PHASE-II EVALUATION OF ORAL ESTRAMUSTINE AND ORAL ETOPOSIDE IN HORMONE-REFRACTORY ADENOCARCINOMA OF THE PROSTATE

Purpose: Estramustine and etoposide (VP-16) have been demonstrated to inhibit the growth of prostate cancer cells in experimental models. Th is led us to evaluate the effectiveness of this combination in the tre atment of patients with metastatic prostate carcinoma refractory to ho rmone therapy. Patients and Methods: Estramustine 15 mg/kg/d and VP-16 50 mg/m(2)/d, were administered orally in divided doses for 21 days. P atients were then taken off therapy for 7 days and the cycle then repe ated. Therapy continued until evidence of disease progression. Results : Forty-two patients have been enrolled onto this trial with a minimum of 40 weeks follow-up. Of 18 patients with measurable soft tissue dis ease, three demonstrated a complete response (CR) and six a partial re sponse (PR) for longer than 2 months. Of these 18 patients, pretreatme nt prostate-specific antigen (PSA) levels decreased by at least 75% in five men (28%) and by at least 50% in nine (50%). The median survival duration has not been reached in those patients who demonstrated a re sponse either by soft tissue or PSA criteria. Of 24 patients with dise ase limited to bone, six (25%) demonstrated improvement and nine (38%) demonstrated stability in their bone scans. Five men (21%) demonstrat ed a decrease of at least 75% in pretreatment PSA levels and 14 (58%) demonstrated at least a 50% decrease; the median survival duration has not been reached in these patients. Pretreatment performance status i s an important predictor of survival. Conclusion: We conclude that the combination of estramustine and VP-16 is an active oral regimen in ho rmone-refractory prostate cancer.