title: Pharmacogenetic approach for capecitabine or 5-fluorouracil selection to be combined with oxaliplatin as first-line chemotherapy in advanced colorectal cancer.
abstract: 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.
authors.affiliation: Medical Oncology Service, Hospital Universitari Germans Trias i Pujol-Institut Català d'Oncologia, Badalona, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Martinez-Balibrea
authors.forename: Albert
authors.initials: A
authors.lastname: Abad
authors.forename: Enrique
authors.initials: E
authors.lastname: Aranda
authors.forename: Javier
authors.initials: J
authors.lastname: Sastre
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Manzano
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz-Rubio
authors.forename: Auxiliadora
authors.initials: A
authors.lastname: Gómez-España
authors.forename: Jorge
authors.initials: J
authors.lastname: Aparicio
authors.forename: Teresa
authors.initials: T
authors.lastname: García
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Maestu
authors.forename: Anna
authors.initials: A
authors.lastname: Martínez-Cardús
authors.forename: Alba
authors.initials: A
authors.lastname: Ginés
authors.forename: Elisabet
authors.initials: E
authors.lastname: Guino
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010071:Oxaloacetates; D018579:Patient Selection; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil