Interferon alpha-2a shows antitumor activity in combination with 5-fluorouracil against human colon carcinoma xenografts: a study in reference to thymidylate synthetase activity inhibition.

To clarify the mode of antitumor activity shown by a combination of recombinant human interferon alpha-2a (IFN) and 5-fluorouracil (5-FU), experimental therapy was performed on human colon carcinoma (Co-4) xenografts serially transplanted into nude mice, using IFN and 5-FU, either alone or in combination. IFN alone showed dose-dependent antitumor activity and 5-FU also revealed a moderate antitumor effect. Although IFN, given as 600,000 units/mouse daily sc x 14, and 5-FU, given as 60 mg/kg q4d x 3 ip, showed additive antitumor activity against Co-4, the thymidylate synthetase (TS) inhibition rate was unchanged in the tumors treated with the IFN/5-FU combination in comparison with those treated with 5-FU alone. This suggests that the antitumor activity of IFN and 5-FU in combination does not involve augmentation of the TS inhibition by 5-FU.