Enzalutamide: A Novel Antiandrogen for Patients with Castrate-Resistant Prostate Cancer
Enzalutamide: A Novel Antiandrogen for Patients with Castrate-Resistant Prostate Cancer
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DOI：
10.1158/1078-0432.ccr-12-2910
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发表时间：
2013-03-15
影响因子：
11.5
通讯作者：
Kelly, Wm Kevin
中科院分区：
文献类型：
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作者：
Hoffman-Censits, Jean;Kelly, Wm Kevin
Enzalutamide（MDV 3100，Xtandi，Medivation\Astellas）是一种口服雄激素受体信号传导抑制剂，可阻断雄激素受体相互作用，抑制雄激素受体易位至细胞核，损害雄激素受体与DNA的结合，并抑制辅激活因子募集和受体介导的DNA转录。在一项在既往接受过多西他赛治疗的进行性去势抵抗性前列腺癌（CRPC）男性患者中比较Enzalutamide与安慰剂的III期随机研究中，Enzalutamide显示总生存期改善（18.4 vs. 13.6个月，HR，0.63; P < 0.001）。此外，所有次要终点，包括前列腺特异性抗原（PSA）下降的患者比例、软组织缓解、生活质量缓解、至PSA进展时间、放射学无进展生存期和至首次放射学骨骼事件的时间，均显著有利于Enzalutamide治疗患者。疲乏、腹泻和潮热在enzalutamide治疗患者中很常见，5例（0.6%）患者报告了癫痫发作。Enzalutamide是一种新型疗法，可非常有效地阻断雄激素信号传导途径，该途径在CRPC发生期间不受调节。临床前研究沿着的关键试验导致其在2012年9月被美国食品药品监督管理局（FDA）批准，将进行审查。临床癌症研究; 19（6）; 1335-9。(C)2012年AACR。
Enzalutamide (MDV3100, Xtandi, Medivation\Astellas) is an oral inhibitor of androgen receptor signaling that blocks androgen receptor interaction, inhibits translocation of the androgen receptor to the nucleus, impairs androgen receptor binding to DNA, and inhibits coactivator recruitment and receptor-mediated DNA transcription. In a phase III randomized study comparing enzalutamide with placebo in men with progressive castration-resistant prostate cancer (CRPC) who were previously treated with docetaxel, enzalutamide showed an improvement in overall survival (18.4 vs. 13.6 months, HR, 0.63; P < 0.001). In addition, all secondary endpoints including proportion of patients with prostate-specific antigen (PSA) decline, soft-tissue response, quality-of-life response, time to PSA progression, radiographic progression-free survival, and the time to the first radiographic skeletal event all significantly favored patients treated with enzalutamide. Fatigue, diarrhea, and hot flashes were common in patients treated with enzalutamide, with seizures reported in 5 (0.6%) of the patients. Enzalutamide is a novel therapy that very potently blocks the androgen signaling pathway, which is unregulated during the development of CRPC. The preclinical studies along with the pivotal trials that led to its approval by the U.S. Food and Drug Administration (FDA) in September 2012 will be reviewed. Clin Cancer Res; 19( 6); 1335-9. (C) 2012 AACR.