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.
KeywordsFatigue Toxicity Sarcoma Diarrhea Pyrimidinedione
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- 1.Kawaguchi, Y., Nakamura, Y., Sato, T., Takeda, S., Marunaka, T., Fujii, S.: Studies on the fate of 5-fluoro-1,3-bis(tetrahydro-2-furanyl)-2,4-pyrimidinedione (FD-1), a new antitumor agent. 1. Absorption, distribution, excretion and metabolism of FD-1 administered orally to rats. Yakugaku Zasshi 98, 525 (1978)PubMedGoogle Scholar
- 2.Unemi, N., Takeda, S., Kitasato, K., Kajihara, M.: Studies on the antitumor activity of 1,3-bis(tetrahydro-2-furanyl)-5-fluoro-2,4-pyrimidinedione (FD-1), a new antitumor agent. 1. Antitumor activity of FP-1 by the oral administration. Chemotherapy 26, 200 (1978)Google Scholar
- 3.Yasumoto, M., Marunaka, Y., Hashimoto, S., Harima, K., Suzue, T.: Process for producing N 1-(2-tetrahydrofuryl)-5-fluorouracil. Japanese published unexamined patent application 50–50384 (1975)Google Scholar