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阿斯利康的AZD9291,是一种口服的小分子第三代表皮生长因子酪氨酸激酶抑制剂(EGFR-TKI),能同时对付非小细胞肺癌的EGFR基因突变(包括18,19,21突变)和EGFR-TKI获得性耐药(T790M)。AZD9291与WZ4002和CO-1686一样,也是基于嘧啶骨架,但有所区别,AZD9291对EGFR野生的肿瘤细胞也有一定的杀伤力(表现在腹泻,皮疹等副作用方面会比WZ4002和CO-1686大一些,但相对易瑞沙和特罗凯要小的多)。
Technical Data
CAS#: 1421373-65-0
Chemical Formula: C28H33N7O2
M.Wt.: 499.62
IUPAC/Chemical name:
N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide.
AZD-9291 is a potent and selective mutated forms EGFR inhibitor(Exon 19 deletion EGFR IC50=12.92 nM, L858R/T790M EGFR IC50= 11.44 nM, wild type EGFR IC50= 493.8 nM)
临床形态是AZD9291 mesylate(甲磺酸盐),分子量为595.71。
论坛υīСКī翻译的一篇内容:
"The ESMO abstract details data for 27 enrolled patients with 6 patients across 3 dose escalation cohorts and 9 patients in a T790M+ expansion cohort.
欧洲临床肿瘤协会年会概述详细表述了(经AZD9291临床试药的)数据,该数据招募27名病患,其中6名病患接受了3个不同剂量的增量用药,9名病患为T790M阳性。
In terms of safety, the most common adverse events were Grade-1 (G-1) with maximum G-1 diarrhea and rash toxicity in the 20, 40 and 80mg cohorts.
就安全性而言,最常见的不良事情为等级1,包括等级最强的1级腹泻和剂量在20,40,80MG时皮疹毒性。
Diarrhea and rash are also toxicities typical of Iressa and Tarceva," said Kozul.
腹泻及皮疹也是易瑞沙和特罗凯的常见毒性,KOZUL说。
"In terms of efficacy, 1) for the 20mg cohort, 2/6 patients cohort demonstrated a partial response (PR) and both of these patients had confirmed T790M+ status;
就有效性而言,1)剂量在20MG时,6名病患中有2名给出了一个部分反馈(反馈有效),而他们两者经确认为T790M阳性。
2) for the 40mg cohort, 2/6 patients demonstrated 2 unconfirmed PRs and the T790M status of these patients in unknown;
2)剂量在40MG时,6名病患中有2名给出2个不确定的部分反馈,他们的T790M状态暂不清楚。
3) for the 80mg cohort, no data have yet been provided. Dose escalation continues as well as recruitment into the T790M+ expansion cohort," he added.
3)剂量在80MG时,尚没有数据提供。增量试验仍在进行中,T790M阳性扩增病员也在招募中。
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Response data for AZN’s drug AZD9291 includes 2 confirmed partial responses at the first (20 mg/day) dose level in
patients whose NSCLC tumors harbored a T790M mutation and 2 unconfirmed responses in the 40 mg dose (T790M
status unknown).
阿斯利康的AZD9291的反馈数据包括2条已经确认的部分反馈,这两天反馈基于第一阶段(20MG/每天),这两名病人为非小细胞肺癌且T790M变异。另2条不确定的反馈基于40MG的剂量(T790M状态未知)
To date, 27 patients have been treated across 20, 40 and 80 mg dose levels (n = 18) and in T790M+
expansion cohorts (n = 9) and no dose limiting toxicities have been reported. Both dose escalation and recruitment into a
T790M expansion cohort are ongoing.
目前,27名病人已经接受了20,40和80MG的剂量(N=18)和T790M阳性扩增组群(N=9),并且没有报告有剂量限制毒性产生。这一增量试验及T790M阳性扩增的人员招募仍在进行中。
http://www.inspire.com/groups/lu ... one-on-trial-t790m/
这儿有一个外国肺癌病人服用160mg AZD9291每天的剂量,发生严重腹泻,腹绞痛、乏力和体重减轻。
在没有进一步的详细数据前,初步的建议是:AZD9291单药,从40mg每天一次开始,如果一周后,耐受良好,加量到80mg每天。AZD9291单药与其它药联用,使用40mg每天的剂量。
胃溶胶囊,空腹服用,每天一次。
剂量换算:临床量/非正版量=1:1.2,那么40mg AZD9291=48mg,80mg AZD9291=96mg
不需要辅料。
补充说明:AZD9291的最大耐受剂量未知,估计大于160mg每天,最低有效剂量是20mg每天,对于具体的病人,个体差异很大,药物代谢情况也不一样,个体的最佳剂量需要灵活调整。
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