Phase II trial of estramustine and etoposide in androgen-sensitive metastatic prostate carcinoma

Background: Early chemohormonal therapy in metastatic prostate cancer may offer an advantage by simultaneously targeting androgen-dependent and -independent clones. Hence, a phase II trial was conducted to evaluate the efficacy and toxicity of estramustine and etoposide in hormone-sensitive metastatic prostate cancer. Patient and Methods: Eligibility consisted of untreated metastatic prostate cancer, adequate organ function, and a performance status of 0 to 2 by Zubrod criteria. A 21-day schedule of oral estramustine (10 mg/kg/day) and etoposide (50 mg/m²/day) was administered every 28 days. Hormonal therapy was allowed at the end of the protocol therapy. Toxicity was assessed weekly, PSA levels were assessed with each cycle, and objective response was evaluated every 3 cycles. Results: Twenty-one patients were enrolled (10 white, 11 black) with a median age of 59.5 years (range, 42-79 years), a median PSA of 338 ng/mL (range, 0.9-20,000 ng/mL), and a median Gleason score of 8 points. Ten patients had bone-only metastases, 11 had measurable disease, of whom 4 had visceral metastases. A total of 128 cycles were administered (median, 6 cycles). No dose reductions were required. Nineteen patients were able to be evaluated for response. Severe toxicities included thromboembolic events and anemia in 2 patients each and fatigue in 1 patient. There were no episodes of febrile neutropenia. Response was observed in 8 of 11 patients (73%) with measurable disease. Median PSA nadir after therapy was 0.45 ng/mL, and undetectable PSA (<0.1 ng/mL) was achieved in 4 patients. Median time to PSA progression was 16.65 months. At a median follow-up of 34 months, 18 patients were alive. The 1-, 2-, and 3-year overall survival rates were 90%, 82%, and 72% respectively. Median survival has not yet been reached. Conclusion: The combination of estramustine and etoposide is well tolerated, and has promising activity in newly diagnosed metastatic prostate cancer.