Phase I trial of weekly paclitaxel plus oral estramustine phosphate in patients with hormone-refractory prostate cancer.

OBJECTIVES: To exploit the favorable dose intensity and safety profile of weekly paclitaxel, we conducted a Phase I trial of paclitaxel by 3-hour infusion in combination with estramustine phosphate (EM) in men with hormone-refractory prostate cancer (HRPC). The antimicrotubule drug combination of paclitaxel by 96-hour infusion plus EM is active in HRPC. METHODS: Twenty-four patients with metastatic HRPC and progressive tumor after antiandrogen withdrawal were enrolled in this study. Oral EM was taken at a dose of 600 mg/m(2) daily for the initial 21 patients and on a reduced schedule of 280 mg twice daily for the final 3 patients. Paclitaxel was escalated from 60 to 118 mg/m(2). RESULTS: The major toxicities were gastrointestinal and thromboembolic complications related to daily oral dosing of EM. Of the first 21 patients, one third (n = 7) discontinued therapy within 4 weeks because of protracted nausea and/or thrombotic complications. Dose-limiting toxicities at 118 mg/m(2) paclitaxel were fatigue and hepatotoxicity. Of 13 patients with measurable soft-tissue lesions, 6 had objective partial regressions, and 9 (37.5%) of 24 patients (95% confidence interval 19.1% to 59.1%) with elevated prostate-specific antigen levels had a 50% or greater decline of at least 4 weeks' duration. CONCLUSIONS: Weekly paclitaxel at doses of 60 to 107 mg/m(2) were feasible in combination with oral EM, but daily oral EM produced unacceptable toxicity. On the basis of these results, a Phase II trial of weekly paclitaxel with the reduced dose and schedule of EM was initiated by the Eastern Cooperative Oncology Group to assess further the benefits and risks of this treatment in men with metastatic HRPC.

A phase II study of gemcitabine and 5-fluorouracil in metastatic pancreatic cancer: an Eastern Cooperative Oncology Group Study (E3296).

Gemcitabine has recently been compared favorably to 5-fluorouracil (5-FU) as the standard chemotherapy for advanced pancreas cancer. Based on phase I data that combining gemcitabine with 5-FU is safe and has evidence for clinical activity, a phase II trial was conducted by the Eastern Cooperative Oncology Group (ECOG). Patients with metastatic disease, good performance status and organ function were eligible and enrolled after providing informed consent. Patients were given gemcitabine (1,000 mg/m(2)) followed by 5-FU (600 mg/m(2)) weekly for 3 weeks of every 4. Of 37 patients enrolled over a 3-month period, 36 were eligible. Partial responses were seen in 5 patients (14%). Median survival was 4.4 months with a 1-year survival rate of 8.6%. A randomized trial of the combination of 5-FU and gemcitabine versus gemcitabine alone is currently accruing patients in ECOG.