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Thymidylate synthase inhibition by an oral regimen consisting of tegafur-uracil (UFT) and low-dose leucovorin for patients with gastric cancer.

AbstractPURPOSE:
5-Fluorouracil (5-FU) remains a standard therapy for patients with advanced gastric cancer. There has been no study using an oral regimen with a combination of tegafur, a masked compound of 5-FU, and leucovorin in gastric cancer. The purpose of this study was to determine whether orally administered low-dose leucovorin enhances thymidylate synthase (TS) inhibition when added to tegafur-uracil (UFT) in patients with gastric cancer.
METHODS:
A group of 26 patients with resectable gastric cancer were assigned to one of two regimens: UFT alone or UFT plus leucovorin. UFT, equivalent to 400 mg/day tegafur, with or without 30 mg/day leucovorin, was administered orally in divided daily doses every 12 h for 3 consecutive days prior to surgery. Tumor specimens were taken immediately following gastrectomy, and the TS inhibition rate (TSIR) was determined using a ligand-binding assay.
RESULTS:
The TSIR was significantly higher in the UFT plus leucovorin group than in the UFT alone group (P < 0.01). The TSIR in the patients treated with UFT alone ranged between 14% and 50%, while six of the eight patients treated with UFT plus leucovorin had a TSIR of 55% or higher. The remaining two patients in the group treated with UFT plus leucovorin, with a TSIR of 31% and 44%, had undifferentiated tumors.
CONCLUSION:
Our results suggest that orally administered low-dose leucovorin can add to the efficacy of UFT in patients with gastric cancer, and provide preliminary data for a randomized clinical trial.
AuthorsT Ichikura, S Tomimatsu, Y Okusa, T Yahara, K Uefuji, S Tamakuma
JournalCancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 38 Issue 5 Pg. 401-5 ( 1996) ISSN: 0344-5704 [Print] Germany
PMID8765432 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antimetabolites, Antineoplastic
  • Drug Combinations
  • UFT(R) drug
  • Tegafur
  • Uracil
  • Thymidylate Synthase
  • Leucovorin
Topics
  • Administration, Oral
  • Aged
  • Antimetabolites, Antineoplastic (pharmacology)
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Drug Combinations
  • Female
  • Humans
  • Leucovorin (administration & dosage)
  • Male
  • Neoplasm Staging
  • Prospective Studies
  • Stomach Neoplasms (drug therapy, enzymology, pathology)
  • Tegafur (administration & dosage)
  • Thymidylate Synthase (antagonists & inhibitors, metabolism)
  • Uracil (administration & dosage)

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