Oral estramustine and cyclophosphamide in patients with metastatic hormonerefractory prostate carcinoma - A phase II study

BACKGROUND. Nearly all cases of metastatic prostate carcinoma progress, aft er hormonal ablation, to a hormone refractory status. To the authors' knowl edge no standard chemotherapy for patients with hormone refractory prostate carcinoma (HRPC) exists. In a prospective study, the efficacy and toxicity of an oral combination of estramustine and cyclophosphamide were evaluated . METHODS. Between March 1996 and April 1998, 32 consecutive patients (median age 74 years; range, 53-84 pears) with metastatic HRPC were treated with o ral estramustine (10 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day) for 14 days every 28 days. Inclusion criteria were previous complete androgen blockade, antiandrogen withdrawal evaluation, and clinical or biochemical d isease progression. Response assessment was based on a decrease greater tha n or equal to 50% in the prostate specific antigen (PSA) level associated w ith improvement (or no worsening) in Eastern Cooperative Oncology Group (EC OG) performance status (PS) and relief of bone pain (if present). RESULTS. All patients were evaluable for efficacy and toxicity. PSA levels decreased by at least 50% in 14 patients (43.7%) (95% confidence interval, 26.5-60.9), remained stable in 12 patients (37.5%), and rose in 6 patients (18.8%). ECOG PS was 0 in 5 of 14 patients, improved from 1 to 0 in 7 patie nts, and remained unchanged in 2 patients. Bone pain, present in 8 of 14 pa tients, disappeared in 7 and was partially relieved in 1. The median durati on of response was 30 weeks (range, 8-88+ weeks). An objective partial resp onse was obtained in two cases. Toxicity was mild and mainly gastrointestin al (World Health Organization [WHO] Grade 1). No cases of WHO Grade 3-4 hem atologic toxicity occurred. CONCLUSIONS. The oral combination of estramustine and cyclophosphamide appe ars to be safe and effective in patients with HRPC. In responding patients its use shows a clinical benefit in terms of improvement of ECOG PS and pai n control. Cancer 2000;88:1438-44. (C) 2000 American Cancer Society.