Docetaxel and Prednisone in Treating Patients With Hormone-Refractory Metastatic Prostate Cancer

OBJECTIVES:

Primary

• Compare the time to treatment failure in patients with hormone-refractory metastatic prostate cancer treated with two different schedules of docetaxel in combination with prednisone.

Secondary

• Compare overall survival of patients treated with these regimens.
• Compare the response rate in patients treated with these regimens.
• Compare the safety of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.
• Compare the need for epoetin beta in patients treated with these regimens.
• Determine the effect of epoetin beta on hemoglobin response rate, transfusion rate, and quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center and WHO performance status (0-1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive docetaxel IV over 1 hour on days 1 and 15 and oral prednisone once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive docetaxel IV over 1 hour on day 1 and prednisone once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients who experience anemia (hemoglobin < 11 g/dL) receive epoetin beta subcutaneously once weekly during chemotherapy.

Quality of life is assessed at baseline, every 6 weeks during study treatment, at completion of study treatment, and then every 2 months thereafter.

After completion of study treatment, patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 360 patients (180 per treatment arm) will be accrued for this study within 4 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the prostate

• Metastatic disease by imaging or clinical examination
• Hormone-refractory disease, defined as prostate-specific antigen (PSA) level > 10 µg/L AND rising between 2 sequential measurements
• Testosterone within castration levels by orchiectomy or medical castration comprising luteinizing hormone-releasing hormone (LHRH) analogues

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Neutrophil count ≥ 1,500/mm^3
• Hemoglobin ≥ 11.0 g/dL
• Platelet count ≥ 100,000/mm^3

Hepatic

• ALT and AST ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin normal
• Alkaline phosphatase ≤ 6 times ULN (unless due to the presence of extensive bone disease)
• No serious liver disease

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No ischemic or thromboembolic cardiac disease
• No myocardial infarction within the past 12 months
• No other serious cardiac disease

Pulmonary

• No pulmonary emboli

Immunologic

• No active infection
• No autoimmune disease, including any of the following:

• Lupus
• Scleroderma
• Rheumatoid polyarthritis

Other

• No active peptic ulcer
• No unstable diabetes mellitus
• No contraindication to corticosteroids
• No other malignant disease within the past 5 years except basalioma
• No functional iron deficiency (i.e., transferrin saturation < 20%) that cannot be treated with iron supplementation
• No other serious illness or medical condition

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 2 months since prior recombinant human epoetin alfa or any other erythropoiesis-stimulating drug

Chemotherapy

• At least 3 weeks since prior estramustine

Endocrine therapy

• See Disease Characteristics
• At least 3 weeks since prior antiandrogen treatment
• Concurrent chemical castration with LHRH allowed provided patient has begun treatment prior to study entry

• No initiation of chemical castration therapy during study treatment

Radiotherapy

• No prior radiotherapy to > 25% of bone marrow
• No prior radioisotope therapy
• Concurrent local palliative radiotherapy for pain allowed

Surgery

• See Disease Characteristics
• At least 4 weeks since prior surgery

Other

• No other prior cytostatic treatment
• Concurrent bisphosphonates allowed provided patient has begun treatment prior to study entry

• No initiation of bisphosphonates during study treatment