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Clinical Trial
. 2012 Aug 9;12:349.
doi: 10.1186/1471-2407-12-349.

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

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Free PMC article
Clinical Trial

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 et al. BMC Cancer. .
Free PMC article

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.

Figures

Figure 1
Figure 1
Progression-free survival according toKRASstatus.
Figure 2
Figure 2
Overall survival according to KRAS status.

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References

    1. Bamford S, Dawson E, Forbes S. et al. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br J Cancer. 2004;91(2):355–358. - PMC - PubMed
    1. Etienne-Grimaldi MC, Formento JL, Francoual M. et al. KRAS mutations and treatment outcome in colorectal cancer patients receiving exclusive fluoropyrimidine therapy. Clin Cancer Res. 2008;14(15):4830–4835. doi: 10.1158/1078-0432.CCR-07-4906. - DOI - PubMed
    1. Andreyev HJ, Norman AR, Cunningham D. et al. RAS mutations in patients with colorectal cancer: the multicenter "RASCAL" study. J Natl Cancer Inst. 1998;90(9):675–684. doi: 10.1093/jnci/90.9.675. - DOI - PubMed
    1. Maughan TS, Adams RA, Smith CG. et al. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet. 2011;377(9783):2103–2114. doi: 10.1016/S0140-6736(11)60613-2. - DOI - PMC - PubMed
    1. Bokemeyer C, Bondarenko I, Makhson A. et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009;27(5):663–671. doi: 10.1200/JCO.2008.20.8397. - DOI - PubMed

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