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Annals of Oncology 2006 17(Supplement 2):ii46-ii48; doi:10.1093/annonc/mdj921
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© 2006 European Society for Medical Oncology

symposium article

Small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer

T. Cascone, M. P. Morelli and F. Ciardiello*

Cattedra di Oncologia Medica, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale ‘F. Magrassi e A. Lanzara’, Seconda Università degli Studi di Napoli, Napoli, Italy

* Correspondence to: Fortunato Ciardiello, Cattedra di Oncologia Medica, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale "F. Magrassi e A. Lanzara", Seconda Università degli Studi di Napoli, Via S. Pansini, 5 – 80131 Naples, Italy. Tel: +39-081-5666745; Fax: 39-081-5666728; E-mail: fortunato.ciardiello{at}unina2.it

Despite recent developments in the diagnosis and conventional treatment of non small cell lung cancer (NSCLC), the prognosis remains unsatisfactory, with 5-year survival rates of approximately 15% for all stages. To date, chemotherapy represents the standard treatment for advanced-non small lung cancer, but efficacy of currently available cytotoxic drugs is modest. Median survival does not exceed 8–10 months. New treatment strategies are needed and considerable hope has been placed in therapies that specifically target the molecular mechanisms of tumour growth. One molecular target of particular relevance to lung cancer pathogenesis is the epidermal growth factor receptor (EGFR), a cell membrane receptor tyrosine kinase. Several inhibitors of EGFR fuctinonal activation have been developed. Amon these, erlotinib (Tarceva) and gefitinib (Iressa) are two orally bioavailable, small molecule EGFR inhibitors of the tyrosine kinase enzymatic activity which prevent EGFR autophosphorylation and activation. In monotherapy, gefitinib and erlotinib have determinated a 10–20% response rate and a 30–50% symptom improvement in previously treated, chemotherapy refractory, advanced NSCLC patients. Furthermore, a randomized, placebo controlled, multicenter phase III study has shown a two months improvement in median survival with erlotinib in the second or third line treatment of metastatic NSCLC patients. We will summarize the clinical evidence on the anticancer activity of small molecule EGFR inhibitors.

Key words: non-small cell lung cancer, growth factor receptors, EGFR, small molecule tyrosine kinase inhibitors


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