LARGE-SCALE TRIAL FOR ADJUVANT TREATMENT IN HIGH-RISK RESECTED COLORECTAL CANCERS - RATIONALE TO TEST THE COMBINATION OF LOCO-REGIONAL AND SYSTEMIC CHEMOTHERAPY AND TO COMPARE L-LEUCOVORIN PLUS 5-FU TO LEVAMISOLE PLUS 5-FU

Background: Failure rate of colorectal cancer after surgical resection remains around 50% and adjuvant treatments are clearly required. Pati ents and methods: All patients with serosal involvement and/or lymph n ode metastases are at risk of recurrence (Dukes-Astler Coller B2, Cl, C2). For thirty years many randomized trials testing chemotherapy and radiation therapy (rectum) have been conducted and some have demonstra ted some kind of significant activity. We have analysed these trials a nd proposed with the EORTC GI tract cooperative group a new prospectiv e 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 c hemotherapy with 5-FU + MeCCNU +/- oncovin and only one (NSABP COI ant ROI) has demonstrated some significant benefit in term of survival. T he combination of 5-FU + levamisole has been tested in 4 trials; in tw o there was a trend in favor of the treated group and in the intergrou p trial there was a very significant increase in survival for Duke C p atients. Six trials have tested the efficacy of post-operative local c hemotherapy (intraportal); 3 demonstrated a significant increased surv ival and 2 a decrease in hepatic recurrence rate. Among the ongoing tr ials the EORTC 40911 aims to evaluate the interest of combining system ic chemotherapy (5-FU + levamisole or 5-FU + 1 folinic acid) to post-o perative local chemotherapy (intraportal or intraperitoneal). In recta l cancer, preoperative radiation therapy significantly decreases the l ocal recurrence rate, more than post-operative radiation therapy. The combination of post-operative radiation therapy with chemotherapy incr eases significantly survival rate. Presently patients with mobile rect al tumor located at the middle or the upper part of the rectum should be when possible randomized in trials such as the EORTC 40911. Concern ing patients with large tumor located at the inferior part of the rect um new trials combining preoperative radiotherapy chemotherapy will be initiated. Conclusions: Some randomized trials using polychemotherapy have resulted in increasing survival rate in adjuvant setting regardi ng patients with colorectal cancer. New trials have been initiated to further improve these encouraging results.