Defective Mismatch Repair Status as a Prognostic Biomarker of Disease-Free Survival in Stage III Colon Cancer Patients Treated with Adjuvant FOLFOX Chemotherapy
Open Access
- 30 November 2011
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 17 (23), 7470-7478
- https://doi.org/10.1158/1078-0432.ccr-11-1048
Abstract
Purpose: Adding oxaliplatin to adjuvant 5-fluorouracil (5-FU) chemotherapy improves 3-year disease-free survival (DFS) after resection of stage III colon cancer. Several studies suggest that patients with tumors exhibiting defective mismatch repair (MMR) do not benefit from adjuvant 5-FU chemotherapy, but there are few data on 5-FU–oxaliplatin (FOLFOX) adjuvant chemotherapy in this setting. The aim of this study was to evaluate the prognostic value of MMR status for DFS in patients with stage III colon cancer receiving adjuvant FOLFOX chemotherapy. Experimental Design: MMR status was determined by microsatellite instability testing or immunohistochemistry in 303 unselected patients with stage III colon cancer receiving adjuvant FOLFOX chemotherapy in 9 centers. Cox proportional hazards models were used to examine the association between MMR status and 3-year DFS. Results: The 3-year DFS rate was significantly higher in the 34 patients (11.2% of the study population) with defective MMR tumors (90.5%) than in patients with proficient MMR tumors (73.8%; log-rank test; HR = 2.16; 95% CI, 1.09–4.27; P = 0.027). In multivariate analysis, MMR status remained an independent significant prognostic factor for DFS (HR = 4.48; 95% CI, 1.34–14.99; P = 0.015). Conclusion: MMR status is an independent prognostic biomarker for DFS in patients with stage III colon cancer receiving adjuvant FOLFOX chemotherapy. Clin Cancer Res; 17(23); 7470–8. ©2011 AACR.Keywords
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This publication has 38 references indexed in Scilit:
- Two or three year disease-free survival (DFS) as a primary end-point in stage III adjuvant colon cancer trials with fluoropyrimidines with or without oxaliplatin or irinotecan: Data from 12,676 patients from MOSAIC, X-ACT, PETACC-3, C-06, C-07 and C89803European Journal Of Cancer, 2011
- DNA Mismatch Repair Status and Colon Cancer Recurrence and Survival in Clinical Trials of 5-Fluorouracil-Based Adjuvant TherapyJNCI Journal of the National Cancer Institute, 2011
- Defective Mismatch Repair As a Predictive Marker for Lack of Efficacy of Fluorouracil-Based Adjuvant Therapy in Colon CancerJournal of Clinical Oncology, 2010
- Microsatellite instability in colorectal cancer—the stable evidenceNature Reviews Clinical Oncology, 2010
- Clinical impact of microsatellite instability in colon cancer following adjuvant FOLFOX therapyCancer Chemotherapy and Pharmacology, 2009
- Impact of p53 expression and microsatellite instability on stage III colon cancer disease-free survival in patients treated by 5-fluorouracil and leucovorin with or without oxaliplatinAnnals Of Oncology, 2009
- DNA mismatch repair (MMR)‐dependent 5‐fluorouracil cytotoxicity and the potential for new therapeutic targetsBritish Journal of Pharmacology, 2009
- Platinum Resistance: The Role of DNA Repair PathwaysClinical Cancer Research, 2008
- A review of GERCOD trials of bimonthly leucovorin plus 5-fluorouracil 48-h continuous infusion in advanced colorectal cancer: evolution of a RegimenEuropean Journal Of Cancer, 1998