Perichemotherapy antibiotics improve PDAC survival in patients treated with gemcitabine
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Key takeaways:
- Antibiotic receipt in the month before or after gemcitabine treatment improved survival in metastatic pancreatic ductal adenocarcinoma.
- Results suggest perichemotherapy antibiotics may improve PDAC outcomes.
Receipt of perichemotherapy antibiotics correlated with improved survival in patients with metastatic pancreatic ductal adenocarcinoma treated with gemcitabine, but not fluorouracil, according to results in JAMA Network Open.
“The rapid development of multifactorial resistance to chemotherapy is an important contributor to the dismal prognosis in pancreatic ductal adenocarcinoma (PDAC),” Daniel J. Fulop, BA, of the Henry D. Janowitz Division of Gastroenterology at the Icahn School of Medicine at Mount Sinai, and colleagues wrote. “Some preclinical studies have similarly discovered bacteria-mediated mechanisms of fluorouracil resistance while others have identified bacteria-mediated mechanisms of fluorouracil activation.
“Small retrospective studies of patients with PDAC have found associations between antibiotic exposure and improved treatment outcomes, particularly among patients receiving gemcitabine. Collectively, these studies suggest that antibiotics may affect outcomes in patients with PDAC.”
Using the population-based Surveillance, Epidemiology and End Results-Medicare linked database, Fulop and colleagues analyzed survival outcomes among 3,850 patients with primary metastatic PDAC (mean age, 74.2 years; 54.6% women) who were treated with first-line gemcitabine (81.8%) or fluorouracil (18.2%) chemotherapy. Of those, 56.6% received antibiotics and were matched with patients who did not receive antibiotics. Researchers analyzed 1,672 propensity-matched pairs.
According to results, median survival among all patients who received peritreatment antibiotics was 7.3 months (95% CI, 6.9-7.7) compared with 6.8 months (95% CI, 6.5-7.2) among patients who did not receive antibiotics. When grouped by first-line chemotherapy, median survival of patients receiving gemcitabine was 7.1 months (95% CI, 6.8-7.5) in the antibiotic group vs. 6.5 months (95% CI, 6.2-6.8) in the nonantibiotic group, and 8.6 months (95% CI, 7.3-9.7) vs. 9.2 months (95% CI, 8.3-10.1), respectively, for patients treated with fluorouracil.
Researchers also reported that receipt of peritreatment antibiotics was associated with improved overall survival (HR = 0.93; 95% CI, 0.86-0.99). When grouped by chemotherapy, antibiotic receipt with gemcitabine correlated with an 11% improvement in overall survival (HR = 0.89; 95% CI, 0.83-0.96) and a 16% improvement in cancer-specific survival (HR = 0.84; 95% CI, 0.77-0.92). However, there was no association between peritreatment antibiotics and overall (HR = 1.08; 95% CI, 0.9-1.29) or cancer-specific (HR = 1.12; 95% CI, 0.9-1.36) survival in the fluorouracil group.
In a subgroup analysis of patients treated with gemcitabine and antibiotics, nonpenicillin beta-lactams associated with an 11% survival benefit (HR = 0.89; 95% CI, 0.81-0.97).
“Perichemotherapy antibiotics were associated with improved survival among patients treated with first-line gemcitabine, but not fluorouracil, suggesting a potential role for perichemotherapy antibiotic treatment in patients with metastatic PDAC receiving gemcitabine,” Fulop and colleagues concluded. “We recommend that prospective studies investigate the effect of perichemotherapy administration of antibiotics with high pancreatic penetration and gram-negative coverage on survival in diverse populations of patients with metastatic PDAC treated with gemcitabine.”
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