Renal safety of ibandronate 6 mg infused over 15 min versus 60 min in breast cancer patients with bone metastases: a randomized open-label equivalence trial.

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.