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The antitumor activity and toxicity of 5-fluorouracil (FUra) and 5'-deoxy-5-fluorouridine (dFUR) were compared in female Fischer rats bearing transplanted dimethylhydrazine-induced colon tumors. The therapeutic effects of FUra and dFUR were not affected by the initial tumor size, but were dependent on the dose and duration of treatment. The maximal response rate of 80-90% cures was obtained with 7-day infusions of 35 mg-kg-1-day-1 FUra or 500 mg-kg-1-day-1 dFUR. The host toxicity of FUra and dFUR in tumor-bearing or normal rats included gastrointestinal and central nervous system disturbances. Toxicity related death was preceded by a greater than 20% animal weight loss and other signs of gastrointestinal disturbances. The maximal therapeutic dose of FUra was identical to the toxic dose which caused 40% death in normal rats. By contrast, the maximal therapeutic dose of dFUR did not cause toxic death, and the threshold lethal dose of dFUR was 40% higher than the maximally therapeutic dose, indicating a better therapeutic index for dFUR in this rat tumor.
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