Synergy between 5,10-dideaza-5,6,7,8-tetrahydrofolic acid and methotrexate in mice bearing L1210 tumors.
In vivo studies with 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), an inhibitor of glycinamide ribonucleotide transformylase, indicate that at doses ranging from 2.5 to 10 mg/kg, it prolongs the survival of mice implanted with L1210 tumors. Lower doses of this agent have no effect. Parallel studies with methotrexate indicate that DDATHF is not as potent or as efficacious as methotrexate in this animal model. Low doses of DDATHF combined with low doses of methotrexate can cause a significant increase in the survival of L1210 tumor-bearing mice, suggesting synergism between these two antifolates.
Ferguson
K
K
Medical Research Division, American Cyanamid Company, Pearl River, NY 10965.
Boschelli
D
D
Hoffman
P
P
Oronsky
A
A
Whiteley
J
J
Webber
S
S
Galivan
J
J
Freishiem
J
J
Hynes
J
J
Kerwar
S S
SS
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005493:Folic Acid Antagonists / Q000627:therapeutic use* / Q000633:toxicity; D007928:Lethal Dose 50; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use* / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D013763:Tetrahydrofolates / Q000627:therapeutic use* / Q000633:toxicity
D005493:Folic Acid Antagonists; D013763:Tetrahydrofolates; C045894:lometrexol; D008727:Methotrexate