[METHODS] A sample size of 86 patients ( 21-22 / arm ) was calculated under the hypothesis that the addition of capecitabine or VPA to SCRT can improve the TRG1 rate from 5 % to 20 % , with one-sided alpha = 0.10 and 80 % power.Several biomarkers will be evaluated comparing normal mucosa with tumor ( TP , TS , VEGF , RAD51 , XRCC1 , Histones/proteins acetylation , HDAC isoforms ) and on blood samples ( polymorphisms of DPD , TS , XRCC1 , GSTP1 , RAD51 and XRCC3 , circulating endothelial and progenitors cells ; PBMCs-Histones/proteins acetylation ) .