Phase III study of mitoxantrone plus low dose prednisone versus low dose prednisone alone in patients with asymptomatic hormone refractory prostate cancer.

PURPOSE: We compared median time to treatment failure of men with asymptomatic, hormone refractory, progressive prostate cancer treated with mitoxantrone plus prednisone versus prednisone alone. MATERIALS AND METHODS: In a multicenter phase III trial 120 men with asymptomatic, progressive, hormone refractory prostate cancer were randomly assigned to treatment with mitoxantrone and prednisone or prednisone alone. Patients received 12 mg./m. mitoxantrone intravenously once every 3 weeks for 6 cycles and 5 mg. prednisone twice daily with or without mitoxantrone. Time to treatment failure was assessed as an aggregate end point comprised of time to disease progression, time to toxicity or death, or time to initiation of alternate therapy. RESULTS: Median followup was 21.8 months. Median time to treatment failure and median time to progression were the same: time to treatment failure and time to progression in the mitoxantrone and prednisone group was 8.1 months compared to 4.1 months in the prednisone alone group (p = 0.017 versus p = 0.018). More patients (27 or 48%) treated with mitoxantrone and prednisone achieved a 50% or greater reduction in prostate specific antigen levels than those who received only prednisone (15 or 24%, p = 0.007). There was no significant difference in median survival between the 2 groups, which was 23 and 19 months, respectively. Death was mainly attributable to disease progression. CONCLUSIONS: Patients with hormone refractory prostate cancer who are asymptomatic but had progressive disease had a significantly higher response rate when treated with mitoxantrone and prednisone as demonstrated by the 50% or greater decrease in prostate specific antigen compared to treatment with prednisone alone. Time to treatment failure was significantly prolonged in the chemotherapy treated group but survival rates were not different.