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

From the Hamilton Regional Cancer Centre, Hamilton, Ontario, Canada; Centre Paul Papin, Angers, France; Comprehensive Cancer Institute, Huntsville, AL; Bendigo Hospital, Bendigo, and Andrew Love Cancer Centre, Geelong, Australia; Feist-Weiller Cancer Center, Shreveport, LA; Medizinische Klinik III, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany; Boston Cancer Group, Memphis, TN; Institut Jules Bordet, Brussels, Belgium; and Novartis Pharma, Basel, Switzerland.

Address reprint requests to Pierre P. Major, MD, Hamilton Regional Cancer Center, 699 Concession St, Hamilton L8V 5C2, Canada; email pierre.major{at}hrcc.on.ca

PURPOSE: 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 AND METHODS: Patients with moderate to severe HCM (corrected serum calcium [CSC] 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.

RESULTS: 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.

CONCLUSION: 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.

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