Inmunohistochemical expression of thymidilate synthase, ERCC1, pKDR, and LDH5 as predcitive markers of efficacy in patients with advanced colon cancer treated with XELOX or FOLFOX with or without bevacizumab.

Abstract

e14671 Background: Low Thymidilate Synthase (TS) and ERCC1 expression have been related with efficacy of Fluoropirimidines and Platinum compounds respectively. High expression of angiogenic related proteins pKDR and LDH5 have been related with worse prognosis. The aim of our study is to analyze the inmunohistochemical expression of these proteins and their role as predictive markers of efficacy in advanced colorectal carcinoma. Methods: Retrospective study of patients with advanced colorectal cancer treated in first line with FOLFOX or XELOX +/- Bevacizumab between 2007 and 2011. Inmunoreactivity has been scored for staining intensity and proportion of positive cells. Staining was semiquantitative evaluated: intensity scored as none (0), to Strong (3), and percentage was categorized into five groups 0 = 0%, 1 (1-25%), 2 (26-50%), 3 (51-75%), 4 (76-100%). Staining and percentage scores were multiplied to obtain final T score (range 0-12), low expression was defined as T score <7, and high expression as T score ≥ 7. Results: 112 patients met inclusion criteria. Median age 68 years, 66 male (58.9%), 87 ECOG 0-1 (77.7%) and 58 (51,7%) with primary tumor removed before chemotherapy treatment. Seventy-five patients received bevacizumab (66.9%). Overall response rate was 56,3%, disease control rate 76.8%, and 18.8% of patients underwent surgery after treatment. Median PFS was 12 months and median OS 23 months. Preliminary results of TS expression showed 33.3% of patients with high vs 66.7% with low expression. There were not differences in response rate (60.7 vs 57.6%, p= 0.49), PFS (12 vs 13 m, p=0.48) or OS (22 vs 20 m, p= 0.6) between patients with low and high TS expression. Inmunohistochemical expression of ERCC1, LDH5 and pKDR is currently ongoing. Conclusions: Low inmunohistochemical expression of Thymidilate Synthase is not associated in our study with better outcomes in patients with advanced colon cancer treated with XELOX/FOLFOX +/- bevacizumab. Predictive value of ERCC1, LDH5 and pKDR expression is been evaluated, pending final results.