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Open Access Highly Accessed Research article

Effect of KRAS codon13 mutations in patients with advanced colorectal cancer (advanced CRC) under oxaliplatin containing chemotherapy. Results from a translational study of the AIO colorectal study group

Anke Reinacher-Schick1109*, Karsten Schulmann1, Dominik P Modest2, Nina Bruns1, Ulrich Graeven3, Malgorzata Jaworska4, Richard Greil5, Rainer Porschen6, Dirk Arnold7, Wolff Schmiegel189 and Andrea Tannapfel4

Author affiliations

1 Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany

2 Department of Internal Medicine III, Klinikum der Universität, München, Germany

3 Department of Hematology, Oncology and Gastroenterology, Kliniken Maria Hilf, Mönchengladbach, Germany

4 Institute of Pathology, Ruhr-University Bochum, Bochum, Germany

5 3rd Medical Department with Hematology and Medical Oncology, Oncologic Centre Paracelsus Medical University, Salzburg, Austria

6 Klinikum Bremen-Ost, Bremen, Germany

7 Hubertus Wald Cancer Center, University Hospital Hamburg, Hamburg, Germany

8 Department of Gastroenterology & Hepatology, Berufsgenossenschaftliches Klinikum Bergmannsheil, Ruhr-University Bochum, Bochum, Germany

9 Center for Clinical Studies in Oncology within PURE, Ruhr-University Bochum, Bochum, Germany

10 Medical Department, Knappschaftskrankenhaus, Ruhr-University Bochum, In der Schornau 23-25, Bochum, 44892, Germany

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Citation and License

BMC Cancer 2012, 12:349  doi:10.1186/1471-2407-12-349

Published: 9 August 2012

Abstract

Background

To evaluate the value of KRAS codon 13 mutations in patients with advanced colorectal cancer (advanced CRC) treated with oxaliplatin and fluoropyrimidines.

Methods

Tumor specimens from 201 patients with advanced CRC from a randomized, phase III trial comparing oxaliplatin/5-FU vs. oxaliplatin/capecitabine were retrospectively analyzed for KRAS mutations. Mutation data were correlated to response data (Overall response rate, ORR), progression-free survival (PFS) and overall survival (OS).

Results

201 patients were analysed for KRAS mutation (61.2% males; mean age 64.2 ± 8.6 years). KRAS mutations were identified in 36.3% of tumors (28.8% in codon 12, 7.4% in codon 13). The ORR in codon 13 patients compared to codon 12 and wild type patients was significantly lower (p = 0.008). There was a tendency for a better overall survival in KRAS wild type patients compared to mutants (p = 0.085). PFS in all patients was not different in the three KRAS genetic groups (p = 0.72). However, we found a marked difference in PFS between patients with codon 12 and 13 mutant tumors treated with infusional 5-FU versus capecitabine based regimens.

Conclusions

Our data suggest that the type of KRAS mutation may be of clinical relevance under oxaliplatin combination chemotherapies without the addition of monoclonal antibodies in particular when overall response rates are important.

Trial registration number

2002-04-017

Keywords:
Codon 13 mutation; Colorectal cancer; KRAS; Oxaliplatin; Prognosis