title: The history, mechanism and clinical use of oral 5-fluorouracil derivative chemotherapeutic agents.
abstract: The role of oral chemotherapy has been getting expanded because of the potential advantage in patients' convenience and better quality of life as well as in cost-effectiveness as compared with intravenous chemotherapy. In this article, the history, mechanism of anti-tumor activity, and clinical use of oral chemotherapy using 5-fluorouracil (5-FU) derivative chemotherapeutic agents are reviewed. Pharmacological analysis has revealed that 5-FU, a basic chemotherapeutic agent widely used against a variety of malignant tumors, shows a time dependent anti-tumor activity, and that continuous maintenance of 5-FU concentration in blood is the optimal method in 5-FU administration. UFT, a combination drug of ftorafur (tetrahydrofuranyl-5-fluorouracil, tegafur, FT) and uracil, has been developed to have potent anti-tumor activity by maintaining higher 5-FU concentration in blood and tumor tissues for a long time. FT is a pro-drug that releases 5-FU continuously, and uracil is added to inhibit degradation of the released 5-FU. Clinically, oral administration of UFT has proved to be effective as an adjuvant therapy after surgery for some malignant tumors such as non-small cell lung cancer. Moreover, UFT has proved to be effective for inoperable advanced malignancies such as colorectal cancer, especially in combination with leucovorin or cisplatin. Recently, S-1, a more active oral 5-FU derivative chemotherapeutic agent has been developed in Japan. Several factors to affect anti-tumor effects and/or toxicities of 5-FU and the derivatives, such as thymidylate synthase activity, dehydropyrimidine dehydrogenase activity and p53 status, are also discussed in the article. In conclusion, oral administration of 5-FU derivatives such as UFT may have several clinical advantages over intravenous 5-FU administration.
authors.affiliation: Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Fukuse
authors.forename: H
authors.initials: H
authors.lastname: Wada
authors.forename: M
authors.initials: M
authors.lastname: Fukushima
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000266:history / Q000494:pharmacology / Q000627:therapeutic use*; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000266:history / Q000494:pharmacology / Q000627:therapeutic use*; D049673:History, 20th Century; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000266:history
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil