Antitumor activity and toxicity of ACNU, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride,comparing two divided doses and a single dose

Summary In order to determine whether it is possible to reduce the toxicity of the nitrosoureas, including the delayed type of hematologic toxicity, without diminishing antitumor activity by administering the drug according to a new treatment schedule other than the single high-dose treatment schedule, we examined the antitumor activity against murine tumors and toxicities to host mice of a nitrosourea derivative, 3-(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), which was administered according to two divided doses schedule. Experimental results indicated that the toxicity of ACNU with respect to lethality, as well as weight loss of host mice, was alleviated by administering ACNU (IV) at one-half of LD₁₀ (20 mg/kg) on 2 successive days. However, no impairment of the antitumor activity of ACNU in various murine tumor systems was observed in comparison with that of ACNU administered according to the single high-dose schedule. The delayed type of hematologic toxicity (leukopenia) could not be alleviated by this treatment schedule.