title: Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy.
abstract: The primary end point of the study was the analysis of associations between polymorphisms with putative influence on 5-fluorouracil/irinotecan activity and progression-free survival (PFS) of patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy. Peripheral blood samples from 146 prospectively enrolled patients were used for genotyping polymorphisms in thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), excision repair cross-complementation group-1 (ERCC 1) xeroderma pigmentosum group-D (XPD), X-ray cross-complementing-1 (XRCC 1), X-ray cross-complementing-3 (XRCC 3) and uridine diphosphate-glucuronosyltransferases-A1 (UGT1 A1). TS 3'-UTR 6+/6+ and XRCC3-241 C/C genotypes were associated with adverse PFS. Hazard ratio for PFS achieved 2.89 (95% confidence interval=1.56-5.80; P=0.002) in 30 patients (20%) with both risk genotypes. Risk for Grade III-IV neutropenia was significantly associated with UGT1A1*28 7/7 genotype. These promising findings deserve further investigations and their validation in independent prospective studies.
authors.affiliation: Institute of Biochemistry G Fornaini, University of Urbino, Urbino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ruzzo
authors.forename: F
authors.initials: F
authors.lastname: Graziano
authors.forename: F
authors.initials: F
authors.lastname: Loupakis
authors.forename: D
authors.initials: D
authors.lastname: Santini
authors.forename: V
authors.initials: V
authors.lastname: Catalano
authors.forename: R
authors.initials: R
authors.lastname: Bisonni
authors.forename: R
authors.initials: R
authors.lastname: Ficarelli
authors.forename: A
authors.initials: A
authors.lastname: Fontana
authors.forename: F
authors.initials: F
authors.lastname: Andreoni
authors.forename: A
authors.initials: A
authors.lastname: Falcone
authors.forename: E
authors.initials: E
authors.lastname: Canestrari
authors.forename: G
authors.initials: G
authors.lastname: Tonini
authors.forename: D
authors.initials: D
authors.lastname: Mari
authors.forename: P
authors.initials: P
authors.lastname: Lippe
authors.forename: F
authors.initials: F
authors.lastname: Pizzagalli
authors.forename: G
authors.initials: G
authors.lastname: Schiavon
authors.forename: P
authors.initials: P
authors.lastname: Alessandroni
authors.forename: L
authors.initials: L
authors.lastname: Giustini
authors.forename: P
authors.initials: P
authors.lastname: Maltese
authors.forename: E
authors.initials: E
authors.lastname: Testa
authors.forename: E T
authors.initials: ET
authors.lastname: Menichetti
authors.forename: M
authors.initials: M
authors.lastname: Magnani
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D020869:Gene Expression Profiling / Q000379:methods*; D005838:Genotype; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics; D011446:Prospective Studies
chemical_list: D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin