A Phase III Randomized Study of Patients With High Risk, Hormone-Naive Prostate Cancer: Androgen Blockade With 4 Cycles of Immediate Chemotherapy Versus Androgen Blockade With Delayed Chemotherapy

Brief Summary

Detailed Description

OBJECTIVES: Primary * Compare the survival of patients with high-risk hormone-naive prostate cancer treated with androgen blockade with concurrent chemotherapy vs delayed chemotherapy. Secondary * Compare biochemical control in patients treated with these regimens. * Determine the toxicity of these regimens in these patients. * Compare the time to clinical failure, as measured by progression on bone scan or CT scan or a prostate-specific antigen (PSA) doubling time of ≤ 32 weeks, in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior therapy (surgery vs radiotherapy and/or brachytherapy vs both), original combined Gleason score (6 vs 7 vs 8-10), and prior vaccine therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive androgen blockade (AB) comprising a luteinizing-hormone releasing-hormone agonist continuously and oral flutamide or oral bicalutamide once daily for at least 1 month. Within 4 weeks of initiation of AB, patients begin chemotherapy. Patients receive 1, and only 1, of the following chemotherapy regimens: * Regimen A: Patients receive oral estramustine 3 times daily on days 1-5 and docetaxel IV on day 3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. * Regimen B: Patients receive oral estramustine 3 times daily on days 1-5 and paclitaxel IV on days 3, 10, 17, 24, 31, and 38. Treatment repeats every 56 days for 4 courses in the absence of disease progression or unacceptable toxicity. * Regimen C: Patients receive oral ketoconazole 3 times daily on days 1-7, 15-21, and 29-35; doxorubicin IV on days 1, 15, and 29; vinblastine IV on days 8, 22, and 36; and oral estramustine 3 times daily on days 8-14, 22-28, and 36-42. Treatment repeats every 56 days for 4 courses in the absence of disease progression or unacceptable toxicity. * Regimen D: Patients receive oral estramustine 3 times daily on days 1-4 and docetaxel IV over 1 hour on days 3, 10, and 17. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. * Regimen E: Patients receive docetaxel IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. * Regimen F: Patients receive docetaxel IV on days 1, 8, and 15. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. * Regimen G: With approval from the protocol chair, patients may receive a regimen that has been demonstrated in a published phase II study to have at least a 50% response rate as measured by PSA decrease from baseline over 2 measurements 28 days apart or a decrease in measurable soft tissue disease by 50% in 2 dimensions. * Arm II: Patients receive AB as in arm I. Patients continue with AB until clinical failure, at which time patients receive chemotherapy as in arm I. Patients who have a response may continue to receive chemotherapy beyond 4 courses. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 1,050 patients will be accrued for this study within 4-6 years.

Primary Outcomes

Secondary Outcomes

• Time to Clinical Failure(Time from study entry to positive scan or positive disease evaluation of the pelvis or chest or a PSA doubling time ≤ 32 weeks)
• Biochemical control(From date of randomization to the date of first PSA failure defined as a PSA doubling time <= 32 weeks)
• Frequency of non-hematologic (>= grade 3), hematologic (grade >=4) and fatal (grade 5) toxicities(From the beginning of treatment to 90 days post treatment)