Current knowledge and future directions of the selective epidermal growth factor receptor inhibitors erlotinib (Tarceva) and gefitinib (Iressa).
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.
Siegel-Lakhai
Wandena S
WS
The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam. apwla@slz.nl
Beijnen
Jos H
JH
Schellens
Jan H M
JH
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D005260:Female; D005544:Forecasting; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D011799:Quinazolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib