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 albumin-corrected serum calcium level > or =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 < or =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 (< or =38 degrees 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.
Kawada
Kenji
K
Department of Oncology/Hematology, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan.
Minami
Hironobu
H
Okabe
Keniichi
K
Watanabe
Toru
T
Inoue
Keniichi
K
Sawamura
Morio
M
Yagi
Yasuo
Y
Sasaki
Tsuneo
T
Takashima
Shigemitsu
S
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000150:complications; D002118:Calcium / Q000097:blood; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006258:Head and Neck Neoplasms / Q000150:complications; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy* / Q000209:etiology; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000150:complications; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications; D009369:Neoplasms / Q000150:complications*; D016896:Treatment Outcome; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D002118:Calcium