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Media type:
E-Article
Title:
Impact of antibiotics (ATB) on the recurrence of resected colorectal cancer (CRC): Results of EVADER-1 a nation-wide pharmacoepidemiologic study
Description:
4106 Background: Recent studies suggest that ATB increase the overall risk of CRC incidence through disruption of gut microbiota. Impact of ATB on the risk of CRC recurrence after curative resection remains unknown. Methods: Using the French nation-wide Institut National du Cancer (INCa – Système National des Données de Santé) database of cancer patients, all newly diagnozed localized CRC patients resected between 01/2012 and 12/2014 were involved. The perioperative ATB intake (6 month before until 1 year after surgery) was classified according to the spectrum, doses and period of use. The primary endpoint was 3-year Disease-Free Survival (3-DFS), stratified on chemotherapy (chemo) administration (yes/no), and assessed using multivariate Cox models. Results: Out of 219,884 CRC patients, the present study included 36,640 patients: male 53%, age≥75 years 39%, left colon/rectal 59%, exposure to chemo 44%, at least one ATB intake 74%. At 3-years, 29% of patients had recurred and 18% had died. In multivariate analysis, in patients not receiving chemo, ATB intake as an out-patient was significantly associated with better 3-DFS [HR (one ATB only) = 0.88 (0.82-0.94)]. This effect remained in the same range whatever the number of ATB or cumulative exposure to ATB. In patients receiving chemo, ATB intake as an out-patient had a significant detrimental effect on 3-DFS [HR (one ATB only) = 1.15 (1.08-1.23)], increasing with the number of ATB [HR (≥5 ATB) = 1.54 (1.39-1.71)] and longer exposure [HR ( > 30 days) = 1.39 (1.31-1.48)]. Penicillin A, quinolones and ATB combinations were associated with worse 3-DFS. The timing of ATB intake related to chemo revealed that the strongest deleterious effect was observed when ATB were taken during chemo [HR = 1.64 (1.53-1.75)]. No difference in the mean number of chemo cycle was observed comparing patients receiving ATB or not. Conclusions: This nation-wide study is the first to suggest that ATB modulate 3-DFS in resected CRC with a differential impact according to chemo exposure. Importantly, ATB intake with chemo is detrimental in a dose- and time-dependent manner suggesting that dysbiosis of gut microbiota during adjuvant chemo might increase risk of recurrence.