Prostate cancer is one of the most common cancers affecting men worldwide.1 Current cancer statistics estimate that more than 200,000 men are diagnosed with prostate cancer in the US each year,2 and five-year worldwide prevalence is approaching 2.5 million cases.3 Approximately 50% of patients will experience disease recurrence after local therapy consisting of radiation or prostatectomy.4 Although advances in the treatment of prostate cancer have extended life expectancy, 65% to 75% of patients with advanced disease will develop bone metastases, resulting in accelerated bone resorption and a loss of skeletal integrity that is associated with significant skeletal morbidity, including pathologic fractures, spinal cord compression, and debilitating bone pain.5
The incidence of skeletal complications experienced by patients with metastatic prostate cancer is illustrated by the placebo group of a recent study of zoledronic acid in men with hormone-refractory prostate cancer (HRPC) and bone metastases.6,7 In this study, nearly 50% of patients receiving placebo experienced = 1 skeletal complication and 33% suffered severe bone pain requiring palliative radiotherapy. A recent study showed that these skeletal complications result in significant decreases in quality-of-life scores.8 Therefore, therapies that prevent skeletal complications and reduce bone pain could translate into improvements in quality of life.
Bisphosphonates are potent inhibitors of bone resorption that have demonstrated clinical benefit for the treatment of malignant bone disease and are the standard of care for the prevention of skeletal complications in patients with bone metastases from breast cancer.9 Several studies have evaluated the efficacy of bisphosphonates – including etidronate, clodronate, pamidronate, ibandronate, and zoledronic acid – in patients with bone metastases from prostate cancer. However, until the recent trial evaluating the efficacy of zoledronic acid in men with HRPC and bone metastases, no bisphosphonate has demonstrated statistically significant long-term reductions in skeletal morbidity or durable pain reduction in this patient population in a randomized placebo-controlled trial.6