Some Effects of Cyclophosphamide (Cytoxan) on Normal Mice and Mice With L1210 Leukemia2

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Abstract
The effects of N,N-bis-(β-chloroethyl)-N′,O-propylene phosphoric acid ester diamide, or cyclophosphamide, were evaluated in normal and leukemic mice. The overt manifestations of toxicity are described. Four days after an LD50 of cyclophosphamide, the bone marrow and spleen were aplastic. On the 6th day the marrow and spleen showed an unusual degree of megakaryocyte hyperplasia. Cyclophosphamide has been shown to be active against advanced L1210 leukemia. The effectiveness of the drug was markedly dependent upon the treatment regimen, but was independent of the route of administration. Treatment once weekly produced considerably greater increases in median survival than a daily or a 3 times weekly schedule. A regimen of treatment every 11th day was as effective in prolonging survival as a once weekly regimen, but a higher dose was required. Cyclophosphamide was much more effective than amethopterin or nitrogen mustard in prolonging the survival of mice with advanced L1210 leukemia when the optimum treatment regiment for each agent was used. The 6-mercaptopurine-resistant leukemia (L1210/AG-R) was as susceptible to the antileukemic action of cyclophosphamide as the parental L1210 strain.