在ALK-rearranged Ceritinib非小细胞肺癌。
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肖,金正日DW,用R,谭DS, Felip E, Chow LQ, Camidge博士,Vansteenkiste J, Sharma年代,德不是T, rie GJ,所罗门BJ,狼J,托马斯·M,舒勒米,刘G,澳网,刘YY,金水酒米,碳化硼铝,恩格尔曼农协
在ALK-rearranged Ceritinib非小细胞肺癌。
郑传经地中海J。2014年3月27日,370 (13):1189 - 97。doi: 10.1056 / NEJMoa1311107。
- PubMed ID
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24670165 (在PubMed]
- 文摘
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背景:非小细胞肺癌(NSCLC)窝藏的间变性淋巴瘤激酶基因(碱性)重排是敏感筛选抑制剂crizotinib但阻力总是发展。Ceritinib (LDK378)是一种新的筛选抑制剂,临床前研究表明抗肿瘤能力大于crizotinib。方法:在这第一阶段的研究中,我们进行口头ceritinib 50至750毫克每天一次剂量的晚期癌症患者窝藏在碱性基因改变。处于扩张阶段的研究中,患者接受最大耐受剂量。患者评估来确定安全,药代动力学性质,和ceritinib的抗肿瘤活性。肿瘤活检是ceritinib治疗前识别电阻突变筛选在一组与非小细胞肺癌患者在治疗crizotinib疾病进展。结果:共有59名患者参加剂量递增阶段。ceritinib的最大耐受剂量750毫克每天一次;dose-limiting有毒事件包括腹泻、呕吐、脱水、转氨酶水平升高、低磷酸盐血。这个阶段是紧随其后的是一个扩张阶段,一个额外的71患者治疗,患者总数为130。 Among 114 patients with NSCLC who received at least 400 mg of ceritinib per day, the overall response rate was 58% (95% confidence interval [CI], 48 to 67). Among 80 patients who had received crizotinib previously, the response rate was 56% (95% CI, 45 to 67). Responses were observed in patients with various resistance mutations in ALK and in patients without detectable mutations. Among patients with NSCLC who received at least 400 mg of ceritinib per day, the median progression-free survival was 7.0 months (95% CI, 5.6 to 9.5). CONCLUSIONS: Ceritinib was highly active in patients with advanced, ALK-rearranged NSCLC, including those who had had disease progression during crizotinib treatment, regardless of the presence of resistance mutations in ALK. (Funded by Novartis Pharmaceuticals and others; ClinicalTrials.gov number, NCT01283516.).
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