Administration Schedules

Enormous efforts have been made recently to improve efficacy of 5-FU treatment, either by changing the infusion schedule or changing its biochemical modulation in combination with novel cytotoxic agents.

In view of the short plasma half-life of 5-FU, most authors believe that continuous administration of 5-FU (CIFU) is the superior 5-FU schedule compared to bolus regimens. Continuous infusion of 5-FU seems to inhibit predominantly DNA synthesis, whereas bolus administration of 5-FU inhibits RNA splicing and DNA synthesis, resulting in different toxicity and efficacy profiles (24,25).

Several randomized studies comparing CIFU versus bolus 5-FU with or without leucovorin (LV) suggest the superiority of CIFU over bolus 5-FU in terms of improved RR and reduced toxicity profile (26, 27, 28). However, no improvements in survival were noted (26,27). A meta-analysis from seven randomized studies with a total of

I,219 patients confirmed superior response of CIFU over bolus regimens (22% vs. 14%, p = 0.0002), with statistically significant superior OS in patients treated with CIFU compared with those patients who received a bolus 5-FU regimen (12.4 months vs.

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