OBJECTIVES:

• Compare the efficacy of androgen suppression and radiotherapy with or without subsequent paclitaxel, estramustine, and etoposide, in terms of overall and disease-free survival, biochemical and local control, and freedom from distant metastasis, in patients with localized high-risk prostate cancer.
• Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to prostate-specific antigen level (≤ 10 ng/mL vs 11-100 ng/mL), tumor stage (T1-2 vs T3-4), Gleason score (7 vs 8-10), and prior hormone use (yes vs no). Patients are randomized to one of two treatment arms.

All patients receive androgen suppression comprising a luteinizing hormone-releasing hormone (LHRH) agonist AND bicalutamide OR flutamide for 4 months. Beginning 8 weeks after the initiation of androgen suppression, all patients undergo radiotherapy once daily, 5 days a week, for 7-8 weeks. Patients who received prior androgen suppression therapy count time to radiotherapy from start date of prior hormonal therapy.

• Arm I: Patients continue androgen suppression therapy (LHRH agonist only) for approximately 20 more months after radiotherapy is completed.
• Arm II: Patients continue therapy as in arm I and receive chemotherapy beginning 28 days after completing radiotherapy. Chemotherapy comprises oral estramustine 3 times daily and oral etoposide twice daily on days 1-14 and paclitaxel IV over 1 hour on day 2. Chemotherapy repeats every 21 days for 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 1,440 patients will be accrued for this study within 6 years.

DISEASE CHARACTERISTICS:

• Histologically proven prostate cancer at high risk for relapse as determined by either of the following:

  • Prostate-specific antigen (PSA) 20-100 ng/mL and Gleason score at least 7 (any T stage)
  • Clinical stage at least T2, Gleason score at least 8, and PSA no greater than 100 ng/mL
• Negative lymph nodes
• No metastatic disease

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• Zubrod 0 or 1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 130,000/mm^3
• Hemoglobin at least 11.4 g/dL

Hepatic:

• AST no greater than 2 times upper limit of normal

Renal:

• Creatinine no greater than 2.5 mg/dL

Other:

• No other invasive cancer within the past 5 years except superficial nonmelanomatous skin cancer
• No major medical or psychiatric illness that would preclude study participation
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 5 years since prior chemotherapy

Endocrine therapy:

• At least 60 days since prior finasteride for prostatic hypertrophy
• At least 90 days since prior testosterone
• No more than 30 days since initiation of prior pharmacologic androgen ablation for prostate cancer

Radiotherapy:

• No prior pelvic radiotherapy
• No concurrent intensity-modulated radiotherapy

Surgery:

• No prior radical prostatectomy
• No prior cryosurgery for prostate cancer
• No prior orchiectomy