Originally published as JCO Early Release 10.1200/JCO.2005.05.116 on February 28 2005

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Zoledronic Acid Significantly Reduces Skeletal Complications Compared With Placebo in Japanese Women With Bone Metastases From Breast Cancer: A Randomized, Placebo-Controlled Trial

From the Hyogo Medical Center for Adults, Akashi; National Hospital Organization Shikoku Cancer Center, Matsuyama; National Cancer Center Hospital E, Kashiwa; St Luke’s International Hospital; Sanno Medical Plaza Oncology Center; University of Tokyo, Tokyo; Kanagawa Cancer Center, Yokohama; Gunma University, Maebashi, Japan; Novartis Pharmaceuticals Corporation, E Hanover, NJ

Address reprint requests to Norio Kohno, MD, Chairman, Department of Surgery, Hyogo Medical Center for Adults, 13-70 Kitaojicho Akashi 673-0021, Japan; e-mail: norio{at}tiger.interq.or.jp

PURPOSE: To investigate the efficacy and safety of zoledronic acid for the treatment of bone metastases from breast cancer.

PATIENTS AND METHODS: Women with bone metastases (N = 228) were randomly assigned to receive 4 mg zoledronic acid (n = 114) or placebo (n = 114) via 15-minute infusions every 4 weeks for 1 year. The primary efficacy end point was the skeletal-related event (SRE) rate ratio between treatment groups. An SRE was defined as pathologic fracture, spinal cord compression, and radiation or surgery to bone. Secondary end points included percentage of patients with at least one SRE, time-to-first SRE, and Andersen-Gill multiple-event analysis.

RESULTS: The SRE rate ratio at 1 year (excluding HCM and adjusted for prior fracture) was 0.61 (permutation test; P = .027), indicating that zoledronic acid reduced the rate of SRE by 39% compared with placebo. The percentage of patients with at least one SRE (excluding HCM) was significantly reduced by 20% by zoledronic acid (29.8% v 49.6% for placebo; P = .003). Zoledronic acid significantly delayed time-to-first SRE (median not reached v 364 days; Cox regression; P = .007) and reduced the risk of SREs by 41% in multiple event analysis (risk ratio = 0.59; P = .019) compared with placebo. Zoledronic acid was well tolerated with a safety profile similar to placebo. No patient treated with zoledronic acid had grade 3 or 4 serum creatinine increase.

CONCLUSION: Zoledronic acid significantly reduced skeletal complications compared with placebo across multiple end points in Japanese women with bone metastases from breast cancer.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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• Progress in the Management of Bone Metastases: One Continent at a Time?
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  JCO 2005 23: 3299-3301 [Full Text]

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