Abiraterone and increased survival in metastatic prostate cancer.
Abiraterone and increased survival in metastatic prostate cancer.
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DOI：
10.1056/nejmoa1014618
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发表时间：
2011-05-26
期刊：
影响因子：
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通讯作者：
COU-AA-301 Investigators
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文献类型：
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作者：
de Bono JS;Logothetis CJ;Molina A;Fizazi K;North S;Chu L;Chi KN;Jones RJ;Goodman OB Jr;Saad F;Staffurth JN;Mainwaring P;Harland S;Flaig TW;Hutson TE;Cheng T;Patterson H;Hainsworth JD;Ryan CJ;Sternberg CN;Ellard SL;Fléchon A;Saleh M;Scholz M;Efstathiou E;Zivi A;Bianchini D;Loriot Y;Chieffo N;Kheoh T;Haqq CM;Scher HI;COU-AA-301 Investigators
睾丸外雄激素的生物合成可能有助于去势抵抗性前列腺癌的进展。我们评估了一种雄激素生物合成抑制剂醋酸阿比特龙是否延长了接受化疗的转移性去势抵抗性前列腺癌患者的总生存期。我们以2:1的比例随机分配1195名先前接受过多西他赛的患者，每天两次接受5mg强的松和1000mg醋酸阿比特龙（797名患者）或安慰剂（398名患者）。主要终点为总生存期。次要终点包括前列腺特异性抗原（PSA）进展的时间（根据预先指定的标准PSA水平升高），根据基于预先指定标准的放射学发现的无进展生存期，以及PSA反应率。中位随访12.8个月后，醋酸阿比特龙-强的松组的总生存期长于安慰剂-强的松组（14.8个月vs 10.9个月；风险比为0.65；95%可信区间为0.54 ~ 0.77；P<0.001）。由于这些结果超出了研究终止的预定标准，因此在中期分析时对数据进行了盲法分析。所有次要终点，包括PSA进展时间（10.2个月对6.6个月，P<0.001）、无进展生存期（5.6个月对3.6个月，P<0.001）和PSA缓解率（29%对6%，P<0.001），均有利于治疗组。与安慰剂-强的松组相比，醋酸阿比特龙-强的松组报告的与矿皮质激素相关的不良事件，包括液体潴留、高血压和低钾血症更频繁。醋酸阿比特龙对雄激素生物合成的抑制延长了转移性去势抵抗性前列腺癌患者既往接受化疗的总生存期。（由美洲狮生物技术资助；cu - aa -301 ClinicalTrials.gov编号，NCT00638690。）
Biosynthesis of extragonadal androgen may contribute to the progression of castration-resistant prostate cancer. We evaluated whether abiraterone acetate, an inhibitor of androgen biosynthesis, prolongs overall survival among patients with metastatic castration-resistant prostate cancer who have received chemotherapy. We randomly assigned, in a 2:1 ratio, 1195 patients who had previously received docetaxel to receive 5 mg of prednisone twice daily with either 1000 mg of abiraterone acetate (797 patients) or placebo (398 patients). The primary end point was overall survival. The secondary end points included time to prostate-specific antigen (PSA) progression (elevation in the PSA level according to prespecified criteria), progression-free survival according to radiologic findings based on prespecified criteria, and the PSA response rate. After a median follow-up of 12.8 months, overall survival was longer in the abiraterone acetate–prednisone group than in the placebo–prednisone group (14.8 months vs. 10.9 months; hazard ratio, 0.65; 95% confidence interval, 0.54 to 0.77; P<0.001). Data were unblinded at the interim analysis, since these results exceeded the preplanned criteria for study termination. All secondary end points, including time to PSA progression (10.2 vs. 6.6 months; P<0.001), progression-free survival (5.6 months vs. 3.6 months; P<0.001), and PSA response rate (29% vs. 6%, P<0.001), favored the treatment group. Mineralocorticoid-related adverse events, including fluid retention, hypertension, and hypokalemia, were more frequently reported in the abiraterone acetate–prednisone group than in the placebo–prednisone group. The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among patients with metastatic castration-resistant prostate cancer who previously received chemotherapy. (Funded by Cougar Biotechnology; COU-AA-301 ClinicalTrials.gov number, NCT00638690.)