TY - JOUR
T1 - New approaches to EGFR inhibition for locally advanced or metastatic squamous cell carcinoma of the head and neck (SCCHN)
AU - Agulnik, Mark
N1 - Funding Information:
Acknowledgments This work was supported by Boehringer Ingel-heim Pharmaceuticals, Inc. (BIPI). Writing and editorial assistance was provided by Staci Heise, PhD of MedErgy, which was contracted by BIPI for these services. The author meets criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE), is fully responsible for all content and editorial decisions, and was involved at all stages of manuscript development. The author received no compensation related to the development of the manuscript.
PY - 2012/12
Y1 - 2012/12
N2 - Despite recent advances in radiotherapy and chemotherapy, survival rates for squamous cell carcinoma of the head and neck (SCCHN) have remained poor. The focus of SCCHN therapy has more recently shifted to the molecular level, particularly the epidermal growth factor receptor (EGFR/ErbB) pathway. Several agents that target the EGFR pathway, including monoclonal antibodies and tyrosine kinase inhibitors, are under investigation for SCCHN. Searches of PubMed and results of key oncology congresses were performed to identify relevant articles and abstracts. The EGFR-targeted monoclonal antibody cetuximab is approved for the treatment of locally advanced SCCHN in combination with radiotherapy, for first-line treatment of recurrent or metastatic SCCHN in combination with platinum-based chemotherapy and 5-fluorouracil, and for recurrent or metastatic SCCHN following progression with platinum-based chemotherapy. Other investigational EGFR-targeted monoclonal antibodies (e.g., panitumumab, nimotuzumab, zalutumumab) are in clinical development for SCCHN. Inhibition of the tyrosine kinase domain of EGFR has also been explored as a therapeutic approach in SCCHN using small-molecule reversible inhibitors, such as gefitinib and erlotinib. However, a key challenge in SCCHN is the development of resistance, and strategies are being pursued to delay or overcome resistance to EGFR-targeted agents. These strategies include development of agents that inhibit multiple ErbB receptors simultaneously (e.g., lapatinib) or that bind multiple ErbB family receptors irreversibly (e.g., afatinib, PF-00299804) and investigation of combinations of agents that target multiple pathways implicated in the pathogenesis of SCCHN. Ongoing large clinical trials are evaluating these emerging agents and combinations for the treatment of SCCHN.
AB - Despite recent advances in radiotherapy and chemotherapy, survival rates for squamous cell carcinoma of the head and neck (SCCHN) have remained poor. The focus of SCCHN therapy has more recently shifted to the molecular level, particularly the epidermal growth factor receptor (EGFR/ErbB) pathway. Several agents that target the EGFR pathway, including monoclonal antibodies and tyrosine kinase inhibitors, are under investigation for SCCHN. Searches of PubMed and results of key oncology congresses were performed to identify relevant articles and abstracts. The EGFR-targeted monoclonal antibody cetuximab is approved for the treatment of locally advanced SCCHN in combination with radiotherapy, for first-line treatment of recurrent or metastatic SCCHN in combination with platinum-based chemotherapy and 5-fluorouracil, and for recurrent or metastatic SCCHN following progression with platinum-based chemotherapy. Other investigational EGFR-targeted monoclonal antibodies (e.g., panitumumab, nimotuzumab, zalutumumab) are in clinical development for SCCHN. Inhibition of the tyrosine kinase domain of EGFR has also been explored as a therapeutic approach in SCCHN using small-molecule reversible inhibitors, such as gefitinib and erlotinib. However, a key challenge in SCCHN is the development of resistance, and strategies are being pursued to delay or overcome resistance to EGFR-targeted agents. These strategies include development of agents that inhibit multiple ErbB receptors simultaneously (e.g., lapatinib) or that bind multiple ErbB family receptors irreversibly (e.g., afatinib, PF-00299804) and investigation of combinations of agents that target multiple pathways implicated in the pathogenesis of SCCHN. Ongoing large clinical trials are evaluating these emerging agents and combinations for the treatment of SCCHN.
KW - Epidermal growth factor receptor (EGFR)
KW - Monoclonal antibody
KW - Resistance
KW - Squamous cell carcinoma of the head and neck
KW - Tyrosine kinase inhibitor
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U2 - 10.1007/s12032-012-0159-2
DO - 10.1007/s12032-012-0159-2
M3 - Review article
C2 - 22252310
AN - SCOPUS:84867997123
VL - 29
SP - 2481
EP - 2491
JO - Medical Oncology
JF - Medical Oncology
SN - 1357-0560
IS - 4
ER -