title: Efficacy of bisphosphonates in the management of skeletal complications of bone metastases and selection of clinical endpoints.
abstract: Bisphosphonates are the current standard of palliative care for patients with bone lesions from breast cancer and multiple myeloma. This article discusses the selection of endpoints and statistical methods used to assess clinical efficacy of bisphosphonate therapies in patients with bone metastases. Recent studies of pamidronate and zoledronic acid have set the standards for the design and conduct of multicenter, randomized, placebo-controlled trials to assess the clinical benefit of bisphosphonates in patients with bone metastases. Studies of zoledronic acid have demonstrated objective, significant, and enduring benefits in patients with a broad range of primary cancers, including prostate cancer, using robust clinical endpoints. Other bisphosphonates, including clodronate, have been investigated for the treatment of bone metastases, but these studies have been relatively small. This review first considers issues of trial design and analysis, with particular emphasis on the statistical requirements for the rigorous analysis of multiple events occurring in the same patient, and then reviews the results of bisphosphonate trials in patients with breast or prostate cancers metastatic to bone in the light of these statistical considerations.
authors.affiliation: Hamilton Regional Cancer Center, Department of Medicine, McMaster University, 699 Concession St., Hamilton, Ontario, Canada L8V 5C2.
authors.forename: Pierre P
authors.initials: PP
authors.lastname: Major
authors.forename: Richard
authors.initials: R
authors.lastname: Cook
mesh_terms: D001859:Bone Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D004002:Clodronic Acid / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D005598:Fractures, Spontaneous / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology / Q000517:prevention & control; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D015233:Models, Statistical; D010146:Pain / Q000209:etiology / Q000517:prevention & control; D000077268:Pamidronate; D011471:Prostatic Neoplasms / Q000473:pathology*; D016032:Randomized Controlled Trials as Topic; D013117:Spinal Cord Compression / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D004002:Clodronic Acid; D000077211:Zoledronic Acid; D000077268:Pamidronate