Hormone Therapy Plus Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Prostate Cancer
- Conditions
- Prostate Cancer
- Interventions
- Drug: Luteinizing hormone releasing hormone [LHRH] agonistRadiation: Radiation therapy
- Registration Number
- NCT00004054
- Lead Sponsor
- Radiation Therapy Oncology Group
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 397
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Hormones and RT Luteinizing hormone releasing hormone [LHRH] agonist Androgen suppression (AS) (Luteinizing hormone releasing hormone agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]). AS will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of radiation therapy (RT). Hormones and RT plus Chemotherapy estramustine phosphate sodium AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT. Hormones and RT plus Chemotherapy Radiation therapy AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT. Hormones and RT Radiation therapy Androgen suppression (AS) (Luteinizing hormone releasing hormone agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]). AS will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of radiation therapy (RT). Hormones and RT bicalutamide Androgen suppression (AS) (Luteinizing hormone releasing hormone agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]). AS will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of radiation therapy (RT). Hormones and RT flutamide Androgen suppression (AS) (Luteinizing hormone releasing hormone agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]). AS will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of radiation therapy (RT). Hormones and RT plus Chemotherapy etoposide AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT. Hormones and RT plus Chemotherapy bicalutamide AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT. Hormones and RT plus Chemotherapy flutamide AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT. Hormones and RT plus Chemotherapy paclitaxel AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT. Hormones and RT plus Chemotherapy warfarin AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT.
- Primary Outcome Measures
Name Time Method Overall Survival (5-year Rate Reported) From the date of randomization to the date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at date of last contact. This analysis was planned to occur when all patients had been potentially followed for 5 years.
- Secondary Outcome Measures
Name Time Method Rate of Biochemical Failure at 5 Years From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years. Biochemical failure uses the American Society for Radiation Oncology (ASTRO) definition of prostate-specific antigen (PSA) rises on three consecutive occasions, with biochemical failure date being midway between the last non-rising PSA and the first rise in PSA. Time to biochemical failure is defined as time from randomization to biochemical failure, last known follow-up (censored), or death (competing risk). Biochemical failure rates are estimated using the cumulative incidence method.
Rate of Local Progression at 5 Years From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years. Local progression is defined as documented clinical local and/or regional progression. Time to local progression is defined as time from randomization to local progression, last known follow-up (censored), or death (competing risk). Local progression rates are estimated using the cumulative incidence method.
Disease-free Survival Rate at 5 Years From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years. Disease-free survival (DFS) was measured from the date of randomization to the date of documentation of progression (local, distant, biochemical failure), death, or last follow-up (censored). The Kaplan-Meier method was used to estimate DFS rates.
Rate of Distant Metastasis at Five Years From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years. Distant metastasis (DM) is defined as documented metastatic disease. Time to distant metastasis is defined as time from randomization to distant metastatic disease, last known follow-up (censored), or death (competing risk). Distant metastasis rates are estimated using the cumulative incidence method.
Trial Locations
- Locations (54)
Lutheran General Cancer Care Center
🇺🇸Park Ridge, Illinois, United States
Greater Baltimore Medical Center and Cancer Center
🇺🇸Baltimore, Maryland, United States
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Saint John Regional Hospital
🇨🇦Saint John, New Brunswick, Canada
University Cancer Center at University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Methodist Cancer Center at Methodist Hospital
🇺🇸Indianapolis, Indiana, United States
Baptist Hospital of Miami
🇺🇸Miami, Florida, United States
University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Foundation for Cancer Research and Education
🇺🇸Phoenix, Arizona, United States
University of Colorado Cancer Center at University of Colorado Health Sciences Center
🇺🇸Denver, Colorado, United States
South Jersey Regional Cancer Center
🇺🇸Millville, New Jersey, United States
Akron General Medical Center
🇺🇸Akron, Ohio, United States
Monmouth Medical Center
🇺🇸Long Branch, New Jersey, United States
John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital
🇺🇸Allentown, Pennsylvania, United States
Akron City Hospital
🇺🇸Akron, Ohio, United States
Cancer Care Ontario-London Regional Cancer Centre
🇨🇦London, Ontario, Canada
Veterans Affairs Medical Center - East Orange
🇺🇸East Orange, New Jersey, United States
Dixie Regional Medical Center
🇺🇸Saint George, Utah, United States
St. Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
CCOP - North Shore University Hospital
🇺🇸Manhasset, New York, United States
Arthur G. James Cancer Hospital - Ohio State University
🇺🇸Columbus, Ohio, United States
CCOP - Southern Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
Fox Chase Cancer Center at St. Francis Medical Center
🇺🇸Trenton, New Jersey, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Ellis Fischel Cancer Center at University of Missouri - Columbia
🇺🇸Columbia, Missouri, United States
Atlantic City Medical Center
🇺🇸Pomona, New Jersey, United States
LDS Hospital
🇺🇸Salt Lake City, Utah, United States
Herbert Irving Comprehensive Cancer Center at Columbia University
🇺🇸New York, New York, United States
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
CCOP - Columbus
🇺🇸Columbus, Ohio, United States
Wellspan Health - York Cancer Center
🇺🇸York, Pennsylvania, United States
CCOP - Dayton
🇺🇸Dayton, Ohio, United States
Delaware County Memorial Hospital
🇺🇸Drexel Hill, Pennsylvania, United States
CCOP - MainLine Health
🇺🇸Wynnewood, Pennsylvania, United States
University of Texas - MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
CCOP - St. Vincent Hospital Cancer Center, Green Bay
🇺🇸Green Bay, Wisconsin, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
St. Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Medical College of Wisconsin Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Albert Einstein Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
Sutter Health Western Division Cancer Research Group
🇺🇸Greenbrae, California, United States
Mount Diablo Medical Center
🇺🇸Concord, California, United States
CCOP - Santa Rosa Memorial Hospital
🇺🇸Santa Rosa, California, United States
Ball Memorial Hospital Cancer Center
🇺🇸Muncie, Indiana, United States
Markey Cancer Center at University of Kentucky Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
Mary Bird Perkins Cancer Center
🇺🇸Baton Rouge, Louisiana, United States
CCOP - Ochsner
🇺🇸New Orleans, Louisiana, United States
Anne Arundel Oncology Center
🇺🇸Annapolis, Maryland, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Marquette General Hospital
🇺🇸Marquette, Michigan, United States
CCOP - Toledo Community Hospital
🇺🇸Toledo, Ohio, United States
St. Luke's Hospital Cancer Center
🇺🇸Bethlehem, Pennsylvania, United States
All Saints Cancer Center at All Saints Healthcare
🇺🇸Racine, Wisconsin, United States