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.
Publication types
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Clinical Trial
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / therapeutic use*
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Carcinoma, Non-Small-Cell Lung / drug therapy*
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Carcinoma, Non-Small-Cell Lung / genetics
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Carcinoma, Non-Small-Cell Lung / mortality
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Case-Control Studies
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Diarrhea / chemically induced
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Diarrhea / genetics
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Disease-Free Survival
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ErbB Receptors / antagonists & inhibitors
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ErbB Receptors / genetics*
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Exanthema / chemically induced
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Exanthema / genetics
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Female
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Gefitinib
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Gene Expression Regulation, Neoplastic*
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Homozygote
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Humans
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Introns
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Kaplan-Meier Estimate
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / genetics
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Lung Neoplasms / mortality
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Male
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Middle Aged
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Odds Ratio
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Polymorphism, Genetic*
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Promoter Regions, Genetic
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Protein Kinase Inhibitors / adverse effects
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Protein Kinase Inhibitors / therapeutic use*
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Quinazolines / adverse effects
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Quinazolines / therapeutic use*
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Risk Assessment
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Risk Factors
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Treatment Outcome
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Quinazolines
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EGFR protein, human
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ErbB Receptors
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Gefitinib