[Bisphosphonates and bone metastases]

Bisphosphonates, potent inhibitors of bone resorption have been emerging as the standard treatment of tumor-induced hypercalcemia during the 90's. All uncontrolled phase II studies up to 1992 had demonstrated efficacy in reducing morbidity in terms of bone pain, fracture and hypercalcemia. Other studies on intravenous bisphosphonates, with no other anti-tumor treatment, even demonstrated sclerosis of osteolytic breast cancer bone metastases. Randomised phase III studies only began after 1992. In multiple myeloma, one study with oral clodronate has reported a decrease in bone events and two other studies, one with intravenous pamidronate and the other with oral clodronate have both reported a decrease in skeletal events and bone pain. In breast cancer patients with bone metastases, five large studies have been reported: three with intravenous pamidronate, one with oral pamidronate and one with oral clodronate. All these studies have demonstrated the superiority of bisphosphonates over placebo on both bone pain and bone events, but have failed to show an increase in duration of survival. Bisphosphonates should therefore be considered as an important part of the palliative treatment in breast cancer patients with bone metastases. On the other hand, no definite conclusion can be drawn on the role of bisphosphonates in the treatment of prostatic carcinoma bone metastases yet. However, bisphosphonates should be considered as part of the standard therapy in managing painful lesions in patients with multiple myeloma, breast cancer and prostatic cancer. Nevertheless, further studies are needed with bisphosphonates in the adjuvant setting before bone metastases appear. Could new and more potent bisphosphonates such as zoledronate further reduce bone metastases morbidity?