Breast-Cancer Adjuvant Therapy with Zoledronic Acid
Breast-Cancer Adjuvant Therapy with Zoledronic Acid
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DOI：
10.1056/nejmoa1105195
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发表时间：
2011-10-13
影响因子：
158.5
通讯作者：
Bell, Richard
中科院分区：
文献类型：
--
作者：
Coleman, Robert E.;Marshall, Helen;Bell, Richard
数据表明，辅助使用双膦酸盐可降低早期乳腺癌患者的复发率和死亡率。我们进行了一项研究，以确定是否与唑来膦酸治疗，除了标准的辅助治疗，将改善疾病的结果，在这样的patients. METHODS在这个开放标签的3期研究，我们随机分配3360例患者接受标准的辅助全身治疗，无论有或没有唑来膦酸。唑来膦酸每3 - 4周给药一次，共6次，然后每3 - 6个月给药一次，完成5年的治疗。该研究的主要终点是无病生存期。第二次中期分析显示，已经越过了预先设定的缺乏益处的界限。在中位随访59个月时，两组之间在主要终点方面没有显著差异，各组的无病生存率均为77（唑来膦酸组校正的风险比为0.98; 95%置信区间[CI]为0.85 - 1.13; P = 0.79）。唑来膦酸组377例患者和对照组375例患者发生疾病复发或死亡。死亡人数-唑来膦酸组243人，对照组276人-也相似，导致唑来膦酸组的总生存率为85.4%，对照组为83.1%（校正风险比，0.85; 95%CI，0.72 - 1.01; P = 0.07）。在唑来膦酸组中，有17例确诊的颌骨骨坏死病例（累积发生率，1.1%; 95%CI，0.6 - 1.7; P < 0.001）和9例疑似病例;对照组中没有病例。其他不良反应的发生率在两个研究groups. CONCLUSIONSSThese研究结果不支持唑来膦酸在乳腺癌的辅助治疗中的常规使用。（由诺华制药和国家癌症研究网络资助; AZURE当前对照试验编号，ISRCTN 79831382。
BACKGROUNDData suggest that the adjuvant use of bisphosphonates reduces rates of recurrence and death in patients with early-stage breast cancer. We conducted a study to determine whether treatment with zoledronic acid, in addition to standard adjuvant therapy, would improve disease outcomes in such patients.METHODSIn this open-label phase 3 study, we randomly assigned 3360 patients to receive standard adjuvant systemic therapy either with or without zoledronic acid. The zoledronic acid was administered every 3 to 4 weeks for 6 doses and then every 3 to 6 months to complete 5 years of treatment. The primary end point of the study was disease-free survival. A second interim analysis revealed that a prespecified boundary for lack of benefit had been crossed.RESULTSAt a median follow-up of 59 months, there was no significant between-group difference in the primary end point, with a rate of disease-free survival of 77% in each group (adjusted hazard ratio in the zoledronic acid group, 0.98; 95% confidence interval [CI], 0.85 to 1.13; P = 0.79). Disease recurrence or death occurred in 377 patients in the zoledronic acid group and 375 of those in the control group. The numbers of deaths - 243 in the zoledronic acid group and 276 in the control group - were also similar, resulting in rates of overall survival of 85.4% in the zoledronic acid group and 83.1% in the control group (adjusted hazard ratio, 0.85; 95% CI, 0.72 to 1.01; P = 0.07). In the zoledronic acid group, there were 17 confirmed cases of osteonecrosis of the jaw (cumulative incidence, 1.1%; 95% CI, 0.6 to 1.7; P < 0.001) and 9 suspected cases; there were no cases in the control group. Rates of other adverse effects were similar in the two study groups.CONCLUSIONSThese findings do not support the routine use of zoledronic acid in the adjuvant management of breast cancer. (Funded by Novartis Pharmaceuticals and the National Cancer Research Network; AZURE Current Controlled Trials number, ISRCTN79831382.)