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
Current Cancer Therapy Reviews
Title: Methodological Issues of Clinical Research with EGFR Inhibitors
Volume: 3 Issue: 4
Author(s): Alessandro Morabito, Maria Carmela Piccirillo, Katia Monaco, Fabiano Falasconi, Nicola Normanno and Francesco Perrone
Affiliation:
Keywords: EGFR, gefitinib, erlotinib, lapatinib, cetuximab, panitumumab
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.
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Morabito Alessandro, Piccirillo Carmela Maria, Monaco Katia, Falasconi Fabiano, Normanno Nicola and Perrone Francesco, Methodological Issues of Clinical Research with EGFR Inhibitors, Current Cancer Therapy Reviews 2007; 3 (4) . https://dx.doi.org/10.2174/157339407782497031
DOI https://dx.doi.org/10.2174/157339407782497031 |
Print ISSN 1573-3947 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6301 |
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argeted Protein Degradation is gaining momentum in cancer therapy, it facilitate targeting undruggable proteins, it overcome cancer resistance and avoid undesirable side effects. Thus small molecules degraders have emerged as novel therapeutic strategy. Targeted protein degradation (TPD), the process of eliminating a protein of interest hold a great promise for ...read more
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