Therapies directed against epidermal growth factor receptor in aerodigestive carcinomas.
BACKGROUND
Malignancies arising from the aerodigestive epithelium, including lung, head and neck, and esophageal carcinomas, are the leading causes of cancer-related mortality worldwide. Given the biological importance of epidermal growth factor receptor (EGFR) in cancer development and progression, EGFR inhibitors have emerged as promising novel therapies.


OBJECTIVE
To summarize the current status of EGFR inhibitors in aerodigestive carcinomas (ADCs), highlight ongoing research designed to optimize their therapeutic effectiveness, and consider the future role of these agents.


METHODS
Systematic MEDLINE search of English-language literature (1966-April 2007) performed using the terms EGFR, EGFR inhibitors, monoclonal antibodies, tyrosine kinase inhibitors, lung cancer, head and neck cancer, esophageal cancer, and EGFR predictive factors. Quality assessment of selected studies included clinical pertinence, with an emphasis on controlled study design, publication in peer-reviewed journals, adequate number of enrolled patients, objectivity of measurements, and techniques used to minimize bias.


RESULTS
The role of EGFR in ADC pathogenesis has been extensively studied, and multiple EGFR inhibition strategies are under evaluation. Erlotinib, an EGFR tyrosine kinase inhibitor used as a single agent, and cetuximab, an anti-EGFR monoclonal antibody used in combination with radiation, have conferred survival benefit in 1 trial of patients with advanced non-small cell lung cancer (median survival, 6.7 vs 4.7 months; hazard ratio, 0.70; 95% confidence interval, 0.58-0.87; P < .001) and in 1 trial of patients with locally advanced head and neck squamous cell carcinoma (median survival, 49 vs 29.3 months; hazard ratio, 0.74; 95% confidence interval, 0.57-0.97; P = .03), respectively. However, other trials have not shown these degrees of improvement. EGFR inhibitors toxicities include rash, diarrhea, and hypomagnesemia. Somatic mutations and other molecular tumoral characteristics offer opportunities for treatment individualization and optimal patient selection for anti-EGFR therapy.


CONCLUSIONS
EGFR is a promising therapeutic target in ADC. Further translational research is needed to optimize ways of inhibiting EGFR using single-agent or combination regimens and to identify patients who benefit the most from these therapies.
Karamouzis
Michalis V
MV
Division of Hematology-Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania 15232, USA.
Grandis
Jennifer R
JR
Argiris
Athanassios
A
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000068818:Cetuximab; D004815:Epidermal Growth Factor / Q000502:physiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D004815:Epidermal Growth Factor; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000068818:Cetuximab