Original Research| Volume 131, P9-15, May 2020

Download started.


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

Published:April 02, 2020DOI:


      • Microbiota changes may have a role on anti-cancer treatment efficacy.
      • Antibiotics during the oncologic treatment associated with worse survival in LAHNC.
      • Antibiotic treatment correlated with increased risk of locoregional relapse.



      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.


      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.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Hu B.
        • Elinav E.
        • Huber S.
        • Strowig T.
        • Hao L.
        • Hafemann A.
        • et al.
        Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer.
        Proc Natl Acad Sci U S A. 2013 Jun 11; 110: 9862-9867
        • Wilson I.D.
        • Nicholson J.K.
        Gut microbiome interactions with drug metabolism, efficacy, and toxicity.
        Transl Res J Lab Clin Med. 2017; 179: 204-222
        • Roy S.
        • Trinchieri G.
        Microbiota: a key orchestrator of cancer therapy.
        Nat Rev Canc. 2017; 17: 271-285
        • Vétizou M.
        • Pitt J.M.
        • Daillère R.
        • Lepage P.
        • Waldschmitt N.
        • Flament C.
        • et al.
        Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota.
        Science. 2015 Nov 27; 350: 1079-1084
        • Li H.
        • Jia W.
        Cometabolism of microbes and host: implications for drug metabolism and drug-induced toxicity.
        Clin Pharmacol Ther. 2013 Nov; 94: 574-581
        • Daillère R.
        • Vétizou M.
        • Waldschmitt N.
        • Yamazaki T.
        • Isnard C.
        • Poirnier-Colame V.
        • et al.
        Enterococcus hirae and barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects.
        Immunity. 2016 18; 45: 931-943
        • Crawford P.A.
        • Gordon J.I.
        Microbial regulation of intestinal radiosensitivity.
        Proc Natl Acad Sci U S A. 2005 Sep 13; 102: 13254-13259
        • Iida N.
        • Dzutsev A.
        • Stewart C.A.
        • Smith L.
        • Bouladoux N.
        • Weingarten R.A.
        • et al.
        Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment.
        Science. 2013 Nov 22; 342: 967-970
        • Viaud S.
        • Saccheri F.
        • Mignot G.
        • Yamazaki T.
        • Daillère R.
        • Hannani D.
        • et al.
        The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide.
        Science. 2013 Nov 22; 342: 971-976
        • Gui Q.-F.
        • Lu H.-F.
        • Zhang C.-X.
        • Xu Z.R.
        • Yang Y.H.
        Well-balanced commensal microbiota contributes to anti-cancer response in a lung cancer mouse model.
        Genet Mol Res. 2015 May 25; 14: 5642-5651
        • Pflug N.
        • Kluth S.
        • Vehreschild J.J.
        • Bahlo J.
        • Tacke D.
        • Biehl L.
        • et al.
        Efficacy of antineoplastic treatment is associated with the use of antibiotics that modulate intestinal microbiota.
        OncoImmunology. 2016 Jun; 5e1150399
        • Bhide S.A.
        • Ahmed M.
        • Barbachano Y.
        • Newbold K.
        • Harrington K.J.
        • Nutting C.M.
        Sequential induction chemotherapy followed by radical chemo-radiation in the treatment of locoregionally advanced head-and-neck cancer.
        Br J Canc. 2008 Jul 8; 99: 57-62
        • Bhide S.A.
        • Ahmed M.
        • Rengarajan V.
        • Powell C.
        • Miah A.
        • Newbold K.
        • et al.
        Anemia during sequential induction chemotherapy and chemoradiation for head and neck cancer: the impact of blood transfusion on treatment outcome.
        Int J Radiat Oncol Biol Phys. 2009 Feb 1; 73: 391-398
        • Miah A.B.
        • Schick U.
