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Current Knowledge and Future Directions of the Selective Epidermal Growth Factor Receptor Inhibitors Erlotinib (Tarceva^®) and Gefitinib (Iressa^®)

^a The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; ^b Slotervaant Hospital, Amsterdam, The Netherlands; ^c Faculty of Pharmaceutical Sciences, Division of Drug Toxicology, Utrecht University, Utrecht, The Netherlands

Correspondence: Wandena S. Siegel-Lakhai, The Netherlands Cancer Institute, Department of Medical Oncology/Department of Pharmacy and Pharmacology, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. Telephone: 31-0-20-512-4481; e-mail: apwla{at}slz.nl

Gefitinib (Iressa^®; AstraZeneca Pharmaceuticals, Wilmington, DE, http://www.astrazeneca-us.com) and erlotinib (Tarceva^®; OSI Pharmaceuticals, Inc., Melville, NY, http://www.osip.com) are so-called small molecules that selectively inhibit epidermal growth factor receptor (EGFR) tyrosine kinase activity. Both drugs received registration approval by the U.S. Food and Drug Administration (FDA) for the second- and third-line treatment of non-small cell lung cancer (NSCLC), but the failure of gefitinib to show a survival advantage over placebo has resulted in a discussion about the registration of gefitinib. Recently published results have revealed that mutations in the tyrosine kinase domain of EGFR are strongly associated with increased gefitinib and erlotinib sensitivity in patients with advanced NSCLC. Here, we present the current knowledge and the future directions of the EGFR tyrosine kinase inhibitors gefitinib and erlotinib.

Key Words. EGFR tyrosine kinase inhibitors • Gefitinib • Erlotinib • Targeted therapy • EGFR tyrosine kinase domain mutations

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