Bisphosphonates to Prevent Skeletal Complications in Men With Metastatic Prostate Cancer

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Abstract
The literature on clinical trials of bisphosphonates in men with metastatic prostate cancer is reviewed to familiarize the reader with biology of bone metastases and rationale for use of bisphosphonates. A MEDLINE review of the literature on prostate cancer and bisphosphonates was performed. In uncontrolled clinical trials bisphosphonates improved pain and analgesic scores in men with symptomatic bone metastases. In a randomized controlled trial of men with bone metastases and progressive disease after first line hormonal therapy zoledronic acid decreased the skeletal related events, a composite end point defined as fracture, surgery or radiation therapy to bone, or change in antineoplastic therapy for bone pain. Randomized controlled trials with other bisphosphonates reported no significant benefit in men with bone metastases. Problems with the study populations, drug bioavailability and potency, statistical power and end point definition may have contributed to the negative results of these other studies. Zoledronic acid decreases the risk of skeletal related events in men with bone metastases and disease progression after first line hormonal therapy. Additional clinical research is needed to evaluate the optimal timing, schedule and duration of bisphosphonate treatment in men with metastatic prostate cancer. Additional research is also necessary to determine whether bisphosphonates can prevent bone metastases in men with high risk nonmetastatic prostate cancer.