Journal Article

Impact of excision repair cross-complementing gene 1 (ERCC1) on the outcomes of patients with advanced gastric cancer: correlative study in Japan Clinical Oncology Group Trial JCOG9912

Y. Yamada, N. Boku, T. Nishina, K. Yamaguchi, T. Denda, A. Tsuji, Y. Hamamoto, K. Konishi, Y. Tsuji, K. Amagai, S. Ohkawa, Y. Fujita, H. Nishisaki, H. Kawai, A. Takashima, J. Mizusawa, K. Nakamura and A. Ohtsu

in Annals of Oncology

Published on behalf of European Society for Medical Oncology

Volume 24, issue 10, pages 2560-2565
Published in print October 2013 | ISSN: 0923-7534
Published online July 2013 | e-ISSN: 1569-8041 | DOI: https://dx.doi.org/10.1093/annonc/mdt238
Impact of excision repair cross-complementing gene 1 (ERCC1) on the outcomes of patients with advanced gastric cancer: correlative study in Japan Clinical Oncology Group Trial JCOG9912

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Background

Since the best chemotherapy regimen for each patient with advanced gastric cancer is uncertain, we aimed to identify molecular prognostic or predictive biomarkers from biopsy specimens in JCOG9912, a randomized phase III trial for advanced gastric cancer.

Patients and methods

Endoscopic biopsy specimens from primary lesions were collected in 445 of 704 randomized patients in JCOG9912. We measured the mRNA expression of excision repair cross-complementing group 1 (ERCC1), thymidylate synthase, dihydropyrimidine dehydrogenase, and five other genes, then, categorized them into low and high groups relative to the median, and examined whether gene expression was associated with efficacy end point.

Results

Multivariate analyses showed that high ERCC1 expression [HR 1.37; 95% confidence interval (CI) 1.08–1.75; P = 0.010], performance status ≥1 (HR 1.45; 95% CI 1.13–1.86; P = 0.004), and number of metastatic sites ≥2 (HR 1.66; 95% CI 1.28–1.86; P < 0.001) were associated with a poor prognosis, and recurrent disease (versus unresectable; HR 0.75; 95% CI 0.56–1.00; P = 0.049) was associated with a favorable prognosis. None of these molecular factors were a predictive marker for choosing irinotecan plus cisplatin or 5-fluorouracil rather than S-1.

Conclusion

These correlative analyses suggest that ERCC1 is an independent prognostic factor for overall survival in the first-line treatment of gastric cancer.

Clinical Trial Number

C000000062, www.umin.ac.jp.

Keywords: dihydropyrimidine dehydrogenase; excision repair cross-complementing gene 1; gastric cancer; prognostic factor; thymidylate synthase; vascular endothelial growth factor

Journal Article.  3213 words.  Illustrated.

Subjects: Medical Oncology

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