Thymidine synthase, thymidine phosphorylase, and excision repair cross-complementation group 1 expression as predictive markers of capecitabine plus cisplatin chemotherapy as first-line treatment for patients with advanced oesophageal squamous cell carcinoma.
BACKGROUND
Our purpose was to evaluate thymidine synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementation group 1 (ERCC1) expression as biomarkers for capecitabine and cisplatin (XP) combination chemotherapy in patients with metastatic oesophageal squamous cell cancer.


METHODS
A total of 113 patients with metastatic oesophageal squamous cell cancer were treated with XP chemotherapy at the Samsung Medical Center between 2003 and 2007, of whom 72 had available clinical data and paraffin blocks for immunohistochemistry of TS, TP, and ERCC1.


RESULTS
The median age of the 72 patients was 62 years. The overall response rate (RR) was 51.4%. The median progression-free survival (PFS) and overall survival (OS) were 4.2 and 12.0 months, respectively. High expression of TS and TP was associated with a higher RR than was low expression of TS and TP (54.1 vs 40.5%, P=0.022). Strong ERCC1 expression and a low TS score were identified as unfavourable independent risk factors for PFS (HR 10.71, 95% confidence interval (CI) 2.1-54.7, P=0.004 for strong ERCC1 expression; and HR 2.9, 95% CI 1.0-7.9, P=0.044 for low TS score). Strong ERCC1 expression was identified as an unfavourable independent risk factor for OS (HR 3.73, 95% CI 1.39-10.0, P=0.009).


CONCLUSIONS
These data indicate that expression of TS, TP, and ERCC1 may be predictive markers for response and survival in patients with metastatic oesophageal squamous cell cancer receiving XP chemotherapy.
Lee
S
S
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710, Korea.
Park
Y H
YH
Kim
K H
KH
Cho
E Y
EY
Ahn
Y C
YC
Kim
K
K
Shim
Y-M
YM
Ahn
J S
JS
Park
K
K
Im
Y-H
YH
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004720:Endonucleases / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000378:metabolism*; D016896:Treatment Outcome
D004268:DNA-Binding Proteins; D003841:Deoxycytidine; D000069287:Capecitabine; D013940:Thymidylate Synthase; D013939:Thymidine Phosphorylase; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin; D005472:Fluorouracil