The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status.
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.
Jover
Rodrigo
R
Unidad de Gastroenterología, Hospital General Universitario de Alicante, Alicante, Spain. jover_rod@gva.es
Zapater
Pedro
P
Castells
Antoni
A
Llor
Xavier
X
Andreu
Montserrat
M
Cubiella
Joaquín
J
Balaguer
Francesc
F
Sempere
Laura
L
Xicola
Rosa M
RM
Bujanda
Luis
L
Reñé
Josep M
JM
Clofent
Juan
J
Bessa
Xavier
X
Morillas
Juan D
JD
Nicolás-Pérez
David
D
Pons
Elisenda
E
Payá
Artemio
A
Alenda
Cristina
C
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
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D005472:Fluorouracil