Pathogenesis and bisphosphonate treatment of skeletal events and bone pain in metastatic cancer: focus on ibandronate.

Bone metastases are the most common cause of pain in patients with advanced cancer, and are associated with progressive skeletal destruction, spinal problems, and hypercalcaemia. Radiotherapy, analgesia, and surgery are the accepted treatment options for chronic malignant bone pain, with a stepped approach being generally recommended. In the past decade, the bisphosphonates, which reduce bone turnover, increase bone mass, and decrease the risk of fracture, have become established as an effective treatment in patients with cancer metastasising to bone. The nitrogencontaining bisphosphonate, ibandronate, has been shown to reduce the risk of skeletal events after oral or intravenous administration in controlled clinical trials in various malignancies, and to confer significant palliation of bone pain and improvements in health-related quality of life in patients with metastatic breast cancer, in particular. Tolerability of this agent has been good, with very low frequencies of acute-phase reactions and osteonecrosis of the jaw, and no evidence of acute nephrotoxicity.

Bone pain reduction in patients with metastatic breast cancer treated with ibandronate-results from a post-marketing surveillance study.

BACKGROUND: Pain relief is an important treatment goal for breast cancer patients with metastatic bone disease and treatment should be associated with a low rate of side effects. This interim analysis of a prospective non-interventional study documents the efficacy and safety of the amino-bisphosphonate ibandronate in the treatment of metastatic bone disease under real-life conditions. PATIENTS AND METHODS: For up to 24 weeks 913 breast cancer patients received IV infusions of 6 mg ibandronate every 3-4 weeks or 50 mg of oral ibandronate once daily. Efficacy variables included pain severity, analgesic use, and skeletal-related events; the major safety parameter was renal function, assessed by serum creatinine levels. Subgroup analyses were performed according to pretreatment with bisphosphonates (none, ibandronate, or other bisphosphonates). RESULTS: At baseline, patients with ibandronate pretreatment tended to have lower mean pain scores and lower serum creatinine levels than those pre-treated with other bisphosphonates. Over the observation period, analgesic use did not increase. Among the 712 patients reporting pain at baseline, 70% achieved an improvement in pain severity during treatment with ibandronate, and there was no evidence to suggest relevant differences in mean pain reductions with IV or oral administration of ibandronate or according to prior bisphosphonate treatment. Skeletal-related events were rare (7%). Changes in serum creatinine levels during ibandronate treatment were small and both formulations of ibandronate were rated as well tolerated by physicians and patients. CONCLUSIONS: Data from this non-interventional study confirm the analgesic efficacy and safety profile of IV and oral ibandronate under real-life conditions.