RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining hormone therapy with chemotherapy and androgen suppression may kill more tumor cells. It is not yet known which treatment regimen is more effective for prostate cancer.

PURPOSE: Randomizedphase III trial to compare the effectiveness of chemotherapy plus hormone therapy versus androgen suppression alone as initial therapy in patients with prostate cancer that is metastatic or that cannot be removed surgically.

OBJECTIVES:

• Determine the clinical benefit, as measured by time to progression and overall survival, of chemo/hormonal therapy compared to androgen ablation alone, when given as the initial systemic treatment in patients with acinar adenocarcinoma of the prostate that is not amenable to local therapy.
• Validate the clinical significance of PSA criteria for progression.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients are treated with medical or surgical castration followed by an anti-androgen therapy with either flutamide, bicalutamide, or nilutamide.
• Patients receive chemo/hormonal therapy for 3 eight week courses, followed by total androgen blockade. Each course consists of 6 weeks of cytotoxic therapy with doxorubicin, ketoconazole, vinblastine, and estramustine followed by 2 weeks of rest. These patients are also maintained on hydrocortisone both during treatment and during rest. Patients in arm II have a long-term central venous access device inserted.

PROJECTED ACCRUAL: A total of 368 patients will be accrued for this study.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven acinar adenocarcinoma of the prostate
• Metastatic or locally advanced disease that either is not appropriately treated with surgery or radiation, or has recurred following previous "definitive" local therapy
• No CNS metastases
• No histologic subtypes, such as pure ductal or any component of small cell carcinoma
• Elevated PSA (at least 1.0 ng/mL in patients with prior prostatectomy or 4.0 ng/mL in those with prostate in place)

PATIENT CHARACTERISTICS: Age:

• Not specified

Performance status:

• Zubrod 0-2

Life expectancy:

• At least 3 years

Hematopoietic:

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

Hepatic:

• Conjugated bilirubin no greater than 0.8 mg/dL or total bilirubin no greater than 1.5 mg/dL
• Transaminase no greater than 4 times upper limit of normal

Renal:

• Creatinine clearance at least 40 mL/min

Cardiovascular:

• No evidence of bifascicular block on EKG
• No evidence of active ischemia on EKG
• No prior history of transient ischemic attack
• No evidence of congestive heart failure

Other:

• No active peptic ulcer disease
• No regular use of antacid or H2 blockers
• No known or predicted achlorhydria
• No concurrent use of terfenadine, astemizole, omeprazole, or cisapride
• No second malignancy unless curatively treated
• No history of deep venous thrombosis
• No history of pulmonary embolism
• No serious co-morbidity
• HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior cytotoxic systemic therapy

Endocrine therapy:

• Prior androgen deprivation therapy allowed if given for no more than 6 months to downstage primary
• No androgen deprivation therapy within 1 year prior to study

Radiotherapy:

• No prior cytotoxic systemic therapy (including systemic strontium-89 irradiation)
• Prior definitive radiotherapy to the prostate and/or one metastatic site allowed
• At least 8 weeks since radiotherapy to the pelvis
• At least 3 weeks since radiotherapy to a single metastatic site

Surgery:

• Prior prostatectomy allowed

Other:

• No concurrent anti-anginal therapy or aggressive anticoagulants