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Head and Neck Cancer

Cetuximab in the Treatment of Locally Advanced Head and Neck Cancer Rainald Knecht

Chairman, Ear, Nose and Throat Department and Clinic, University Medical Center Hamburg-Eppendorf


Locally advanced squamous cell cancer of the head and neck (LA SCCHN) includes various cancers of the oral cavity, pharynx and larynx that have spread from the primary site but have not metastasised. Due to poor public awareness of SCCHN and its symptoms, about 50–70% of cases are diagnosed only when the disease has become locally advanced; prognosis by this time is poorer than during earlier stages. Combinations of chemotherapy with radiotherapy have produced greater efficacy in treating LA SCCHN over radiotherapy alone in various clinical trials, but this approach increases the incidence of toxicities. An alternative therapeutic approach is to use the monoclonal antibody cetuximab (Erbitux®). Cetuximab targets epidermal growth factor receptor (EGFR), which is overexpressed in LA SCCHN, and this overexpression of EGFR is associated with poor prognosis. A number of recent phase II and III clinical trials have demonstrated that cetuximab is an effective and safe treatment for LA SCCHN. One large phase III clinical trial demonstrated that the addition of cetuximab to radiotherapy in patients with LA SCCHN provides substantial efficacy and quality of life benefits, including improvements in overall survival, disease-free survival, response rate and European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 parameters, without markedly affecting safety and tolerability. Other, smaller phase II studies in patient populations having either resectable or non-resectable tumours have demonstrated the benefits of adding cetuximab to other chemotherapy/radiotherapy regimens for LA SCCHN. Cetuximab is currently the only targeted biological therapy approved for use in combination with radiation therapy for LA SCCHN. In conclusion, cetuximab represents a significant advance in the treatment of LA SCCHN. Furthermore, based on the data from the large phase III trial, the most recent European Society for Medical Oncology (ESMO) guidelines recommend the use of cetuximab in combination with radiotherapy in LA SCCHN.


Cetuximab, epidermal growth factor receptor, Erbitux®, squamous cell carcinoma of the head and neck, locally advanced head and neck cancer

Disclosure: The author received medical writing and editorial assistance from Touch Briefings, London, UK. Rainald Knecht is on the advisory boards of sanofi-aventis and Merck Serono. Received: 24 August 2009 Accepted: 22 September 2010 Citation: European Oncology & Haematology, 2011;7(1):16–23 Correspondence: Rainald Knecht, Martinistraße 52, 20246 Hamburg, Germany. E:

Support: The publication of this article was funded by Merck Serono. The views and opinions expressed are those of the author and not necessarily those of Merck Serono.

Squamous cell cancers of the head and neck (SCCHN) include a range of diseases consisting of cancers of the lip, gums, tongue, salivary glands, other oral cavity sites, nasal cavity, paranasal sinuses, pharynx and larynx. Locally advanced (LA) SCCHN tumours are at a stage at which they have locally spread from the primary site but have not yet advanced to a point of metastasis to other body sites. The poor recognition and low public awareness of SCCHN symptoms in its early stages results in about 501

–70%2 of

patients presenting with LA disease (stage III, IVb). Of these patients, approximately half subsequently develop locoregional or distant recurrences3

with LA SCCHN is approximately 50%.1

and the five-year survival rate in all patients Unlike most cancers, in

which the primary cause of death is metastasis, the main reason for treatment failure and death in LA SCCHN is local recurrence. This article will focus on the treatment of LA SCCHN with cetuximab. A separate article reviewing targeted therapies in combination with chemotherapy for the treatment of recurrent and/or metastatic SCCHN by Pol Specenier and Jan Vermorken was published previously in European Oncology.4


Current Therapeutic Approaches for LA SCCHN Patients presenting with LA SCCHN are usually treated with a combination of surgery, radiotherapy and chemotherapy. However, a minority of patients are suitable for potentially curative salvage surgery. Patients with LA SCCHN, especially where the tumour has not spread substantially from the primary site, are usually given treatment including either radiation therapy or surgery. Chemotherapy and irradiation can be given concomitantly (chemoradiotherapy) or sequentially, the chemotherapy often being given as the initial therapy (induction chemotherapy). Methotrexate was traditionally the first choice for chemotherapy, but it has now largely been superseded by platinum-based agents such as carboplatin or cisplatin, often administered with 5-fluorouracil (5-FU).

The suitability of induction chemotherapy for LA SCCHN therapy is controversial in terms of whether it is more effective than sequential therapy5

continuing to evolve.6–8

and treatment strategies for induction chemotherapy are The standard induction chemotherapy regimen

consists of a platinum agent and 5-FU (often referred to as PF). More © TOUCH BRIEFINGS 2011

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