Synergistic Action of Cyclophosphamide and 1,3-Bis(2-Chloroethyl)-1-Nitrosourea on a Transplanted Murine Lymphoma2

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Abstract
Dose-survival curves for lymphoma cells in the spleen and liver of tumor-bearing mice after treatment with cyclophosphamide (CY) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were obtained. These curves, measured through 8 decades of survival with the endpoint dilution assay of Hewitt, revealed that the reasons for the failure of these two drugs to cure animals with advanced lymphoma were different. Whereas BCNU was limited by host toxicity at doses that might have effected a cure, CY was limited by the presence of a CY-insensitive population of cells in the liver and the spleen of the host following treatment. Seventy percent of mice with advanced lymphoma could be cured of their malignancy by combinations of these two drugs. A similar synergistic action of a number of other chemotherapeutic agents in conjunction with either CY or BCNU was also demonstrated.