• Time to progression [ Designated as safety issue: No ]
  

• Major bone scan response [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Compare the clinical efficacy of hormonal ablative therapy combined with doxorubicin and zoledronate with or without strontium chloride Sr 89, in terms of progression-free survival, in patients with androgen-dependent prostate cancer and bone metastases.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to the number of bony metastases (≤ 6 vs > 6). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive hormonal ablative therapy comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy. Patients also receive doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses; and a single dose of strontium chloride Sr 89 IV over 1-2 minutes on day 1.
• Arm II: Patients receive hormonal ablative therapy, doxorubicin, and zoledronate as in arm I.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 80 patients (40 per treatment arm) will be accrued for this study within 20 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed prostate cancer

  • Osteoblastic metastases on bone scan or CT scan

• Androgen-dependent disease

  • Previously treated with neoadjuvant or intermittent hormonal ablative therapy* at least 3 years ago AND has reinitiated hormonal ablative therapy within 3 months before study entry NOTE: *Therapy was less than 3 years in duration
• No symptomatic bulky lymphadenopathy causing scrotal or pedal edema
• No significant local invasive disease with bladder invasion
• No evidence or suspicion of myelodysplastic syndromes by complete blood count and bone marrow biopsy
• No small cell carcinoma, purely lytic bone metastasis, or bulky (i.e., ≥ 5 cm) visceral or nodal disease in the absence of bone involvement by biopsy
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• Not specified

Performance status

• ECOG 0-3 OR
• Karnofsky 40-100%

Life expectancy

• More than 3 months

Hematopoietic

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

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal
• Bilirubin normal

Renal

• Creatinine ≤ 3.0 mg/dL
• Calcium level ≥ 8 mg/dL

Cardiovascular

• LVEF ≥ 45%
• No history of congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Fertile patients must use effective contraception
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to zoledronate or other study drugs
• No other malignancy within the past 5 years except nonmelanoma skin cancer
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance
• No untreated symptomatic spinal cord compressions
• No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Prior doxorubicin allowed provided the cumulative dosage was ≤ 250 mg/m^2
• No more than 1 prior chemotherapy regimen

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• No prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium

Surgery

• Not specified

Other

• Prior zoledronate allowed provided treatment was no more than 3 months in duration
• Other prior bisphosphonates allowed
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer therapy