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Factors Influencing the Specificity of Action of an Antileukemic Agent (Aminopterin). Time of Treatment and Dosage Schedule^*

( Laboratory of Chemical Pharmacology and Biometrics Section, National Cancer Institute, Bethesda, Md.)

The antileukemic specificity of action of aminopterin, defined in terms of the relative effect of drug on host and tumor, was demonstrated to vary with the time of treatment following tumor implantation and the schedule of treatment. Comparisons of the relative antileukemic effectiveness of the various treatments employed were made at equal cost in drug dose mortality response. Administration of aminopterin at 3 or 4 days following tumor implantation was more effective than earlier or later administration in increasing the survival time of leukemic mice. Two of the multiple treatment schedules employed were more effective in prolonging the survival time of the leukemic mice than any of the single treatments.

^* The authors wish to acknowledge the technical assistance of Don Dennis and Ina R. Hughes.

This paper is based on experiments conducted at the United States Public Health Service Hospital, Baltimore, Maryland.

National Institutes of Health, Public Health Service, Dept. of Health, Education, and Welfare.

Received 12/10/53.