Should continuous infusion 5-fluorouracil become the standard of care in the USA as it is in Europe?
The mechanism of action of 5-fluorouracil (5-FU) and its pharmacologic behavior are influenced by its mode of administration. Several clinical studies have been conducted with the purpose of evaluating the difference between the continuous (CI 5-FU) and the bolus infusion of 5-FU (BI 5-FU). We focus our review on the studies relevant to the treatment of colorectal cancer, both in the adjuvant and metastatic setting. While individual trials fail to show a survival benefit for CI 5-FU, a meta-analyses of 7 trials shows an improvement in overall survival (OS) over BI 5-FU in metastatic colorectal cancer treatment. All trials in the same setting reveal a different toxicity profile for CI 5-FU that is generally more favorable than BI 5-FU. In the adjuvant setting, CI 5-FU allows the duration of therapy to be shortened by half without compromising the efficacy. CI 5-FU is the regimen of choice when given concurrently with radiation. When given in combination with other cytotoxic agents, CI 5-FU seems to be associated with less toxicity and potentially higher efficacy. Oral fluoropyrimidines, especially capecitabine, appear to behave in similar manner to CI 5-FU and may offer a convenient alternative to the usage of infusion pumps and indwelling catheters. While clinical trials are ongoing to compare capecitabine to CI 5-FU, we believe that CI 5-FU should be offered to patients in the United States given its favorable toxicity profile and higher efficacy in several settings.
El-Khoueiry
Anthony B
AB
Division of Medical Oncology, Kenneth Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles, 90033, USA. elkhouei@usc.edu
Lenz
Heinz-Josef
HJ
D000230:Adenocarcinoma / Q000188:drug therapy*; D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005060:Europe; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D014481:United States
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil