A multicenter and open label clinical trial of zoledronic acid 4 mg in patients with hypercalcemia of malignancy.

Background: Hypercalcemia of malignancy is a serious complication of cancer. The objective of this study was to investigate the efficacy and safety of zoledronic acid, a new-generation bisphosphonate and the most potent inhibitor of bone resorption identified to date, for hypercalcemia of malignancy in Japanese patients. Methods: Patients with hypercalcemia of malignancy, defined as an album in-corrected serum calcium level >= 12.0 mg/dl, were treated with a single dose of zoledronic acid, 4 mg, by 15 min infusion. Clinical end-points included the proportion of patients with complete response, which was defined as a decrease of corrected serum calcium <= 10.8 mg/dl by day 10, and time to relapse, which is defined as the duration in days between the date of infusion and last available corrected serum calcium < 11.6 mg/dl. Results: Twenty-seven patients were enrolled in this study and 25 patients were evaluable for the efficacy of zoledronic acid. The mean corrected serum calcium level decreased from 14.5 to 9.6 mg/dl by day 10. The complete response rate was 84%. The median time to relapse was 23 days, ranging from 0 to 56 days. The most frequently observed adverse event was fever (<= 38 degrees C). Electrolyte abnormalities suspected to be drug related including grade 3 or 4 hypo-calcemia, hypophosphatemia and hypokalemia were observed in 11 patients; however, all patients were asymptomatic. No serious adverse events associated with renal toxicity were reported. Conclusions: Zoledronic acid is well tolerated and is effective for hypercalcemia of malignancy in Japanese patients.