S0032, Combination Chemotherapy Plus Hormone Therapy in Treating Patients With Metastatic Prostate Cancer
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Androgens can stimulate the growth of prostate cancer cells. Drugs such as goserelin, leuprolide, flutamide, or bicalutamide may stop the adrenal glands from producing androgens. Combining chemotherapy with hormone therapy may kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus hormone therapy in treating patients who have metastatic prostate cancer.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Evaluation of Early Oral Estramustine, Oral Etoposide and Intravenous Paclitaxel in Combination With Hormone Therapy in Patients With High-Risk Metastatic Adenocarinoma of the Prostate|
- Progression-free Survival [ Time Frame: 0-5 years (assessed every 3 months if no progression when the chemotherapy had been finished. Once off chemotherapy, assessed every 3 months until progression) ] [ Designated as safety issue: No ]Measured from time of registration to time of first documentation of progression determined from the prostate-specific antigen (PSA) level, clinical criteria, or symptomatic deterioration. PSA progression is defined as a 25% increase greater than baseline. If the patient's PSA level had decrease during the study, a 25% increase from the nadir PSA level, with absolute value of >=5 ng/mL is considered progression. CLinical progress is defined as the appearance of any new lesion at any site or death without documented progression. Symptomatic deterioration is defined as a global deterioration of the health status requiring discontinuation of treatment without objective evidence of progression.
- Overall Survival (OS) [ Time Frame: 0-5 years ] [ Designated as safety issue: No ]Overall survival is defined from the date of registration to date of death from any cause
- Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [ Time Frame: up to 5 years after registration ] [ Designated as safety issue: Yes ]Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
|Study Start Date:||December 2001|
|Study Completion Date:||July 2011|
|Primary Completion Date:||June 2010 (Final data collection date for primary outcome measure)|
Experimental: Hormone therapy, estramustine, etoposide and paclitaxel
Hormone therapy (leuprolide, bicalutamide, nilutamide, goserelin, flutamide), estramustine, etoposide and paclitaxel
Other Name: estramustine phosphate sodiumDrug: etoposide Drug: flutamide Drug: goserelin Drug: leuprolide
Other Name: leuprolide acetateDrug: nilutamide Drug: paclitaxel
- Determine the progression-free and overall survival in patients with high-risk metastatic adenocarcinoma of the prostate treated with early estramustine, etoposide, and paclitaxel with combined androgen-blockade therapy.
- Determine the type, frequency, and severity of toxicity of this regimen in this patient population.
OUTLINE: This is a multicenter study.
- Androgen-blockade therapy: Patients receive a standard regimen of luteinizing hormone-releasing hormone agonist therapy comprising either goserelin subcutaneously once monthly or once every 3 months or leuprolide intramuscularly once monthly, once every 3 months, or once every 4 months. Patients also receive a standard regimen of antiandrogen therapy comprising oral bicalutamide, oral flutamide, or oral nilutamide once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
- Chemotherapy: Beginning 14-30 days after initiation of androgen-blockade therapy, patients receive oral estramustine three times daily and oral etoposide once daily on days 1-14 and paclitaxel IV over 1 hour on day 2. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months until disease progression, every 6 months for 2 years, and then annually for 3 years.
PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 2 years.