        • Bhide S.A.
        • Guerrero-Urbano M.T.
        • Clark C.H.
        • Bidmead A.M.
        • et al.
        A phase II trial of induction chemotherapy and chemo-IMRT for head and neck squamous cell cancers at risk of bilateral nodal spread: the application of a bilateral superficial lobe parotid-sparing IMRT technique and treatment outcomes.
        Br J Canc. 2015 Jan 6; 112: 32-38
        • Zitvogel L.
        • Tesniere A.
        • Kroemer G.
        Cancer despite immunosurveillance: immunoselection and immunosubversion.
        Nat Rev Immunol. 2006 Oct; 6: 715-727
        • van Vliet M.J.
        • Harmsen J.
        • de Bont E.S.J.M.
        • Tissing W.J.E.
        The role of intestinal microbiota in the development and severity of chemotherapy-induced mucositis.
        PLoS Pathog. 2010; 6e1000879
        • Sharma A.
        • Rath G.K.
        • Chaudhary S.P.
        • Thakar A.
        • Mohanti B.K.
        • Bahadur S.
        Lactobacillus brevis CD2 lozenges reduce radiation- and chemotherapy-induced mucositis in patients with head and neck cancer: a randomized double-blind placebo-controlled study.
        Eur J Canc. 2012; 48: 875-881
        • van Vliet M.J.
        • Tissing W.J.
        • Dun C.A.
        • Meessen N.E.
        • Kamps W.A.
        • de Bont E.S.
        • et al.
        Chemotherapy treatment in pediatric patients with acute myeloid leukemia receiving antimicrobial prophylaxis leads to a relative increase of colonization with potentially pathogenic bacteria in the gut.
        Clin Infect Dis. 2009; 49: 262-270
        • Sonalika W.G.
        • Amsavardani Tayaar S.
        • Bhat K.G.
        • Patil B.R.
        • Muddapur M.V.
        Oral microbial carriage in oral squamous cell carcinoma patients at the time of diagnosis and during radiotherapy - a comparative study.
        Oral Oncol. 2012 Sep; 48: 881-886
        • Loimu V.
        • Collan J.
        • Vaalavirta L.
        • Bäck L.
        • Kapanen M.
        • Mäkitie A.
        • et al.
        Patterns of relapse following definitive treatment of head and neck squamous cell cancer by intensity modulated radiotherapy and weekly cisplatin.
        Radiother Oncol. 2011; 98: 34-37
        • Wijers O.B.
        • Levendag P.C.
        • Harms E.R.
        • Gan-Teng A.M.
        • Schmitz P.I.
        • Hendriks W.D.
        • et al.
        Mucositis reduction by selective elimination of oral flora in irradiated cancers of the head and neck: a placebo-controlled double-blind randomized study.
        Int J Radiat Oncol Biol Phys. 2001; 50: 343-352
        • Mallick S.
        • Benson R.
        • Rath G.K.
        Radiation induced oral mucositis: a review of current literature on prevention and management.
        Eur Arch Oto-Rhino-Laryngol. 2016; 273: 2285-2293
        • Ham J.C.
        • Driessen C.M.
        • Hendriks M.P.
        • Fiets E.
        • Kreike B.
        • Hoeben A.
        • et al.
        Prophylactic antibiotics reduce hospitalisations and cost in locally advanced head and neck cancer patients treated with chemoradiotherapy: a randomised phase 2 study.
        Eur J Canc Oxf Engl 1990. 2019; 113: 32-40
        • Nerina D.
        • Carlo M.M.
        In response to Ham et al: antibiotics effect on outcome in head and neck cancer.
        Eur J Canc. 2019; 117: 119-120
        • Pinato D.J.
        • Howlett S.
        • Ottaviani D.
        • Urus H.
        • Patel A.
        • Mineo T.
        • et al.
        Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer.
        JAMA Oncol. 2019; 12 (Published online September)
        • Chen D.
        • Wu J.
        • Jin D.
        • Wang B.
        • Cao H.
        Fecal microbiota transplantation in cancer management: current status and perspectives.
        Int J Canc. 2019; 145: 2021-2031