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Paclitaxel, Estramustine Phosphate, and Carboplatin in Patients With Advanced Prostate Cancer

From the Genitourinary Oncology Service, Division of Solid Tumor, Department of Medicine, Departments of Nursing, Radiology, Pharmacology, Clinical Chemistry, and Nuclear Medicine, and Division of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, and Department of Medicine, Joan and Sanford Weill Medical College of Cornell University, New York, NY; Lank Center for Genitourinary Oncology, Department of Adult Oncology, Dana-Farber Cancer Institute, and Division of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Genitourinary Oncology Service, Department of Medical Oncology, University of California San Francisco, San Francisco, CA.

Address reprint requests to William Kevin Kelly, DO, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Box 473, New York, NY 10021-6007; email kellyw{at}mskcc.org

PURPOSE: To determine the safety and activity of weekly paclitaxel in combination with estramustine and carboplatin (TEC) in patients with advanced prostate cancer.

PATIENTS AND METHODS: In a dose-escalation study, patients with advanced prostate cancer were administered paclitaxel (weekly 1-hour infusions of 60 to 100 mg/m²), oral estramustine (10 mg/kg), and carboplatin (area under the curve, 6 mg/mL-min every 4 weeks). Paclitaxel levels were determined 0, 30, 60, 90, and 120 minutes and 18 hours after infusion, and a concentration-time curve was estimated. Once a safe dose was established, a multi-institutional phase II trial was conducted in patients with progressive androgen-independent disease.

RESULTS: Fifty-six patients with progressive androgen-independent disease were treated for a median of four cycles. The dose of paclitaxel was escalated from 60 to 100 mg/m² without the occurrence of DLT. Posttherapy decreases in serum prostate-specific antigen levels of 50%, 80%, and 90% were seen in 67%, 48%, and 39% (95% confidence interval, 55% to 79%, 35% to 61%, 26% to 52%) of the patients, respectively. Of the 33 patients with measurable disease, two (6%) had a complete response and 13 (39%) had a partial response. The overall median time to progression was 21 weeks, and the median survival time for all patients was 19.9 months. Major grade 3 or 4 adverse effects were thromboembolic disease (in 25% of patients), hyperglycemia (in 38%), and hypophosphatemia (in 42%). Significant leukopenia, thrombocytopenia, and peripheral neuropathy were not observed.

CONCLUSION: TEC has significant antitumor activity and is well tolerated in patients with progressive androgen-independent prostate cancer.

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