Colorectal cancer in the adjuvant setting: perspectives on treatment and the role of prognostic factors

In patients with stage III colorectal cancer (CRC) who have undergone potentially curative resection, adjuvant treatment with 6 months' of 5-fluorouracil (5-FU) plus folinic acid (FA) is generally accepted as standard treatment and leads to a 5% to 10% improvement in absolute survival when compared with a no-chemotherapy control. In stage II CRC, the benefit of adjuvant chemotherapy has yet to be established. In metastatic CRC, randomized trials of irinotecan have consistently demonstrated that use of the drug, either alone or in combination with 5-FU/FA, prolongs survival. To investigate whether this benefit can be extended to patients with earlier disease, a series of multicenter trials are randomizing stage III colon cancer patients to adjuvant 5-FU/FA regimens with or without the addition of irinotecan. The role of adjuvant irinotecan is also being assessed in stage II colon cancer and in patients with rectal tumors. The risk/benefit ratio of adjuvant therapy in both stage III and stage II disease would be decreased if patients at the highest risk of relapse could be identified. Data from retrospective analyses suggest that DNA indexes, angiogenesis and some genetic/biological markers (loss of heterozygosity at chromosome 18 and the presence of microsatellite instability) identify prognostic differences in colon cancer patients. Their value as a guide to the intensity of adjuvant therapy required should be tested by randomized trial, as should the use of markers such as thymidilate synthase overexpression as a means of tailoring drug choice to tumor characteristics.