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BMC Cancer. 2012; 12: 349.
Published online Aug 9, 2012. doi:  10.1186/1471-2407-12-349
PMCID: PMC3442969
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-Schick,corresponding author1,9,10 Karsten Schulmann,1 Dominik P Modest,2 Nina Bruns,1 Ulrich Graeven,3 Malgorzata Jaworska,4 Richard Greil,5 Rainer Porschen,6 Dirk Arnold,7 Wolff Schmiegel,1,8,9 and Andrea Tannapfel4
1Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
2Department of Internal Medicine III, Klinikum der Universität, München, Germany
3Department of Hematology, Oncology and Gastroenterology, Kliniken Maria Hilf, Mönchengladbach, Germany
4Institute of Pathology, Ruhr-University Bochum, Bochum, Germany
53rd Medical Department with Hematology and Medical Oncology, Oncologic Centre Paracelsus Medical University, Salzburg, Austria
6Klinikum Bremen-Ost, Bremen, Germany
7Hubertus Wald Cancer Center, University Hospital Hamburg, Hamburg, Germany
8Department of Gastroenterology & Hepatology, Berufsgenossenschaftliches Klinikum Bergmannsheil, Ruhr-University Bochum, Bochum, Germany
9Center for Clinical Studies in Oncology within PURE, Ruhr-University Bochum, Bochum, Germany
10Medical Department, Knappschaftskrankenhaus, Ruhr-University Bochum, In der Schornau 23-25, Bochum, 44892, Germany
corresponding authorCorresponding author.
Anke Reinacher-Schick: Anke.Reinacher/at/rub.de; Karsten Schulmann: karsten.schulmann/at/rub.de; Dominik P Modest: dominik.modest/at/med.uni-muenchen.de; Nina Bruns: nina.bruns/at/web.de; Ulrich Graeven: ullrich.graeven/at/mariahilf.de; Malgorzata Jaworska: malgorzata.jaworska/at/rub.de; Richard Greil: greil/at/salk.at; Rainer Porschen: rainer.porschen/at/klinikum-bremen-ost.de; Dirk Arnold: d.arnold/at/uke.de; Wolff Schmiegel: wolff.schmiegel/at/rub.de; Andrea Tannapfel: andrea.tannapfel/at/rub.de
Received September 18, 2011; Accepted June 26, 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
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