Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York.
JAMA Netw Open. 2023 Mar 1;6(3):e234254. doi: 10.1001/jamanetworkopen.2023.4254.
The prognosis for patients with metastatic pancreatic ductal adenocarcinoma (PDAC) is dismal, due in part to chemoresistance. Bacteria-mediated mechanisms of chemoresistance suggest a potential role for antibiotics in modulating response to chemotherapy.
To evaluate whether use of peritreatment antibiotics is associated with survival among patients with metastatic PDAC treated with first-line gemcitabine or fluorouracil chemotherapy.
DESIGN, SETTING, AND PARTICIPANTS: Using the population-based Surveillance, Epidemiology, and End Results-Medicare linked database, this retrospective cohort study analyzed data for patients diagnosed with PDAC between January 1, 2007, and December 31, 2017. Data analysis was conducted between September 1, 2021, and January 15, 2023. The population-based sample included 3850 patients with primary metastatic PDAC treated with first-line gemcitabine or fluorouracil chemotherapy. Patients who received antibiotics were matched based on propensity scores to patients who did not receive antibiotics.
Receipt of 5 or more days of oral antibiotics or 1 injectable antibiotic in the month before or after beginning first-line chemotherapy.
Overall survival and cancer-specific survival. The end of follow-up was December 31, 2019, for overall survival and December 31, 2018, for cancer-specific survival.
Of the 3850 patients treated with first-line gemcitabine (3150 [81.8%]) or fluorouracil (700 [18.2%]), 2178 (56.6%) received antibiotics. The mean (SD) age at diagnosis was 74.2 (5.8) years and patients were predominantly women (2102 [54.6%]), White (3396 [88.2%]), and from metropolitan areas (3393 [88.1%]) in the northeastern or western US (2952 [76.7%]). In total, 1672 propensity-matched pairs were analyzed. Antibiotic receipt was associated with an 11% improvement in overall survival (hazard ratio [HR], 0.89; 95% CI, 0.83-0.96; P = .003) and a 16% improvement in cancer-specific survival (HR, 0.84; 95% CI, 0.77-0.92; P < .001) among patients treated with gemcitabine. In contrast, there was no association between antibiotic receipt and 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) among patients treated with fluorouracil. In a subgroup of gemcitabine-treated patients who received antibiotics, nonpenicillin β-lactams were associated with an 11% survival benefit (HR, 0.89; 95% CI, 0.81-0.97; P = .01).
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 PDAC outcomes.
转移性胰腺导管腺癌 (PDAC) 患者的预后不佳，部分原因是化疗耐药。细菌介导的化疗耐药机制表明抗生素在调节化疗反应方面可能发挥作用。
评估在接受吉西他滨或氟尿嘧啶一线化疗治疗的转移性 PDAC 患者中，围化疗期使用抗生素是否与生存相关。
设计、设置和参与者：本回顾性队列研究使用基于人群的监测、流行病学和最终结果-医疗保险链接数据库，分析了 2007 年 1 月 1 日至 2017 年 12 月 31 日期间诊断为 PDAC 的患者的数据。数据分析于 2021 年 9 月 1 日至 2023 年 1 月 15 日进行。基于人群的样本包括 3850 例接受吉西他滨或氟尿嘧啶一线化疗治疗的原发性转移性 PDAC 患者。接受抗生素治疗的患者根据倾向评分与未接受抗生素治疗的患者进行匹配。
在开始一线化疗前或后 1 个月内接受 5 天或以上的口服抗生素或 1 次注射用抗生素。
总生存和癌症特异性生存。随访结束日期为 2019 年 12 月 31 日（总生存）和 2018 年 12 月 31 日（癌症特异性生存）。
在接受吉西他滨（3150 例 [81.8%]）或氟尿嘧啶（700 例 [18.2%]）一线治疗的 3850 例患者中，2178 例（56.6%）接受了抗生素治疗。诊断时的平均（SD）年龄为 74.2（5.8）岁，患者主要为女性（2102 例 [54.6%]）、白人（3396 例 [88.2%]）和来自美国东北部或西部的大都市地区（3393 例 [88.1%]）。共分析了 1672 对匹配的倾向评分。抗生素治疗与总生存改善 11%相关（风险比 [HR]，0.89；95% CI，0.83-0.96；P = .003），与癌症特异性生存改善 16%相关（HR，0.84；95% CI，0.77-0.92；P < .001）在接受吉西他滨治疗的患者中。相比之下，在接受氟尿嘧啶治疗的患者中，抗生素治疗与总生存（HR，1.08；95% CI，0.90-1.29；P = .41）或癌症特异性生存（HR，1.12；95% CI，0.90-1.36；P = .29）无关联。在接受吉西他滨治疗且接受抗生素治疗的患者亚组中，非青霉素类β-内酰胺类抗生素与 11%的生存获益相关（HR，0.89；95% CI，0.81-0.97；P = .01）。
在本队列研究中，在接受吉西他滨治疗的患者中，围化疗期使用抗生素与生存改善相关，但在接受氟尿嘧啶治疗的患者中则不然，这表明抗生素可能调节细菌介导的吉西他滨耐药，并有可能改善 PDAC 结局。
