Phase 2 Study of Cyclophosphamide, Etoposide, and Estramustine in Patients With Castration-Resistant Prostate Cancer.

ABSTRACT

BACKGROUND: There are no effective chemotherapies for patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease has failed to respond to taxanes or patients who do not wish to receive intravenous drugs. We hypothesized that low doses of multiple medications with prolonged exposure would result in a high response rate and low toxicity. PATIENTS AND METHODS: Patients with mCRPC were eligible for this phase 2 trial. The primary endpoint was a prostate-specific antigen decrease of more than 50%. CEE consisted of cyclophosphamide (50 mg/m2), etoposide (50 mg/m2), and estramustine 280 mg provided orally once a day for 14-day cycles every 28 days. RESULTS: Fifty-two patients were enrolled and included in all evaluations. The prostate-specific antigen response rate was 46% in all patients, 53% in chemotherapy-naive subjects, and 31% after docetaxel chemotherapy. Thirty subjects had measurable lesions, 1 (3%) had complete response, 2 (7%) partial response, and 22 (73%) stable disease, for a clinical benefit of 83%. Sixty percent experienced an improvement in their performance status, and 65% reported improvement in their pain. The median overall survival was 18.6 months in all patients, 20.4 months in chemotherapy-naive patients and 11.3 months in patients whose disease progressed while receiving docetaxel therapy. Grade 3/4 treatment-related toxicities included 20% neutropenia, 10% thrombocytopenia, 10% deep-vein thrombosis, 8% anemia, 8% fatigue, 4% death, and 2% anorexia and stomatitis. CONCLUSION: CEE was an all-oral, easy-to-administer, and effective triple-drug therapy for patients with mCRPC.