A phase I/II study of weekly paclitaxel and 3 days of high dose oral estramustine in patients with hormone-refractory prostate carcinoma

BACKGROUND. The maximum tolerated dose (MTD) and efficacy of weekly 1-hour paclitaxel with 3 days of high dose oral estramustine were evaluated in pat ients with hormone-refractory prostate carcinoma. METHODS. Patients enrolled in cohorts of three received two cycles of six w eekly treatments with 1 week of rest: Cohort I received paclitaxel 40 mg/m( 2) and estramustine 600 mg/m(2), and Cohorts II-IV received paclitaxel 60 m g/m(2), 75 mg/m(2), or 90 mg/m(2), respectively, and estramustine 900 mg/m( 2). Toxicity was assessed weekly, and response was measured by serum prosta te specific antigen (PSA), abdominal computed tomography scans, and bone sc ans at Week 13. RESULTS. Eighteen patients were enrolled, with 12 in Cohorts III and IV. Fo ur patients did not complete treatment. Grade 3 toxicity included one patie nt with nausea and diarrhea in Cohort III and one patient each with neutrop enia and edema followed by Grade 4 thromboembolism in Cohort IV. Grade 1-2 anemia or myelotoxicity were not observed; 3 patients had neuropathy, 5 pat ients had hair loss, and 8 patients had gastrointestinal symptoms. A declin e in the serum PSA level greater than or equal to 50% occurred in none of t hree patients, one of three patients, four of six patients, and four of six patients in Cohorts I-ni respectively. An intent-to-treat analysis showed responses in 9 of 18 patients (50%) in Cohorts I-IV, with 9 of 15 responder s (60%) in Cohorts II-TV. Seven patients achieved declines in serum PSA lev els > 75%. The median duration of PSA response was 16.7 weeks. Response was observed in one of three patients with measurable disease. CONCLUSIONS, The MTD for 1-hour weekly paclitaxel was 90 mg/m(2) with 3 day s of 900 mg/m2 estramustine. Hematologic and neurotoxicity were reduced mar kedly, and gastrointestinal symptoms were ameliorated, but thromboembolic e vents were unaffected. PSA response rates were within the expected 60% rang e for these agents. Cancer 2001;91:2039-45, (C) 2001 American Cancer Societ y.