Large scale trial for adjuvant treatment in high risk resected colorectal cancers

Abstract

Background Failure rate of colorectal cancer after surgical resection remains around 50% and adjuvant treatments are clearly required. Patients and methods All patients with serosal involvement and/or lymph node metastases are at risk of recurrence (Dukes-Astler Coller B2, C1, C2). For thirty years many randomized trials testing chemotherapy and radiation therapy (rectum) have been conducted and some have demonstrated some kind of significant activity. We have analysed these trials and proposed with the EORTC GI tract cooperative group a new prospective randomized trial (40911). Results In colon cancer, five trials have tested single agent systemic chemotherapy and failed to demonstrated a significant increase in survival. Four trials have tested systemic chemotherapy with 5-FU + MeCCNU ± oncovin and only one (NSABP COI ant ROI) has demonstrated some significant benefit in term of survival. The combination of 5-FU + levamisole has been tested in 4 trials; in two there was a trend in favor of the treated group and in the intergroup trial there was a very significant increase in survival for Duke C patients. Six trials have tested the efficacy of post-operative local chemotherapy (intraportal); 3 demonstrated a significant increased survival and 2 a decrease in hepatic recurrence rate. Among the ongoing trials the EORTC 40911 aims to evaluate the interest of combining systemic chemotherapy (5-FU + levamisole or 5-FU + 1 folinic acid) to postoperative local chemotherapy (intraportal or intraperito-neal). In rectal cancer, preoperative radiation therapy significantly decreases the local recurrence rate, more than post-operative radiation therapy. The combination of postoperative radiation therapy with chemotherapy increases significantly survival rate. Presently patients with mobile rectal tumor located at the middle or the upper part of the rectum should be when possible randomized in trials such as the EORTC 40911. Concerning patients with large tumor located at the inferior part of the rectum new trials combining preoperative radiotherapy chemotherapy will be initiated. Conclusion Some randomized trials using polychemotherapy have resulted in increasing survival rate in adjuvant setting regarding patients with colorectal cancer. New trials have been initiated to further improve these encouraging results.