A phase II trial of oral estramustine and oral etoposide in hormone refractory prostate cancer

Objectives. We previously demonstrated that the combination of oral estramustine (15 mg/kg/day) and oral etoposide (50 mg/m²/day) is effective first-line therapy for the treatment of hormone refractory prostate cancer. We initiated a new Phase II trial utilizing a lower dose of estramustine (10 mg/kg/day) and allowing previous chemotherapy treatment. Methods. Estramustine (10 mg/kg/day) and etoposide (50 mg/m²/day) 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 patients with measurable soft tissue disease, 8 (53%) had a partial response (PR). Seven of these 8 patients also demonstrated a decrease in baseline prostate-specific antigen (PSA) of more than 50%. The median survival of all patients was 56 weeks. Of 47 patients with disease limited to the bone, 16 (34%) had a PR to therapy based on decrease in pretreatment PSA of more than 50%. Overall. 24 (39%) of 62 patients demonstrated a decrease in pretreatment PSA levels of at least 50% from baseline. 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 hemoglobin, 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 combination of oral estramustine (10 mg/kg/day) and oral etoposide (50 mg/m²/day) is an active regimen for hormone refractory, prostate cancer.