Impact of ABCG2 polymorphisms on the clinical outcome and toxicity of gefitinib in non-small-cell lung cancer patients.

Abstract:

AIMS:The current study investigates whether or not functional polymorphisms in the ATP-binding cassette transporter gene ABCG2 might affect gefitinib activity and/or toxicity in non-small-cell lung cancer (NSCLC) patients. MATERIALS & METHODS:Towards this end, ABCG2 polymorphisms and expression were assessed in DNA and tumors from 94 NSCLC patients treated with gefitinib, whereas their associations with toxicity/response and time-to-progression/overall survival were evaluated using Pearson-χ(2) and log-rank-test, respectively. RESULTS:Patients carrying an ABCG2 -15622T/T genotype or harboring at least one TT copy in the ABCG2 (1143C/T, -15622C/T) haplotype developed significantly more grade 2/3 diarrhea (p < 0.01). No associations were found between polymorphisms and outcome. Consistently, ABCG2 protein levels in tumors were not significantly different between patients harboring different ABCG2 variants. CONCLUSION:The ABCG2 -15622C/T polymorphism and ABCG2 (1143C/T, -15622C/T) haplotype resulted in a gefitinib-dependent, moderate-to-severe diarrhea suggesting that these pharmacogenetic markers should be considered to optimize NSCLC treatment.

journal_name

Pharmacogenomics

journal_title

Pharmacogenomics

authors

Lemos C,Giovannetti E,Zucali PA,Assaraf YG,Scheffer GL,van der Straaten T,D'Incecco A,Falcone A,Guchelaar HJ,Danesi R,Santoro A,Giaccone G,Tibaldi C,Peters GJ

doi

10.2217/pgs.10.172

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

159-70

issue

2

eissn

1462-2416

issn

1744-8042

journal_volume

12

pub_type

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