EGFr inhibitor toxicity| Volume 90, ISSUE 2, P166-171, February 2009

Download started.


High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: Results of a survey in EORTC institutes

Published:November 03, 2008DOI:



      Examination of the rate of grade III or grade IV radiation dermatitis during treatment of head and neck cancer (HNC) with radiotherapy (RT) and concurrent cetuximab in EORTC centres.

      Materials and method

      A questionnaire was sent to all members of the EORTC Radiation Oncology Group and Head and Neck Group (111 institutions) to evaluate the widespread use of cetuximab and radiotherapy in HNC and to estimate the frequency of grades III and IV skin reactions in the radiation portals associated with this protocol. Co-morbidities, RT schedules and co-medications were also recorded.


      We received responses from 28 institutions in 11 countries. A total of 125 HNC patients from 15 institutions were treated with cetuximab and concurrent RT. Information about the skin reactions was available from 71 patients. Of these 36 had no grade III/IV adverse effects in the RT field, 15 had a grade III and 20 had grade IV radiation dermatitis. No detectable relation of grades III and IV radiation dermatitis with co-morbidities such as liver insufficiency or renal dysfunction was found.


      According to the results of the questionnaire, grade III/IV radiation dermatitis is observed in 49% of HNC patients treated with cetuximab and concurrent RT. A systematic clinical monitoring of cutaneous side effects during RT plus cetuximab is advised to ensure the safety of this protocol.


      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 Radiotherapy and Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Bonner J.A.
        • Harari P.M.
        • Giralt J.
        • et al.
        Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck.
        N Engl J Med. 2006; 354: 567-578
        • Budach W.
        • Bolke E.
        • Homey B.
        Severe cutaneous reaction during radiation therapy with concurrent cetuximab.
        N Engl J Med. 2007; 357: 514-515
        • Bonner J.A.
        • Ang K.
        More on severe cutaneous reaction with radiotherapy and cetuximab.
        N Engl J Med. 2007; 357 (author reply 1873): 1872-1873
        • Lord H.K.
        • Junor E.
        • Ironside J.
        Cetuximab is effective, but more toxic than reported in the Bonner Trial.
        Clin Oncol (R Coll Radiol). 2008; 20: 96
        • Calais G.
        • Alfonsi M.
        • Bardet E.
        • et al.
        Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma.
        J Natl Cancer Inst. 1999; 91: 2081-2086
        • Harari P.M.
        • Allen G.W.
        • Bonner J.A.
        Biology of interactions: antiepidermal growth factor receptor agents.
        J Clin Oncol. 2007; 25: 4057-4065
        • Bentzen S.M.
        • Saunders M.I.
        • Dische S.
        • Bond S.J.
        Radiotherapy-related early morbidity in head and neck cancer: quantitative clinical radiobiology as deduced from the CHART trial.
        Radiother Oncol. 2001; 60: 123-135
        • Dische S.
        • Saunders M.
        • Barrett A.
        • Harvey A.
        • Gibson D.
        • Parmar M.
        A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer.
        Radiother Oncol. 1997; 44: 123-136
        • Elliott E.A.
        • Wright J.R.
        • Swann R.S.
        • et al.
        Phase III Trial of an emulsion containing trolamine for the prevention of radiation dermatitis in patients with advanced squamous cell carcinoma of the head and neck: results of radiation therapy oncology group trial 99–13.
        J Clin Oncol. 2006; 24: 2092-2097
        • Merlano M.
        • Garrone O.
        Treatment of advanced head and neck cancer with cetuximab.
        Int J Biol Markers. 2007; 22: S71-76
        • Berger B.
        • Belka C.
        Severe skin reaction secondary to concomitant radiotherapy plus cetuximab.
        Radiat Oncol. 2008; 3: 5
        • Bernier J.
        • Bonner J.
        • Vermorken J.B.
        • et al.
        Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck.
        Ann Oncol. 2008; 19: 142-149
        • Amorino G.P.
        • Hamilton V.M.
        • Valerie K.
        • Dent P.
        • Lammering G.
        • Schmidt-Ullrich R.K.
        Epidermal growth factor receptor dependence of radiation-induced transcription factor activation in human breast carcinoma cells.
        Mol Biol Cell. 2002; 13: 2233-2244
        • Lacouture M.E.
        Mechanisms of cutaneous toxicities to EGFR inhibitors.
        Nat Rev Cancer. 2006; 6: 803-812
        • Schutze C.
        • Dorfler A.
        • Eicheler W.
        • et al.
        Combination of EGFR/HER2 tyrosine kinase inhibition by BIBW 2992 and BIBW 2669 with irradiation in FaDu human squamous cell carcinoma.
        Strahlenther Onkol. 2007; 183: 256-264
        • Mascia F.
        • Mariani V.
        • Girolomoni G.
        • Pastore S.
        Blockade of the EGF receptor induces a deranged chemokine expression in keratinocytes leading to enhanced skin inflammation.
        Am J Pathol. 2003; 163: 303-312
        • Alison M.R.
        • Sarraf C.E.
        The role of growth factors in gastrointestinal cell proliferation.
        Cell Biol Int. 1994; 18: 1-10
        • Gueven N.
        • Dittmann K.
        • Mayer C.
        • Rodemann H.P.
        Bowman–Birk protease inhibitor reduces the radiation-induced activation of the EGF receptor and induces tyrosine phosphatase activity.
        Int J Radiat Biol. 1998; 73: 157-162
        • Fehrmann A.
        • Dorr W.
        Effect of EGFR-inhibition on the radiation response of oral mucosa: experimental studies in mouse tongue epithelium.
        Int J Radiat Biol. 2005; 81: 437-443