title: Optimal use of the combination of irinotecan and 5-fluorouracil.
abstract: 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 intergroup 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.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine of Northwestern University, Chicago, IL 60611, USA.
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D000077146:Irinotecan
chemical_list: D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin