The clinical and cost considerations of bisphosphonates in preventing bonecomplications in patients with metastatic breast cancer or multiple myeloma

The bisphosphonates are potent inhibitors of osteoclast-mediated bone resor ption and are now the treatment of choice for the management of hypercalcae mia of malignancy. The incidences of hypercalcaemia and other skeletal comp lications (bone pain, pathological fracture) remain high despite apparent r esponses to systemic therapy, with particularly high event rates in women w ith advanced skeletal metastases of breast cancer. This review focuses on s tudies addressing the long-term efficacy of bisphosphonates to reduce skele tal complications in breast cancer (5 studies) and multiple myeloma (4 stud ies); with particular reference to controlled studies of sufficient magnitu de and duration to allow confidence in the estimation of efficacy. Bearing in mind the limitations of differences in trial design and the lack of direct studies comparing drugs; adequate exposure to a bisphosphonate r educes the incidence of skeletal complication by 30 to 40% in both breast c ancer and multiple myeloma. Oral clondronate and intravenous pamidronate ha ve similar efficacy in both diseases, but the duration of efficacy may diff er between drugs. Both agents have shown intriguing survival benefits in su bgroups of patients. The numbers needed to treat (NNT) to prevent a skeletal complication during one year are lowest in metastatic skeletal disease in breast cancer (NNTT < 8) but also compare very favourably with other disease for patients with recurrent nonskeletal breast cancer or multiple myeloma (NNTs 7 to 31 depen ding on the complication to be prevented). Treatment costs of both breast c ancer and multiple myloma are driven by inpatient and outpatient hospital v isits so that bisphosphonate regimens should be developed that reduce both. Further research is required to determine if subgroups of patients can be b etter identified that will derive particular benefit, or perhaps no benefit at all, from bisphosphonate therapy. It is not known whether more potent b isphosphonates will deliver greater clinical efficacy in the future.