[Comparison between continuous intravenous and oral administration of 5-FU with LV]

In case of 5-fluorouracil (5-FU)/leucovorin (LV) treatment, which is one of the most effective forms of chemotherapy for colorectal carcinoma, 5-FU is usually continuously infused from the venous route. However, since this continuous infusion limits the patients' active daily life, oral administration is preferable. In the present study, we evaluated the efficacy and side effects of orally administered 5-FU/LV.

In the continuous intravenous infusion group (civ group), colon 26 bearing mice were cannulated into central vein from external jugular vein. From this route, either 5, 10, or 20 mg/kg of 5-FU was continuously infused for 7 days (n = 6). In another group, either 10, 20, 40 mg/kg of 5-FU was infused orally (po group, n = 6). The other 6 animals were used for the non-treatment group. In the next series, 100 mg/kg of LV was added for each group above. Tumor volume, thymidylate synthase inhibition rate (TSIR) and body weight were measured at the end of infusion. During the experimental period, mice had free access to chow and water.

The tumor/control (T/C) volumes ratio showed that approximately twice the orally administered 5-FU dose had an anti-tumor effect equal to that of 5-FU administered intravenously. Synergic antitumor effects by LV were only revealed in the civ group. Significant body weight loss was recognized only in the po group at a 5-FU dose of more than 20 mg/kg. In summary, since the modulation effect of LV was recognized only with continuously intravenous infusion of 5-FU, further improvement of oral administration is required in the LV/5-FU combination therapy.