BACKGROUND: Hormonotherapy temporarily controls symptoms in 80% of patients 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 etoposide and alkylating agents such as estramustine was recently reported. We began a prospective Phase II study of an oral combination of cyclophosphamide (CPM) and VP-16 in patients with hormone-refractory [correction of 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 continued until there was evidence of disease progression. RESULTS: From November, 1992, to February, 1995, 20 patients with HRPC were entered into the study. Patients were eligible if they had an ECOG performance status (PS) of 0 to 2. All of the patients presented with bone metastasis, and 70% presented with bone pain. Seventy-five percent had failed at least two hormonal manipulations. The mean duration of treatment was 5 months (range 2-12). Performance status improved in 26% of the patients, and bone pain was relieved in 71%. An objective response was defined as a decrease of 50% or more in the prostate-specific antigen (PSA) level. One patient demonstrated a complete response, and six patients had partial responses assessed by PSA plasma levels (objective response rate: 35%). The mean duration of response was 8 +/- 6 months (range: 2-24). Median survival was 11 months. Toxicities were minimal. CONCLUSIONS: The combination of oral CPM and VP-16 may be an active and well tolerated regimen for patients with HRPC.
BACKGROUND: Hormonotherapy temporarily controls symptoms in 80% of patients 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 etoposide and alkylating agents such as estramustine was recently reported. We began a prospective Phase II study of an oral combination of cyclophosphamide (CPM) and VP-16 in patients with hormone-refractory [correction of 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 continued until there was evidence of disease progression. RESULTS: From November, 1992, to February, 1995, 20 patients with HRPC were entered into the study. Patients were eligible if they had an ECOG performance status (PS) of 0 to 2. All of the patients presented with bone metastasis, and 70% presented with bone pain. Seventy-five percent had failed at least two hormonal manipulations. The mean duration of treatment was 5 months (range 2-12). Performance status improved in 26% of the patients, and bone pain was relieved in 71%. An objective response was defined as a decrease of 50% or more in the prostate-specific antigen (PSA) level. One patient demonstrated a complete response, and six patients had partial responses assessed by PSA plasma levels (objective response rate: 35%). The mean duration of response was 8 +/- 6 months (range: 2-24). Median survival was 11 months. Toxicities were minimal. CONCLUSIONS: The combination of oral CPM and VP-16 may be an active and well tolerated regimen for patients with HRPC.