Schedule-dependent cytotoxicity of 5-fluorouracil in mice

The cytotoxic effect of 5-fluorouracil (FUra) given as a 24-hour infusion against both AKR and L1210 leukemias was quantitated by spleen colony assays. The antitumor effect was enhanced in AKR leukemia but was reduced in L1210 leukemia when FUra was given as a 24-hour infusion compared to when the drug was given as an iv bolus injection. No difference in cytotoxicity was noted for these two schedules against normal hematopoietic stem cells in either AKR or (BALB/c X DBA/2)F1 mice. The pharmacokinetics of FUra given as an infusion was similar in the mice bearing these two transplantable leukemias, which ruled out the possibility that the pharmacokinetics of FUra was the cause of the difference observed. Finally, correlation was good between the spleen colony assays and the therapeutic effect defined by life-span assays for both leukemias.