NEW YORK (Reuters Health) - In non-small-cell lung cancers (NSCLCs), a high EGFR gene copy number is associated with increased sensitivity to gefitinib and improved survival, according to a report in the Journal of the National Cancer Institute for May 4th.
The findings also support previous reports linking EGFR mutations with enhanced gefitinib sensitivity (see Reuters Health report February 23, 2005). However, further analysis showed that the copy number was the only EGFR parameter predictive of patient survival.
“Because only high EGFR gene copy number was associated with prolonged survival in the multivariable analysis, and because fluorescence in situ hybridization (FISH) is a readily available clinical test, the EGFR FISH analysis represents an ideal test for selecting candidate NSCLC patients for gefitinib therapy,” Dr. Fred R. Hirsch, from the University of Colorado Cancer Center in Aurora, and colleagues write.
The findings are based on analysis of EGFR parameters in tumors obtained from 102 NSCLC patients who were treated with gefitinib 250 mg daily. The authors also looked at Akt activation, which has been linked to gefitinib sensitivity in previous studies.
Amplification of the EGFR gene was associated with significant improvement in treatment response, disease control rate and time to progression. In addition, patients with EGFR gene amplification survived 18.7 months, on average, compared with just 7.0 months for other subjects.
As noted, EGFR mutations were not significantly linked to survival and 40% of patients with such mutations had progressive disease.
The authors also found that regardless of EGFR status, Akt activation was associated with significantly better outcomes.
In a related editorial, Dr. Frederic J. Kaye, from the NCI and National Naval Medical Center in Bethesda, Maryland, comments that “this study reminds us that much still remains to be learned about this new family of kinase inhibitor drugs.”
“Unfortunately, it appears that it may be easier to predict drug resistance than drug efficacy,” he added.
Source: J Natl Cancer Inst 2005;97:621-623,643-655. [ Google search on this article ]
MeSH Headings:Genetic Techniques: Health Occupations: Human Activities: Medicine: Membrane Proteins: Investigative Techniques: Receptors, Cell Surface: Receptor, Epidermal Growth Factor: Receptors, Gastrointestinal Hormone: Survival: Clinical Medicine: Receptors, Growth Factor: Receptors, Peptide: Receptor Protein-Tyrosine Kinases: Gene Expression Profiling: Analytical, Diagnostic and Therapeutic Techniques and Equipment: Anthropology, Education, Sociology and Social Phenomena: Biological SciencesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
