[Theoretical construction of chemotherapeutic tactics for advanced or recurrent gastrointestinal carcinoma].

Abstract

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.

• Authors: K Omura, K Kawakami, E Kanehira
• Journal: Gan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 28 Issue 1 Pg. 63-8 (Jan 2001) ISSN: 0385-0684 [Print] Japan
• PMID: 11201382 (Publication Type: English Abstract, Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Antineoplastic Agents
• Thymidylate Synthase
• Cisplatin
• Fluorouracil

Topics

• Antimetabolites, Antineoplastic (pharmacology)
• Antineoplastic Agents (pharmacology)
• Cisplatin (pharmacology)
• Fluorouracil (pharmacology)
• Gastrointestinal Neoplasms (drug therapy, enzymology, pathology)
• Humans
• Thymidylate Synthase (drug effects, metabolism)