The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status

Rodrigo Jover, Pedro Zapater, Antoni Castells, Xavier Llor, Montserrat Andreu, Joaquín Cubiella, Francesc Balaguer, Laura Sempere, Rosa M. Xicola, Luis Bujanda, Josep M. Reñé, Juan Clofent, Xavier Bessa, Juan D. Morillas, David Nicolás-Pérez, Elisenda Pons, Artemio Payá, Cristina Alenda

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    148 Citations (Scopus)

    Abstract

    Aims: The aim of this study is to evaluate if mismatch repair (MMR) defective colorectal cancer has a different response to adjuvant 5-fluorouracil (5-FU) chemotherapy in a cohort of patients prospectively followed during 5 years. Methods: The cohort included 754 surgically treated patients with colorectal cancer. MMR status was diagnosed by MLH1 and MSH2 immunohistochemistry and microsatellite instability analysis. Median follow-up was 49.2 months (range 1-73). At inclusion, 505 patients were diagnosed as TNM II or III stage, analysis of the efficacy of adjuvant chemotherapy was made on this population. Adjuvant chemotherapy was applied to 248 patients (98.2% 5-FU based). Results: MMR deficiency was found in 76 patients (10.1%). No differences were found in overall survival (log-rank p = 0.3) or disease-free survival (log-rank p = 0.3) regarding MMR status. Adjuvant chemotherapy improves survival in patients in the II or III stage, but this improvement is only evident in patients with MMR-competent tumours (log-rank p = 0.00001). Survival of patients with MMR-defective tumours does not improve with adjuvant chemotherapy (log-rank p = 0.7). A multivariate analysis showed an independent effect of the interaction between MMR status and adjuvant chemotherapy (Hazard ratio 2.04; 95% confidence interval: 1.42-2.93). Conclusion: In a cohort of colorectal cancer patients, those with MMR-deficient tumours seem not to benefit from 5-FU-based chemotherapy. © 2008 Elsevier Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)365-373
    JournalEuropean Journal of Cancer
    Volume45
    Issue number3
    DOIs
    Publication statusPublished - 1 Feb 2009

    Keywords

    • 5-Fluorouracil
    • Colorectal cancer
    • Microsatellite instability
    • Prognosis
    • Treatment

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