The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status
Section snippets
Background
In the last 15–20 years, adjuvant chemotherapy for colorectal cancer has demonstrated efficacy and it is commonly used.1 To date, the appropriateness of chemotherapy is decided according to the TNM stage. Since the early 1990s, 5-fluorouracil (5-FU) is the mainstay drug in adjuvant chemotherapy in colorectal cancer, but in the last years, new drugs, such as oxaliplatin and irinotecan, as well as target drugs acting in key points in the tumourigenic cascade, such as cetuximab or bevacizumab have
Patients and methods
Between November 2000 and October 2001, all newly diagnosed colorectal cancer patients in 25 hospitals were included in the EPICOLON study, a clinical epidemiology survey aimed at establishing the incidence of hereditary non-polyposis colorectal cancer in Spain.12, 13 Ten of these 25 centres agreed to participate in a nested prospective follow-up investigation. Exclusion criteria were familial adenomatous polyposis, personal history of inflammatory bowel disease and patient’s refusal to
Relation between mismatch repair status and colorectal cancer prognosis
The cohort included 754 patients. Median follow-up was 49.2 months (range 1–73). Sixteen patients (2.1%) were not operated on due to advanced disease. The rest were surgically treated. Seventy-six (10.1%) tumours were MMR-deficient and 678 (89.9%) were MMR-proficient. Seven patients had germline mutations in MLH1 (n = 5) or MSH2 (n = 2) gene. Characteristics of patients at diagnosis, according to mismatch repair status can be seen in Table 1. We found no significant differences between patients
Discussion
The main finding of this study is that the efficacy of adjuvant 5-FU chemotherapy, in terms of mortality or tumour recurrence, is significantly different depending on the mismatch repair status of colorectal cancer. Patients in stage II or III disease, which tumours show a competent mismatch repair status, obtained an important benefit from 5-FU chemotherapy, improving their overall survival and disease-free survival to almost a 20%. However, patients having MMR-deficient tumours seem not to
Conflict of interest statement
All the authors disclose any financial or personal relationships with other people or organisations that could inappropriately influence (bias) our work in this manuscript.
Acknowledgements
This work was supported by grants from the Fondo de Investigación Sanitaria (FIS 01/0104) and from the Instituto de Salud Carlos III (RC03/02 and RC03/10).
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