Association of antibiotic exposure with the mortality in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy: A hospital-based retrospective cohort study

Abstract

BackgroundPreclinical studies showed that antibiotic exposure played a role in clinical outcomes in patients with chemotherapy via modulation of microbiota. However, it remains unknown whether antibiotic exposure during the bevacizumab therapy affects the clinical outcomes in metastatic colorectal cancer(mCRC) patients. This study aimed to examine the association between the antibiotic medication and the clinical outcomes in mCRC patients with bevacizumab therapy.MethodsThis retrospective cohort analysis included 147 mCRC patients treated with bevacizumab. The hazard ratio of death was estimated using three Cox proportional hazards models with (1) never vs ever; (2) never vs 1–6 days and 7–40 days;(3) increase per day, and further tested using propensity score matching (PSM) and landmark analysis. A smooth curve technique was used to explore the shape of dose-response relationship.ResultsCompared with the non-antibiotic group, antibiotic exposure was inversely associated with the mortality in the antibiotic group after adjustment for demographic and other potential confounders (a history of medication: HR, 0.650(95%CI: 0.360 to 1.173); an increase per day: HR, 0.967(CI: 0.924 to 1.011); 1–6 days: HR, 0.859(CI: 0.441 to 1.674); 7–40 days: HR, 0.474(CI: 0.225 to 0.999); P for trend = 0.040). A test for the interaction between sex was statistically significant (p = 0.016). A similar result was found as measured by landmark and PSM analysis. Significant negative dose-response relationship was shown by smooth curve analysis in the male patients but not female after adjustment for confounders(p = 0.028). No association was found between the antibiotic medication and adverse events of bevacizumab.ConclusionAntibiotic exposure could be inversely associated with the mortality in mCRC patients treated with bevacizumab.

Bacterial cancer therapy in autochthonous colorectal cancer affects tumor growth and metabolic landscape

“…However, this very artificial system also demonstrates the importance of the microbiota in protecting the host as even STm ∆aroA could invade and infect systemically. Treating cancer patients with antibiotics prior to surgery is common practice, however in light of the importance of diverse microbiota for controlling cancer (28,29) it has become apparent it is not optimal for patient outcome, with anti-biotic preconditioning leading to worse outcomes (57)(58)(59). Our data do not exclude that there could be certain microbiota compositions that will enable more effective therapy, as with checkpoint blockade therapy (28,29,59), and thus analyzing microbiomes may be something to consider when starting human clinical trials with orally delivery BCT.…”

Comprehensive review of targeted therapy for colorectal cancer

“…477,478 Antibiotic use, which might dramatically reduce gut microbial diversity and density, was found to be related to poor survival in patients with metastatic CRC who had received bevacizumab therapy. 479 However, the influence of the microbiota on anti-VEGF agents is still a matter of debate because of the controversial reported results 480,481 in renal cell cancer-based studies stating an unclear role of antibiotics in VEGF-blockade therapy.…”

The Association of Gut Microbiota and Complications in Gastrointestinal-Cancer Therapies

“…A retrospective study showed that patient outcomes can be improved during immunotherapy with bevacizumab using antibiotics. Patients with metastatic colorectal carcinoma had lower mortality rates if treated with antibiotics for a more extended period [36]. Another study showed that Fusobacterium nucleatum was abundant in colorectal-carcinoma patients with recurrence after chemotherapy.…”