Summary: Continuous long time lasting infusional therapy have become the point of interest in Oncology. On the other hand, some serious side effects are the limiting factor for such treatment. Chronotherapy, as time dependent drug administration, is a new approach how to minimize side effects, and increase therapeutical index even for long lasting continuous drug administration. The authors has reviewed current knowledge about fluoropyrimidine chronobiology, research about creating the time dependent scheme for Floxuridine in preclinical studies, and current clinical studies for intrahepatic, intraarterial Floxuridine administration. In series of murine studies, it was found that far less Floxuridine toxicity was observed when mice were treated during their mid - to late activity phase. This time span corresponds to the circadian human stage between 14:00 and 20:00 hr. According to these results was established the time dependent scheme for Floxuridine administration with the maximum amount of the dialy dose given between 15:00 and 21:00 hr whereas the minimum amount was given between 3:00 and 9:00 hr. The clinical studies have proved that Floxuridine intrahepatic continuous circadian-modified infusion has lower hepatotoxicity, signes of cholangitis, treatment related jaundice, dose reduction necessity, possibility of the dose increasing by 70 % compared to continuous constatnt rate infusion.
Intrahepatic, intra-arterial administration of Fluxuridin using chronotherapy
