Epoetin Alfa in Treating Fatigue in Patients With Advanced Solid Tumors Who Are Not Receiving Chemotherapy

A Placebo Controlled Trial Of Short-Term, High-Dose Epoetin Alfa In Advanced Cancer Outpatients With Mild Fatigue

RATIONALE: Epoetin alfa may help improve energy levels and quality of life in patients who have advanced solid tumors.

PURPOSE: Randomized clinical trial to study the effectiveness of epoetin alfa in treating fatigue in patients who are not receiving chemotherapy for advanced solid tumors.

OBJECTIVES:

• Determine the efficacy of epoetin alfa in treating fatigue in patients with advanced solid tumors who are not receiving chemotherapy.
• Determine the efficacy of this drug on functional status and overall quality of life in these patients.
• Correlate self-reported level of energy with other commonly occurring symptoms (e.g., pain, depression, anxiety, dyspnea, appetite disturbance, or sleep disturbance) in these patients.
• Correlate anemia with other common symptoms in these patients.
• Determine the internal consistency of fatigue self-report using three single-item measures of this symptom and the responsiveness of each item to change over time in these patients.

OUTLINE: This is a double-blind, placebo-controlled, randomized, multicenter study. Patients are stratified according to participating center, ECOG performance status (0-1 vs 2-3), and hemoglobin prior to study (10 mg/dL or less vs greater than10 mg/dL). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive epoetin alfa subcutaneously (SC) once weekly for 6 weeks.
• Arm II: Patients receive placebo SC once weekly for 6 weeks. Patients in either arm that do not respond to therapy may receive an additional 6 weeks of open-label epoetin alfa SC once weekly.

In both arms, quality of life and fatigue are assessed at baseline and at 3 and 6 weeks. If patients receive an additional 6 weeks of therapy, quality of life and fatigue are also assessed at 9 and 12 weeks.

PROJECTED ACCRUAL: A total of 128 patients (64 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of stage III or IV invasive non-myeloid malignancy

• Not currently hospitalized

• At least somewhat bothered by fatigue based on self-report

  • No significant psychological distress indicated by total score of 6 or more on questions 1 and 2 of the Three-Question Screening Survey (3QSS)
  • No score less than 2 on question 3 of 3QSS indicating low level of fatigue within the past week

• No uncontrolled brain metastases or leptomeningeal involvement

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Eastern Cooperative Oncology Group (ECOG) 0-3

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Hemoglobin at least 8.5 g/dL but no greater than 11 g/dL
• No anemia due to factors other than cancer or chemotherapy (e.g., iron or folate deficiency, hemolysis, or bleeding)
• No prior or concurrent hematological disease

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No uncontrolled hypertension (diastolic blood pressure greater than 100 mm Hg or systolic blood pressure greater than 200 mm Hg)
• No significant uncontrolled concurrent cardiovascular disease or dysfunction not attributable to malignancy or chemotherapy
• No history of deep-vein thrombosis

Pulmonary:

• No significant uncontrolled concurrent pulmonary disease or dysfunction not attributable to malignancy or chemotherapy

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 3 months after study participation
• Able to understand and complete self-report symptom assessment forms in English
• No serious concurrent infection
• No known hypersensitivity to mammalian cell-derived products or human albumin
• No uncontrolled seizures
• No significant uncontrolled concurrent endocrine, neurologic, gastrointestinal, or genitourinary system disease or dysfunction not attributable to malignancy or chemotherapy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Chemotherapy
• More than 4 weeks since prior biologic therapy (e.g., interferon or interleukin-2)
• More than 2 months since prior red blood cells (RBC) transfusion
• More than 1 month since prior epoetin alfa or investigational forms of epoetin alfa (e.g., gene-activated, novel erythropoiesis-stimulating protein)
• Concurrent non-myelosuppressive therapy (e.g., monoclonal antibody infusions, antiangiogenesis inhibitors, or signal transduction inhibitors) allowed
• No other concurrent biologic therapy

Chemotherapy:

• No prior high-dose chemotherapy (e.g., with bone marrow or stem cell transplantation)
• More than 4 weeks since prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy:

• Concurrent hormonal therapy allowed (e.g., luteinizing hormone-releasing hormone agonists or tamoxifen)

Radiotherapy:

• More than 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• Not specified