Antitumor properties of a new folate analog, 10-deaza-aminopterin, in mice

A new folate analog, 10-deaza-aminopterin, was substantially more active than methotrexate, following sc administration in mice, against three of five ascites tumors and two of three solid tumors. For ascites tumors, maximum increases in lifespan (using 6--12 mg/kg q2d X 5) with 10-deaza-aminopterin versus methotrexate were + 171.2%/+ 149.8% against L1210 leukemia, +118.4%/+109.1% against P815 plasmacytoma, +64%/+20.9% against Ehrlich ascites carcinoma, +84.2%/+44.8% against Taper liver tumor, and greater than +159.6%/+64.0% against Sarcoma 180 with longterm survivors after 10-deaza-aminopterin. In a smaller number of experiments comparing LD10 dosages (given q2d X 5) of aminopterin, methotrexate, and 10-deaza-aminopterin, aminopterin was the least effective and 10-deaza-aminopterin was the most effective against the L1210 leukemia, Sarcoma 180, and Ehrlich ascites tumors. Following oral administration (3--6 mg/kg q2d X 5), a twofold greater increase in survival time was obtained against the L1210 leukemia with 10-deazaaminopterin (+122.8%) versus methotrexate (+57%). At a dosage of 6 mg/kg q1d X 5 against solid tumors, the relative tumor volumes (treated/control X 100%) were 12%/41% for Sarcoma 180, 16%/31% for Taper liver tumor, and 20%/30% for Ehrlich ascites carcinoma. Overall, the data suggest a broader spectrum of effective antitumor action in mice and a potential for the expanded clinical utility of this category of agent.