Effect of long-term bisphosphonate treatment on morbidity due to bone metastases in breast cancer patients.

The effect of long-term bisphosphonate (APD) treatment on the morbidity from bone metastases in breast cancer patients was studied in a controlled clinical trial. 131 patients were randomized between treatment with APD (300 mg/day orally) or control. Systemic treatment for breast cancer was left to the discretion of the physician. The distribution of cases according to age, receptor status and previous treatment was similar in both groups. Patients were examined at 3-month intervals, while bone scans and radiography of relevant lesions in the skeleton were performed every 6 months. After a median follow-up of 13 months, the morbidity in the treated group was significantly less than in the controls. This concerned the occurrence of hypercalcemia, bone pain and fractures, and the need for radiotherapy of osteolytic lesions. In this interim analysis, APD treatment more than halved the requirement for specific treatment of bone lesions. The treatment is simple and well tolerated at a relatively low dosage. A higher oral dose was precluded due to gastrointestinal toxicity. Because the effect of APD on skeletal morbidity was not complete, efforts should be made to develop more effective and less toxic bisphosphonates.