High dose methotrexate is used for the treatment of:
Methotrexate (Mtx) It is one of the oldest and highly efficacious antineoplastic drugs; inhibits dihydrofolate reductase (DHFRase)-blocking the conversion of dihydrofolic acid (DHFA) to tetrahydrofolic acid (THFA) which is an essential coenzyme required for one carbon transfer reactions in de novo purine synthesis and amino acid interconversions. The inhibition is pseudoirreversible because Mtx has 50,000 times higher affinity for the enzyme than the normal substrate. Methotrexate is apparently curative in choriocarcinoma.Highly effective in maintaining remission in children with acute leukaemias, but not good for inducing remission: 2.5-15 mg/day. It is also useful in other malignancies, rheumatoid ahritis, psoriasis and as immunosuppressant The use of folinic acid rescue has permitted much higher doses of Mtx and has enlarged its scope to many difficult-to-treat neoplasms ESSENTIALS OF MEDICAL PHARMACOLOGY K.D.TRIPATHI SIXTH EDITION PAGE NO:823
Osteosarcoma
Rhabdomyosarcoma
Retinoblastoma
Ewing's sarcoma
Chemotherapy