Comparing cell kinetic studies of the effect of ftorafur and 5-fluorouracil on the L 1210 ascites tumor

Summary

Ftorafur (FT), a 2-tetrahydrofuryl derivative of 5-fluorouracil (5-FU) was introduced into cancer chemotherapy with the hope to obtain a therapeutic effect comparable to 5-FU with a smaller dose and less side effects. A comparison of the effect of FT and 5-FU on the proliferation of L 1210 ascites tumor cells in the present work has shown that both drugs result in an inhibition of DNA synthesis due to an inhibition of thymidylate synthetase. However, the extent of the effect of FT is reduced, i.e., to achieve a cell kinetic effect comparable to that of 5-FU, 60 times the equimolecular FT dose has to be applied. Thus, there is no dose-saving effect of FT compared to 5-FU. A depotlike 5-FU effect of FT due to a slow release of 5-FU from FT as described in the literature could not be confirmed in the present study either. The effect of FT on the proliferation of L 1210 ascites tumor cells did not last longer than that of 5-FU. In contrast to 5-FU a severe side effect, viz., a drastic decrease of the body temperature from 39.1 °C to 31.6°C, was observed. That means that FT cannotonly be effective by a release of 5-FU. This toxic side effect must be due to a different mechanism of action of FT. A significant increase in the median life span could only be achieved by the application of 5-FU (180 μg/g). An equimolecular FT-dose did not result in an increase of the median life span. Based on the present study, the advantages of FT compared to 5-FU described in the literature cannot be confirmed. The present work shows that cell kinetic studies in animals are a useful tool to test the effect of new drugs in chemotherapy.