Low thymidylate synthase expression in the primary tumor predicts favorable clinical outcome in resected gastric cancer patients treated with adjuvant tegafur.
OBJECTIVE
To assess the thymidylate synthase protein (TS) in tumor cells of resected gastric cancer patients treated with adjuvant tegafur (TG), we reviewed the outcome of 94 randomized patients treated either with adjuvant TG plus mitomycin C (MMC) or MMC alone.


METHODS
TS was determined in 76 out of 94 patients, previously randomized to receive adjuvant TG, 500 mg/m(2)/day p.o. for 6 months plus four courses of MMC, 10- 20 mg/m(2) i.v. every 6 weeks or MMC alone. An immunohistochemical assessment with the monoclonal antibody TS-106 was performed.


RESULTS
Low TS was observed in 38 patients (20 treated with TG-MMC and 18 with MMC) and high TS in the other 38 patients (21 treated with TG-MMC and 17 with MMC). After 10 years' median follow-up time, 61% of adjuvant TG-MMC patients and 43% of MMC patients were alive and disease-free. Disease-free survival and overall survival were significantly better for patients treated with TG-MMC compared to MMC adjuvant (p = 0.0277 and p = 0.05), and low-TS compared to high-TS patients (p = 0.0184 and p = 0.0198). In 38 low-TS patients we observed an 83% chance to be disease-free in TG-MMC-treated patients and 55% in MMC-treated patients (p = 0.04).


CONCLUSIONS
A low TS level determines a subset of patients that may benefit from adjuvant oral TG when added to MMC showing a 5-year cure rate of more than 80%.
Grau
Juan J
JJ
Oncology Department, Hospital Clinic, Institute of Hemato-Oncology, University of Barcelona, Barcelona, Spain. jjgrau@medicina.ub.es
Domingo-Domenech
Josep
J
Morente
Vanesa
V
Pera
Manuel
M
Garcia-Valdecasas
Juan C
JC
Fuster
Josep
J
Bombí
Antoni
A
Mellado
Begoña
B
Albanell
Joan
J
Gascón
Pere
P
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000601:surgery; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage; D013940:Thymidylate Synthase / Q000032:analysis*; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D005641:Tegafur; D016685:Mitomycin; D013940:Thymidylate Synthase