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Targeted Therapy for the Treatment of Advanced Non-small Cell Lung Cancer*: A Review of the Epidermal Growth Factor Receptor Antagonists

Gerard A. Silvestri, MD, FCCP; M. Patricia Rivera, MD, FCCP
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*From the Divisions of Pulmonary and Critical Care Medicine (Dr. Silverstri), Medical University of South Carolina, Charleston, SC; and the University of North Carolina at Chapel Hill (Dr. Rivera), Chapel Hill, NC.

Correspondence to: Gerard A. Silvestri, MD, FCCP, Medical University of South Carolina, Room 812 CSB, 171 Ashley Ave, Charleston, SC 29425; e-mail: silvestri@musc.edu.



Chest. 2005;128(6):3975-3984. doi:10.1378/chest.128.6.3975
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Lung cancer is the most common cause of cancer death. The vast majority of patients present with non-small cell lung cancer (NSCLC) in advanced inoperable stages. The current first-line treatment for patients with advanced NSCLC includes chemotherapy and palliative radiotherapy, but most patients relapse and eventually succumb to the disease. Advances in our knowledge of cancer cell biology have led to the development of specific molecular-targeted therapeutic agents. Mutations in the epidermal growth factor receptor (EGFR) have been identified in NSCLC cells, and overexpression of the EGFR and its ligands is a common feature of many cancers; therefore, EGFR has become an attractive target for various antitumor strategies. Aberrant signaling from the EGFR is known to be important in the development and progression of NSCLC. Two oral EGFR inhibitors, gefitinib and erlotinib, are small-molecule agents that selectively inhibit the intracellular tyrosine kinase activity of the EGFR. Both have demonstrated antitumor activity in patients with advanced NSCLC who have failed all prior treatment regimens. In addition, the anti-EGFR monoclonal antibody cetuximab has shown promising activity in both first-line and second-line settings in patients with advanced NSCLC. Furthermore, patients with severe comorbidities who would not be eligible for systemic chemotherapy are candidates for these targeted therapies. Finally, these agents have also been shown to be effective for relieving symptoms, maintaining stable disease, and improving quality of life without the adverse events that may be associated with cytotoxic cancer therapies. This report will review the mechanism of action, indications, contraindications, patient selection, and efficacy and side effects of this new class of compounds. It is important for pulmonologists to be aware of this class of compounds, as they can provide benefit to patients with NSCLC who may not have been previously considered for antitumor therapy.

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