Optimal Treatment Regimens for 5′‐Deoxy‐5‐fluorouridine, with or without (E)‐5‐(2‐Bromovinyl)‐2′‐deoxyuridine, against Various Tumors in Mice

The antitumor activity of 5′‐deoxy‐5‐fluorouridine (DFUR), a prodrug of 5‐fluorouracil (5‐FU), is markedly enhanced if DFUR treatment is combined with (E)‐5‐(2‐bromovinyl)‐2′‐deoxyuridine (BVDU). Combined oral administration of DFUR (10 mg/kg) and BVDU (10 mg/kg) three times (every 3 h) per day for 5 days afforded greater antitumor activity than a single dose of DFUR (300 mg/kg/day) for 5 days in mice bearing either adenocarcinoma 755 or Lewis lung carcinoma, while in the colon 26 system the antitumor effects of both treatment regimens were equivalent. Thus, a low‐dose regimen of DFUR when combined with BVDU provides a similar or greater antitumor activity than a high‐dose regimen of DFUR that is not combined with BVDU. The area under the curve of plasma 5‐FU following a treatment with the combination of DFUR (10 mg/kg) and BVDU (10 mg/kg) was equal to that following DFUR (300 mg/kg) treatment.