Treatment of bone complications in advanced prostate cancer: rationale for bisphosphonate use and results of a phase III trial with zoledronic acid.

Prostate cancer often metastasizes to bone during disease progression. Patients who develop bone metastases have a high risk of developing skeletal complications, including pathologic fractures, spinal cord compression, and severe bone pain. Bisphosphonate therapy is widely used for the prevention of skeletal complications in patients with bone lesions from multiple myeloma and breast cancer. Until recently, however, no bisphosphonate had ever shown objective clinical benefit in patients with prostate cancer and osteoblastic bone lesions. A recent multicenter, randomized, placebo-controlled trial found zoledronic acid (4 mg) to be a safe and effective therapy in patients with bone metastases from hormone-refractory prostate cancer. Zoledronic acid significantly reduced the proportion of patients who experienced skeletal complications and extended the time to first skeletal complication. Further, zoledronic acid significantly reduced the risk of skeletal complications over this 15-month study and provided consistent reductions in bone pain that were significant at the 3- and 9-month time points compared with placebo. These results suggest that zoledronic acid may become an important advancement in the care of patients with prostate cancer metastatic to bone. The role of zoledronic acid in the treatment of patients with prostate cancer continues to evolve.