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.