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.
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.
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.
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.
Adverse events associated with the use of Xalkori may include, but are not limited to, the following:
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.
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Cui JJ, Tran-Dube´ M, Shen H, Nambu M, Kung PP, Pairish M, Jia L, Meng J, Funk L, Botrous I, McTigue M, Grodsky N, Ryan K, Padrique E, Alton G, Timofeevski S, Yamazaki S, Li Q, Zou H, Christensen J, Mroczkowski B, Bender S, Kania RS, Edwards MP Structure Based Drug Design of Crizotinib (PF-02341066), a Potent and Selective Dual Inhibitor of Mesenchymal-Epithelial Transition Factor (c-MET) Kinase and Anaplastic Lymphoma Kinase (ALK). Journal of Medicinal Chemistry 2011 Aug 18
For additional information regarding Xalkori or ALK+ non-small cell lung cancer, please visit the Xalkori web page.