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Efficacy of Adjuvant Chemotherapy in Colon Cancer With Microsatellite Instability: A Large Multicenter AGEO Study
David Tougeron1, Guillaume Mouillet1, Isabelle Trouilloud1
1Affiliations of authors: Department of Gastroenterology (DT, GS, CS), Department of Medical Oncology (AF), and Department of Molecular Oncology (LKT), Poitiers University Hospital , Poitiers , France ; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC) - EA 4331, Poitiers University , Poitiers (DT, CS); Methodology and Quality of Life in Oncology Unit, Besançon University Hospital , Besançon , France (GM); Department of Gastroenterology, Ambroise Paré Hospital , Boulogne-Billancourt , France (IT); Department of Gastroenterology (TL) and Department of Biochemistry (JCP), Tours University Hospital , Tours , France , UMR GICC CNRS 7292, Tours François Rabelais University, Tours (TL); Paris Descartes University, Cochin Hospital , Paris , France (RC); Department of Gastroenterology (TA) and Department of Medical Oncology (CDG), Avicenne Hospital , Bobigny , France ; Department of Gastroenterology, Bordeaux Nord Aquitaine Clinic , Bordeaux , France (CL); Department of Gastroenterology, Jean Mermoz Lyon Hospital , Lyon , France (PA); Department of Gastroenterology, Nantes University Hospital , Nantes , France (EC, TMB); Department of Gastroenterology, Rouen University Hospital , Rouen , France (DS, PM); Department of Medical Oncology, Saint-Antoine Hospital , Paris , France (TB); Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, APHP , Paris , France (JT, AZ); Paris Descartes University, Sorbonne Paris Cité , Paris , France (RC, JT, AZ).
Background:
Deficient mismatch repair (dMMR) colon cancer (CC) is reportedly resistant to 5-fluorouracil (5FU) adjuvant chemotherapy while preliminary data suggest chemosensitivity to oxaliplatin. We assessed the efficacy of fluoropyrimidine with and without oxaliplatin in a large cohort of dMMR CC patients.
Methods:
This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for stage II or III dMMR CC between 2000 and 2011. Prognostic factors were analyzed using Cox models, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided.
Results:
A total of 433 dMMR CC patients were included (56.8% stage II, 43.2% stage III). Mean follow-up was 47.0 months. The patients received surgery alone (n = 263) or surgery plus adjuvant chemotherapy consisting of fluoropyrimidine with (n = 119) or without (n = 51) oxaliplatin. Adjuvant chemotherapy was administered to 16.7% of stage II and 69.0% of stage III CC patients. As compared with surgery alone, adjuvant oxaliplatin-based chemotherapy improved disease-free survival (DFS) in multivariable analysis (HR = 0.35, 95% CI = 0.19 to 0.65, P < .001), contrary to adjuvant fluoropyrimidine alone (HR = 0.73, 95% CI = 0.36 to 1.49, P = .38). In the subgroup analysis, the DFS benefit of oxaliplatin-based chemotherapy was statistically significant in multivariable analysis only in stage III (HR = 0.41, 95% CI = 0.19 to 0.87, P = .02).
Conclusion:
This study supports the use of adjuvant chemotherapy with fluoropyrimidine plus oxaliplatin in stage III dMMR CC.
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