Hormone Therapy Plus Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Prostate Cancer
Hormone Therapy Plus Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Prostate Cancer
RATIONALE: Hormones can stimulate the production of prostate cancer cells. Hormone therapy
 may fight prostate cancer by reducing the production of androgens. Radiation therapy uses
 high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to
 stop tumor cells from dividing so they stop growing or die. It is not yet known whether
 hormone therapy plus radiation therapy is more effective with or without combination
 chemotherapy for prostate cancer.

 PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy plus
 radiation therapy with or without combination chemotherapy in treating patients who have
 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