Clinical experience with intravenous estramustine phosphate, paclitaxel, and carboplatin in patients with castrate, metastatic prostate adenocarcinoma

BACKGROUND The combination of paclitaxel, oral estramustine phosphate (EMP), and carboplatin (TEC) has shown antitumor activity in patients with castrate, metastatic prostate carcinoma. To improve the therapeutic efficacy and reduce the toxicity of TEC, the authors substituted intravenous (i.v.) EMP for oral EMP based on single‐agent studies demonstrating an improved safety profile with i.v. EMP. METHODS Patients with progressive, castrate, metastatic prostate carcinoma were treated with up to 6 4‐week cycles of i.v. EMP (500–1500 mg/m2 per week), paclitaxel (100 mg/m2 per week), and carboplatin (target area under the curve = 6 mg/mL every 4 weeks). RESULTS Thirty patients were treated in 6 dose cohorts. Deep venous thrombosis occurred in 5 of 30 patients (17%). Other common Grade 3/4 (according to National Cancer Institute Common Toxicity Criteria) toxicities included hepatic toxicity (23%) and leukopenia (24%). Posttherapy prostate specific antigen declines > 50% were seen in 18 of 30 patients (60%), and declines > 80% were seen in 15 of 30 patients (50%). Eleven of 17 patients (65%) with measurable soft tissue disease achieved a partial response. Four of 27 patients (15%) with osseous metastases demonstrated improvement on bone scan. CONCLUSIONS Intravenous EMP was administered safely with paclitaxel and carboplatin and produced clinical outcomes similar to the outcomes achieved with the TEC regimen. Substitution of i.v. EMP for the oral formulation was found to result in a lower incidence of severe nausea but increased hepatic toxicity. Cancer 2003. © 2003 American Cancer Society. To improve the therapeutic efficacy and reduce the toxicity of combined paclitaxel, estramustine phosphate (EMP), and carboplatin (TEC), the authors substituted intravenous (i.v.) EMP for oral EMP based on single‐agent studies that demonstrated an improved safety profile with i.v. EMP. Intravenous EMP could be administered safely with paclitaxel and carboplatin with clinical outcomes similar to the outcomes achieved with the TEC regimen. Intravenous EMP resulted in a lower incidence of severe nausea but increased hepatic toxicity.