Cetuximab: its unique place in head and neck cancer treatment

Abstract

Head and neck cancer is the sixth most common cancer worldwide. At present, globally about 650,000 new cases of squamous cell carcinoma of the head and neck (SCCHN) are diagnosed each year. The epidermal growth factor receptor (EGFR) is almost invariably expressed in SCCHN. Overexpression of the EGFR is a strong and independent unfavorable prognostic factor in SCCHN. Cetuximab is a chimeric monoclonal antibody, which binds with high affinity to the extracellular domain of the human EGFR, blocking ligand binding, resulting in inhibition of the receptor function. It also targets cytotoxic immune effector cells towards EGFR-expressing tumor cells (antibody dependent cell-mediated cytotoxicity). The addition of cetuximab to radiotherapy (RT) improves locoregional control and survival when compared to RT alone. The addition of cetuximab to platinum-based chemoradiation (CRT) is feasible but does not lead to an improved outcome. Cetuximab plus RT has never been compared prospectively to CRT, which therefore remains the standard treatment for patients with locoregionally advanced SCCHN for whom surgery is not considered the optimal treatment, provided they can tolerate CRT. The addition of cetuximab to platinum-based chemotherapy prolongs survival in patients with recurrent or metastatic SCCHN. The combination of a platinum-based regimen and cetuximab should be considered as the standard first line regimen for patients who can tolerate this treatment.

Treatment effect of buparlisib, cetuximab and irradiation in wild-type or PI3KCA-mutated head and neck cancer cell lines

“…4a). In both cell lines, as expected [22], we observed a slight up-regulation of pEGFR/EGFR by RT and a down-regulation of its expression after cetuximab treatment as previously shown [1,23]. The small down-regulation of pEGFR/EGFR in sequence 2 when compared to cetuximab resulted completely abolished by RT in CAL33 (p<0.01 vs sequence 2, Fig.…”

“…Previously, our group [27] used an orthotopic head and neck cancer model to confirm the efficacy of the combination of cetuximab and RT. Several other studies suggested a synergistic effect of cetuximab in combination with radiotherapy and, indeed, this combined treatment has become a therapeutic option for HNSCC patients in whom platinumbased chemotherapy has failed [1,5]. In this study, we treated cells with their ID 50 prior to all treatments with the aim of evaluating the impact of this strategy on cell proliferation and on the expression of molecular factors related to irradiation (i.e., EGFR) or implicated in DNA damage repair (XRCC1 and ERCC1).…”

“…Head and neck cancer is the sixth most common cancer in the world and each year about 650,000 cases of squamous cell carcinoma of head and neck (HNSCC) are diagnosed [1]. Many preclinical studies on HNSCC have demonstrated synergistic effects when combining targeted therapy with irradiation (RT) [2,3].…”

Benefits of Multifaceted Chemopreventives in the Suppression of the Oral Squamous Cell Carcinoma (OSCC) Tumorigenic Phenotype

“…While conceptually appealing, the collective clinical data from small molecule receptor antagonists and tyrosine kinase inhibitors have been disappointing [8-10]. The EGFR chimeric monoclonal antibody, cetuximab, was ineffective both as monotherapy and also when combined with platinum-based chemoradiation in patients with advanced OSCC [8]. Small molecular tyrosine kinase receptor inhibitors e.g.…”

Does CYP2E1 RsaI/PstI polymorphism confer head and neck carcinoma susceptibility?

“…Head and neck carcinoma (HNC) is a group of biologically similar cancers originating from the head and neck regions and has ranked the sixth most frequent malignant cancer in the world [1] . HNC often severely affect the life qualities of patients because it impairs the body appearance, and influences speaking, swallowing, and breathing.…”