Chemotherapy With or Without Biological Therapy in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy

OBJECTIVES:

• Compare the effect of estramustine, mitoxantrone, and vinorelbine vs isotretinoin, interferon alfa, and paclitaxel on PSA response in patients with metastatic hormone-refractory prostate cancer.
• Determine the toxic effects of each regimen in this patient population.
• Determine the effect of each regimen on pain, fatigue, and quality of life in these patients.
• Determine the objective response rate among the subset of patients who have bidimensionally measurable disease to each regimen after treatment.
• Determine the effect of each regimen on peripheral blood mononuclear cell BCL-2 in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease (measurable vs nonmeasurable and elevated PSA). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive vinorelbine IV over 10 minutes on days 2 and 9 followed by mitoxantrone IV over 10 minutes on day 2 only. Oral estramustine is administered every 12 hours on days 1-5. Courses repeat every 3 weeks in the absence of unacceptable toxicity, disease progression, or administration of the maximum cumulative dose of mitoxantrone.
• Arm II: Patients receive oral isotretinoin and interferon alfa subcutaneously on days 1 and 2 and paclitaxel IV over 1 hour on day 2 weekly for 6 weeks. Courses repeat every 8 weeks in the absence of unacceptable toxicity or disease progression.

Quality of life is assessed at baseline, on day 2 of courses 2, 4, and 6 (arm I), on day 22 of course 1 and day 1 of courses 2 and 3 (arm II), and then at completion of treatment.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 70-114 patients (35-57 per arm) will be accrued for this study within 14-23 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate
• Evidence of progressive metastatic disease (e.g., bone, pelvic mass, lymph node, liver or lung metastases)

• Radiologic evidence of hydronephrosis only does not constitute evidence of metastatic disease
• Must not have an elevated serum alkaline phosphatase or PSA level as only evidence of disease
• If bone metastases only (i.e., lacking soft tissue disease), must have PSA level of at least 20 ng/mL
• If soft tissue metastases and/or visceral disease, must have either bidimensionally measurable disease or PSA level of at least 20 ng/mL
• Must have had prior bilateral orchiectomy or other primary hormonal therapy (e.g., estrogen therapy or LHRH blocker plus flutamide) with evidence of treatment failure
• No carcinomatous meningitis or brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 4,000/mm^3
• Granulocyte count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• See Disease Characteristics
• Bilirubin no greater than 1.5 mg/dL
• SGOT/SGPT no greater than 2 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL OR
• Creatinine clearance at least 50 mL/min

Cardiovascular:

• No active angina pectoris
• No New York Heart Association class III or IV heart disease
• No myocardial infarction within the past 6 months
• No deep venous thrombosis
• LVEF at least 50% by MUGA

Other:

• Fertile patients must use effective contraception during and for 1 month after study
• Prior malignancy allowed provided curatively treated and disease free for appropriate time period for specific cancer
• No other serious medical illness or active infection that would preclude protocol therapy
• No concurrent prolonged exposure to sunlight
• No concurrent alcohol consumption

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy, including neoadjuvant chemotherapy or single-agent estramustine

Endocrine therapy:

• See Disease Characteristics
• If no prior bilateral orchiectomy, must continue LHRH agonist therapy (e.g., depot leuprolide or goserelin)
• At least 4 weeks since prior flutamide or flutamide with evidence of progressive disease
• At least 6 weeks since prior bicalutamide with evidence of progressive disease

Radiotherapy:

• More than 4 weeks since prior radiotherapy
• No prior strontium chloride Sr 89, samarium Sm 153 lexidronam pentasodium, or other radioisotope therapies

Surgery:

• See Disease Characteristics

Other:

• Recovered from all toxic effects due to prior treatment for prostate cancer
• No concurrent milk, milk products, antacids, calcium-containing drugs, or any food with estramustine (arm I only)
• No concurrent vitamin supplements containing vitamin A (arm II only)