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

Objectives. To investigate the effect of the bisphosphonate clodronate on t he occurrence of skeletal events (hypercalcaemia, fractures and radiotherap y) 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 antineoplas tic treatment for metastatic breast cancer with bone involvement were rando mized 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 eval uable control patients. The time to the first skeletal event was significan tly longer in the clodronate group than in the control group (P = 0.015) an d the most distinct difference was a lower occurrence of fractures in the c lodronate group (P = 0.023). After 15 months the effect of clodronate tende d to decline as the need for radiotherapy increased in the clodronate group compared with the control group (P = 0.069). Significant improvements in s everal quality-of-life aspects were seen in both groups during the first 6 months, but there was no significant difference between the groups. No effe ct was observed on time to radiologically evaluated disease progression in bone or on survival. The most frequent side-effects resulting in discontinu ation of clodronate were nausea and diarrhoea. Conclusion, Oral clodronate is associated with a temporary reduction of mor bidity related to bone metastases in breast cancer patients.