Clinical experience with gefitinib: an update.
Gefitinib is an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that blocks signal transduction pathways involved in cell proliferation. This drug demonstrated impressive and durable responses in patients with heavily pretreated non-small cell lung cancer (NSCLC). In two large phase II trials, responses were observed in 9-19% of unselected patients, along with symptom improvement and benefit in quality of life. Biological mechanisms underlying TKI sensitivity have recently been discovered. There is evidence that specific EGFR gene mutations and/or amplification confer a particularly sensitive phenotype, especially in individuals with tumors demonstrating activation of the anti-apoptotic protein Akt. However, in all so far conducted clinical trials, no patient selection has been made, providing a logical explanation for the negative results observed in large phase III studies. In the present review, we will summarize the results observed in clinical trials with gefitinib. We will present results obtained in NSCLC and in other solid tumor, focusing on biological and clinical markers predicting drug sensitivity.
Cappuzzo
Federico
F
Bellaria Hospital, Department of Medical Oncology, Bologna, Italy. federico.cappuzzo@ausl.bo.it
Finocchiaro
Giovanna
G
Metro
Giulio
G
Bartolini
Stefania
S
Magrini
Elisabetta
E
Cancellieri
Alessandra
A
Trisolini
Rocco
R
Castaldini
Luciano
L
Tallini
Giovanni
G
Crino
Lucio
L
D002986:Clinical Trials as Topic; D000077156:Gefitinib; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077156:Gefitinib