Randomized, double-blind, controlled trial of mitoxantrone/prednisone and Clodronate versus mitoxantrone/prednisone and placebo in patients with hormone-refractory prostate cancer and pain

Purpose : To compare the incidence of palliative response in patients with hormone-resistant prostate cancer (HRPC) treated with mitoxantrone and prednisone (MP) plus clodronate with that of patients treated with MP plus placebo. Materials and Methods: Men with HRPC, bone metastases, and bone pain were randomly assigned to receive clodronate 1,500 mg administered intravenously (IV) or placebo every 3 weeks, in combination with mitoxantrone 12 mg/m(2) IV every 3 weeks and prednisone 5 mg orally bid. Patients completed the present pain intensity (PPI) index and Prostate Cancer-Specific Quality-of-Life Instrument at each treatment visit and used a diary to record analgesic use on a daily basis. The primary end point was a reduction to zero or of two points in the PPI or a decrease of 50% in analgesic intake, without increase in either. Results: The study accrued 209 eligible patients over 44 months. One hundred sixty patients (77%) had mild PPI scores (1 or 2), and 49 (24%) had moderate PPI scores (3 or 4). The primary end point of palliative response was achieved in 46 (46%) of 104 patients on the clodronate arm and in 41 (39%) of 105 patients on the placebo arm (P = .54). The median duration of response, symptomatic disease progression-free survival, overall survival, and overall quality of life were similar between the arms. Subgroup analysis suggested possible benefit in patients with more severe pain. Conclusion: MP provides useful palliation in symptomatic men with HRPC. Clodronate does not increase the rate of palliative response or overall quality of life. Clodronate may be beneficial to patients who have moderate pain, but this requires further confirmation. (C) 2003 by American Society of Clinical Oncology.