Preliminary study on the optimal dosage schedule for oral tegafur/uracil (UFT) chemotherapy

Background: We evaluated a new dose-intensive schedule for oral UFT (tegafur and uracil in a molar ratio of 1:4) administered for 5 consecutive days followed by 2 drug-free days (weekly-5 method), in comparison with conventional daily administration (weekly-7 method), in Yoshida-sarcoma- bearing rats. Methods: The single dose of 20 mg/kg of UFT for rats corresponds to the human single dose when converted to dose per unit of body- surface area. The drug was administered 3 times a day for the weekly-5 method and twice a day for the weekly-7 method. A 7-day period was considered 1 course. The total doses per course were almost the same in both methods. Antitumor efficacy and survival effect were evaluated after 3 courses. Body weight changes and food consumption were also measured as indices of toxicity. The plasma pharmacokinetics were analyzed by simulating dosage patterns. Results: Significant tumor-growth inhibition was seen with both the weekly-5 and the weekly-7 methods as compared to the control. Moreover, the weekly-5 method showed higher tumor-growth inhibition and a better survival effect than the weekly-7 method. These results appear to be related to the duration of plasma concentrations of 5-FU being maintained above a certain concentration for a longer time with the weekly-5 method. Food consumption with the weekly-5 method recovered to the control level after the drug-free period, and body weight gain was also favorable. Conclusion: The results of this study suggest that the dose-intensive method of administering UFT orally for the weekly-5 method is a useful dosage schedule. Thus, this dosage schedule is recommended for use in clinical trials.