JOURNAL ARTICLE
REVIEW

Crizotinib: a drug that crystallizes a unique molecular subset of non-small-cell lung cancer

Sai-Hong Ignatius Ou
Expert Review of Anticancer Therapy 2012, 12 (2): 151-62
22316363
Crizotinib (Pfizer, CA, USA) is an oral small-molecule RTK inhibitor that targets ALK and MET, and potentially other RTKs. Crizotinib was approved by the US FDA on 26 August 2011 for the treatment of ALK-rearranged non-small-cell lung cancer (NSCLC), as detected by ALK break-apart FISH assay. This conditional approval was based on response rates of 50-61% from 255 ALK-rearranged NSCLC patients enrolled in two ongoing single-arm crizotinib trials. Side effects of crizotinib mostly consist of grade 1-2 gastrointestinal events (nausea, vomiting, diarrhea and constipation), grade 1-2 edema and fatigue, grade 1 visual disorders, rare cases of elevated liver enzymes and pneumonitis (1.6%). Confirmatory trials comparing crizotinib to standard chemotherapy in upfront (ClinicalTrials.gov identifier: NCT01154140) and salvage (ClinicalTrials.gov identifier: NCT00932451) treatment settings of ALK-rearranged NSCLC are ongoing. It took an unprecedented rapid 4 years from the publication of the discovery of ALK-rearranged NSCLC in August 2007 to the conditional approval of crizotinib in August 2011.

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