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

Author(s): Martinez-Balibrea E, Abad A, Aranda E, Sastre J, Manzano JL, Diaz-Rubio E, Gomez-Espana A, Aparicio J, Garcia T, Maestu I, Martinez-Cardus A, Gines A, Guino E, Spanish Group for the Treatment of Digestive Tumours

Affiliation(s): Medical Oncology Service, Hospital Universitari Germans Trias i Pujol-Institut Catala d'Oncologia, Badalona, Barcelona, Spain.

Publication date & source: 2008-06, Eur J Cancer., 44(9):1229-37. Epub 2008 Apr 28.

Publication type: Clinical Trial, Phase III; Multicenter Study; Randomized Controlled Trial

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 fluroropyrimidine/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 +6bp/+6bp (hazards ratio, HR=2.62, p=0.007) and ERCC1-118C/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 (6.8m, 9.6m and 25.8m 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 +6bp/+6bp and ERCC1-118C/T or C/C genotypes may better receive capecitabine instead of 5FU in an oxaliplatin-based first-line treatment.

Page last updated: 2008-11-03

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