Major Pierre P, Cook Richard
Hamilton Regional Cancer Center, Department of Medicine, McMaster University, 699 Concession St., Hamilton, Ontario, Canada L8V 5C2.
Am J Clin Oncol. 2002 Dec;25(6 Suppl 1):S10-8. doi: 10.1097/00000421-200212001-00003.
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.
双膦酸盐是目前乳腺癌和多发性骨髓瘤骨转移患者姑息治疗的标准药物。本文讨论了用于评估双膦酸盐疗法对骨转移患者临床疗效的终点指标选择和统计方法。近期有关帕米膦酸和唑来膦酸的研究为设计和开展多中心、随机、安慰剂对照试验设定了标准，以评估双膦酸盐对骨转移患者的临床益处。唑来膦酸的研究已证明，使用可靠的临床终点指标，对于包括前列腺癌在内的多种原发癌患者具有客观、显著且持久的益处。其他双膦酸盐，如氯膦酸，也已被研究用于治疗骨转移，但这些研究规模相对较小。本综述首先考虑试验设计和分析问题，特别强调对同一患者发生的多个事件进行严格分析的统计要求，然后根据这些统计考量回顾双膦酸盐对乳腺癌或前列腺癌骨转移患者试验的结果。
