Clinical experience with gefitinib: An update

Federico Cappuzzo, Giovanna Finocchiaro, Giulio Metro, Stefania Bartolini, Elisabetta Magrini, Alessandra Cancellieri, Rocco Trisolini, Luciano Castaldini, Giovanni Tallini, Lucio Crino

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)31-45
Number of pages15
JournalCritical Reviews in Oncology/Hematology
Volume58
Issue number1
DOIs
Publication statusPublished - Apr 2006

Fingerprint

Non-Small Cell Lung Carcinoma
Biomarkers
Clinical Trials
erbB-1 Genes
Apoptosis Regulatory Proteins
Epidermal Growth Factor Receptor
Pharmaceutical Preparations
Protein-Tyrosine Kinases
Patient Selection
Signal Transduction
Neoplasms
Quality of Life
Cell Proliferation
Phenotype
Mutation
gefitinib

Keywords

  • EGFR
  • Gefitinib
  • Non-small cell lung cancer
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Cappuzzo, F., Finocchiaro, G., Metro, G., Bartolini, S., Magrini, E., Cancellieri, A., ... Crino, L. (2006). Clinical experience with gefitinib: An update. Critical Reviews in Oncology/Hematology, 58(1), 31-45. https://doi.org/10.1016/j.critrevonc.2005.08.008

Clinical experience with gefitinib : An update. / Cappuzzo, Federico; Finocchiaro, Giovanna; Metro, Giulio; Bartolini, Stefania; Magrini, Elisabetta; Cancellieri, Alessandra; Trisolini, Rocco; Castaldini, Luciano; Tallini, Giovanni; Crino, Lucio.

In: Critical Reviews in Oncology/Hematology, Vol. 58, No. 1, 04.2006, p. 31-45.

Research output: Contribution to journalArticle

Cappuzzo, F, Finocchiaro, G, Metro, G, Bartolini, S, Magrini, E, Cancellieri, A, Trisolini, R, Castaldini, L, Tallini, G & Crino, L 2006, 'Clinical experience with gefitinib: An update', Critical Reviews in Oncology/Hematology, vol. 58, no. 1, pp. 31-45. https://doi.org/10.1016/j.critrevonc.2005.08.008
Cappuzzo, Federico ; Finocchiaro, Giovanna ; Metro, Giulio ; Bartolini, Stefania ; Magrini, Elisabetta ; Cancellieri, Alessandra ; Trisolini, Rocco ; Castaldini, Luciano ; Tallini, Giovanni ; Crino, Lucio. / Clinical experience with gefitinib : An update. In: Critical Reviews in Oncology/Hematology. 2006 ; Vol. 58, No. 1. pp. 31-45.
@article{db103c7d225c422d9f09f7735d464bfd,
title = "Clinical experience with gefitinib: An update",
abstract = "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.",
keywords = "EGFR, Gefitinib, Non-small cell lung cancer, Tyrosine kinase inhibitor",
author = "Federico Cappuzzo and Giovanna Finocchiaro and Giulio Metro and Stefania Bartolini and Elisabetta Magrini and Alessandra Cancellieri and Rocco Trisolini and Luciano Castaldini and Giovanni Tallini and Lucio Crino",
year = "2006",
month = "4",
doi = "10.1016/j.critrevonc.2005.08.008",
language = "English",
volume = "58",
pages = "31--45",
journal = "Critical Reviews in Oncology/Hematology",
issn = "1040-8428",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Clinical experience with gefitinib

T2 - An update

AU - Cappuzzo, Federico

AU - Finocchiaro, Giovanna

AU - Metro, Giulio

AU - Bartolini, Stefania

AU - Magrini, Elisabetta

AU - Cancellieri, Alessandra

AU - Trisolini, Rocco

AU - Castaldini, Luciano

AU - Tallini, Giovanni

AU - Crino, Lucio

PY - 2006/4

Y1 - 2006/4

N2 - 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.

AB - 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.

KW - EGFR

KW - Gefitinib

KW - Non-small cell lung cancer

KW - Tyrosine kinase inhibitor

UR - http://www.scopus.com/inward/record.url?scp=33644935076&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644935076&partnerID=8YFLogxK

U2 - 10.1016/j.critrevonc.2005.08.008

DO - 10.1016/j.critrevonc.2005.08.008

M3 - Article

C2 - 16531062

AN - SCOPUS:33644935076

VL - 58

SP - 31

EP - 45

JO - Critical Reviews in Oncology/Hematology

JF - Critical Reviews in Oncology/Hematology

SN - 1040-8428

IS - 1

ER -