Logistic Regression Model of the Clinical Response to 5-Fluorouracil Based Chemotherapy for Metastatic Colorectal Cancer Patients

• Published in: Anticancer research 2006-09, Vol.26 (5B), p.3885-3892
• Main Authors: RABINOVITCH-CHABLE, Hélène, DURAND, Karine, STURTZ, Franck G, GENET, Dominique, MARIN, Benoit, DZUGAN, Hélène, LEOBON, Sophie, TUBIANA-MATHIEU, Nicole, PREUX, Pierre-Marie, PARAF, Francois, COOK-MOREAU, Jeanne
• Format: Article
• Language: English
• Subjects: Aged; Base Sequence; Biological and medical sciences; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; DNA Primers; Female; Fluorouracil - therapeutic use; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Logistic Models; Male; Medical sciences; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 0250-7005; 1791-7530

Several genes have been involved in drug resistance but none are currently used in the drug decision process. To address this problem, mRNA levels were measured for the 5-fluorouracil metabolism-related genes, thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase in tumor samples of 40 patients with synchronous metastatic colon cancer by quantitative RT-PCR. Drug response and overall survival were also obtained for each patient. A logistic regression model was defined to calculate a response predicting score (RPS) with gene expression levels. This RPS split responders from non-responders as, at the best statistical threshold (0.35), the area of receiver operating characteristic (ROC) curve established with this method was 0.82 and sensitivity and specificity were respectively 100 % and 65.4 %. Furthermore patients with scores above 0.35 tended to have better overall survival than those with a score less than 0.35 (p=0.09).