ESTRAMUSTINE PHOSPHATE VERSUS PLACEBO AS 2ND LINE TREATMENT AFTER ORCHIECTOMY IN PATIENTS WITH METASTATIC PROSTATE-CANCER - DAPROCA STUDY-9002

Purpose: We compared the effect of 560 mg. estramustine phosphate dail y to placebo as a supplement to standard palliative therapy in patient s with progressive disease after bilateral orchiectomy as first line t herapy for metastatic prostate cancer. Materials and Methods: In a dou ble-blind multicenter study 131 patients with processing metastatic ho rmone refractory prostate cancer were randomized to receive 280 mg. es tramustine phosphate 2 times daily versus placebo. End points were cli nical progression and death. Adverse events, decrease in prostate spec ific antigen (PSA) and subjective response were also assessed. Results : Adverse events were common in both groups but breast tenderness/gyne comastia and diarrhea were more frequent among patients in the estramu stine phosphate group. Subjective responses were few (9 of 50 estramus tine phosphate and 4 of 57 placebo cases, p = 0.15). Median observatio n time for survival was 43 months and 124 patients died. Median time t o subjective progression and median overall survival did not differ si gnificantly between the 2 groups at 4.6 and 9.4 months in the estramus tine phosphate group versus 5.0 and 6.1 months in the placebo group. O f 61 patients in the estramustine phosphate group 29 achieved a reduct ion in PSA of more than 25% at 1 month of followup compared to only 3 of 68 receiving placebo. A decrease in PSA after 1 month correlated si gnificantly with survival. Conclusions: Although this study did not pr ove estramustine phosphate to be superior to placebo in terms of proto col end points, it generates the hypothesis that prolonged survival ma y be achieved with estramustine phosphate treatment in a subgroup of p atients and that this may be predicted by a decrease in PSA after 1 mo nth of therapy.