Factors influencing the specificity of action of an antileukemic agent (aminopterin); multiple treatment schedules plus delayed administration of citrovorum factor.

It has been shown that the relative effect of aminopterin on tumor and host, expressed quanti tatively as the specificity of action of the drug, may be altered by the manner in which the drug is employed (2-4). Two of the procedures reported increased the antileukemic specificity of action of aminopterin. (a) Delayed treatment with citrovorum factor (CF): At equal cost in drug dose mortality, a single dose of aminopterin, when fol lowed 12 or 24 hours later by a single massive dose of CF, was more effective than a single dose of aminopterin alone in increasing the survival time of leukemic mice. (6) Appropriate multiple treat ment schedules with aminopterin : At equal cost in drug dose mortality, three treatments with amin opterin, spaced 2 days apart, resulted in more extensive survival time of leukemic mice than a single treatment with aminopterin. A similar in crease in survival time was apparent following two treatments with aminopterin spaced 4 days apart. The current experiments were conducted to in vestigate whether these two methods for increas ing the antileukemic specificity of action of amin opterin would supplement each other. For this purpose, a preliminary experiment was conducted to determine the optimal time for administration of delayed CF following treatment with amin opterin.