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Combined targeted therapies in non-small cell lung cancer: a winner strategy?

Cascone, Tinaa; Gridelli, Cesareb; Ciardiello, Fortunatoa

doi: 10.1097/CCO.0b013e328011beec
Lung and mediastinum
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Purpose of review Current treatment modalities provide limited improvement in the natural course of lung cancer, and prognosis remains poor. Lung cancer is a malignancy with great molecular heterogeneity. The complexity of the signalling process leading to cancer cell proliferation and to the neoplastic phenotype supports the necessity of interfering at different stages to avoid cancer cell resistance to therapy.

Recent findings Use of several agents with multiple growth factor receptor or intracellular targets has shown encouraging results in phase I and II clinical trials in non-small cell lung cancer. ZD6474 is a dual epidermal growth factor receptor and vascular endothelial growth factor receptor 2 small-molecule tyrosine kinase inhibitor; sorafenib is an oral kinase inhibitor of Raf-1 and is also active against vascular endothelial growth factor receptors 2 and 3, platelet-derived growth factor receptor β, and c-KIT. Sunitinib is a vascular endothelial growth factor receptor 1, 2, and 3, c-KIT, and platelet-derived growth factor receptor α and β tyrosine kinase inhibitor.

Summary Combined use of epidermal growth factor receptor–tyrosine kinase inhibitor erlotinib and the humanized vascular endothelial growth factor receptor monoclonal antibody bevacizumab in advanced, chemotherapy-refractory non-small cell lung cancer has shown promising results.

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

bDivisione di Oncologia Medica, Ospedale ‘S G Moscati’, Avellino, 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 5666732; e-mail: fortunato.ciardiello@unina2.it

© 2007 Lippincott Williams & Wilkins, Inc.