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Br J Cancer. 2013 Jan 15;108(1):115-20. doi: 10.1038/bjc.2012.526. Epub 2012 Nov 22.

KRAS mutational status affects oxaliplatin-based chemotherapy independently from basal mRNA ERCC-1 expression in metastatic colorectal cancer patients.

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1
Department of Medical Oncology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli n 8, 00168 Rome, Italy.

Abstract

BACKGROUND:

In this study, we evaluated the possibility that KRAS mutational status might be predictive of oxaliplatin (OXA) efficacy. We also explored the role of excision repair cross complementing group-1 (ERCC-1).

METHODS:

Ninety anti-epidermal growth factor receptor-naive advanced colorectal cancer patients were retrospectively analysed. In all patients KRAS mutational status was assessed. In 60 patients mRNA ERCC-1 expression was also investigated. Response rate (RR) and progression-free survival (PFS) after FOLFOX-6┬▒bevacizumab were evaluated according to KRAS status and mRNA ERCC-1 expression.

RESULTS:

Among 90 patients 47% wild-type (wt) and 53% mutated (mt) KRAS tumours were found. Response rate was 26% in the wt KRAS group, whereas it was 56% in the mt KRAS group; the difference is statistically significant in the total sample (P=0.008) and when only patients receiving FOLFOX-6┬▒bevacizumab as first-line are considered (P=0.01). Progression-free survival was longer in mt than in wt KRAS patients over all patients (10 vs 8 months, respectively, P=0.001) and in those treated as first-line (10 vs 8 months, respectively, P=0.0069). Mt KRAS patients experienced a longer survival (24 vs 18 months; P=0.01). ERCC-1 mRNA expression was not found to correlate with FOLFOX activity in our analysis.

CONCLUSION:

Our results suggest that activating mutation of KRAS oncogene may predict response to OXA. Basal expression of ERCC-1 mRNA does not explain the high efficacy of FOLFOX-6 in mt KRAS patients.

PMID:
23175150
PMCID:
PMC3553525
DOI:
10.1038/bjc.2012.526
[Indexed for MEDLINE]
Free PMC Article
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