Oral clodronate in breast cancer patients with bone metastases: a randomized study

Objectives. To investigate the effect of the bisphosphonate clodronate on the occurrence of skeletal events (hypercalcaemia, fractures and radiotherapy) in breast cancer patients with bone metastases. Design. Prospective, randomized, controlled, clinical trial. Setting. A department of oncology in a university hospital, Subjects, One hundred patients who received first-line systemic antineoplastic treatment for metastatic breast cancer with bone involvement were randomized to receive clodronate as two 400 mg capsules twice a day for 2 years or no additional therapy, Results, In the clodronate group the number of skeletal events was reduced to 14 events in 48 evaluable patients as compared with 21 events in 51 evaluable control patients. The time to the first skeletal event was significantly longer in the clodronate group than in the control group (P = 0.015) and the most distinct difference was a lower occurrence of fractures in the clodronate group (P = 0.023). After 15 months the effect of clodronate tended to decline as the need for radiotherapy increased in the clodronate group compared with the control group (P = 0.069). Significant improvements in several quality-of-life aspects were seen in both groups during the first 6 months, but there was no significant difference between the groups. No effect was observed on time to radiologically evaluated disease progression in bone or on survival. The most frequent side-effects resulting in discontinuation of clodronate were nausea and diarrhoea. Conclusion, Oral clodronate is associated with a temporary reduction of morbidity related to bone metastases in breast cancer patients.