Phase I/II study of weekly docetaxel and vinblastine in the treatment of metastatic hormone-refractory prostate carcinoma.

BACKGROUND Phase II trials have shown that taxanes have clinical activity as single agents as well as in combination with microtubule inhibitors in the treatment of hormone-refractory prostate cancer. Recent phase III trials with docetaxel have reported a survival benefit. Most trials also report significant toxicity, including thromboembolic disease. We conducted a phase I/II study to evaluate the maximum-tolerated dose, response rate, and effects on quality of life of the combination of docetaxel and vinblastine. METHODS Twenty men with hormone-refractory prostate cancer were treated after experiencing hormonal failure. Patients were enrolled in cohorts of three and treated with three weekly doses of docetaxel (20, 25, 30, 35, or 40 mg/m 2 ) administered as 30-minute infusion and vinblastine (3 mg/m 2 ) bolus. Treatment cycles were repeated every 28 days. Follow-up assessments included prostate-specific antigen level determinations, computed tomographic scans, bone scans, Brief Pain Inventory, and Functional Assessment of Cancer Therapy-Prostate Instrument (FACT-P). Toxicity was graded by National Cancer Institute common toxicity criteria. RESULTS The maximum tolerated dose of docetaxel was 35 mg/m 2 . Twelve of the 19 patients (63%; 95% Cl 38%-84%) evaluable patients achieved a 50% reduction in prostate-specific antigen level that persisted for 24-80 weeks. Four of eight patients with measurable soft tissue disease had a partial response. Median time to disease progression was 50 weeks. Sixteen patients completed the Brief Pain Inventory at least three times. Twelve patients reported moderate-to-severe pain scores (≥ 4) at baseline. Of these 12 patients, 11 reported that their worst pain score improved by at least two levels, and five of the 12 reported decreased opioid requirements. Seventeen patients completed the FACT-P at baseline and on at least two additional visits. Nine of these 17 (53%) reported improvement in Trial Outcome Index (sum of physical, functional, prostate subscales) by > 6 points. Anemia was common; 12/20 patients required epoetin, and two required transfusions. Venous thrombosis developed in four patients during treatment. Only two patients discontinued treatment because of toxicity. CONCLUSIONS This combination of weekly docetaxel and vinblastine is effective, well tolerated, and associated with improved quality of life in most of the patients treated. Although estramustine was not given, the risk of thromboembolic disease remains significant.