ReviewCetuximab in the management of locoregionally advanced head and neck cancer: Expanding the treatment options?
Introduction
Head and neck carcinomas encompass a number of different tumour types affecting various anatomical sites. Cancers of the oral cavity, larynx and pharynx together account for around 5% of global cancer incidence.1 Squamous cell carcinomas of the head and neck (SCCHN) are associated with a relatively high risk of developing second primary malignancies. The survival of patients with SCCHN is related to disease stage, performance status and comorbidities.2, 3, 4
In this review we discuss the role of the epidermal growth factor receptor (EGFR)-targeting IgG1 monoclonal antibody (MAb) cetuximab in current and future treatment strategies for locoregionally advanced SCCHN.
Section snippets
Radiotherapy and concurrent chemoradiotherapy
Locoregionally advanced SCCHN is generally treated with curative intent and aggressive treatment approaches are commonly used. Where disease is resectable, surgery followed by conventionally fractionated radiotherapy is a standard treatment option.5 However, patients at a high risk of relapse may benefit from the post-operative administration of radiotherapy and concurrent chemotherapy (chemoradiotherapy) and this is now considered a standard of care in this setting.5 Concurrent
Induction chemotherapy
The use of a sequential approach, whereby chemotherapy (induction chemotherapy) is administered prior to radiotherapy or concurrent chemoradiotherapy, is being evaluated as an alternative option for patients with locoregionally advanced, unresectable disease. This approach has already been validated in the setting of larynx preservation in patients with resectable disease, when induction chemotherapy is followed by radiation therapy in good responders.38 Data from a subset analysis of patients
Safety and tolerability of cetuximab
The most common adverse events observed with cetuximab are skin reactions, which may develop in more than 80% (any grade) of patients. Acne-like rash is the most frequently observed skin reaction. There is an indication from some studies in SCCHN that the severity of rash is associated with efficacy.18, 57, 58 In the Bonner trial, in patients receiving cetuximab, the risk of death was significantly lower in patients developing grade 2 or higher rash than in those with grade 1 rash or no rash
Conclusions
The role of cetuximab in the treatment of locoregionally advanced head and neck cancer continues to develop. The data from a phase III trial support the role of cetuximab plus radiotherapy as an effective treatment option for patients with locoregionally advanced SCCHN. Adding cetuximab to radiotherapy led to significant improvements in locoregional control and survival and these survival improvements were maintained long-term, with a nine percentage point advantage for cetuximab plus
Conflict of interest statement
J. Bourhis reports receiving advisory board honoraria from GlaxoSmithKline, Merck KGaA and sanofi-aventis. J.-L. Lefebvre reports receiving lecture and advisory board honoraria from Merck KGaA and sanofi-aventis. J.B. Vermorken reports receiving lecture and advisory board honoraria from Amgen, Boehringer Ingelheim, Lilly, Merck KGaA and sanofi-aventis.
Acknowledgement
Editorial support for the production of this manuscript was funded by Merck KGaA.
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2012, Cancer/RadiotherapieCitation Excerpt :The EGF receptor (EGFR) is a transmembrane glycoprotein possessing tyrosine kinase activity. The EGFR is abnormally activated in HNSCC, and overexpression of this receptor is associated with more aggressive disease [3]. Cetuximab is a chimeric human-murin immunoglobulin G1 monoclonal antibody highly selective for the EGFR [5].
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