. Monthly results will be tracked on a run chart for 6–12 months and statistically analyzed. PRELIMINARY RESULTS: Pre-intervention records of deceased veterans were reviewed from January to March 2003. Of the 36 veterans, 83% were prescribed an EDK, only 67% of which included morphine sulfate. EDKs were completely delivered 65% of the time. Post-intervention outcome measures for the past 4 months have shown an upward trend, approaching 100% for the month of July. CONCLUSIONS: A multidisciplinary quality improvement project based on a PDSA cycle can be an effective intervention to the use and delivery of EDKs.

Abstract PA-30

Patient-Reported Symptom Complaints Associated with 5-Fluorouracil (5-FU) + Irinotecan (IRI) or Oxaliplatin (OXALI) in Colorectal Cancer (CRC) Barry Fortner1, Kimary Kulig2, Ling Zhu1, Samuel Wagner2, Johnetta Blakely3, Lee Schwartzberg3 1 Accelerated Community Oncology Research Network, Memphis, Tennessee; 2Pfizer Outcomes Research, New York, New York, 3 The West Clinic, Memphis, Tennessee BACKGROUND: Although toxicities have been documented in CRC clinical trials, less has been done to explore patient-reported severity of these same toxicities in actual clinical practice. Medicare’s recent emphasis on quality of supportive care further highlights the need to understand and treat these symptoms. This study describes results of preliminary analyses in CRC chemotherapy patients through use of a validated patient report tool. METHODS: A database generated from two large community oncology practices was accessed, and CRC patients who

SYMPTOM

Abstract PA-29

Item Validation of Patient Care Monitor Version 2 (PCM2.0) Using Nursing Interview and PCM1.0 Barry V. Fortner, Lee S. Schwartzberg, Arthur C. Houts Supportive Oncology Services, Memphis, Tennessee; The West Clinic, Memphis Tennessee BACKGROUND: The PCM1.0 assessment system brought state-ofthe-art technology to assessing cancer patients in community oncology, where over 80% of all cancer patients in the United States are assessed and treated. PCM1.0 is a psychometrically reliable and valid measure of patient symptoms, functioning, and QOL. The system is tablet-computer based. This investigation

VOLUME 3, NUMBER 5, SUPPLEMENT 3

compares PCM1.0 with a new expanded version, PCM2.0, and with a structured interview by expert oncology nurse. METHODS: Cancer patients (n = 75) completed PCM1.0 and PCM2.0 in counterbalanced order and also were interviewed by one of three expert oncology nurses. Validity was examined at the item level using nursing interview results as the gold standard. Problems were judged as being either present or absent and, if present, were rated for severity on a 0–10 severity scale. Interjudge reliability between nursing interviewers was established for 30 cases using tape recordings of interviews. Item correlations and paired t test were used to assess comparability of rated severity. Kappa was used to assess agreement for presence/absence of any single problem at the item level. Receiver operating characteristics (ROC) analysis was computed for all 87 items and related statistics were reported.

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Fatigue, tiredness, or weakness Rash or dry skin or itching Daytime sleepiness Physical pain Nausea or vomiting Trouble w/ diarrhea or constipation Trouble sleeping Numbness or tingling Burning in hands or feet Fever or chills

5-FU + OXALI MODERATE SEVERE n (%) n (%)

5-FU + IRI MODERATE SEVERE n (%) n (%)

43 (38.05) 38 (33.63) 18 (31.58) 9 (15.79) 28 (24.78) 10 (8.85) 34 (30.09) 30 (26.55) 28 (24.78) 33 (29.20)

15 (13.27) 24 (21.24) 21 (18.58) 28 (24.78)

9 (15.79) 2 (3.51) 10 (17.54) 12 (21.05) 15 (26.32) 17 (29.82)

6 9 5 13

(10.53) (15.79) (8.77) (22.81)

42 (37.17) 23 (20.35) 13 (22.81) 9 (15.79) 35 (30.97) 21 (18.58) 9 (15.79) 4 (7.02) 24 (21.24) 7 (6.19) 4 (7.02) 2 (3.51) 15 (13.27)

7 (6.19)

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5 (8.77) 1 (1.75)

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2005 Chicago Supportive Oncology Conference

completed at least one Cancer Care Monitor (CCM), a patient report measure including 38 physical cancer-related symptoms, were eligible. CCM scores reported within 28 days of a 5-FU + IRI or OXALI administration between 8/1/03 and 7/31/04 were selected. Patients indicated severity on an 11-point Likert scale (0 = No problem; 1–3 = Mild; 4–6 = Moderate; 7–9 = Severe; 10 = As bad as possible). RESULTS: In all, 57 IRI patients (mean age, 57 years; male = 63%) and 113 OXALI patients (mean age, 58 years; male = 50%) contributed 9 and 10 CCM administrations per patient, respectively. Frequencies of selected symptoms are in the table. CONCLUSIONS: A wide range of high-severity symptoms were reported at even greater frequencies than in clinical trials relying on clinician-rated toxicity. A patient self-report tool is valuable for longitudinal assessment of frequency and severity of symptoms and can emphasize the need for quality supportive care. Our ongoing study will delineate treatment-specific differences in symptom reporting.

