In vivo advantage of combined administration with CPT‐11 and 5‐fluorouracil in rats

In vivo effect of a bolus combination with 5‐fluorouracil (5‐FU) and CPT‐11 was studied against experimental rat lung cancer, SLC cells. 5‐FU and CPT‐11, when administrated individually, showed dose‐dependent inhibition against the tumor (ID 50 , 7.0 mg/kg/day and 16.0 mg/kg/day, respectively). 5‐FU synergistically enhanced the sensitivity of the tumor cells to CPT‐11 and permitted the administration of approximately a one‐third lower dose of CPT‐11 to obtain the same inhibition against the tumor cell growth. The ID 50 of CPT‐11 alone (16.0 mg/kg/day) was reduced to 4.8 mg/kg/day when combined with 5‐FU at 2.5 mg/kg. There were no deaths caused by toxicity in the combination group, and for lower doses (less than 4 mg/kg/day) of CPT‐11 combined with 2.5 mg/kg/day of 5‐FU, all rats showed less than 10% body weight loss at the end of the experiments. When the tumor weights were evaluated by using isoeffect plot analysis, the data points resulting from the combination showed a synergistic interaction between these agents. There was no significant increase of toxicity as assessed by the body weight. The results might support for the use of the combination of 5‐FU and CPT‐11 in cancer chemotherapy.