Preoperative chemoradiotherapy has become a standard part of treatment protocols in stage II and III rectal cancer. Compared to postoperative chemoradiotherapy, the advantage of preoperative application of chemotherapeutics and irradiation includes improved compliance, reduced toxicity, and downstaging of the tumor in a substantial number of patients. The latter may enhance the rate of curative surgery, permit sphincter preservation in patients with low-sited tumors, and have a positive impact on the quality of life of these patients (Sauer et al, 2004).~The most widely used chemotherapeutic agent in colorectal cancer has been 5-fluorouracil (5-FU), and numerous attempts have been made to improve its efficacy, including biomodulation and protracted infusion. It has been demonstrated that biomodulation with leucovorin or levamisole was not effective in rectal cancer (Tepper et al, 2002), and protracted infusion of 5-FU was superior to bolus injection (O'Connell et al, 1994). New oral chemotherapeutic agents including capecitabine have been introduced and tried in colorectal cancer. Capecitabine is a tumor-selective fluoropyrimidine carbamate designed to achieve a higher intratumoral 5-FU level with lower systemic toxicity than intravenous administration of 5-FU (Shimma et al, 2000). It passes intact through the intestinal mucosa and is converted to 5-FU, preferentially in tumor tissue by thymidine phosphorylase (Schuller et al, 2000 ; Ishikawa et al, 1998 ; Miwa et al, 1998). Theoretically, oral capecitabine mimics the effect of protracted infusion of 5-FU without complications accompanying intravenous delivery (Liu et al, 1997). Moreover, experimental data using human cancer xenografts demonstrated up-regulation of thymidine phosphorylase by radiation (Sawada et al, 1999), constituting a synergistic effect. In two randomized Phase III trials, capecitabine showed a superior overall response rate and safety profile compared with 5-FU/lecovorinin for metastatic colorectal cancer (Van Cutsem et al, 2001; Hoff et al, 2001; Twelves, 2002). Intensity modulated radiotherapy (IMRT)-based radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. (Ballonoff et al, 2008)~With such encouraging outcomes, investigators initiated a prospective study to evaluate the efficacy and toxicity of short course preoperative chemoradiotherapy utilizing Intensity Modulated Radiation Therapy (IMRT) in combination with capecitabine in patients with resectable rectal carcinoma.
Intensity modulated radiotherapy (IMRT)-based radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Investigators initiated a prospective study to evaluate the efficacy and toxicity of short course preoperative chemoradiotherapy utilizing Intensity Modulated Radiation Therapy (IMRT) in combination with capecitabine in patients with resectable rectal carcinoma.