XALKORI(crizotinib)是一种口服酪氨酸激酶受体遏抑剂。Crizotinib的分子式是C21H22Cl2FN5O。分子量是450.34道尔顿。Crizotinib化学上称为(R)-3-[1-(2:6-Dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1H-pyrarizonaol-4-yl]pyridin-2-i amine.
其化学布局式为

XALKORI® (crizotinib)胶囊，口服
美国初始批准： 2011

制造商：
辉瑞公司实验室

类药物：
酪氨酸激酶抑制剂。

活性成分（S）：
Crizotinib 200mg，每日250毫克;帽。
指示（S）：
治疗局部晚期或转移性非小细胞肺癌（NSCLC），间变性淋巴瘤激酶（ALK）阳性作为一个FDA批准的试验检测。

药理学：
易位可以影响ALK基因在致癌融合蛋白的表达。形成ALK融合蛋白基因的表达和信号，这可能会导致增加表达这些蛋白的肿瘤细胞增殖和生存的激活和失调的结果。 Crizotinib是一种受体酪氨酸激酶，包括ALK，肝细胞生长因子受体（HGFR C - MET），并Recepteur D' Origine南泰斯（RON）抑制剂。

临床试验：
Crizotinib在两个多中心，单臂研究（研究A和B）进行了调查。 ALK阳性的NSCLC在研究A，被认定使用Vysis ALK的休息，除了鱼探头套件。 ALK阳性的NSCLC在研究B，被认定使用了当地的临床试验分析。在这两项研究的主要疗效终点是客观反应率（ORR），根据在实体瘤疗效评价标准。反应持续时间也进行评估。在研究完成后，136例患者进行了分析研究和119例在研究B。在研究治疗时间中位数为22周和32周在调查评估的基础研究A研究B的，有1个完整和67个部分反应的ORR为50％（95％CI：42％，59％ ），并在研究B，有2个完整和ORR为61％（95％CI为69个部分反应：52％，70％）。在第8周的治疗，取得了79％（研究）和55％的客观肿瘤反应（研究二）。反应持续时间中位数分别为41.9周（研究）和48.1周（研究二）。

法律分类：
接收

成人：
燕子整体。 250毫克，每日两次。剂量中断和/或剂量减少到200毫克，每日两次，可能需要个人的安全性/耐受性的基础上，再以250毫克，每日一次，如有必要。血液学和非血液学毒性：看到文学的剂量减少。

儿童：
不成立的。

警告/注意事项：
严重肺炎的风险：肺部症状监测;永久终止如果发生。监视器与差CBCS，谷丙转氨酶，总胆红素每月，和更频繁地在2-4级的海拔，或如果出现发烧/感染;暂停，降低剂量，或永久停止所示。先天性长QT综合征，避免。历史或QTc延长的倾向（例如，瑞士法郎，缓慢性心律失常，电解质紊乱，伴随药物延长QT间期）：考虑监测心电图，电解质定期永久终止，如果发生四级QTc延长。 ALK阳性的非小细胞肺癌治疗前的测试与FDA批准的试验。肝功能损害。严重肾功能不全或终末期肾病。怀孕（目录四）避免。在治疗过程中使用适当的避孕后至少90天。哺乳母亲：不推荐。

相互作用（S）：
避免随之而来的CYP3A的强抑制剂（如阿扎那韦，克拉霉素，茚地那韦，伊曲康唑，酮康唑，奈法唑酮），西柚汁，或强CYP3A的诱导剂（如卡马西平，苯巴比妥，苯妥英钠，利福布丁，利福平，圣约翰草）。避免与CYP3A的底物（如，阿芬太尼，环孢素，ergots，芬太尼）伴随着狭窄的治疗指数。中度CYP3A的抑制剂的注意事项。合用CYP3A代谢的药物，可能需要减少剂量。

