RESUMO
PURPOSE: The aim of this study was to demonstrate the renal safety equivalence of ibandronate 6 mg infused over 15 min versus 60 min, in patients with bone metastases of breast cancer. PATIENTS AND METHODS: Patients were females having breast cancer with at least one bone metastasis. Exclusion criteria were renal failure (creatinine clearance < 30 mL/min), tooth/jaw disorder or uncontrolled severe disease. Eligible patients were randomly assigned to receive nine ibandronate 6 mg i.v. infusions over either 15 min or 60 min. The primary outcome was the 95% confidence interval (CI) of the difference in creatinine clearance between groups, 28 days after the last infusion. The equivalence margin was ±8 mL/min. RESULTS: Overall 334 patients were randomized (165-15 min infusions vs. 169 to 60 min infusions, 325 (159 vs. 166) were analyzed by intent-to-treat, and 312 (151 vs. 161) were analyzed per protocol. Per protocol, the 15 min-60 min difference in creatinine clearance [95% CI] was -3.00 [-8.18, 2.18]. By intent-to-treat, this difference was-2.91 [-7.99, 2.16]. Death and serious adverse event rates did not differ between groups. Three serious adverse events were considered related to ibandronate: an osteonecrosis of the jaw (15-min group), a pain in jaw and an enamel cracking (60-min group). Two renal failures, reported in the 60 min group, were not considered related to ibandronate. None occurred in the 15 min group. CONCLUSION: Ibandronate may be infused over 15 min without clinically significant consequence on renal safety.