Hormone Therapy Compared With Combination Chemotherapy in Treating Patients With Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as ketoconazole may stop the production of androgens. 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 is more effective than combination chemotherapy in treating prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy with that of combination chemotherapy in treating patients who have prostate cancer that has been previously treated with androgen suppression.

Detailed Description
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OBJECTIVES: Compare time to objective progression in patients with prostate cancer and a rising prostate-specific antigen (PSA) after androgen suppression when treated with second-line hormonal therapy (ketoconazole and hydrocortisone) vs combination chemotherapy (docetaxel and estramustine). Compare time to PSA progression and correlate this with time to objective progression in patients treated with these regimens. Compare the quality of life in patients treated with these regimens. Compare overall survival of patients treated with these regimens. Compare the natural history of progression in patients treated with these regimens. Identify prognostic indicators of clinical outcome by immunohistochemical evaluation of apoptopic biomarkers in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior treatment with bisphosphonates (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral ketoconazole three times daily and oral hydrocortisone twice daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive oral estramustine three times daily on days 1-5 and docetaxel IV over 1 hour on day 2. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, on day 1 of week 9, at 6 months and 1 year, and then annually for up to 10 years or until beginning of first non-protocol therapy. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years. PROJECTED ACCRUAL: A total of 590 patients (295 per treatment arm) will be accrued for this study within 4 years.

Official Title
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A Phase III Randomized Trial for Evaluating Second Line Hormonal Therapy (Ketoconazole/Hydrocortisone) Versus Paclitaxel/Estramustine Combination Chemotherapy on Progression Free Survival in Asymptomatic Patients With a Rising PSA After Hormonal Therapy for Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: docetaxel
* Drug: estramustine phosphate sodium
* Drug: ketoconazole
* Drug: therapeutic hydrocortisone


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate that was continuously treated with androgen suppression Rising prostate-specific antigen (PSA), defined as PSA > 5 ng/mL, rising on 2 consecutive measurements at least 4 weeks apart Gleason score 7 or higher and/or seminal vesicle involvement at diagnosis Patients previously treated with antiandrogen or glucocorticoid therapy must meet the following criteria: Must show a continued rise in PSA after stopping antiandrogen (flutamide, bicalutamide, or nilutamide) or glucocorticoid (dexamethasone or prednisone) At least 4 weeks continued rise in PSA after flutamide or nilutamide (6 weeks for bicalutamide) Testosterone less than 50 ng/dL Patients who have not undergone surgical castration must continue primary androgen suppression to maintain castrate levels of testosterone No progressive or measurable local or metastatic disease (including bone metastases) PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Granulocyte count at least 2,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic: SGOT no greater than 2 times upper limit of normal Bilirubin no greater than 1.5 mg/dL Renal: Creatinine no greater than 1.7 mg/dL Cardiovascular: No American Heart Association class III or IV heart disease No uncontrolled congestive heart failure No life-threatening cardiac arrhythmias Other: Fertile patients must use effective contraception No other prior malignancy unless curatively treated and disease-free for appropriate time period for specific cancer No preexisting peripheral neuropathy greater than grade 1 No known hypersensitivity to polysorbate 80 PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 5 years since prior systemic chemotherapy Endocrine therapy: See Disease Characteristics At least 4 weeks since prior hydrocortisone No prior ketoconazole Radiotherapy: At least 28 days since prior radiotherapy to primary site No prior palliative radiotherapy No concurrent radiotherapy Surgery: See Disease Characteristics Other: Recovered form prior therapy At least 7 days since prior parenteral antibiotics for active infection No concurrent digitalis No concurrent H_2 blockers or proton pump inhibitors (arm I only) Concurrent bisphosphonates allowed provided they were initiated prior to study therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: docetaxel|nan|
|Drug: estramustine phosphate sodium|nan|
|Drug: ketoconazole|nan|
|Drug: therapeutic hydrocortisone|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

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