Defective mismatch repair status as a prognostic biomarker of disease-free survival in stage III colon cancer patients treated with adjuvant FOLFOX chemotherapy.

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.

• Authors: Aziz Zaanan, Jean-François Fléjou, Jean-François Emile, Guetz Gaëtan Des, Peggy Cuilliere-Dartigues, David Malka, Cédric Lecaille, Pierre Validire, Christophe Louvet, Philippe Rougier, Aimery de Gramont, Franck Bonnetain, Françoise Praz, Julien Taïeb
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 17 Issue 23 Pg. 7470-8 (Dec 01 2011) ISSN: 1557-3265 [Electronic] United States
• PMID: 21998335 (Publication Type: Journal Article)
• Copyright: ©2011 AACR.

Chemical References

• Biomarkers, Tumor
• Organoplatinum Compounds
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor
• Chemotherapy, Adjuvant
• Colonic Neoplasms (drug therapy, genetics)
• DNA Mismatch Repair
• Disease-Free Survival
• Female
• Fluorouracil (therapeutic use)
• Humans
• Leucovorin (therapeutic use)
• Male
• Middle Aged
• Organoplatinum Compounds (therapeutic use)
• Prognosis
• Proportional Hazards Models