Cyclophosphamide Therapy

Abstract

Since 1946 when mechlorethamine hydrochloride (nitrogen mustard), an alkylating agent, was first reported to exert a suppressive effect on rapidly dividing cells,¹many new alkylating agents have been synthesized. A few have weathered clinical trial and have proven their effectiveness in the control of chronic leukemias and lymphomas and palliation of patients with malignant tumors. These include triethylene melamine (T.E.M.), triethylene thiophosphoramide (thio-TEPA) and chlorambucil (Leukeran). Recently Arnold, Bourseaux, and Brock²reported the development of a new alkylating agent, cyclophosphamide^*(<i>N,N</i>-bis (β-chloroethyl)-<i>N</i>,<i>O</i>-propylene phosphoric acid ester diamide monohydrate) which promised certain advantages over existing alkylating agents. Clinical trials conducted by Gross and Lambers^3,4in Germany showed the beneficial effects in 9 of 23 patients with malignant lymphoma. Cyclophosphamide (Cytoxan^*) was made available in this country for clinical trial in 1959. An early report by Coggins, Ravdin, and Eisman⁶suggested its continued appraisal in