ABSTRACT
The history of alkylating agent chemotherapy dates to the First World War. The chemical warfare agent sulphur mustard (mustard gas; Fig. 1), fi rst used in September 1917, was one of the most lethal of all the poisonous chemicals used during the war. However, soldiers (and civilians) exposed to sulphur mustard developed bone marrow suppression and lymphoid aplasia (Krumbhaar and Krumbhaar 1919). These medical observations led to evaluation of sulphur mustard as an antitumour agent, and in December 1942, to secret human clinical trials of its nitrogen-based less toxic analogue-nitrogen mustard (chlormethine)—to treat patients with high white blood cell counts (lymphoid leukaemia) and lymphomas (Gilman 1963). Chlormethine became the pioneer of antineoplastic chemotherapy. Thus, alkylating agents are the oldest class of anticancer agents and remain a major cornerstone today of treatment for leukaemias, lymphomas and solid tumours.
