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Clinical Investigations of 6-Azathymine A Thymine Analog^*

( Division of Clinical Chemotherapy, Sloan-Kettering Institute for Cancer Research; Departments of Pediatrics and Medicine, Memorial and James Ewing Hospitals; and Cornell University Medical College, New York, N.Y.)

Twenty-four patients received azathymine. All fourteen children and two of the adults had acute leukemia; the other adults had a variety of solid tumors. All of the children had previously responded to Methotrexate and had then become resistant to it. Azathymine did not produce any improvement in any patient.

The hepatotoxic effect of azathymine was striking in the adults and occurred in the absence of objective regression of the neoplastic disease. Liver damage also occurred in one child.

Azathymine exerts a specific renal effect, causing hyperuricemia associated with a decrease in the excretion of uric acid. This occurs early in the course of therapy and with doses that do not cause liver function changes.

^* These studies were supported by research grants C-1889, CY-2329, and CY-3215 from the National Cancer Institute of the National Institutes of Health, Public Health Service; the American Cancer Society, the Damon Runyon Memorial Fund for Cancer Research, the Lasker Foundation, the Grant Foundation, and the Black-Stevenson Fund.

Received 9/25/59.