Pierre Major1. 1. Department of Medicine, McMaster University, 699 Concession Street, Hamilton, Ontario, Canada L8V 5C2. Pierre.major@hrcc.on.ca
Abstract
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.
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.
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