Phase II trial of paclitaxel, estramustine, etoposide, and carboplatin in the treatment of patients with hormone-refractory prostate carcinoma.

BACKGROUND Preclinical data suggest that the combination of intravenous (i.v.) paclitaxel, carboplatin, oral etoposide, and oral estramustine (TEEC) has significant activity in patients with advanced, hormone-refractory prostate carcinoma. The authors conducted this clinical trial to evaluate the addition of carboplatin to the three-drug combination of paclitaxel, estramustine, and etoposide (TEE). METHODS Twenty patients with carcinoma of the prostate that was progressing despite hormone therapy were enrolled on this Phase II trial. Patients were treated with oral estramustine, 280 mg three times daily, and oral etoposide, 50 mg/m2, once daily on Days 1-7, with i.v. paclitaxel, 135 mg/m2, over 1 hour followed by carboplatin (area under the curve, 5) on Day 2 of each 21-day treatment cycle. Patients were evaluated for response after three cycles, and three additional cycles were given to responding or stable patients. RESULTS Nineteen patients were evaluable for response, and 12 patients had measurable disease at baseline. The measurable response rate was 58% (7 of 12 patients; 95% confidence interval [95% CI], 28-85%), and all of those were partial responses. Eleven patients had decreases >50% from their baseline prostate specific antigen levels during therapy, for a response rate of 58% (95% CI, 34-80%) by this criterion. The median time to disease progression was 5.5 months, with a median survival of 14.2 months. Major toxicities included Grade (according to version 2 of the National Cancer Institute Common Toxicity Criteria) 4 neutropenia in 4 patients, Grade 4 thrombocytopenia in 4 patients, and anemia > or = Grade 3 in 4 patients. One patient had a deep vein thrombosis. CONCLUSIONS The combination of TEEC was active in patients with hormone-refractory prostate carcinoma. The regimen was tolerable, with primarily hematologic toxicity. The addition of carboplatin to TEE did not appear to add to the efficacy of the three-drug combination of antimicrotubule agents.