Infusions of fluorouracil and leucovorin: Effects of the timing and semi-intermittency of drug delivery

Alfredo Falcone, Giacomo Allegrini, Andrea Antonuzzo, Isa Brunetti, Elisabetta Pfanner, Monica Lencioni, Gianluca Masi, Romano Danesi, Mario Del Tacca, Pierfranco Conte

Research output: Contribution to journalArticlepeer-review


Preclinical and clinical studies have demonstrated that the circadian modulation of 5-FU delivery may reduce toxicities and improve antitumor activity. However, the relative importance of the timing of 5-FU delivery has not been clinically addressed. The aims of this study were to determine the toxicities, the maximum tolerable doses and the activity of a regimen with 5-fluorouracil (5-FU) and leucovorin (LV) administered as a 14-day continuous infusion according to a flat or three different chronomodulated rhythms in patients with metastatic gastrointestinal carcinomas. A total of 113 patients entered the study and their characteristics were comparable among the four groups. Toxicities included mainly stomatitis and diarrhea, and a reduced toxicity was observed in all the three chronogroups that allowed the delivery of higher dose intensities. Response rates were not significantly different among the four groups. These results suggest that a reduction in 5-FU+LV toxicity and an increase in 5-FU dose intensity can be obtained by a nonsinusoidally circadian modulated infusion. However, the reduction in toxicity observed seems to be dependent mainly on the quasi-intermittency and not on the timing of 5-FU+LV delivery.

Original languageEnglish
Pages (from-to)195-201
Number of pages7
Issue number3
Publication statusPublished - Oct 1999


  • 5-fluorouracil
  • Chronoinfusion
  • Gastrointestinal carcinoma
  • Leucovorin
  • Phase I-II
  • Randomized trial

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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