This page contains a Flash digital edition of a book.
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


Abstract


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.


Keywords


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: r.knecht@uke.uni-hamburg.de


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


16


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


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92