Inhibition of Development of Sarcoma 180 by 4-Amino-N10-Methyl Pteroylglutamic Acid.

Abstract

The folic acid antagonist 4-amino-N10-methyl pteroylglutamic acid was studied for its ability to affect the transplantable mouse sarcoma 180. One day after tumor implantation the drug was injd. intraperit. at doses of 2.5 mg., 2 mg., 1.5 mg., and 1 mg./kg. for 7 days. At the 2 highest doses tumor growth was markedly inhibited but many animals died of toxicity. At the 1.5 mg./kg. dose the tumor inhibitory effect was marked and was associated with little toxicity. Below this level the effect on the tumor was not great. There was no evidence that the tumor was completely destroyed, since growth proceeded normally when injns. were stopped. When treatment was delayed 4 to 7 days the inhibition was considerably decreased. 4-Amino-N10-methyl pteroylglutamic acid appeared to have the most favorable therapeutic index of any of the many folic acid antagonists previously studied.