THE THERAPEUTIC EFFECTS OF ORALLY-ADMINISTERED 5'-DEOXY-5-FLUOROURIDINE, 1-(2-TETRAHYDROFURYL)-5-FLUOROURACIL AND 5-FLUOROURACIL ON EXPERIMENTAL MURINE TUMORS

Abstract

The antitumor effects of three 5-fluorouracil-related compounds, 5''-deoxy-5-fluorouridine (5''-DFUR), 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) and 5-fluorouracil (5-FU) itself, on several experimental murine tumors were compared after oral administration. 5''-DFUR showed strong antitumor activity against the solid type of four kinds of tumors tested with a wide range of effective doses, and also showed moderate antitumor activity against three kinds of solid tumors with a narrow range of effective doses. 5''-DFUR was effective against a few kinds of ascites tumors. In general, the antitumor activity of FT-207 was not very strong, with narrow ranges of effective doses under the present conditions. 5-FU showed strong toxicity but at lower doses its antitumor effectiveness was almost the same as that of FT-207. When the doses were divided into three and the divided dose was given orally three times a day for five consecutive days to mice bearing L1210 leukemia, this modality (with any of the three drugs) enhanced the ILS of the mice by two to three times in the case of the ascites type but not the solid type of L1210. The chemotherapeutic index in oral treatment of the solid type of tumors was higher for 5''-DFUR than for FT-207 or 5-FU. The minimum lethal doses in oral administration for five consecutive days were about 3, 1.5 and 0.5 mmol/kg/day for 5''-DFUR, FT-207 and 5-FU, respectively. In conclusion, 5''-DFUR appeared to have stronger antitumor activity and less toxicity than FT-207 and 5-FU, and it is therefore expected to be clinically useful.