肿瘤
词汇介绍
拓展阅读
解析
Crizotinib
释 义 n. 克唑替尼(药物名称)
例 句 Crizotinib activity in patients with ROS1-translocated tumours was confirmed. 克唑替尼在ROS1易位肿瘤患者中的活性得到证实。
概述
概述
克唑替尼,商品名叫Xalkori,赛可瑞。为粉红色硬胶囊剂,内容物为白色结晶粉末。是辉瑞制药研制的一种口服酪氨酸激酶受体抑制剂,在美国于2011年上市,用于治疗间变性淋巴瘤激酶(ALK)阳性的局部晚期和转移的非小细胞肺癌(NSCLC)。克唑替尼是酪氨酸激酶受体包括ALK、肝细胞生长因子受体(HGFR、c-Met)、ROS1和酪氨酸激酶(RON)的一种抑制剂。易位可影响ALK基因导致致癌融合蛋白的表达。ALK融合蛋白的形成导致激活和基因表达和增加细胞增殖有贡献信号的调节异常而生存肿瘤表达这些蛋白。克唑蒂尼就是通过阻断对肿瘤细胞生长与存活起关键作用的多种细胞通路,导致肿瘤的稳定或消退。其为口服胶囊,剂量为250 mg和200 mg。
本质
克唑蒂尼胶囊硬壳含250 mg或200 mg的克唑蒂尼胶体二氧化硅,微晶纤维素,无水磷酸氢钙,羟基乙酸淀粉钠,硬脂酸镁和硬胶囊胶囊壳为无活性成分。粉红色不透明胶囊壳组分含明胶,二氧化钛,和氧化铁红。白色不透明胶囊壳组分含明胶和二氧化钛。印刷油墨含有虫胶,丙二醇,强氨水溶液,氢氧化钾,和黑色氧化铁。
用法用量
克唑替尼胶囊的推荐剂量为250 mg,口服,每日两次。若患者在临床治疗中获益应持续用药。胶囊应整粒吞服。克唑替尼胶囊与食物同服或不同服均可。若漏服一剂克唑替尼胶囊,则补服漏服剂量的药物,除非距下次服药时间短于6小时。根据不同患者安全性与耐受性可中断治疗或减少剂量。如需减少剂量,则降低克唑替尼胶囊至200 mg口服,每日两次。若需要进一步减少剂量,则根据患者安全性和耐受性,将剂量调整为250 mg口服,每日一次。
适应症
(1)ALK-阳性转移非小细胞肺癌:克唑蒂尼是一种用于治疗通过FDA批准的检测确认为间变性淋巴瘤激酶(ALK)阳性的晚期或转移的非小细胞肺癌(NSCLC)患者的激酶抑制剂。(2)ROS-1阳性非小细胞肺癌:克唑替尼是适用为有转移NSCLC其肿瘤为ROS1-阳性患者的治疗。
不良反应
肝功能异常:比平常更加疲惫,皮肤变黄,眼睛白色球变黄,尿液变暗或呈棕色(茶色);恶心,呕吐,食欲不振;胃部右侧疼痛;皮肤瘙痒,或比平时更容易擦伤;肺炎:感觉呼吸困难,咳嗽,发烧。头晕,昏厥,胸部不适。视觉效应(闪光,视力模糊,重影,一般在服用克唑替尼后不久就会出现);神经病(神经麻痹,神经结合处,末端或者肌肉发麻);头昏眼花,疲倦;水肿(身体组织积液,引起手足水肿);肠胃不适(恶心,呕吐,腹泻,便秘,食道咽喉不适);食欲不振,味觉减退;皮疹等。
药代动力学
吸收:口服单剂量克唑替尼,平均4-6小时克唑替尼的吸收达到峰值。每日服用250 mg克唑替尼2次,15天内可达并保持稳态血药浓度,平均累积率为4.8。当剂量超出每日2次、每次200-300 mg的剂量范围,稳态系统药物暴露的增加略高于剂量的增加比例。单剂量口服给药250 mg后,克唑替尼的平均绝对生物利用度为43%(范围:32 - 66%)。
Brigatinib versus Crizotinib in ALK-Positive Non–Small-Cell Lung Cancer复制标题
吉美替尼与克唑替尼治疗ALK阳性非小细胞肺癌的比较
发表时间:2018-11-22
影响指数:70.7
作者: D.R. Camidge
期刊:N. Engl. J. Med.
A total of 275 patients underwent randomization; 137 were assigned to brigatinib and 138 to crizotinib. At the first interim analysis (99 events), the median follow-up was 11.0 months in the brigatinib group and 9.3 months in the crizotinib group. The rate of progression-free survival was higher with brigatinib than with crizotinib (estimated 12-month progression-free survival, 67% [95% confidence interval {CI}, 56 to 75] vs. 43% [95% CI, 32 to 53]; hazard ratio for disease progression or death, 0.49 [95% CI, 0.33 to 0.74]; P<0.001 by the log-rank test). The confirmed objective response rate was 71% (95% CI, 62 to 78) with brigatinib and 60% (95% CI, 51 to 68) with crizotinib; the confirmed rate of intracranial response among patients with measurable lesions was 78% (95% CI, 52 to 94) and 29% (95% CI, 11 to 52), respectively. No new safety concerns were noted. Among patients with ALK-positive NSCLC who had not previously received an ALK inhibitor, progression-free survival was significantly longer among patients who received brigatinib than among those who received crizotinib. (Funded by Ariad Pharmaceuticals; ALTA-1L ClinicalTrials.gov number, NCT02737501.).
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