A PHASE-II TRIAL OF ORAL ESTRAMUSTINE AND ORAL ETOPOSIDE IN HORMONE-REFRACTORY PROSTATE-CANCER

Objectives. We previously demonstrated that the combination of oral es tramustine (15 mg/kg/day) and oral etoposide (50 mg/m(2)/day) is effec tive first-line therapy for the treatment of hormone refractory prosta te cancer. We initiated a new Phase II trial utilizing a lower dose of estramustine (10 mg/kg/day) and allowing previous chemotherapy treatm ent. Methods. Estramustine (10 mg/kg/day) and etoposide (50 mg/m(2)/da y) were administered orally for 21 of 28 days. Sixty-two patients were enrolled with a minimum of 26 weeks of follow-up. Results. Of 15 pati ents with measurable soft tissue disease, 8 (53%) had a partial respon se (PR). Seven of these 8 patients also demonstrated a decrease in bas eline prostate-specific antigen (PSA) of more than 50%. The median sur vival of all patients was 56 weeks. Of 47 patients with disease limite d to the bone, 16 (34%) had a PR to therapy based on decrease in pretr eatment PSA of more than 50%. Overall, 24 (39%) of 62 patients demonst rated a decrease in pretreatment PSA levels of at least 50% from basel ine. Twenty-two patients received previous chemotherapy. There were no differences in survival or disease response in patients treated with previous chemotherapy compared with untreated patients. Pretreatment h emoglobin, PSA, alkaline phosphatase and lactate dehydrogenase levels were not significant prognostic factors, but performance status was an important predictor of survival. Conclusions. We conclude that the co mbination of oral estramustine (10 mg/kg/day) and oral etoposide (50 m g/m(2)/day) is an active regimen for hormone refractory prostate cance r. (C) 1997, Elsevier Science Inc. All rights reserved.