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

BMC Cancer

Anke Reinacher-Schick²  Karsten Schulmann⁴  Dominik P Modest³  Nina Bruns⁴  Ulrich Graeven¹  Malgorzata Jaworska⁸  Richard Greil⁷  Rainer Porschen⁶  Dirk Arnold⁵  Wolff Schmiegel²  Andrea Tannapfel⁸ 

[1] Department of Hematology, Oncology and Gastroenterology, Kliniken Maria Hilf, Mönchengladbach, Germany

[2] Center for Clinical Studies in Oncology within PURE, Ruhr-University Bochum, Bochum, Germany

[3] Department of Internal Medicine III, Klinikum der Universität, München, Germany

[4] Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany

[5] Hubertus Wald Cancer Center, University Hospital Hamburg, Hamburg, Germany

[6] Klinikum Bremen-Ost, Bremen, Germany

[7] 3rd Medical Department with Hematology and Medical Oncology, Oncologic Centre Paracelsus Medical University, Salzburg, Austria

[8] Institute of Pathology, Ruhr-University Bochum, Bochum, Germany

关键词: Prognosis;    Oxaliplatin;    KRAS;    Colorectal cancer;    Codon 13 mutation;   

Others  :  1080259
DOI  :  10.1186/1471-2407-12-349

 received in 2011-09-18, accepted in 2012-06-26,  发布年份 2012

【 摘 要 】

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

【 授权许可】

   
2012 Reinacher-Schick et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1 .

Figure 2 .

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