Pharmacogenetic approach for capecitabine or 5-fluorouracil selection to be combined with oxaliplatin as first-line chemotherapy in advanced colorectal cancer

We studied the role of TS (5'VNTR, 5'SNP and 3'UTR), XRCC1-399, XPD-751, ERCC1-118 and XRCC3-241 genetic polymorphisms in tailoring fluroropyrimicline/oxaliplatin treatment. For this purpose, 110 XELOX (capecitabine/oxaliplatin)- or FUOX (fluorouracil/oxaliplatin)-treated metastatic colorectal cancer patients were selected prospectively for genotyping. In the FUOX group, TS-3'UTR +6 bp/+6 bp (hazards ratio, HR = 2.62, p = 0.007) and ERCC1-118 C/T or C/C (HR = 1.96, p = 0.050) genotypes correlated with a shorter progression free survival (PFS). When analysed jointly, the higher the number of favourable genotypes (FG) the longer the PFS (6.8 m, 9.6 m and 25.8 m for 0, 1 or 2 FG; p = 0.005). Disease-control rate was 100% in patients with 2 FG (87% and 38.5% for 1 or 0 FG; p = 0.001). In the multivariate analysis, ERCC1-118 (HR = 2.12, p = 0.0037) and TS-3'UTR (HR = 2.68, p = 0.006) were strong independent prognostic factors. According to this, patients harbouring TS-3'UTR +6 bp/+6 bp and ERCC1-118 C/T or C/C genotypes may better receive capecitabine instead of 5FU in an oxaliplatin-based first-line treatment. (C) 2008 Elsevier Ltd. All rights reserved.