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


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.


CONCLUSIONS
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.
Spindler
K-L G
KG
Department of Oncology, Danish Colorectal Cancer Group South, Vejle Hospital, Denmark. Electronic address: Karen-Lise.Garm.Spindler@slb.regionsyddanmark.dk.
Andersen
R F
RF
Department of Biochemistry, Danish Colorectal Cancer Group South, Vejle Hospital, Denmark.
Jensen
L H
LH
Department of Oncology, Danish Colorectal Cancer Group South, Vejle Hospital, Denmark.
Ploen
J
J
Department of Oncology, Danish Colorectal Cancer Group South, Vejle Hospital, Denmark.
Jakobsen
A
A
Department of Oncology, Danish Colorectal Cancer Group South, Vejle Hospital, Denmark.
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004720:Endonucleases / Q000235:genetics; D004815:Epidermal Growth Factor / Q000235:genetics*; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011110:Polymorphism, Genetic / Q000235:genetics*; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000235:genetics; D016896:Treatment Outcome
D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D004815:Epidermal Growth Factor; D000069287:Capecitabine; D013940:Thymidylate Synthase; C071447:ERCC1 protein, human; D004720:Endonucleases; D005472:Fluorouracil