Impact of antibiotic use during curative treatment of locally advanced head and neck cancers with chemotherapy and radiotherapy

Eur J Cancer. 2020 May:131:9-15. doi: 10.1016/j.ejca.2020.02.047. Epub 2020 Apr 2.

Abstract

Background: 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).

Material and methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Anti-bacterial agents; Chemotherapy; Head and neck neoplasms; Microbiota; Radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / adverse effects*
  • Chemoradiotherapy / adverse effects
  • Chemoradiotherapy / methods*
  • Disease-Free Survival
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / immunology
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / prevention & control
  • Progression-Free Survival
  • Prospective Studies
  • Retrospective Studies

Substances

  • Anti-Bacterial Agents