Methotrexate and aminopterin exhibit similar in vitro and in vivo preclinical activity against acute lymphoblastic leukaemia and lymphoma.
Due to the development of neurological toxicity and resistance to methotrexate (MTX), other antifolates have been evaluated for its potential replacement in the treatment of childhood acute lymphoblastic leukaemia (ALL). Aminopterin (AMT) has been suggested to provide clinical advantages over MTX and other antifolates. AMT activity, compared with MTX, was evaluated in ALL and lymphoma preclinical models. The minimum survival fraction at the range of concentrations tested was lower with AMT than with MTX in 3 out of 15 cell lines. Both AMT and MTX significantly extended the event-free survival of mice bearing 3 out of 4 xenografts with equivalent activity.
Kang
Min H
MH
Cancer Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA. min.kang@ttuhsc.edu
Harutyunyan
Narine
N
Hall
Connor P
CP
Papa
Rachael A
RA
Lock
Richard B
RB
D000630:Aminopterin / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D005493:Folic Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D020128:Inhibitory Concentration 50; D008223:Lymphoma / Q000188:drug therapy*; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D051379:Mice; D016513:Mice, SCID; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012008:Recurrence; D012044:Regression Analysis; D023041:Xenograft Model Antitumor Assays
D005493:Folic Acid Antagonists; D000630:Aminopterin; D008727:Methotrexate