Chemotherapy Plus Hormone Therapy Versus Androgen Suppression in Treating Patients With Metastatic or Unresectable Prostate Cancer

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.
• Arm II: 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.

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