Prolongation of the Lifespan of Mice With Advanced Leukemia (L1210) by Treatment With Halogenated Derivatives of Amethopterin

Abstract

Studies were conducted on the influence of 4 halogenated derivatives of amethopterin in increasing the lifespan of mice with systemic leukemia (L1210). Amethopterin was employed as a standard. 3′-Bromoamethopterin appeared to be moderately more effective than amethopterin, but not as effective as 3′-chloroamethopterin. The latter yielded increases in median survival time 13 to 34 percent greater than those observed with amethopterin. The dihalogenated derivatives 3′-bromo-5′-chloroamethopterin and 3′,5′-dichloroamethopterin were extremely effective in this system. Both drugs were capable of extending the median survival time of the mice for the full period of treatment (90 days) and beyond, even when treatment was initiated only several days before death of controls. Some of the animals were still alive after 6 months and were presumably cured. The fact that some of these mice did not accept reinoculation of the leukemia suggests that they may have become immune. The antileukemic action of the halogenated derivatives may be reversed by concomitant administration of citrovorum factor. The implications of the data are discussed with respect to therapy and underlying mechanism.