title: The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  In a cohort of colorectal cancer patients, those with MMR-deficient tumours seem not to benefit from 5-FU-based chemotherapy.
authors: Unidad de Gastroenterología, Hospital General Universitario de Alicante, Alicante, Spain. jover_rod@gva.es
authors: Rodrigo
authors: R
authors: Jover
authors: Pedro
authors: P
authors: Zapater
authors: Antoni
authors: A
authors: Castells
authors: Xavier
authors: X
authors: Llor
authors: Montserrat
authors: M
authors: Andreu
authors: Joaquín
authors: J
authors: Cubiella
authors: Francesc
authors: F
authors: Balaguer
authors: Laura
authors: L
authors: Sempere
authors: Rosa M
authors: RM
authors: Xicola
authors: Luis
authors: L
authors: Bujanda
authors: Josep M
authors: JM
authors: Reñé
authors: Juan
authors: J
authors: Clofent
authors: Xavier
authors: X
authors: Bessa
authors: Juan D
authors: JD
authors: Morillas
authors: David
authors: D
authors: Nicolás-Pérez
authors: Elisenda
authors: E
authors: Pons
authors: Artemio
authors: A
authors: Payá
authors: Cristina
authors: C
authors: Alenda
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D017024:Chemotherapy, Adjuvant / Q000379:methods; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D053843:DNA Mismatch Repair / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D053842:Microsatellite Instability / Q000187:drug effects*; D009367:Neoplasm Staging; D011446:Prospective Studies
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D005472:Fluorouracil