History of Methotrexate (MTX)

Back in the late 1940s, Sidney Farber had worked on ways to prolong life of children ongoing acute leukæmia. He had tested the first anticancer drug in 1947 (Aminopterin) in a very sick child, and delayed the death. This promising work encouraged the search for anti-cancer drugs. Despite testing this compound in children ongoing Acute Leukaemia, he investigated a slightly different cytotoxic agent known at that time as Amethopterin (Methotrexate, MTX).

After evidencing the efficacy and investigating the safety of Methotrexate, the Food and Drug Administration approved the clinical use of Methotrexate in 1953. Scientists obtained very promising results at first but relapses occurred in most cases several years after the treatment. Scientists came with the idea of administering several anticancer compounds simultaneously so as to attack the the spreading cells in different ways. Despite efforts on new combination treatments, most patients relapsed from their cures (according to Camitta et al. (1999), in the 1960s, event-free survival rate for children with ALL was estimated at around 5%).

By using Methotrexate at very low doses for a prolonged period of time, this event-free survival rate has been increased significantly since then. Indeed, the maintenance phase plays a major role in treatment success.

Despite the need for children of adapted suitable formulations, the authorized formulation are the adult tablets containing 2,5 mg of Methotrexate also known as Ledertrexate.