Association of pharmacokinetics or pharmacogenomics with toxicity of erlotinib in patients with advanced non-small cell lung cancer

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The orally administered erlotinib showed large interindividual variability in its pharmacokinetics. The aim of this study was to evaluate the association of pharmacokinetics or pharmacogenomics with toxicity of erlotinib in patients with advanced NSCLC. Plasma concentration of erlotinib was analyzed by high-performance liquid chromatography. The genotypes of ABCG2, ABCB1, ABCC2, CYP3A4, CYP3A5, CYP1A1, and CYP1A2 were analyzed by direct sequencing.There were no statistically significant association of pharmacokinetics or pharmacogenomics with toxicity, such as skin toxicity, diarrhea, stomatitis, liver injury, and interstitial lung disease (ILD) of erlotinib. However, one patient died of drug induced ILD was homozygous for ABCG2 C>A and showed the highest AUC. Additionally, Cmax was trend toward to higher in 4 patients with liver injury than those without (p=0.054). In conclusion, the homozygote of ABCG2 C>A could be associated with elevated erlotinib exposure and drug-induced ILD.