Effect of concurrent calcium leucovorin infusion on 5-fluorouracil cytotoxicity against murine L1210 leukemia.

We examined the effect of concurrent SC infusion of calcium leucovorin (LV) on the action of 5-fluorouracil (FUra) against mouse L1210 leukemia implanted either SC or IP. Mice bearing the SC tumor treated with FUra (100 mg/kg, IP, day 1) plus infusion with either LV (11.5 mg . kg-1 . day-1, days 1-4), or 0.9% NaCl (days 1-4) resulted in an identical increase in median lifespan (ILS) of 28%. Similar experiments with FUra (100 mg/kg) plus LV infusion (115 mg . kg-1 . day-1) or FUra (200 mg/kg) plus LV infusion (115 mg . kg-1 . day-1) resulted in 50% and 59% ILS, respectively, which were not different from that obtained with the same doses of FUra plus 0.9% NaCl infusion. Mice bearing the IP tumor treated with FUra (100 mg/kg, IP, day 1) plus infusion with either LV (11.5 mg . kg-1 . day-1, days 1-4) or 0.9% NaCl (days 1-4) had an identical 56% ILS. Similar experiments with FUra (100 mg/kg) plus LV infusion (115 mg . kg-1 . day-1) or FUra (200 mg/kg) plus LV infusion (115 mg . kg-1 . day-1) resulted in 67% and 94% ILS, respectively, which were not different from those obtained with the same doses of FUra plus 0.9% NaCl infusion. Treatment of normal mice with FUra (200 mg/kg, IP, day 0) plus LV infusion (115 mg . kg-1 . day-1, days 0-3) was no more toxic than FUra plus 0.9% NaCl infusion, judging by similar transient decreases in body weight and no mortality. The data indicate that concurrent infusion with the LV failed to enhance the action of FUra against the mouse L1210 leukemia.