Remarkable antitumor activity of 5'-deoxy-5-fluorouridine in human colorectal tumor xenografts.

5'-Deoxy-5-fluorouridine (doxifluridine) is a prodrug of 5-fluorouracil (5FU) selectively activated by tumor cells. Since in clinical studies the side effects of doxifluridine differed after intravenous (i.v.) or oral administration, and oral route was the most promising in preclinical studies with murine models, in this study the drug was tested orally against a panel of human colorectal tumor xenografts with varying degrees of sensitivity to 5FU. Doxifluridine efficacy was comparable to that of 5FU when it was delivered according to a weekly schedule, but it was statistically higher when it was delivered more frequently. Impressive tumor inhibition (between 90 and 97%) was achieved in 4 out of 5 tumor lines after treatments delivered twice a week or daily 5 times a week. No difference in 5FU activity was observed between weekly and biweekly treatments, or between oral and i.v. injections. Moreover, in one tumor line in which different dosages of doxifluridine were investigated, a marked antitumor effect was obtained with a wide range of tolerated doses (4000-8000 mg/kg). Overall, these data indicated that doxifluridine is well tolerated when given orally and frequently. Using an adequate schedule, the prodrug has a better therapeutic efficacy against a variety of human colon cancer models than 5FU.