Pharmacogenetic Study in Patients with Advanced Non-Squamous Non-Small-Cell Lung Cancer (NSCLC) Treated with Pemetrexed

ABSTRACT Background Pemetrexed (PEM) to be a multitargeted antifolate agent is effective for non-squamous (non-sq) NSCLC. Functional polymorphisms of thymidylate synthase (TS), the reduced folate carrier (SCL19A1) and methylenetetrahydrofolate reductase (MTHFR), which are important enzymes in folate metabolism, have been shown to be correlated with the outcome in patients receiving methotrexate. Recently, the single-nucleotide polymorphism (SNP) of MTHFR was reported to be correlated with a good prognosis in patients receiving PEM. Purpose We retrospectively examined the significance of SNP in MTHFR, SCL19A1 or variable number of tandem repeat (VNTR) in TS as the prognostic factor or the predictive marker for side-effects of PEM. Method Non-Sq NSCLC patients treated with PEM were included in this study. After the PCR amplification of extracted lymphocyte DNA, analysis of sequencing or VNTR in target region was carried out. This study was approved on IRB (#504). Results The frequency of SNP in 35 cases is A1298C (A/A, 37%; A/C, 57%; C/C, 6%), C677T (C/C, 34%; C/T, 57%; T/T, 9%), SCL19A1 (G/G, 24%; G/A, 55%; A/A, 21%), TS tandem repeat (3R/3R, 63%; 2R/3R, 34%; 2R/2R, 3%). The final result of the correlation between PEM and response, overall survival, progression-free survival or side-effects will be reported in this congress.