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Studies on the Chemotherapy of Experimental Brain Tumors: Evaluation of 1,3-Bis(2-chloroethyl)-1-nitrosourea, Cyclophosphamide, Mithramycin, and Methotrexate

Office of the Associate Scientific Director for Experimental Therapeutics, National Cancer Institute, NIH, Bethesda, Maryland 20014

A brain tumor model has been utilized to test 4 chemotherapeutic agents. The model consists of C57BL male mice implanted intracerebrally with carcinogen-induced gliomas. Four tumors were used, all histologically ependymoblastomas, but each differing in its biological behavior. Four agents were tested, each administered i.p. A comparison was made between treated animals and nontreated control animals with respect to median survival time and long-term survival and was statistically evaluated by a modification of the Wilcoxon rank-sum analysis.

1,3-Bis(2-chloroethyl)-1-nitrosourea (NSC 409962) significantly prolonged the life-span of mice bearing the intracerebral gliomas. Increased life-span varied from 10 to 137%. Cyclophosphamide (NSC 26271) less consistently increased survival of glioma-bearing mice. Neither mithramycin (NSC 24559) nor methotrexate (NSC 740) on multiple dose schedules was capable of increasing the life-spans of the animals.

The implications of these data with respect to blood-brain barrier, brain tumor permeability, and the value of the model as a screen for human brain tumor chemotherapy are discussed.

¹ Present address: Neuropsychiatric Service, Memorial Sloan-Kettering Cancer Center, New York, N. Y. 10021.

² Present address: Department of Neurosurgery, University of Minnesota Hospitals, Minneapolis, Minn. 55455.

Received 1/23/70. Accepted 5/29/70.