In a retrospective cohort study reported in JAMA Network Open, Fulop et al found that perichemotherapy use of antibiotics was associated with improved survival in patients with metastatic pancreatic ductal adenocarcinoma receiving first-line gemcitabine-based chemotherapy, but not in those receiving first-line fluorouracil-based chemotherapy.
The study used data from the Surveillance, Epidemiology, and End Results–Medicare linked database on 3,850 patients diagnosed with pancreatic ductal adenocarcinoma between January 2007 and December 2017 who received first-line gemcitabine-based (n = 3,150) or fluorouracil-based chemotherapy (n = 700). Antibiotic use was defined as receipt of at least 5 days of oral antibiotics or one injectable antibiotic in the month before or after beginning first-line chemotherapy. For the analysis, patients who received antibiotics were propensity score–matched to those who did not.
Key Findings
Among the 3,850 patients, 2,178 (57%) received antibiotics. In total, 1,672 propensity score–matched patient pairs were included in the analysis. The end of follow-up was the end of December 2019 for overall survival, and the end of December 2018 for cancer-specific survival.
Among all patients in the propensity score–matched cohort, median overall survival was 7.3 months among those receiving antibiotics vs 6.8 months among those who did not receive antibiotics (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.86–0.99, P = .03). Patients who received antibiotics also had significantly better cancer-specific survival (HR = 0.89, 95% CI = 0.82–0.96, P = .004).
Among patients receiving first-line gemcitabine-based chemotherapy, those who received antibiotics had significantly improved overall survival (HR = 0.89, 95% CI = 0.83–0.96, P = .003) and cancer-specific survival (HR = 0.84, 95% CI = 0.77–0.92, P < .001) vs those who did not receive antibiotics. Among patients receiving first-line fluorouracil-based chemotherapy, there were no significant differences in overall survival (HR = 1.08, 95% CI = 0.90–1.29, P = .41) or cancer-specific survival (HR = 1.12, 95% CI = 0.90–1.36, P = .29) for patients who did vs did not receive antibiotics.
In an analysis by antibiotic class among gemcitabine-treated patients, those who received nonpenicillin β-lactams (n = 880) had significantly improved overall survival vs those not receiving antibiotics (HR = 0.89, 95% CI = 0.81–0.97, P = .01). No other significant associations were observed for antibiotic class.
The investigators concluded, “In this cohort study, receipt of perichemotherapy antibiotics was associated with improved survival among patients treated with gemcitabine, but not fluorouracil, suggesting that antibiotics may modulate bacteria-mediated gemcitabine resistance and have the potential to improve pancreatic ductal adenocarcinoma outcomes.”
Aimee L. Lucas, MD, MS, of Icahn School of Medicine at Mount Sinai, New York, is the corresponding author for the JAMA Network Open article.
Disclosure: The study was supported by the California Department of Public Health, Centers for Disease Control and Prevention’s National Program of Cancer Registries, National Cancer Institute, and others. For full disclosures of the study authors, visit jamanetwork.com.
