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Separate and Sequential Chemotherapy of Mouse Leukemia L1210 with 1-ß-D-Arabinofuranosylcytosine Hydrochloride and 1,3-Bis(2-chloroethyl)-1-nitrosourea¹

^[1] Microbiological Associates, Inc., Bethesda, Maryland 20014
^[2] Cancer Chemotherapy National Service Center, National Cancer Institute, NIH, Bethesda, Maryland 20014

This study describes the therapeutic effectiveness of 1-ß-D-arabinofuranosylcytosine hydrochloride (ara-C) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) administered separately and sequentially in the therapy of advanced mouse leukemia L1210. For sequential therapy, 3 treatment schedules were employed: (a) BCNU once and ara-C daily; (b) BCNU once and ara-C every 2 days; and (c) BCNU once and ara-C every 4 days. Substantial increases in the survival time of the mice were obtained with a single treatment of BCNU at suboptimal doses followed by all the schedules of treatment with ara-C also administered at suboptimal dosage levels. A 0.13 fraction of the highest individual single treatment dose of BCNU when administered with a 0.61 fraction of the optimal individual daily treatment dose of ara-C provided a therapy which was at least 2.5 times more effective than the optimal single treatment dose of BCNU alone and over 3.5 times more effective than the optimal daily dose of ara-C alone. An investigation of the effect of suboptimal levels of ara-C administered on different schedules of treatment following a suboptimal single treatment with BCNU revealed that the therapeutic response was approximately 1.5 times greater when ara-C was injected every 2 or 4 days than when administered daily.

¹ This study was supported by Contract PH-43-64-911 from the Cancer Chemotherapy National Service Center, National Cancer Institute, NIH, USPHS.

Received 9/23/66. Accepted 12/23/66.