In:
Anti-Cancer Drugs, Ovid Technologies (Wolters Kluwer Health), Vol. 33, No. 10 ( 2022-11), p. 1139-1144
Abstract:
Dermatological, gastrointestinal and hepatic toxicities are the most common adverse events associated with gefitinib use. Gefitinib is metabolized by cytochrome P450. Inconsistent associations of single nucleotide genetic polymorphisms of CYP450 and gefitinib-induced adverse effects were reported. We aim to investigate the association between CYP450 genetic polymorphism and the development of gefitinib-associated adverse events. A retrospective cohort study of Chinese patients with metastatic nonsmall cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations who received first-line gefitinib treatment was conducted. Single nucleotide polymorphisms (SNPs) of CYP2D6, CYP3A4 and CYP3A5 were assayed using a multiplex SNP microarray. Risks of development of gefitinib-induced toxicities associated with different SNPs were determined. Among the 152 patients treated with gefitinib, 52 (34.2%) had gefitinib-induced hepatotoxicity, 113 (74.3%) had cutaneous reactions and 53 (34.9%) had gastrointestinal adverse effects. CYP2D6*41 CT, CYP2D6*10 AA and CYP3A4*1/*1G TT genotypes were significantly associated with hepatic, cutaneous and gastrointestinal adverse effects [odds ratio (OR) 3.773; (95% confidence interval {CI},1.046–13.610; P = 0.043), 3.368 (95% CI, 1.000–11.345; P = 0.050) and 20.000 (95% CI, 2.381–167.965; P = 0.006), respectively]. CYP2D6*41 CT, CYP2D6*10 AA and CYP3A4*1/*1G TT genotypes may be associated with increased risks of gefitinib-induced toxicities in the liver, skin and gastrointestinal tract.
Type of Medium:
Online Resource
ISSN:
0959-4973
DOI:
10.1097/CAD.0000000000001360
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2022
detail.hit.zdb_id:
2025803-3
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