title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Ibandronate may be infused over 15 min without clinically significant consequence on renal safety.
authors: University Hospital Jean Minjoz, 3 bd Alexandre Fleming, 25030 Besançon Cedex, France. xavier.pivot@univ-fcomte.fr
authors: Xavier
authors: X
authors: Pivot
authors: Alain
authors: A
authors: Lortholary
authors: Sophie
authors: S
authors: Abadie-Lacourtoisie
authors: Fawzia
authors: F
authors: Mefti-Lacheraf
authors: Eric
authors: E
authors: Pujade-Lauraine
authors: Claudia
authors: C
authors: Lefeuvre
authors: Sarah
authors: S
authors: Letessier
authors: Philippe
authors: P
authors: Morvan
authors: Carole
authors: C
authors: Dür
authors: L
authors: L
authors: Frimat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077557:Ibandronic Acid; D007262:Infusions, Intravenous; D008875:Middle Aged; D051437:Renal Insufficiency / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077557:Ibandronic Acid