Journal article
Crizotinib for the treatment of non-small-cell lung cancer
American journal of health-system pharmacy, Vol.70(11), pp.943-947
06/01/2013
DOI: 10.2146/ajhp120261
PMID: 23686600
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 (NISCLC) 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 NISCLC 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 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.
Details
- Title: Subtitle
- Crizotinib for the treatment of non-small-cell lung cancer
- Creators
- Andrew Timm - University of Wisconsin–MadisonJill M. Kolesar - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- American journal of health-system pharmacy, Vol.70(11), pp.943-947
- Publisher
- Amer Soc Health-System Pharmacists
- DOI
- 10.2146/ajhp120261
- PMID
- 23686600
- ISSN
- 1079-2082
- eISSN
- 1535-2900
- Number of pages
- 5
- Language
- English
- Date published
- 06/01/2013
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984696540802771
Metrics
3 Record Views