Review of a New Antimetabolic Agent, 1,3-Bis(Tetrahydro-2-Furanyl)-5-Fluoro-2,4-Pyrimidinedione (FD-1)
FD-1, a new anticancer drug, is a fluorinated pyrimidine derivative that has shown less acute toxicity than 5-FU and FT-207, and higher antitumor activity than FT-207 in Ehrlich carcinoma, S-180, AH-130, Yoshida sarcoma, and Walker 256. A principal feature of FD-1 is that, in comparison with FT-207, in oral administration it can maintain a higher concentration of 5-FU both in plasma and in tumor tissues. FD-1 is considered to be activated into 5-FU by a drug-metabolizing enzyme system in liver microsomes.
In the phase I study of FD-1, the maximum tolerated dose was greater than 20 mg/kg in a single administration. The dose-limiting factor in FD-1 administration is gastrointestinal toxicity that causes side effects such as nausea and vomiting. The recommended dosage for daily oral administration of FD-1 is 6–12 mg/kg/day.
In the phase I study of the sustained released form of FD-1 (FD-1-S), frequency of nausea and vomiting could be definitely reduced by the oral administration of FD-1-S, which showed higher tolerability. FD-1-S can be continuously administered at a dose ranging from 600 mg to 1200 mg/body/day for 4 weeks and can be expected to have higher efficacy. In further studies on the long-term administration of FD-1-S, CNS toxicity has been reported in some cases.
KeywordsOral Administration Stomach Cancer Daily Oral Administration High Antitumor Activity Ehrlich Carcinoma
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