A comparison has been made, with reference to drug dose mortality response, of the relative effectiveness of the following treatments in influencing the survival time of DBA male mice inoculated with a lymphoid leukemia: (a) aminopterin; (b) aminopterin plus concomitantly administered citrovorum factor; (c) aminopterin plus folic acid; where the folic acid was administered 1 hour early; (d) aminopterin plus concomitantly administered folic acid. To provide a basis for the analyses employed, the experiments, involving single dose administration of antimetabolite and metabolite, were designed to result in a temporal separation of drug mortality and tumor mortality.
With all the treatments employed, as the dose of aminopterin was increased there was a progressive increase of both drug mortality and survival time of animals which succumbed to the leukemia.
On concomitant administration of citrovorum factor or prior administration of folic acid, with a specified dose of aminopterin, both the mortality response and the increase in survival time ordinarily resulting from treatment with that dose of aminopterin were reduced. For equivalent cost in drug dose mortality, aminopterin was more effective in increasing the survival time of animals which succumbed to the leukemia than aminopterin plus concomitantly administered CF or aminopterin plus FA administered early.
On simultaneous administration of FA with aminopterin, the FA did not alter the toxicity to the host or influence the antileukemic action of the aminopterin.
These results are discussed with reference to the mode of action of aminopterin and the possible implications for therapy.
Presented in part at the Forty-fourth Annual Meeting of the American Association for Cancer Research, Chicago, Illinois, April 9–11, 1953.