5-Fluorouracil (5-FU) and irinotecan are now widely used for the treatment of advanced colorectal cancer. The drugs work by different mechanisms, and colon cancers do not generally manifest cross-resistance to the two agents when they are used serially. Most recently, combination regimens with irinotecan, 5-FU, and leucovorin have produced survival benefits superior to 5-FU and leucovorin. In Europe, irinotecan is most frequently combined with an infusion regimen of 5-FU, whereas in the United States bolus 5-FU has been favored until recently. The regimen, commonly known as IFL or the Saltz regimen, consists of irinotecan, bolus 5-FU, and leucovorin given weekly for 4 weeks and then repeated in 6-week cycles. Two inter-group trials reported a significant 60-day mortality rate with the IFL regimen, leading to the description of both a gastrointestinal syndrome and a vascular syndrome. Vigorous management of the gastrointestinal syndrome is now recommended. Furthermore, there are data to suggest that the Infusion 5-FU combination with irinotecan appears to produce a similar survival advantage to IFL with less overall severe toxicity based on cumulative European data for patients with advanced colorectal cancer. Future directions include the testing of a complex array of new agents and the incorporation of laboratory predictors of survival and response as a component of clinical trial design.
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