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 system in liver microsomes. In the plase 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 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.
D000328:Adult; D000368:Aged; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D003692:Delayed-Action Preparations; D004285:Dogs; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009374:Neoplasms, Experimental / Q000188:drug therapy; D051381:Rats; D005641:Tegafur / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D014839:Vomiting / Q000139:chemically induced
D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D005641:Tegafur; C016882:FD 1; D005472:Fluorouracil