[Theoretical construction of chemotherapeutic tactics for advanced or recurrent gastrointestinal carcinoma].
The anti-cancer effect of 5-fluorouracil (5-FU) is significantly affected by the intratumoral environment. Elevated expression of thymidylate synthase (TS), the target enzyme of 5-FU, and a lack of reduced folate or FdUMP results in insufficient inhibition of TS. Further, elevated expression of DPD in the tumor tissue results in a lack of FdUMP. TS-1, which contains tegafur and dihydroxypyridine (CDHP), a potent DPD inhibitor, is a promising anticancer drug. Isovorin has been available in Japan since autumn 1999. In cancer patients, folate deficiency may be derived from increased consumption and/or absorption disturbance of folate. In such situations, sufficient TS inhibition cannot be obtained if 5-FU is administered without supplementation of reduced folate. We describe in detail the metabolism of those substances in relation to the anticancer effect of 5-FU. Further, we show the theoretical construction of first-line and second-line chemotherapy with consideration of TS and DPD expression.
Omura
K
K
Dept. of Surgery I, Kanazawa University Faculty of Medicine.
Kawakami
K
K
Kanehira
E
E
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D013940:Thymidylate Synthase / Q000187:drug effects / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D013940:Thymidylate Synthase; D002945:Cisplatin; D005472:Fluorouracil