Abstract
The pyrimidine analog, 6-azauridine (AZUR), is an inhibitor of de novo pyrimidine biosynthesis and produces significant antineoplastic effects in experimental tumors. Use of this compound in the treatment of acute and chronic leukemia has resulted in a rapid and marked decline in circulating leukemic cells. Satisfactory responses in chronic leukemia, even in the “acute phase” of the disease, have occurred despite the development of temporary resistance. Similar responses in acute leukemia have been observed but no instances of remission have occurred in these short trials. Inhibition of the ability of leukocytes to decarboxylate orotic acid was found in patients receiving AZUR and correlated well with the clinical response in each case. The development of temporary clinical resistance to antileukemic effects was associated with decreased inhibition of this enzyme system in leukocytes removed from patients. The urinary excretion of orotic acid and orotidine in patients receiving AZUR did not correlate with the antileukemic effects and is probably the result of inhibition of pyrimidine metabolism in various body organs.
Published Version
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