S0032, Combination Chemotherapy Plus Hormone Therapy in Treating Patients With Metastatic Prostate Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: 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.

Official Title
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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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: bicalutamide
* Drug: estramustine
* Drug: etoposide
* Drug: flutamide
* Drug: goserelin
* Drug: leuprolide
* Drug: nilutamide
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed high-risk adenocarcinoma of the prostate Clinical stage D2 disease as evidenced by one of the following: Visceral disease (liver, lung, or other viscera) Bone metastases to sites in both the axial (spine, pelvis, ribs, or skull) and appendicular (claviculae, humeri, or femora) skeleton No prior or concurrent (treated or untreated) brain metastases Patients with clinical evidence of brain metastasis must have a negative brain CT or MRI No evidence of untreated spinal cord compression PATIENT CHARACTERISTICS: Age: Over 18 Performance status: Zubrod 0-2 Life expectancy: Not specified Hematopoietic: Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 No active hypercoagulability Hepatic: Not specified Renal: Not specified Cardiovascular: No transient ischemic attacks, stroke, or myocardial infarction within the past 6 months No active coronary artery disease requiring antianginal therapy No active thrombophlebitis Pulmonary: No history of pulmonary embolus Other: No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated stage I or II cancer currently in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior biologic therapy and recovered No concurrent biologic therapy Chemotherapy: No prior cytotoxic chemotherapy No other concurrent chemotherapy Endocrine therapy: Prior androgen-blockade therapy (e.g., luteinizing hormone-releasing hormone agonist and antiandrogen therapy) allowed if administered for a duration of less than 30 days Prior neoadjuvant hormonal therapy allowed Radiotherapy: At least 4 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery: At least 4 weeks since prior surgery and recovered Other: No concurrent bisphosphonates

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hormone therapy, estramustine, etoposide and paclitaxel<br>Hormone therapy (leuprolide, bicalutamide, nilutamide, goserelin, flutamide), estramustine, etoposide and paclitaxel | Drug: bicalutamide<br> <br> Drug: estramustine<br> <br> * Other names: estramustine phosphate sodium;Drug: etoposide<br> <br> Drug: flutamide<br> <br> Drug: goserelin<br> <br> Drug: leuprolide<br> <br> * Other names: leuprolide acetate;Drug: nilutamide<br> <br> Drug: paclitaxel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | 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. | 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) | 
| Overall Survival (OS) | Overall survival is defined from the date of registration to date of death from any cause | 0-5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | 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. | up to 5 years after registration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage IV prostate cancer, recurrent prostate cancer