History

• The earliest anti-cancer drugs were derivatives of Nitrogen Mustard in the mid 1940s. A couple of years later, in 1947, the work of Sydney Farber of the Children’s Hospital, Boston, America paved the way for methotrexate, making this one of the earliest anti-cancer chemotherapy drugs . His key discovery was that the administration of folic acid to cancer sufferers made the condition worse.

• This concept was developed by Lederle Pharmaceuticals, New York, which tested various compounds known as anti-folates, or folate analogues, which resemble folic acid but act to block its action. This research, under the direction of the Indian born Dr. Yellapragada Subba Row , produced the first anti-folate that showed potential as a chemotherapy drug: aminopterin. Although used clinically for a short while, further research led to the manufacture of a variation of aminopterin, amethopterin, which replaced it and is now known as methotrexate.

• Clinical trials were rapidly set up, starting in 1948, which showed methotrexate to be effective at causing remission in leukaemia and curing the fast growing, pregnancy related, cancer choriocarcinoma. Clinical trials continued, including the 1963 National Cancer Institute’s trial into the effect of methotrexate on the reoccurrence of childhood leukaemia, which provided further evidence for its effectiveness .