An Evaluation of 5-Fluorouracil in Malignant Disease

Abstract

Until recently, it was believed that preformed pyrimidines, unlike preformed purines, were not utilized by mammalian tissues, either normal or neoplastic. In 1954, Rutman, Cantarow, and Paschkis (1) observed that uracil was incorporated into preneoplastic rat liver and rat hepatoma. In 1957, Heidelberger, Leibman, Harbers, and Bhargava (2) verified this finding and noted that significant incorporation of uracil occurred into intestinal mucosa and several carcinomas of mice and rats. Because of these findings, many pyrimidine antagonists have been synthesized and evaluated for their effect in malignant disease. Of these drugs, 5-fluorouracil (3), 5-fluorodeoxyuridine (4), and 6-azauridine (5) have been subjected