Crizotinib, 2011年8月26日由FDA批准的治疗肺癌的药物，商品名Xalkori,是ALK抑制剂 (Anaplastic Lymphoma Kinase inhibitor)

Xalkori(crizotinib)批准日期：2011年8月26日；公司：辉瑞Pfizer Inc.

Xalkori (crizotinib)
Company: Pfizer
Approval Status: Approved August of 2011
Treatment for: ALK+ non-small cell lung cancer
Areas: Cancer & Oncology; Respiratory

General Information

Xalkori (crizotinib) is an oral selective, ATP-competitive small molecule dual inhibitor of mesenchymal epithelial transition growth factor (c-Met or hepatocyte growth factor) and ALK tyrosine kinases, both of which are indicated in cancer.

Xalkori is specifically approved for the treatment of locally advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.

Xalkori is supplied as a tablet for oral administration. The recommended dose and schedule of Xalkori is 250 mg orally twice daily. Treatment should continue as long as the patient is deriving clinical benefit from therapy. Capsules should be swallowed whole, with or without food. If a dose of Xalkori is missed, it should be taken as soon as the patient remembers unless it is less than six hours until the next dose. In this case the missed dose should not be taken. Two doses should not be taken at the same time to make up for a missed dose.

Clinical Results

The FDA approval of Xalkori was based on two multi-center, single-arm studies (Studies A and B). Subjects enrolled into these studies had received prior systemic therapy, with the exception of 15 subjects in Study B who had no prior systemic treatment for locally advanced or metastatic disease. In both studies Xalkori was administered at 250 mg orally twice daily.
Study A
Data are from 136 subjects with locally advanced or metastatic ALK-positive NSCLC. The median duration of treatment was 22 weeks. There was one complete and 67 partial responses for an objective response rate of 50%. Seventy-nine percent of objective tumor responses were achieved during the first eight weeks of treatment. The median response duration was 41.9 weeks.
Study B
Data are from 119 subjects with locally advanced or metastatic ALK-positive NSCLC. The median duration of treatment was 32 weeks. There were two complete and 69 partial responses for an objective response rate of 61%. Fifty-five percent of objective tumor responses were achieved during the first eight weeks of treatment. The median response duration was 48.1 weeks.

Side Effects

Adverse events associated with the use of Xalkori may include, but are not limited to, the following:

vision disorder nausea diarrhea vomiting edema constipation

Mechanism of Action

Xalkori (crizotinib) is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), and Recepteur d’Origine Nantais (RON). Translocations can affect the ALK gene resulting in the expression of oncogenic fusion proteins. The formation of ALK fusion proteins results in activation and dysregulation of the gene’s expression and signaling which can contribute to increased cell proliferation and survival in tumors expressing these proteins.

晚期肺癌新药Xalkori（克里唑替尼胶囊 ）和适用类型肺癌诊断技术

美国食品和药物管理局日前通过简化程序批准了美国辉瑞公司研制的一种肺癌新药上市，这是美国药管局6年来首次批准肺癌药物上市

新药名为Xalkori,是一种激酶抑制剂,适用于间变型淋巴瘤激酶基因表达异常的晚期或局部转移的非小细胞肺癌患者,可以通过阻断对肿瘤细胞生长和存活起关键作用的多种细胞通路,使肿瘤保持稳定或消退。

间变型淋巴瘤激酶基因变异被认为是非小细胞肺癌等癌症发生的关键因素,约1%至7%的非小细胞肺癌患者间变型淋巴瘤激酶基因表达异常,此类患者通常不是烟民。

在两项临床试验中,这种药物能够显著缓解非小细胞肺癌患者的症状,中位缓解持续时间均在40周以上，不过尚无数据表明这种药物可以提高患者的生存率，这种药物最常见的副作用为视力障碍、恶心、腹泻、呕吐、水肿与便秘、作为上市后要求的一部分,辉瑞公司将继续开展三期临床试验,以进一步确认其效果。

美国药管局药物评估和研究中心负责人理查德•帕兹杜尔表示,类似Xalkori这样的靶向疗法药物是部分非小细胞肺癌患者的重要选择,最终可能导致副作用较小的疗法问世。

非小细胞肺癌占全部肺癌的85%，这种癌症难以治疗,约有75%的非小细胞肺癌患者在确诊时已是晚期或转移到其他部位,其5年生存率仅为6%。