Current Cancer Therapy Reviews

Kurt S. Zaenker
Institute of Immunology and Experimental Oncology University Witten/Herdecke
Stockumerstraße 10, 58448 Witten
Germany

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Methodological Issues of Clinical Research with EGFR Inhibitors

Author(s): Alessandro Morabito, Maria Carmela Piccirillo, Katia Monaco, Fabiano Falasconi, Nicola Normanno, Francesco Perrone.

Abstract:

The epidermal growth factor receptor (EGFR) signaling plays a key role in tumorigenesis and it has been considered an attractive target for novel antitumoral agents. Small-molecule tyrosine kinase inhibitors such as gefitinib and erlotinib have been approved for the treatment of advanced non-small-cell lung cancer (NSCLC) patients. However, the positive results obtained in early clinical trials with gefitinib were not confirmed in large phase 3 trials, testing the efficacy of this drug in combination with chemotherapy or as single agent. An advantage in overall survival has been observed with erlotinib as single agent in NSCLC, but not in combination with chemotherapy. Conversely, an additive effect has been observed with the combination of the monoclonal antibody cetuximab and irinotecan in heavily pretreated patients with irinotecan-refractory colorectal cancer. The combination of cetuximab and radiotherapy or chemotherapy has also shown efficacy in patients with squamous cancer cell of head and neck. However, the major limit in the development of these agents is the lack of validated predictive markers of response that might allow appropriate selection of patients. In this review, we will discuss the major issues in clinical development of such agents, focusing on the challenges in designing and conducting clinical trials with EGFR inhibitors.

Keywords: EGFR, gefitinib, erlotinib, lapatinib, cetuximab, panitumumab

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Article Details

VOLUME: 3
ISSUE: 4
Page: [292 - 302]
Pages: 11
DOI: 10.2174/157339407782497031
Price: $58