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Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations.
J Thorac Oncol 2010; 5(7):1048-53JT

Abstract

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.

Authors+Show Affiliations

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20512075

Citation

Yeo, Wee-Lee, et al. "Erlotinib at a Dose of 25 Mg Daily for Non-small Cell Lung Cancers With EGFR Mutations." Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer, vol. 5, no. 7, 2010, pp. 1048-53.
Yeo WL, Riely GJ, Yeap BY, et al. Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J Thorac Oncol. 2010;5(7):1048-53.
Yeo, W. L., Riely, G. J., Yeap, B. Y., Lau, M. W., Warner, J. L., Bodio, K., ... Costa, D. B. (2010). Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer, 5(7), pp. 1048-53. doi:10.1097/JTO.0b013e3181dd1386.
Yeo WL, et al. Erlotinib at a Dose of 25 Mg Daily for Non-small Cell Lung Cancers With EGFR Mutations. J Thorac Oncol. 2010;5(7):1048-53. PubMed PMID: 20512075.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. AU - Yeo,Wee-Lee, AU - Riely,Gregory J, AU - Yeap,Beow Y, AU - Lau,Michelle W, AU - Warner,Jeremy L, AU - Bodio,Kelly, AU - Huberman,Mark S, AU - Kris,Mark G, AU - Tenen,Daniel G, AU - Pao,William, AU - Kobayashi,Susumu, AU - Costa,Daniel B, PY - 2010/6/1/entrez PY - 2010/6/1/pubmed PY - 2010/10/12/medline SP - 1048 EP - 53 JF - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JO - J Thorac Oncol VL - 5 IS - 7 N2 - 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. SN - 1556-1380 UR - https://www.unboundmedicine.com/medline/citation/20512075/Erlotinib_at_a_dose_of_25_mg_daily_for_non_small_cell_lung_cancers_with_EGFR_mutations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1556-0864(15)30551-7 DB - PRIME DP - Unbound Medicine ER -