Zoledronic acid: An overview of its current and potential benefits in patients with malignancy

The bisphosphonates, potent inhibitors of bone resorption, have proven especially beneficial in the treatment of hypercalcemia of malignancy. Bisphosphonates have also been shown to reduce the overall skeletal morbidity rate, pathological fractures and the need for palliative or preventive therapy in patients with breast cancer and multiple myeloma. Zoledronic acid is a novel bisphosphonate agent that bone resorption assays show is 2-3 times more potent than pamidronate, while achieving 3-fold greater renal tolerability in vitro and in vivo. Following promising preclinical and early clinical development, zoledronic acid has been shown in randomized controlled trials to be superior to pamidronate in the treatment of hypercalcemia of malignancy. When compared to placebo, zoledronic acid has also been found effective in delaying and reducing skeletal-related events (SREs) in patients with bone metastases from prostate cancer, where osteoblastic lesions are most common. A second trial evaluated zoledronic acid and pamidronate in patients with breast cancer or multiple myeloma. The predefined non-inferiority analysis successfully demonstrated that patients receiving zoledronic acid did as well with regard to SREs as patients receiving pamidronate. A third, placebo-controlled trial evaluated the efficacy of zoledronic acid in patients with bone metastases from other types of cancers. Preliminary analysis suggests an improvement in time to first SRE in patients receiving zoledronic acid. Finally, Phase III clinical research is currently ongoing to assess the efficacy of zoledronic acid in preventing bone metastases in patients with breast and prostate cancer, and preclinical studies are evaluating the possible anti-tumor effects of this important new bisphosphonate.