Gene Expression Signature in Advanced Colorectal Cancer Patients Select Drugs and Response for the Use of Leucovorin, Fluorouracil, and Irinotecan

• DOI: 10.1200/jco.2006.07.4187
• Publication Date: 2007-02-27T23:13:34Z
• Authors: Maguy Del Rio; Franck Molina; Caroline Bascoul-...; Virginie Copois; Frédéric Bibeau; Patrick Chalbos; Corinne Bareil; Andrew Kramar; Nicolas Salvetat; Caroline Fraslon; Emmanuel Conseiller; Virginie Granci; Benjamin Leblanc; Bernard Pau; Pierre Martineau; Marc Ychou
• Keywords: FOLFIRI; Regimen; Gene signature

Purpose In patients with advanced colorectal cancer, leucovorin, fluorouracil, and irinotecan (FOLFIRI) is considered as one of the reference first-line treatments. However, only about half treated respond to this regimen, there no clinically useful marker that predicts response. A major clinical challenge identify subset who could benefit from chemotherapy. We aimed a gene expression profile in primary colon cancer tissue predict chemotherapy Patients Methods Tumor samples 21 were analyzed for profiling using Human Genome GeneChip arrays U133. At end treatment, best observed response, according WHO criteria, was used define responders nonresponders. Discriminatory genes first selected by significance analysis microarrays algorithm area under receiver operating characteristic curve. predictor classifier then constructed support vector machines. Finally, leave-one-out cross validation estimate performance accuracy output class prediction rule. Results determined set 14 response FOLFIRI. Nine nine (100% specificity) 11 12 nonresponders (92% sensitivity) classified correctly, an overall 95%. Conclusion After independent cohort patients, our signature be decision tool assist oncologists selecting FOLFIRI chemotherapy, both adjuvant metastatic setting.