ANTI-TUMOR PROPERTIES OF A NEW FOLATE ANALOG, 10-DEAZA-AMINOPTERIN, IN MICE

  • 1 January 1978
    • journal article
    • research article
    • Vol. 62  (7) , 1047-1052
Abstract
A new folate analog, 10-deazaaminopterin, was substantially more active than methotrexate, following s.c. administration in mice, against 3 of 5 ascites tumors and 2 of 3 solid tumors. For ascites tumors, maximum increases in lifespan (using 6-12 mg/kg q2d .times. 5) with 10-deazaaminopterin vs. 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 > + 159.6%/ + 64.0% against sarcoma 180 with long-term survivors after 10-deazaaminopterin. In a smaller number of experiments comparing LD10 dosages (given q2d .times. 5) of aminopterin, methotrexate and 10-deazaaminopterin, aminopterin was the least effective and 10-deazaaminopterin was the most effective against L1210 leukemia, sarcoma 180 and Ehrlich ascites tumor. Following oral administration (3-6 mg/kg q2d .times. 5), a 2-fold greater increase in survival time was obtained against L1210 leukemia with 10-deazaaminopterin (+ 122.8%) vs. methotrexate (+ 57%). At a dosage of 6 mg/kg q1d .times. 5 against solid tumors, the relative tumor volumes (treated/control .times. 100%) were 12%/41% for sarcoma 180, 16%/31% for Taper liver tumor and 20%/30% for Ehrlich ascites carcinoma. 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.