Infusional 5-FU for advanced colorectal cancer

5-Fluorouracil (5-FU) has been studied over the past two decades in five prospective randomized trials comparing bolus with infusional schedules. Response rates and time to progression are improved with infusional schedules and survival as determined by the proportion of patients alive at 2 years is also superior for infusional administration. Biochemical modulation of infusional 5-FU by leucovorin or interferon does not increase the therapeutic effect (in contrast to the modulation of bolus delivery) but does effect the toxicity profile adversely. Time modulation of infusional 5-FU has been reported to improve response rates, and survival over constant or flat infusion and additional studies are ongoing. A proposed experimental design for a comparative trial in advanced colon cancer is presented to address the questions of the optimal infusion duration; the role of dose intensity; and the role of chronomodulation. The application of infusional 5-FU into the adjuvant setting seems to be a reasonable step, and such trials have been initiated in both the United States and the United Kingdom. Bolus single agent 5-FU should be abandoned as a treatment option for colon cancer.