lometrexol + folic acid

Lometrexol + folic acid is an investigational combination regimen in which lometrexol, a prototype folate antimetabolite, is administered with folic acid to mitigate its dose-limiting toxicities. Lometrexol [(6R)-5,10-dideaza-5,6,7,8-tetrahydrofolate; DDATHF] is a selective inhibitor of glycinamide ribonucleotide formyltransferase (GARFT), a key enzyme in the de novo synthesis of purine nucleotides, thereby blocking tumor cell DNA synthesis and proliferation. Initial clinical development of lometrexol was limited by severe cumulative myelosuppression, including thrombocytopenia and mucositis. Subsequent preclinical and clinical evidence demonstrated that co-administration of folic acid before, during, and after lometrexol dosing can substantially reduce toxicity without abolishing its antitumor activity, enabling repetitive weekly administration in advanced cancer patients. The combination has been investigated especially in cancers refractory to standard antifolates (like methotrexate), including melanoma, renal cell carcinoma, and non-small cell lung cancer[1][2][3][4].

Other names

5,10-dideazatetrahydrofolate + folic acid