Clinical Trials and Future Directions Clinical trials have established combined-modality therapy as the treatment of choice in the postoperative adjuvant treatment of high-risk rectal cancer. [ref: 35,98,133] The most favorable results have been achieved with the use of continuous-infusion 5-FU during external-beam irradiation. [ref: 133] A recently completed randomized study was designed to test the potential benefit of leucovorin and levamisole as modulators of 5-FU when used with radiation therapy in the adjuvant treatment of rectal cancer. The initial results of this study are expected soon. The current national intergroup study is designed to assess further the value of leucovorin and levamisole as modulators of 5-FU and also to test the value of adding preirradiation and postirradiation protracted venous 5-FU infusion to the current standard regimen, in which protracted venous 5-FU infusion is used only during radiation therapy. [ref: 133] A second randomized intergroup study designed to compare preoperative and postoperative adjuvant radiation therapy and chemotherapy in patients with T3-4 rectal cancer is currently under way. This important clinical trial will provide the first scientific comparison of neoadjuvant (preoperative) versus adjuvant (postoperative) treatment of rectal cancer. One of the most important recent advances in the field of oncology resulted from a randomized clinical trial that demonstrated that node-positive patients with completely resected colon cancer experienced improved survival when treated with adjuvant 5-FU and levamisole. [ref: 123] A current randomized clinical trial is attempting to build on these results by comparing 5-FU plus levamisole and radiation therapy versus 5-FU plus levamisole without radiation therapy in selected patients with resected colon cancer at high risk for local recurrence after surgical resection. Although results of treatment with IORT in patients with locally advanced rectal cancer suggest a possible improvement in outcome, scientific evidence is lacking. A European trial in which patients with locally advanced rectal cancer will be randomly assigned to receive or not to receive IORT is being planned and should provide definitive information as to whether this aggressive form of treatment is of value.