The role of bisphosphonates in the treatment of bone metastases--the U.S. experience.
Frequent complications of bone metastases include pain, pathologic fracture, hypercalcemia and spinal cord compression. Lytic bone metastases result from excessive activation of osteoclasts by tumor-produced cytokines. Aredia (pamidronate) is a potent bisphosphonate that inhibits osteoclast activation. In two dose-seeking phase I trials in patients with breast cancer and prostate cancer, repeated intravenous infusion of Aredia was shown to be safe and effective in reducing bone resorption and pain. In a randomized phase III trial of 377 patients with multiple myeloma, Aredia was administered in a dosage of 90 mg i.v. every 4 weeks. Compared with placebo, treatment with Aredia was associated with a significant decrease in bone pain and in the incidence and time to development of all skeleton-related events. Data from two phase III breast cancer trials each involving 300 patients are now being analyzed. The newer bisphosphonates can safely be used together with standard anticancer therapy to provide effective palliation of symptoms caused by lytic bone metastases.
Harvey
H A
HA
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA.
Lipton
A
A
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D001862:Bone Resorption / Q000517:prevention & control; D001943:Breast Neoplasms / Q000188:drug therapy; D002986:Clinical Trials as Topic; D017321:Clinical Trials, Phase I as Topic; D017326:Clinical Trials, Phase III as Topic; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005598:Fractures, Spontaneous / Q000517:prevention & control; D006801:Humans; D006934:Hypercalcemia / Q000517:prevention & control; D007275:Injections, Intravenous; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy; D010010:Osteoclasts / Q000187:drug effects; D010146:Pain / Q000517:prevention & control; D010166:Palliative Care; D000077268:Pamidronate; D010919:Placebos; D011471:Prostatic Neoplasms / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D013117:Spinal Cord Compression / Q000517:prevention & control; D014481:United States
D000970:Antineoplastic Agents; D004164:Diphosphonates; D010919:Placebos; D000077268:Pamidronate