Zoledronic Acid Is Superior to Pamidronate in the Treatment of Hypercalcemia of Malignancy: A Pooled Analysis of Two Randomized, Controlled Clinical Trials

• Published in: Journal of clinical oncology Vol. 19; no. 2; pp. 558 - 567
• Main Authors: MAJOR, P, LORTHOLARY, A, SEAMAN, J, HON, J, ABDI, E, MILLS, G, MENSSEN, H. D, YUNUS, F, BELL, R, BODY, J, QUEBE-FEHLING, E
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 15-01-2001; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Biological and medical sciences; Diphosphonates - therapeutic use; Female; General and cellular metabolism. Vitamins; Humans; Hypercalcemia - drug therapy; Hypercalcemia - etiology; Imidazoles - therapeutic use; Male; Medical sciences; Middle Aged; Neoplasms - complications; Pharmacology. Drug treatments; Randomized Controlled Trials as Topic; Human; Hydroelectrolytic balance disorder; Diphosphonic acid derivatives; Controlled therapeutic trial; Malignant tumor; Antihypercalcemic agent; Bisphosphonates; Inorganic element; Pamidronic acid; Hypercalcemia; Metabolic disorder; Chemotherapy; Randomization; Treatment; Zoledronic acid; Double blind study; Complication; Paraneoplastic syndrome
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2001.19.2.558

Two identical, concurrent, parallel, multicenter, randomized, double-blind, double-dummy trials were conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating hypercalcemia of malignancy (HCM).
Patients with moderate to severe HCM (corrected serum calcium [CSC] > or = 3.00 mmol/L [12.0 mg/dL]) were treated with a single dose of zoledronic acid (4 or 8 mg) via 5-minute infusion or pamidronate (90 mg) via 2-hour infusion. A protocol-specified pooled analysis of the two parallel trials was performed. Clinical end points included rate of complete response by day 10, response duration, and time to relapse.
Two hundred eighty-seven patients were randomized and evaluated for safety; 275 were evaluated for efficacy. Both doses of zoledronic acid were superior to pamidronate in the treatment of HCM. The complete response rates by day 10 were 88.4% (P = .002), 86.7% (P = .015), and 69.7% for zoledronic acid 4 mg and 8 mg and pamidronate 90 mg, respectively. Normalization of CSC occurred by day 4 in approximately 50% of patients treated with zoledronic acid and in only 33.3% of the pamidronate-treated patients. The median duration of complete response favored zoledronic acid 4 and 8 mg over pamidronate 90 mg with response durations of 32, 43, and 18 days, respectively.
Zoledronic acid is superior to pamidronate; 4 mg is the dose recommended for initial treatment of HCM and 8 mg for relapsed or refractory hypercalcemia.