BACKGROUND AND OBJECTIVE: Despite their widespread use in metastatic bone disease, some bisphosphonate drugs are associated with adverse events (AEs), particularly renal toxicity, adding to treatment burdens and increasing healthcare costs. Ibandronic acid is a single-nitrogen bisphosphonate with high efficacy against bone events and metastatic bone pain, and a renal safety profile compar- able to that of placebo. In this study, the safety of ibandronic acid was examined over a period of 4 years.
PATIENTS AND METHODS: During an initial 96-week period, breast cancer patients with bone metastases were randomised in double-blind fashion to placebo or ibandronic acid 6mg administered by intravenous infusion over 1-2 hours every 3-4 weeks as part of a previously reported phase III trial (MF 4265 study). All patients completing the phase III trial were offered open-label active treatment for a further 96 weeks (extension phase). A total of 62 patients received ibandronic acid 6mg in this extension phase and were classified according to their initial treatment (placebo/ibandronic acid 6mg [placebo/6mg] and ibandronic acid 6mg/ibandronic acid 6mg [6mg/6mg] groups). Safety was assessed by AE reports and clinical laboratory evaluations.
RESULTS: During the 4-year study, most patients experienced at least one AE, with malignancy progression being most commonly reported. However, fewer treatment-related AEs were reported in the extension phase (placebo/6mg: 6.3% [1/16]; 6mg/6mg: 13.0% [6/46]) than in the initial phase of the study (placebo: 56.3% [9/16]; 6mg: 67.4% [31/46]). Serious AEs were mainly due to malignancy progression. There were no clinically relevant renal AEs, and in both groups, serum creatinine levels were similar for up to 4 years.
CONCLUSION: This 96-week open-label safety extension of a phase III, placebo-controlled trial demonstrates that long-term use of intravenous ibandronic acid is well tolerated.
- Bone Density Conservation Agents/administration & dosage
- Bone Neoplasms/drug therapy
- Breast Neoplasms/drug therapy
- Diphosphonates/administration & dosage
- Disease Progression
- Drug Administration Schedule
- Follow-Up Studies
- Ibandronic Acid
- Infusions, Intravenous
- Injections, Intravenous
- Leg/blood supply
- Middle Aged
- Neoplasm Metastasis
- Pulmonary Embolism/chemically induced
- Survival Rate
- Thrombosis/chemically induced
- Time Factors
- Treatment Outcome