Epidermal growth factor receptor polymorphisms and clinical outcomes in non-small-cell lung cancer patients treated with gefitinib.

Abstract

The-216G/T, -191C/A, intron 1 and Arg497Lys epidermal growth factor receptor (EGFR) polymorphisms were evaluated in 92 advanced non-small-cell lung cancer patients treated with gefitinib, an EGFR tyrosine-kinase inhibitor. Improved progression free survival (PFS) was found in patients homozygous for the shorter lengths of intron 1 polymorphism (S/S; S=16 or fewer CA repeats; log-rank test (LRT) P=0.03) and for patients carrying any T allele of the -216G/T polymorphism (LRT, P=0.005). When considered together, patients with intron 1 S/S genotype and at least one T allele of -216G/T had improved PFS (LRT P=0.0006; adjusted hazard ratio (AHR), 0.60 (95% confidence interval, 0.36-0.98)) and overall survival (LRT P=0.02; AHR, 0.60 (0.36-1.00)) when compared with all others. The T allele of -216G/T was also associated with significantly higher rates of stable disease/partial response (P=0.01) and a significantly higher risk of treatment-related rash/diarrhea (P=0.004, multivariate model). EGFR intron 1 and -216G/T polymorphisms influence clinical outcomes in gefitinib-treated non-small-cell lung cancer patients.

• Authors: G Liu, S Gurubhagavatula, W Zhou, Z Wang, B Y Yeap, K Asomaning, L Su, R Heist, T J Lynch, D C Christiani
• Journal: The pharmacogenomics journal (Pharmacogenomics J) Vol. 8 Issue 2 Pg. 129-38 (Apr 2008) ISSN: 1473-1150 [Electronic] United States
• PMID: 17375033 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Quinazolines
• EGFR protein, human
• ErbB Receptors
• Gefitinib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, mortality)
• Case-Control Studies
• Diarrhea (chemically induced, genetics)
• Disease-Free Survival
• ErbB Receptors (antagonists & inhibitors, genetics)
• Exanthema (chemically induced, genetics)
• Female
• Gefitinib
• Gene Expression Regulation, Neoplastic
• Homozygote
• Humans
• Introns
• Kaplan-Meier Estimate
• Lung Neoplasms (drug therapy, genetics, mortality)
• Male
• Middle Aged
• Odds Ratio
• Polymorphism, Genetic
• Promoter Regions, Genetic
• Protein Kinase Inhibitors (adverse effects, therapeutic use)
• Quinazolines (adverse effects, therapeutic use)
• Risk Assessment
• Risk Factors
• Treatment Outcome