A phase II trial of estramustine and etoposide in hormone refractory prostate cancer: A Southwest Oncology GroupTrial (SWOG 9407)

BACKGROUND. The combination of oral estramustine and oral etoposide has gen erated response rates of 40-50% in patients with hormone refractory prostat e cancer in single institution trials. This study tested this regimen in a multi-institutional setting. METHODS. Fifty-five patients were accrued over a period of 4 months between I March 1996 and 1 July 1996. Two patients were not analyzable and two pat ients were ineligible. They were given an oral regimen consisting of estram ustine 15 mg/kg/day (capped at 1120 mg per day) and etoposide 50 mg/M-2/day , days 1-21 every 28 days. Patients received a median of two cycles of ther apy. RESULTS. Toxicities included II patients (20%) with grades 3 or 4 granulocy topenia, 5 patients (10%) with grades 3 or 4 edema, and 3 patients (6%) wit h a thrombotic event. There were two treatment-related deaths, one as a res ult of anemia and the other as a result of a myocardial infarction. Of the 32 men who received at least 2 cycles of therapy, 7 men (22%) demonstrated a partial response to this regimen as measured by prostate-specific antigen (PSA) criteria of a 50% decline from pretreatment values. CONCLUSIONS. This trial demonstrates the toxicity of estramustine delivered in high dose. It also illustrates the difficulty of conducting phase II tr ials in prostate cancer in the cooperative group setting where the experien ce and comfort level of oncologists with new agents is less than that of th e physicians at the institution where the therapy was developed. As the act ivity of this regimen with low-dose estramustine is defined, further multi- institutional studies may be warranted. Prostate 46:257-261, 2001. (C) 2001 Wiley-Liss, Inc.