Head and Neck Unit, Royal Marsden Hospital, London, United Kingdom.
Head and Neck Unit, Royal Marsden Hospital, London, United Kingdom; Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom.
Eur J Cancer. 2020 May;131:9-15. doi: 10.1016/j.ejca.2020.02.047. Epub 2020 Apr 2.
Pre-clinical evidence suggests reduced efficacy of anticancer treatment in patients exposed to broad-spectrum antibiotics. It is hypothesised that this phenomenon may be explained by the effects of antibiotics on the composition of the microbiota. To assess this in a clinical setting, we analysed the impact of antibiotics in patients with locally advanced head and neck cancer (LAHNC) treated with curative intent with chemotherapy and radiotherapy (RT).
Retrospective data for LAHNC patients treated with curative intent (245 induction chemotherapy followed by chemoradiation [CRT], 17 surgery followed by post-operative CRT, six CRT, three RT alone and one RT with concurrent cetuximab) were analysed. We evaluated the impact of antibiotics prescribed during primary anti-cancer treatment on progression-free survival (PFS), overall survival (OS) and disease-specific survival (DSS) rates by multivariate Kaplan-Meier and Cox proportional hazards regression analysis.
Among 272 patients, those receiving antibiotics between within 1 week before and 2 weeks after treatment (N = 124) progressed significantly earlier and had lower OS and DSS rates. In the multivariate analysis, administration of antibiotics was independently associated with reduced PFS (hazards ratio [HR] 1.98, P = 0.001), OS (HR 1.85, P = 0.001) and DSS (HR 1.95, P = 0.004). This effect was maintained with independence of reason for prescription, type and time of antibiotic prescription. The negative impact was greater for patients who received two or more courses of antibiotics. Antibiotic treatment was correlated with increased risk of locoregional relapse.
Our data suggest a negative impact of antibiotic therapy on treatment outcomes following CRT with curative intent in patients with LAHNC. This potential harm should be considered when prescribing broad-spectrum and prophylactic antibiotics for such patients.
临床前证据表明,暴露于广谱抗生素的癌症患者的抗癌治疗效果降低。据推测,这种现象可能是抗生素对微生物组组成的影响所致。为了在临床环境中评估这一点,我们分析了接受根治性化疗和放疗(RT)治疗的局部晚期头颈部癌症(LAHNC)患者中抗生素的影响。
回顾性分析了 272 例接受根治性治疗(245 例诱导化疗后行放化疗[CRT]、17 例手术后继行术后 CRT、6 例 CRT、3 例 RT 单独治疗和 1 例 RT 联合西妥昔单抗治疗)的 LAHNC 患者的数据。我们通过多变量 Kaplan-Meier 和 Cox 比例风险回归分析评估了在原发性抗癌治疗期间使用抗生素对无进展生存期(PFS)、总生存期(OS)和疾病特异性生存期(DSS)的影响。
在 272 例患者中,有 124 例(占 45.5%)在治疗前 1 周内和治疗后 2 周内使用抗生素,这些患者的病情进展明显更早,且 OS 和 DSS 率更低。在多变量分析中,使用抗生素与 PFS 降低显著相关(风险比[HR]1.98,P=0.001)、OS(HR 1.85,P=0.001)和 DSS(HR 1.95,P=0.004)。无论处方原因、抗生素类型和使用时间如何,抗生素的使用都与降低 PFS、OS 和 DSS 独立相关。使用两剂或更多抗生素的患者的负面影响更大。抗生素治疗与局部区域复发风险增加相关。
我们的数据表明,在接受 LAHNC 根治性 CRT 的患者中,抗生素治疗对 CRT 后的治疗结果有负面影响。在为接受此类治疗的患者开具广谱和预防性抗生素时,应考虑到这种潜在危害。