Hormone Therapy Plus Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Prostate Cancer

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:

- White blood cell (WBC) count of at least 3,000/mm^3

- Platelet count at least 130,000/mm^3

- Hemoglobin at least 11.4 g/dL

Hepatic:

- Aspartate aminotransferase (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