The New Bisphosphonate Ibandronate in the Treatment of Tumor-Induced Hypercalcemia

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Abstract
Ibandronate is an aminobisphosphonate that specifically binds to bone mineral and inhibits the activity of osteoclasts. It is one of the most potent bisphosphonates that are currently being tested in clinical trials in patients with metabolic bone disorders and with osteoporosis. In animal models, ibandronate is twice, 10 times, 50 times, and 500 times more powerful than risedronate, alendronate, pamidronate, and clodronate, respectively. We retrospectively analyzed the clinical results of three studies with ibandronate in 340 patients and of two studies with pamidronate in 80 patients, leading to the registration of both agents for the treatment of malignant hypercalcemia. Ibandronate can be used in patients with malignant hypercalcemia with and without metastases. A single infusion of 2 to 6 mg ibandronate effectively reduces elevated serum calcium levels. The success of treatment depends on the baseline calcium level and the dose used. The time to normalization of the serum calcium concentration varies between 2 and 7 days, with 4 days being usual in most patients. The median time to relapse (i. e., a re-increase in serum calcium) is 26 days and is similar for all doses. Treatment is more successful in patients with local osteolytic tumors (breast and hematologic tumors, response rates up to 100%) than in those with predominantly humorally induced hypercalcemia in the other solid tumor types. Adverse reactions are minor, generally of no clinical relevance, and rarely require treatment. Local tolerability is excellent. Efficacy of ibandronate (Bondronat® ) is well comparable to that of other bisphosphonates, especially to those with an amino group like pamidronate. Ibandronate provides an effective and well-tolerated treatment for tumor-induced hypercalcemia.

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