The enhanced cytotoxicity of combinations of 1-beta-D-arabinofuranosylcytosine and methotrexate.

Although both 1-beta-D-arabinofuranosylcytosine (ara-C) and methotrexate are presumed to be toxic as a result of their interference with DNA synthesis, results obtained with L1210 cells in vivo suggest that the combination of ara-C and methotrexate is capable of killing cells by a mechanism not related simply to DNA synthesis inhibition. Simultaneous administration of ara-C and methotrexate, or administration of these two agents within a 10-hr interval, independent of order, produces a synergistic cell kill of L1210 cells but a less than additive effect on normal hematopoietic stem cells. The extent of synergy seems dependent upon the dose of ara-C.