不良反应（S）：
视力障碍，胃肠不适，水肿，便秘，3-4级事件：ALT升高，嗜中性白血球减少症，总胆红素升高，肺炎（可能是致命的），QT间期延长。

如何提供：
CAPS - 60

最后更新：
2011年9月12日

如何提供/存储和搬运
 
250毫克胶囊
硬胶囊，粉红色不透明的帽子和身体帽上印黑色墨水“辉瑞”，“250 CRZ”在身体上;提供：

60胶囊瓶：NDC0069-8140-20

200毫克胶囊
硬胶囊，粉红色不透明的帽子和白色不透明体帽上印黑色墨水“辉瑞”，“200 CRZ”对身体可在：
60胶囊瓶：NDC0069-8141-20
储存在室温20°〜25° C（68°〜77° F）;游览允许在15 °至30° C（59 °〜86° F）[见美国药典控制室温]。

While smoking and lung cancer have always been closely linked, recent advances in research have begun to unravel the genetic code behind the disease. Pfizer is revolutionizing treatment for lung cancer patients by targeting the genetic mutations that cause a rare form of this disease called non–small cell lung cancer (NSCLC).

Xalkori (crizotinib), an oral medication used to treat ALK-positive patients with late-stage NSCLC, was approved by the FDA on Friday. In a teleconference on Tuesday, a team of Pfizer’s researchers and lung cancer specialists explained that even though the drug treats a limited number of lung cancer patients, the drug will only go to the patients who stand to benefit from the drug, thereby maximizing its efficiency by eliminating mass use of the drug in populations where it is not effective.

Estimates vary on exactly how many NSCLC patients exhibit the ALK mutation. Data presented at the American Society of Clinical Oncologists meeting earlier this year placed the estimate somewhere around 8%, while Pfizer’s estimates put that number closer to 3% to 5%. At the teleconference, Mark G. Kris, MD, chief of the Thoracic Oncology Service at Memorial Sloan-Kettering Cancer Center in New York City, said that between 6000 and 11,000 patients in the United States with the ALK mutation are diagnosed annually.

To identify which patients are best served by Xalkori, patients are required to undergo a genetic test. The Vysis ALK Break Apart FISH Probe Kit, developed by Abbott Laboratories, is the first test of its kind to identify patients with an abnormal ALK gene. The test will cost about $250 to administer to each patient, roughly in line with similar genetic testing kits, according to Garry Nicholson, President and General Manager of the Pfizer Oncology Business Unit.

Despite being able to only help a minority of lung cancer patients, the specialists at the conference suggested widespread testing. “I would caution against any kind of patient profiling,” Kris said. “I think, in general, you need to test everyone [with lung cancer].”

Representatives from Pfizer estimated that each month of therapy will cost a patient $9600. Patients take Xalkori orally twice daily. A maximum dosage has not been determined, but some patients who started taking Xalkori during clinical trials have been taking the drug for more than a year.

The drug’s approval was based on a number of encouraging studies. Earlier this year, the drug showed marked antitumor activity in a study presented at the 14th World Conference on Lung Cancer in Amsterdam. In early phase II results from the single-arm, open-label PROFILE 1005 trial, 51% of 133 patients who had undergone prior chemotherapy who were treated with crizotinib exhibited an overall response, including 1 patient who experienced a complete response. At 12 weeks into the trial, the disease control rate was 74%, indicating that a proportion of participants achieved stable disease, or partial or complete responses.

Further studies confirmed crizotinib’s effectiveness in treating patients with NSCLC. Two multicenter trials enrolling 255 patients with late-stage ALK-positive NSCLC demonstrated 50% and 61% median objective response rates and mediation duration of response of 42 and 48 weeks, respectively.

However, no one from Pfizer could provide any estimates on how Xalkori affects a patient’s overall survival. Mace Rothenberg, MD, Senior Vice President of Clinical Development, and Medical Affairs in the Oncology Business Unit at Pfizer, said studies to assess how the drug affects overall survival and progression-free survival are currently underway, but no data are available yet, as the trials are currently ongoing.