RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radioactive substances such as strontium-89 may relieve bone pain associated with prostate cancer. It is not yet known whether chemotherapy is more effective with or without strontium-89 in treating bone metastases.

PURPOSE: This randomized phase III trial is studying giving chemotherapy together with strontium-89 to see how well it works compared to chemotherapy alone in treating patients with prostate cancer that has spread to the bone.

OBJECTIVES:

• Compare the effectiveness, in terms of overall survival, of consolidation therapy with or without strontium chloride Sr 89 after induction chemotherapy in patients with androgen-independent prostate cancer.

OUTLINE: This is a randomized study. Patients are stratified according to type of induction chemotherapy (KAVE vs prednisone and docetaxel), number of bony metastases (no more than 20 vs more than 20), ECOG performance status (0-1 vs 2-3), and use of zoledronate (yes vs no).

• Induction therapy: Patients receive 1 of 2 induction therapy regimens.

  • Regimen A (KAVE): Patients receive doxorubicin IV over 24 hours on day 1 and oral ketoconazole three times daily on days 1-7 of weeks 1, 3, and 5. Patients receive vinblastine IV over 30 minutes on day 1 and oral estramustine three times daily on days 1-7 of weeks 2, 4, and 6. Patients receive no treatment on weeks 7 and 8. Treatment repeats every 8 weeks for at least 2 courses* in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients continue to receive oral ketoconazole three times daily until disease progression.

• Regimen B (prednisone and docetaxel): Patients receive oral prednisone twice daily on days 1-21 (days 1-14 of course 5 only) and docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for at least 5 courses in the absence of disease progression or unacceptable toxicity.

  • Consolidation therapy: Patients with a prostate-specific antigen (PSA) response (at least 50% decline in PSA level from baseline at week 16 OR at least 2 PSA levels decreased at least 50% from baseline) are randomized to 1 of 2 consolidation treatment arms.
• Arm I: Patients receive doxorubicin IV over 24 hours once weekly for 6 weeks plus strontium chloride Sr 89 IV once at the beginning of chemotherapy.
• Arm II: Patients receive doxorubicin as in arm I. Patients are followed every 4 weeks until PSA progression and then every 3 months thereafter.

PROJECTED ACCRUAL: Approximately 480 patients (240 randomized) will be accrued for this study within 48 months.

• Drug: docetaxel
• Drug: doxorubicin hydrochloride
• Drug: estramustine phosphate sodium
• Drug: ketoconazole
• Drug: prednisone
• Drug: vinblastine
• Radiation: strontium chloride Sr 89

• Experimental: Patients receive doxorubicin IV over 24 hours on day 1 and oral ketoconazole three times daily on days 1-7 of weeks 1, 3, and 5. Patients receive vinblastine IV over 30 minutes on day 1 and oral estramustine three times daily on days 1-7 of weeks 2, 4, and 6. Treatment repeats every 8 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients continue to receive oral ketoconazole three times daily until disease progression
• Experimental: Patients receive oral prednisone twice daily on days 1-21 (days 1-14 of course 5 only) and docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for at least 5 courses in the absence of disease progression or unacceptable toxicity.
• Experimental: Patients receive doxorubicin IV over 24 hours once weekly for 6 weeks plus strontium chloride Sr 89 IV once at the beginning of chemotherapy.
• Experimental: Patients receive doxorubicin as in consolidation arm I.

DISEASE CHARACTERISTICS:

• Diagnosis of adenocarcinoma of the prostate

  • No small cell carcinoma

• Androgen-independent

  • No evidence of response after either of the following anti-androgen withdrawal periods:

    • Within 4 weeks for flutamide
    • Within 6 weeks for bicalutamide or nilutamide
• Rising prostate-specific antigen (PSA) (at least 5 ng/mL) on at least 2 occasions at least 1 week apart AND bone pain OR worsening bone scan with new lesions in less than 6 months
• Castrate testosterone level no greater than 50 ng/mL (must continue treatment to maintain castrate levels)
• No symptomatic lymphadenopathy (scrotal or pedal edema) or significant local invasive disease (hematuria)
• Osteoblastic metastases on bone scan or CT scan
• No predominant visceral metastases to liver, lungs, or brain

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• Zubrod 0-3

Life expectancy:

• At least 12 weeks

Hematopoietic:

• WBC greater than 3,000/mm^3
• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST and ALT no greater than 2 times ULN

Renal:

• Not specified

Cardiovascular:

• No transient ischemic attack or myocardial infarction within the past 12 months
• No active angina or claudication sufficient to limit activity
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• Fertile patients must use effective contraception
• No prior allergic reaction to compounds of similar biologic or chemical composition to study drugs
• No other conditions (e.g., pernicious anemia) associated with achlorhydria
• No other active malignancy or malignancy that is likely to become active except non-melanoma skin cancer
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• No other uncontrolled concurrent illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior immunotherapy and recovered
• Prior angiogenesis inhibitors and gene therapy allowed

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No prior doxorubicin or vinblastine for patients receiving induction chemotherapy with KAVE (ketoconazole, doxorubicin, vinblastine, estramustine)
• No prior docetaxel for patients receiving induction chemotherapy with prednisone plus docetaxel

Endocrine therapy:

• See Disease Characteristics
• Prior secondary hormonal agents (e.g., aminoglutethimide, diethylstilbestrol, or estramustine) allowed
• Prior steroid therapy (e.g., dexamethasone, prednisone, or hydrocortisone) allowed

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium

Surgery:

• No prior vagotomy

Other:

• No more than 1 prior cytotoxic regimen