Abstract PA-31

Validation of the Functional Assessment of Cancer Therapy-Brain (FACT-Br) Questionnaire and FACT-Br Symptom Index (FBrSI) in Patients with Recurrent High-Grade Gliomas Angel Nickolov1, Jennifer L. Beaumont1, David Victorson1, Amy H. Peterman2, David Cella1, Astra M. Liepa3, Howard A. Fine4 1 Center for Outcomes, Research and Education (CORE), Evanston Northwestern Healthcare, Evanston, Illinois; 2 University of North Carolina, Charlotte, North Carolina; 3Eli Lilly and Company, Indianapolis, Indiana; 4 Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland BACKGROUND: The Functional Assessment of Cancer TherapyBrain (FACT-Br) has been validated previously in a mixed sample of patients with diagnosis of primary brain tumors. The FACT-Br Symptom Index (FBrSI) was later developed in coordination with the National Comprehensive Cancer Network through interviews with expert providers to determine the most important symptom targets when treating advanced cancer. METHODS: The FACT-Br, including FBrSI, was administered to patients with recurrent highgrade gliomas participating in a phase II trial of enzastaurin for the purpose of validating the questionnaire in this population. It was administered prior to start of therapy, at 3 weeks, at 6 weeks, and then every 6 weeks thereafter while on therapy. RESULTS: In this preliminary sample, 71% of patients had a diagnosis of glioblastoma multiforme and 70% had a Karnofsky performance status rating (PSR) of ≥ 90% at baseline. The FACT-Br data were available for 82 patients at baseline, 65 at 3 weeks and 45 at 6 weeks. The 23-item Brain Subscale (BrS) and 15-item FBrSI demonstrated good internal consistency with Cronbach’s alphas at the three assessments of 0.85–0.88 and 0.76–0.86, respectively. Both scales differentiated patients by PSR at all assessments (all P < 0.05). The BrS and FBrSI both demonstrated responsiveness

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to change in PSR (P = 0.001 and 0.003, respectively) at 6 weeks. CONCLUSIONS: Based on distribution- and anchor-based methods, minimally important differences were estimated as 5–7 points for the BrS and 3–4 points for the FBrSI. The BrS and FBrSI may be useful endpoints in the assessment of therapies for recurrent high-grade glioma.

Abstract PA-32

The Life Tape Project, An Existential Intervention for Cancer Patients: A Progress Report Ernest Rosenbaum1, Robert W. Garlan2, Alison L. Siegel3, Shelly Henderson4, Naama Hirschberger5, Lisa D. Butler6, David Spiegel6 1 Department of Medical Oncology and the Comprehensive Cancer Center, University of California, San Francisco; 2 Private Practice, San Jose, California; 3Breast Cancer Clinic and Resource Center, University of California, San Francisco; 4 Pacific Graduate School of Psychology, Palo Alto, California; The Sharett Institute of Oncology, Hadassah University Medical Center, Jerusalem, Israel; 6Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California; BACKGROUND: Confronting cancer, most patients struggle with their mortality and threats to their emotional equilibrium and that of their families. Families may become closer, but, frequently, communication difficulties and isolation increase. The Life Tapes Project (LTP) is an intervention involving a 2-hour video-recorded life history, that is designed to help patients and their families confront this existential crisis. Previous observation and pilot data suggest that patients receive substantial benefits from participation. Preliminary results from a new study, designed to quantify and extend these observations, are reported. METHODS: Patients completed baseline questionnaires before the LTP interview and follow-up packets 2 and 10 weeks after. Measures included, among others, the FACT-G for Quality of Life (QOL) and a measure of perceived benefits of participation covering eight themes suggested by previous research. A final semistructured interview probed possible unwanted effects. RESULTS: The results for the first followup (n = 23 to date) indicated that QOL improved significantly, and substantial benefits (endorsing “very” or “extremely true for me”) were reported by a majority of participants. The most frequently endorsed items related to themes of Imparting Personal Philosophy (74% of participants), Reducing Existential Dread (70%), Gaining Perspective and Meaning (65%), and Improved Communication (57%). Final interviews revealed no unwanted effects. CONCLUSIONS: The LTP provideda powerful, safe, and accessible intervention that can improve family communication and connectedness, promote personal growth, and reduce existential anxiety through the creation of “symbolic immortality.” Requiring minimal equipment and time, the LTP would make an excellent addition to any supportive care program.

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