Abstract
Objective: Zoledronic acid has demonstrated clinical benefit in both early and advanced-stage prostate cancer for the prevention of bone loss and treatment of bone metastases. Herein, the future role of zoledronic acid in the treatment of prostate cancer and novel agents with potential clinical benefit for the treatment of bone metastases will be discussed. Methods: Published studies were identified through MEDLINE searches, review of bibliographies of relevant articles, and review of abstracts from scientific meetings. Results: Data from preclinical studies have demonstrated that zoledronic acid has antitumor potential. Zoledronic acid inhibits proliferation and induces apoptosis in several prostate cancer cell lines and inhibits bone metastases in animal models of prostate cancer. Therefore, clinical trials are under way to assess the efficacy of zoledronic acid in the prevention of bone metastases in patients with prostate cancer or renal cell carcinoma. Currently, new strategies for the treatment and prevention of bone metastases are being investigated. Combinations of zoledronic acid plus other agents, including taxanes and cyclooxygenase-2 (COX-2) inhibitors, have demonstrated additive or synergistic antitumor activity. Other agents are under development that may improve clinical outcomes in patients with bone metastases. These agents include inhibitors of osteoclast-mediated bone resorption, such as cathepsin K inhibitors and osteoprotegerin analogues, and inhibitors of osteoblast activity. Conclusion: The role of zoledronic acid in the treatment and prevention of bone metastases in men with prostate cancer continues to evolve, and new agents are being investigated.
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