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: Randomizedphase III trial to compare the effectiveness of hormone therapy plus radiation therapy with or without combination chemotherapy in treating patients who have prostate cancer.

Condition	Treatment or Intervention	Phase
stage II prostate cancer stage III prostate cancer stage IV prostate cancer	Drug: bicalutamide  Drug: estramustine  Drug: etoposide  Drug: flutamide  Drug: paclitaxel  Procedure: antiandrogen therapy  Procedure: chemotherapy  Procedure: endocrine therapy  Procedure: hormone therapy  Procedure: radiation therapy  Procedure: releasing factor agonist therapy	Phase III

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States
Arizona
      Foundation for Cancer Research and Education, Phoenix,  Arizona,  85013,  United States
California
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States
      Mount Diablo Medical Center, Concord,  California,  94524-4110,  United States
      Sutter Health Western Division Cancer Research Group, Greenbrae,  California,  94904,  United States
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Denver,  Colorado,  80010,  United States
Florida
      Baptist Hospital of Miami, Miami,  Florida,  33176-2197,  United States
Illinois
      Lutheran General Cancer Care Center, Park Ridge,  Illinois,  60068,  United States
Indiana
      Ball Memorial Hospital Cancer Center, Muncie,  Indiana,  47303-3499,  United States
      Methodist Cancer Center at Methodist Hospital, Indianapolis,  Indiana,  46206-1367,  United States
Kentucky
      Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington,  Kentucky,  40536-0293,  United States
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States
      Mary Bird Perkins Cancer Center, Baton Rouge,  Louisiana,  70809,  United States
Maryland
      Anne Arundel Oncology Center, Annapolis,  Maryland,  21401,  United States
      Greater Baltimore Medical Center and Cancer Center, Baltimore,  Maryland,  21204,  United States
Michigan
      Marquette General Hospital, Marquette,  Michigan,  49855,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0010,  United States
      West Michigan Cancer Center, Kalamazoo,  Michigan,  49007,  United States
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
Missouri
      Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia,  Missouri,  65203,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Jersey
      Atlantic City Medical Center, Pomona,  New Jersey,  08240,  United States
      Fox Chase Cancer Center at St. Francis Medical Center, Trenton,  New Jersey,  08629,  United States
      Monmouth Medical Center, Long Branch,  New Jersey,  07740-6395,  United States
      South Jersey Regional Cancer Center, Millville,  New Jersey,  08332,  United States
      Veterans Affairs Medical Center - East Orange, East Orange,  New Jersey,  07019,  United States
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States
Ohio
      Akron City Hospital, Akron,  Ohio,  44304,  United States
      Akron General Medical Center, Akron,  Ohio,  44302,  United States
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210-1240,  United States
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States
Pennsylvania
      Albert Einstein Cancer Center, Philadelphia,  Pennsylvania,  19141-3098,  United States
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States
      Delaware County Memorial Hospital, Drexel Hill,  Pennsylvania,  19026,  United States
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States
      John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital, Allentown,  Pennsylvania,  18105,  United States
      Kimmel Cancer Center at Thomas Jefferson University - Philadelphia, Philadelphia,  Pennsylvania,  19107-5541,  United States
      St. Luke's Hospital Cancer Center, Bethlehem,  Pennsylvania,  18015,  United States
      Wellspan Health - York Cancer Center, York,  Pennsylvania,  17403,  United States
Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States
Utah
      Dixie Regional Medical Center, Saint George,  Utah,  84770,  United States
      LDS Hospital, Salt Lake City,  Utah,  84143,  United States
Washington
      University Cancer Center at University of Washington Medical Center, Seattle,  Washington,  98195-6043,  United States
Wisconsin
      All Saints Cancer Center at All Saints Healthcare, Racine,  Wisconsin,  53405,  United States
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States
      Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center, La Crosse,  Wisconsin,  54601,  United States
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States
      St. Luke's Medical Center, Milwaukee,  Wisconsin,  53215,  United States
      St. Vincent Hospital, Green Bay,  Wisconsin,  54307-3508,  United States
Canada, New Brunswick
      Saint John Regional Hospital, Saint John,  New Brunswick,  E2L 4L2,  Canada
Canada, Ontario
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada

Study chairs or principal investigators

Howard Mark Sandler, MD,  Study Chair,  University of Michigan Comprehensive Cancer Center   

Study ID Numbers:  CDR0000067250; RTOG-9902; CTSU; RTOG-DEV-1020
Record last reviewed:  February 2005
Last Updated:  February 24, 2005
Record first received:  December 10, 1999
ClinicalTrials.gov Identifier:  NCT00004054
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08