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


CONCLUSIONS
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.
Ichikura
T
T
First Department of Surgery, National Defense Medical College, Tokorozawa, Japan.
Tomimatsu
S
S
Okusa
Y
Y
Yahara
T
T
Uefuji
K
K
Tamakuma
S
S
D000284:Administration, Oral; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D009367:Neoplasm Staging; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014498:Uracil / Q000008:administration & dosage
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; D013940:Thymidylate Synthase; D002955:Leucovorin