Crizotinib for the treatment of non-small-cell lung cancer.
Article Details
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Timm A, Kolesar JM
Crizotinib for the treatment of non-small-cell lung cancer.
Am J Health Syst Pharm. 2013 Jun 1;70(11):943-7. doi: 10.2146/ajhp120261.
- PubMed ID
- 23686600 [ View in PubMed]
- Abstract
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety, adverse effects, and dosage and administration of crizotinib in the management of non-small-cell lung cancer (NSCLC) are reviewed. SUMMARY: Crizotinib (Xalkori, Pfizer Inc.) is a novel tyrosine kinase inhibitor approved for the treatment of patients with locally advanced or metastatic NSCLC who exhibit assay-confirmed mutations of the gene coding for anaplastic lymphoma kinase (ALK). The primary biochemical mechanism of crizotinib is to inhibit ALK expression, leading to increased cell proliferation and decreased apoptosis. Crizotinib is metabolized and excreted after O-dealkylation by cytochrome P-450 (CYP) isoenzyme 3A4/5; as crizotinib is also an inhibitor of CYP3A4/5, its use entails a high potential for drug interactions, including confirmed interactions with ketoconazole and rifampin that can alter crizotinib pharmacokinetics. A Phase I trial involving patients with ALK gene mutation-positive NSCLC demonstrated significant disease control with oral crizotinib use, including an overall eight-week response rate of 87% and an estimated six-month survival of 72%. At the standard dosage of 250 mg twice daily, crizotinib is well tolerated. In clinical trials to date, the most common grade 1 or 2 adverse events were nausea, diarrhea, vomiting, and visual disturbances; more severe toxicities included transaminase elevations (less than 7% of patients) and pneumonitis (less than 2% of patients). Hypogonadism leading to low testosterone levels appears to be universal among male patients treated with crizotinib. CONCLUSION: Crizotinib appears to be efficacious and well tolerated in patients with NSCLC and may have future potential applications in treating lymphomas and other cancers driven by ALK or c-MET gene mutations.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Crizotinib Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorDetails Crizotinib Cytochrome P450 3A5 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAbemaciclibCrizotinib The metabolism of Abemaciclib can be decreased when combined with Crizotinib. AcalabrutinibCrizotinib The metabolism of Acalabrutinib can be decreased when combined with Crizotinib. AcenocoumarolCrizotinib The metabolism of Acenocoumarol can be decreased when combined with Crizotinib. AlectinibCrizotinib The metabolism of Alectinib can be decreased when combined with Crizotinib. AlpelisibCrizotinib The metabolism of Alpelisib can be decreased when combined with Crizotinib.