PHASE-II STUDY OF THE ORAL CYCLOPHOSPHAMIDE AND ORAL ETOPOSIDE COMBINATION IN HORMONE-REFRACTORY PROSTATE CARCINOMA PATIENTS

BACKGROUND. Hormonotherapy temporarily controls symptoms in 80% of pat ients with metastatic prostate carcinoma. Once progression occurs, no consensus exists on further therapy. Oral etoposide (VP-16) has shown clinical efficacy in advanced small cell lung carcinoma, breast cancer , germ cell tumors, and lymphomas. A synergistic effect between etopos ide and alkylating agents such as estramustine was recently reported. We began a prospective Phase II study of an oral combination of cyclop hosphamide (CPM) and VP-16 in patients with hormone-refactory prostate carcinoma (HRPC). METHODS. Patients were orally treated with CPM (100 mg/day) and VP-16 (50 mg/day) for 14 days every 28 days. Therapy cont inued until there was evidence of disease progression. RESULTS. From N ovember, 1992, to February, 1995, 20 patients with HRPC were entered i nto the study. Patients were eligible if they had an ECOG performance status (PS) of 0 to 2. All of the patients presented with bone metasta sis, and 70% presented with bone pain. Seventy-five percent had failed al least two hormonal manipulations. The mean duration of treatment w as 5 months (range 2-12). Performance status improved in 26% of the pa tients, and bone pain was relieved in 71%. An objective response was d efined as a decrease of 50% or more in the prostate-specific antigen ( PSA) level. One patient demonstrated a complete response, and six pati ents had partial responses assessed by PSA plasma levels (objective re sponse rate: 35%). The mean duration of response was 8 +/- 6 months (r ange: 2-24). Median survival was 11 months. Toxicities were minimal. C ONCLUSIONS. The combination of oral CPM and VP-16 map be an active and well tolerated regimen for patients with HRPC. (C) 1996 American Canc er Society.