© 2005 Foundation for Promotion of Cancer Research
A Multicenter and Open Label Clinical Trial of Zoledronic Acid 4 mg in Patients with Hypercalcemia of Malignancy
1 Department of Oncology/Hematology, National Cancer Center Hospital East, Kashiwa, Chiba, 2 Department of Internal Medicine and 8 Department of Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, 3 Department of Medical Oncology, National Cancer Center Hospital, Tokyo, 4 Department of Breast Oncology, Saitama Cancer Center, Kitaadachi-gun, Saitama, 5 Department of Internal Medicine, National Hospital Organization Nishigunma National Hospital, Shibukawa, Gunma, 6 Department of Palliative Care Unit, Shakaihoken Kobe Central Hospital, Kobe and 7 Department of Chemotherapy, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
For reprints and all correspondence: Hironobu Minami, Department of Oncology/Hematology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577 Japan. E-mail: hminami{at}east.ncc.go.jp
Received May 10, 2004; accepted October 19, 2004
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 albumin-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°C). Electrolyte abnormalities suspected to be drug related including grade 3 or 4 hypocalcemia, 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.
Key Words: bisphosphonate • hypercalcemia • zoledronic acid
9 Present address: International University of Health and Welfare, 8-5-35 Akasaka, Minato, Tokyo, Japan