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A Phase I Study of Estramustine, Weekly Docetaxel, and Carboplatin Chemotherapy in Patients with Hormone-Refractory Prostate Cancer

¹ Lank Center for Genitourinary Oncology, Department of Medical Oncology and ² Department of Biostatistical Science, Dana-Farber Cancer Institute; ³ Department of Medical Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts; and ⁴ North Shore Cancer Center, Peabody, Massachusetts

Requests for reprints: William K. Oh, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, Email: william_oh{at}dfci.harvard.edu.

Purpose: To define the maximal tolerated dose, safety, and efficacy of docetaxel, carboplatin, and estramustine in patients with hormone-refractory prostate cancer (HRPC).

Methods: Patients with HRPC received docetaxel for 3 weeks, followed by a rest week. Docetaxel (20, 25, 30, 36, or 43 mg/m²) was given on days 2, 9, and 16 of a 28-day cycle. Patients also received estramustine (140 mg p.o. three times daily on days 1-5, 8-12, and 15-19) and carboplatin [area under the curve, AUC (5) or (6) on day 2].

Results: Thirty patients were treated. Five patients received carboplatin [AUC (6)] but experienced delayed thrombocytopenia. After a protocol amendment, 25 subsequent patients received carboplatin [AUC (5)]. Median age was 64 years. Median prostate-specific antigen (PSA) was 117 ng/mL. Fifty-three percent received prior ketoconazole and 10% had mitoxantrone. No dose-limiting toxicities were noted. Although maximal tolerated dose was not reached, docetaxel dose escalation was stopped at 43 mg/m². Significant myelosuppression was not seen until the highest dose level, when seven and four patients experienced grade 3 and 4 toxicities, respectively. Among all patients, PSA declines of 50% occurred in 63%. At the recommended phase II dose, PSA declines of 50% occurred in 75% (95% confidence interval, 43-95). Four of 14 (29%) patients with measurable disease had partial responses. Median survival was 14.6 months.

Conclusions: Estramustine, docetaxel, and carboplatin are well tolerated and active in HRPC. Myelosuppression is the primary toxicity. The recommended phase II dose of docetaxel is 43 mg/m² combined with estramustine and carboplatin. PSA declines were seen at every dose level.

Key Words: chemotheraphy • prostate cancer • hormone refractory • phase I trial • 00-00-09 Genitourinary cancers: prostate

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