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The Use of Zoledronic Acid, a Novel, Highly Potent Bisphosphonate, for the Treatment of Hypercalcemia of Malignancy

Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Hamilton Regional Cancer Centre, Hamilton, Ontario, Canada

Correspondence: Pierre Major, M.D., Hamilton Regional Cancer Centre, 699 Concession Street, Hamilton, Ontario, Canada L8V 5C2. Telephone: 905-387-9495; Fax: 905-304-7334; e-mail: Pierre.major{at}hrcc.on.ca

Background. Hypercalcemia of malignancy is a serious complication of cancer that affects patients with and without bone metastases. A single infusion of pamidronate disodium, a nitrogen-containing bisphosphonate, effectively normalizes serum calcium in the majority of patients treated for up to 1 month. Zoledronic acid is a new-generation, heterocyclic nitrogen-containing bisphosphonate and the most potent inhibitor of bone resorption identified to date.

Methods. The natural history, clinical presentation, and treatment of hypercalcemia of malignancy are reviewed, with a focus on the mechanisms of action and relative efficacy and safety of bisphosphonate therapies.

Results. The improved efficacy of zoledronic acid compared with pamidronate disodium has been demonstrated in a pooled analysis of two randomized clinical trials in patients with hypercalcemia of malignancy. In these trials, both zoledronic acid and pamidronate disodium were safe and well tolerated; however, zoledronic acid treatment resulted in a significantly higher number of complete responses, more rapid calcium normalization, and more durable responses compared with pamidronate disodium.

Conclusions. Given the superior efficacy and comparable safety profile of zoledronic acid compared with pamidronate disodium, zoledronic acid is likely to become the treatment of choice for hypercalcemia of malignancy.

Key Words. Bisphosphonate • Bone metastases • Hypercalcemia of malignancy • Pamidronate disodium • Zoledronic acid

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