Combination Chemotherapy With Ketoconazole in Treating Patients With Prostate Cancer

Inclusion Criteria

• •DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Androgen independent disease progression -Castrate testosterone level of less than 40 ng/dL (if medically achieved, treatment must be maintained continuously) -Prostate specific antigen (PSA) at least 4 ng/mL and rising on at least 2 consecutive measurements No variant histologies such as ductal carcinoma (endometrioid or cribiform) or small cell carcinoma Brain metastases controlled
• •PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod 0-3 Life expectancy: At least 12 weeks Hematopoietic: Absolute neutrophil count at least 1500/mm3 Platelet count at least 100,000/mm3 Hemoglobin greater than 9.5 g/dL (without transfusion support) Hepatic: Bilirubin and transaminase less than 2 times the upper limit of normal Renal: Creatinine no greater than 2.0 mg/dL OR Estimated creatinine clearance at least 35 mL/min Cardiovascular: No clinical history of heart disease Normal ECG OR Ejection fraction (ECHO, MUGA, or ventriculography) at least 45% Other: Spinal cord compression controlled No active peptic ulcer disease No active, or likely to become active, second malignancy
• •PRIOR CONCURRENT THERAPY: Biologic therapy: No prior ketoconazole Chemotherapy: No prior doxorubicin, vinblastine, estramustine, paclitaxel, or etoposide No greater than one prior cytotoxic therapy No other concurrent chemotherapy At least 8 weeks since prior mitomycin At least 60 days since prior suramin Endocrine therapy: No antiandrogen therapy such as flutamide or nilutamide within 4 weeks (6 weeks for bicalutamide) without response OR Progression since antiandrogen withdrawal Prior dexamethasone therapy discontinued Radiotherapy: At least 10 weeks since prior strontium Sr 89 and no more than 1 prior regimen No concurrent strontium Sr 89 Surgery: Not specified Other: No other concurrent therapy for prostate cancer No concurrent H2 blockers, omeprazole, or antacids No concurrent terfenadine and astemizole