Cytotoxic effect of 5-fluorouracil plus cyclophosphamide against transplantable leukemias

The cytotoxic effect of the combination of cyclophosphamide and 5-fluorouracil against AKR and L1210 leukemias was quantitated by a spleen colony assay. We used different sequences, a number of doses of each agent, and different intervals between the agents and noted different degrees of synergistic cell-kill. By proper scheduling of these agents, greater than 100-fold increase in cell killing was noted, an effect not demonstrable for normal hematopoietic stem cells. However, the pattern of response for AKR was opposite to that for L1210 leukemia; we suggest that this reflects a difference in the metabolism of 5-FU.