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Chemotherapy of an Experimental Glioma with Nitrosoureas¹

Division of Neurosurgery, University of Toronto, Toronto, Ontario M5S 1A8 [C.H.T., A.D., R. N., L.L.], and Division of Neurosurgery, Sunnybrook Medical Centre, Toronto, Ontario M4N 3M5, Canada [C.H.T.]

Chemotherapy experiments were performed with 2 nitrosourea drugs in an experimental mouse brain tumor model. Cell suspensions of a transplantable mouse ependymoblastoma were injected i.c. by means of a stereotactic frame. The drugs used were 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea and were given by either i.p. or by direct intraneoplastic (i.n.) injection on the fifth day after tumor cell implantation. Injections i.n. of drugs were made with the stereotactic frame.

Both drugs were highly effective in increasing the median day of death and in yielding large numbers of long-term survivors. Effectiveness was evident after i.p. or i.n. injection. However, with certain dosage schedules such as every 2 hr for 5 injections daily on 2 consecutive days, i.n. injection was more effective and less toxic than i.p. injection. The reason why repeated i.n. injections produced less toxicity than repeated i.p. injections is not definitely known but may be due to local metabolism of the drugs in the tumors and surrounding brain to a less toxic form. This is the first laboratory report of direct i.n. injection of the nitrosoureas, and the authors consider these results encouraging.

¹ Supported by the Ontario Cancer Treatment and Research Foundation Grant 247.

² Associate Professor of Surgery, University of Toronto, Ontario; Head, Division of Neurosurgery, Sunnybrook Medical Centre, Toronto, Ontario, Canada. To whom requests for reprints should be sent, at Division of Neurosurgery, Sunnybrook Medical Centre, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.

³ Medical student, University of Toronto, Faculty of Medicine, Toronto, Ontario, Canada.

Received 5/18/76. Accepted 11/ 9/76.