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Clinical Studies of 6-Azauracil^*

( General Medicine Branch (Chemotherapy Service), National Cancer Institute, National Institutes of Health; and Department of Medicine, Georgetown University School of Medicine and the Georgetown Medical Division (Cancer Chemotherapy Service), D. C. General Hospital, Washington, D.C.)

Toxicity studies with the pyrimidine analog, 6-azauracil, have revealed that the major and perhaps the only adverse effects relate to the central nervous system. These effects usually manifest themselves initially as lethargy, but may go on to a wide spectrum of sensory and motor abnormalities. Electroencephalographic changes regularly occur, and these often precede the clinical effects. The effects of dose schedule and duration of 6-azauracil administration are reported. Children are more susceptible to the effects of 6-azauracil than are adults. A closely related compound, 6-azathymine, produces similar electroencephalographic changes. Attempts to reverse the toxic effects of 6-azauracil with various metabolites were unsuccessful. The above findings, along with several ancillary observations, are presented and discussed.

^* Presented in part at the annual meeting of the American Association for Cancer Research, Chicago, Illinois, April 12–14, 1957.

Received 5/13/59.