ORAL ESTRAMUSTINE AND ORAL ETOPOSIDE FOR HORMONE-REFRACTORY PROSTATE-CANCER

Objectives. Estramustine and etoposide have been shown to inhibit the growth of prostate cancer cells in experimental models. An in vivo syn ergism of the two agents, when administered to patients with metastati c prostate cancer refractory to hormone therapy, has been reported, To confirm these results, we administered this combination to a large nu mber of patients with hormone-refractory prostate cancer (HRPC). Metho ds. Fifty-six patients with metastatic HRPC were treated with oral est ramustine 140 mg three times a day and oral etoposide 50 mg/m(2)/day f or 21 days. Therapy was discontinued for 7 days and the cycle was then repeated. Therapy was continued until evidence of disease progression or unacceptable toxicity occurred. To control for the possible interf erence of an antiandrogen withdrawal effect, all patients discontinued antiandrogen therapy and were not enrolled in the study unless there was evidence of disease progression. Results. Forty-five percent of 33 patients with measurable soft tissue disease demonstrated an objectiv e response, which included five complete and ten partial responses, Am ong 52 patients with osseous disease, 17% showed improvement and 50% s howed stability of bone scan, Thirty patients (58%) demonstrated a dec rease of more than 50% in pretreatment prostate-specific antigen (PSA) levels, The median survival of all patients was 13 months. Good pretr eatment performance status, measurable disease response, improvement o r stability of bone scan, and PSA response were important predictors o f longer survival. Conclusions. We conclude that the combination of es tramustine and etoposide is an active and well-tolerated oral regimen in HRPC. (C) 1997, Elsevier Science Inc. All rights reserved.