Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer
Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer
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DOI：
10.1056/nejmoa1213755
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发表时间：
2013-07-18
影响因子：
158.5
通讯作者：
Sartor, O.
中科院分区：
文献类型：
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作者：
Parker, C.;Nilsson, S.;Sartor, O.
背景镭-223二氯化物（镭-223），α发射体，选择性靶向骨转移瘤与α粒子。在我们的3期、随机、双盲、安慰剂对照研究中，我们将921名接受过、不适合接受或拒绝接受多西他赛的患者随机分为2组：1的比例，接受六次注射镭-223（剂量为每公斤体重静脉注射50 kBq）或匹配的安慰剂;每4周注射一次。此外，所有患者都接受了最佳标准的护理。主要终点是总生存期。主要次要疗效终点包括至首次出现症状性骨骼事件的时间和各种生化终点。一项预先设定的中期分析在314例死亡发生时进行，评估了镭-223与安慰剂对生存率的影响。在安慰剂与镭-223交叉治疗前，对528例死亡患者进行了更新分析。结果在中期分析中，与安慰剂相比，镭-223显著提高了总生存率，（中位数，14.0个月vs. 11.2个月;风险比，0.70; 95%置信区间[CI]，0.55 - 0.88;双侧P=0.002）。对921例患者的最新分析证实了镭-223的生存益处（中位数，14.9个月对11.3个月;风险比，0.70; 95%CI，0.58至0.83; P
BackgroundRadium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases.MethodsIn our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223.ResultsAt the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P