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Effectiveness of Cytoxan against Intracerebrally and Subcutaneously Inoculated Mouse Lymphoid Leukemia L1210

( Laboratory of Chemical Pharmacology, National Cancer Institute, Bethesda, Maryland)

The current studies indicate that Cytoxan is considerably less effective in the treatment of intracerebrally (I.C.) than of subcutaneously (S.C.) inoculated leukemia L1210. Two factors which may contribute to the inability of Cytoxan, or its biologically active form, to produce extensive survival times in I.C. inoculated mice are: reduced efficiency of penetration of the drug into the brain; and the favorable environment afforded by the intracerebral site for the growth of the leukemic cells.

The diminished therapeutic response of I.C. inoculated mice was observed with direct intracerebral administration as well as with the subcutaneous administration of Cytoxan.

Tissue bioassay experiments following treatment with Cytoxan indicated that there was less extensive inhibition in I.C. than in S.C. inoculated mice.

Treatment of mice with Cytoxan prior to inoculation of L1210 provided evidence that, following injection, Cytoxan or an active metabolic product was present in effective levels for approximately 1 hour in blood and tissues, and for a lesser period in the brain.

Received 8/ 2/61.