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. 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. 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. 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.
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 . 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 . 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 . 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 .
Mutations in which gene determine response to both erlotinib and gefitinib?
Mutations in which gene determine response to both erlotinib and gefitinib ?
epidermal growth factor receptor (EGFR) gene
epidermal growth factor receptor (EGFR) gene