Optimum time sequence for the administration of vincristine and cyclophosphamide in vivo.

The cytotoxic effect of the combination of vincristine sulfate and cyclophosphamide was quantitated by the spleen colony assay for both AKRand L1210-transplantable leukemias as well as for normal hematopoietic stem cells. The lethal effect of this combination on the leukemic cell population was found to be schedule dependent. Subadditive cell killing occurred when the drugs were administered together or within a few hr of each other. A marked enhancement of the cytotoxicity was noted when cyclophos phamide was given after vincristine, with a nadir obtained when 12 hr had elapsed between the administration of the two drugs. The observed killing of normal hematopoietic stem cells by this combination was additive independent of the sequence or schedule of administration.