Should Continuous Infusion 5-Fluorouracil Become the Standard of Care in the USA as It Is in Europe?

Abstract

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.

Keywords:

• 5-fluorouracil
• Continuous infusion
• Colorectal cancer
• Thymidilate synthase