title: Germline polymorphisms in EGFR and survival in patients with lung cancer receiving gefitinib.
abstract: The purpose of this study was to evaluate associations between germline epidermal growth factor receptor (EGFR) variants involved in transcriptional regulation and overall survival in white patients with non-small-cell lung cancer (NSCLC) treated with the EGFR tyrosine kinase inhibitor, gefitinib. Of 175 consecutive patients treated with oral gefitinib (250 mg/day), 170 (median age: 67 years; 72% men) were evaluable for genotyping and survival. Fifty-five patients (33%) had stable disease and 17 (10%) had an objective response. The most common of four haplotypes was G-C (EGFR*1) at the EGFR -216G>T and -191C>A loci (frequency, 0.45). After adjusting for performance status, previous platinum-containing chemotherapy and occurrence of skin rash or diarrhea during the first treatment cycle in patients with performance status 0 or 1 (N=139), the absence of EGFR*1 was associated with significantly better survival (hazard ratio: 0.54; 95% confidence interval: 0.32-0.91; P=0.015). The results may help identify patients with NSCLC who can benefit from gefitinib treatment.
authors: Department of Oncology, Scientific Institute University Hospital San Raffaele, Milan, Italy.
authors: V
authors: V
authors: Gregorc
authors: M
authors: M
authors: Hidalgo
authors: A
authors: A
authors: Spreafico
authors: G
authors: G
authors: Cusatis
authors: V
authors: V
authors: Ludovini
authors: R G
authors: RG
authors: Ingersoll
authors: S
authors: S
authors: Marsh
authors: S M
authors: SM
authors: Steinberg
authors: M G
authors: MG
authors: Viganò
authors: D
authors: D
authors: Ghio
authors: E
authors: E
authors: Villa
authors: A
authors: A
authors: Sparreboom
authors: S D
authors: SD
authors: Baker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate / Q000639:trends
chemical_list: D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib