Bisphosphonates in multiple myeloma

The major clinical manifestations of multiple myeloma are related to enhanced bone destruction resulting in osteolytic lesions, osteoporosis, and pathologic fractures in most patients as well as hypercalcemia and spinal cord compression in many individuals. These patients frequently require radiation therapy or surgery. In an attempt to reduce these complications, bisphosphonates have been evaluated in several large randomized trials in patients also receiving chemotherapy. Oral etidronate given daily showed no clinical benefit, whereas the use of oral clodronate daily did reduce the development of new osteolytic lesions but did not significantly affect bone pain or rates of pathologic fractures. A large, randomized, double-blind study was conducted in which Stage III multiple myeloma patients received either pamidronate (90 mg) or placebo as a 4-hour infusion every 4 weeks for 21 cycles in addition to antimyeloma chemotherapy. The proportion of patients with at least one skeletal complication was significantly reduced in the pamidronate group compared with the placebo group. Although survival was not different between the pamidronate and placebo groups overall, patients in whom first-line chemotherapy had failed when they entered the trial lived longer with pamidronate treatment than those receiving placebo. Patients who received pamidronate had significant decreases in bone pain, had less analgesic drug use, and had better Eastern Cooperative Oncology Group performance status than patients receiving placebo. Pamidronate was safe and well tolerated during the trial.