1. ¹Institute of Biochemistry 'G Fornaini', University of Urbino, Urbino, Italy
2. ²Medical Oncology, Hospital of Urbino, Urbino, Italy
3. ³Medical Oncology, Hospital of Livorno, Livorno, Italy
4. ⁴Medical Oncology, University Campus Biomedico, Rome, Italy
5. ⁵Medical Oncology, Hospital of Pesaro, Pesaro, Italy
6. ⁶Medical Oncology, Hospital of Fermo, Fermo, Italy
7. ⁷Medical Oncology, Hospital of Senigallia, Senigallia, Italy
8. ⁸Medical Oncology, Hospital of Livorno and University of Pisa, Livorno, Italy
9. ⁹Medical Oncology, Hospital of Fabriano, Fabriano, Italy
10. ¹⁰Medical Oncology, Hospital of Fano, Fano, Italy

Correspondence: Dr F Graziano, Medical Oncology Unit, Hospital of Urbino, via Bonconte da Montefeltro 61029, Urbino, Italy. E-mail: frada@tin.it

¹¹These authors contributed equally to the study.

Received 19 January 2007; Revised 8 April 2007; Accepted 18 April 2007; Published online 5 June 2007.

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.