PURPOSE: The tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib are 
effective in non-small cell lung cancers (NSCLCs) with epidermal growth factor 
receptor (EGFR) gene mutations. The usual clinical dose of gefitinib (250 mg/d) 
is only one third of its maximum tolerated dose, whereas the dose of erlotinib 
(150 mg/d) is at its maximum tolerated dose. In NSCLC cell lines, both TKIs have 
similar micromolar inhibitory concentrations. We explored whether erlotinib at 
25 mg/d (trough serum concentration similar to gefitinib 250 mg/d) would be 
efficacious in EGFR-mutated NSCLC.
METHODS: To study the inhibitory concentrations of gefitinib and erlotinib, we 
exposed EGFR-mutated cell lines (HCC827, H3255, PC-9, and H1975) to increasing 
concentrations of these TKIs. Further on, we performed a retrospective 
evaluation of seven patients with advanced EGFR-mutated (exon 19 deletions and 
L858R) NSCLC that were given erlotinib at 25 mg/d as their first EGFR TKI.
RESULTS: Gefitinib and erlotinib generated similar inhibitory curves across our 
panel of EGFR-mutated NSCLC cell lines with overlapping mean 50% inhibitory 
concentration 95% confidence intervals for HCC827, PC-9, and H1975. Both drugs 
also displayed a high degree of correlation in mean 50% inhibitory concentration 
(Pearson's r = 0.99, p = 0.0417). Of the seven patients, five patients (71.5%) 
had partial responses to erlotinib 25 mg/d. Median progression-free survival was 
17 months (95% confidence interval, 6-35 months). Toxicities were minimal, with 
only two (28.5%) patients having a rash and none experiencing (0%) diarrhea.
CONCLUSIONS: In NSCLC cell lines, gefitinib and erlotinib have similar 
inhibitory profiles. In patients with NSCLC and EGFR-activating mutations, a 
dose of erlotinib 25 mg/d (equivalent to gefitinib 250 mg/d) leads to impressive 
response rates and progression-free survival similar to the growing experience 
with the approved doses of gefitinib (250 mg/d) and erlotinib (150 mg/d). 
Identifying prospectively the lowest and clinically active dose ranges of 
erlotinib and gefitinib will help further to personalize care for patients with 
tumors harboring EGFR mutations.