The fluoropyrimidines (fluorouracil and floxuridine) introduced as cancer chemotherapeutic agents by Heidelberger and Duschinsky in 1957, have been found to be potent compounds with palliative effects in human cancer of several types.1-3,13 Adenocarcinoma of the breast and colon are the tumors reported most responsive to these agents.4,5 Initial clinical use of fluorouracil (5-FU) was attended by an incidence of morbidity and mortality higher than that previously encountered with other agents used in the palliation of solid tumors. The higher regression rates reported with the fluoropyrimidines hence might have been related to the increased toxicity on all tissues rather than a greater tumor specificity of the new agents per se. For this reason it was thought desirable to design a study in which fluorouracil would be evaluated against another antimetabolite given in doses expected to give the same level of toxic effects on the hematologic and gastrointestinal systems. Since
Comparison of Antimetabolites in the Treatment of Breast and Colon Cancer. JAMA. 1967;200(9):770–778. doi:10.1001/jama.1967.03120220072013
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