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Annals of Oncology Advance Access published online on October 22, 2009
Annals of Oncology, doi:10.1093/annonc/mdp336
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

EGF61A>G polymorphism as predictive marker of clinical outcome to first-line capecitabine and oxaliplatin in metastatic colorectal cancer

K.-L. G. Spindler1,*, R. F. Andersen2, L. H. Jensen1, J. Ploen1 and A. Jakobsen1

1 Department of Oncology, Danish Colorectal Cancer Group South, Vejle Hospital, Denmark
2 Department of Biochemistry, Danish Colorectal Cancer Group South, Vejle Hospital, Denmark

* Correspondence to: Dr K.-L. G. Spindler, Department of Oncology, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark. Tel: +45-79406833; Fax: +45-79406709; E-mail: Karen-Lise.Garm.Spindler{at}slb.regionsyddanmark.dk

Background: The purpose of the present study was to investigate polymorphisms related to the metabolism of fluoropyrimidine and oxaliplatin, thymidylate synthase (TS) and excision repair cross-complementing gene 1 (ERCC1) 118, in metastatic colorectal cancer patients treated with capecitabine and oxaliplatin (XELOX). We also investigated the importance of the EGF61A>G polymorphism, which holds a functional influence on the tyrosine kinase receptor regulation.

Materials and methods: We included 68 patients treated with first-line XELOX. Polymorphism analyses were carried out on pretreatment blood samples. Response was evaluated according to the RECIST. Survival analysis was described by the Kaplan–Meier method and log-rank testing.

Results: The overall response rate was 38% and the median overall survival 19.4 months. A favorable outcome was seen in patients with the EGF61A/G genotype compared with the combined group of A/A and G/G, with response rates of 57% and 18%, respectively (P = 0.001). There was a significantly different progression-free survival (P = 0.018) in favor of the A/G group. The TS and ERCC1 genotypes failed to provide any significant impact on the outcome.

Conclusion: Polymorphism analysis of a simple blood sample is a feasible approach to biomarker analysis and the EGF61A>G polymorphism may influence the effect of first-line XELOX. Consequently, this marker deserves further investigation.

EGF61A>G, ERCC1 118, gene polymorphisms, mCRC, TS, XELOX

Received for publication February 14, 2009. Revision received April 19, 2009. Accepted for publication May 27, 2009.


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