Intermittent high-dose treatment with erlotinib enhances therapeutic efficacy in EGFR-mutant lung cancer

Treatment with EGFR kinase inhibitors improves progression-free survival of patients with EGFR-mutant lung cancer. However, all patients with initial response will eventually acquire resistance and die from tumor recurrence. We found that intermittent high-dose treatment with erlotinib induced apopt...

Full description

Saved in:
Bibliographic Details
Published in:Oncotarget 2015-11, Vol.6 (36), p.38458-38468
Main Authors: Schöttle, Jakob, Chatterjee, Sampurna, Volz, Caroline, Siobal, Maike, Florin, Alexandra, Rokitta, Dennis, Hinze, Yvonne, Dietlein, Felix, Plenker, Dennis, König, Katharina, Albus, Kerstin, Heuckmann, Johannes M, Rauh, Daniel, Franz, Thomas, Neumaier, Bernd, Fuhr, Uwe, Heukamp, Lukas C, Ullrich, Roland T
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - enzymology
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Cell Line, Tumor
Disease-Free Survival
Dose-Response Relationship, Drug
Drug Administration Schedule
Erlotinib Hydrochloride - administration & dosage
Humans
Lung Neoplasms - drug therapy
Lung Neoplasms - enzymology
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Male
Mice
Mice, Nude
Priority Research Paper
Protein Kinase Inhibitors - administration & dosage
Receptor, Epidermal Growth Factor - antagonists & inhibitors
Receptor, Epidermal Growth Factor - genetics
Receptor, Epidermal Growth Factor - metabolism
Xenograft Model Antitumor Assays
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Treatment with EGFR kinase inhibitors improves progression-free survival of patients with EGFR-mutant lung cancer. However, all patients with initial response will eventually acquire resistance and die from tumor recurrence. We found that intermittent high-dose treatment with erlotinib induced apoptosis more potently and improved tumor shrinkage significantly than the established low doses. In mice carrying EGFR-mutant xenografts intermittent high-dose treatment (200 mg/kg every other day) was tolerable and prolonged progression-free survival and reduced the frequency of acquired resistance. Intermittent EGFR-targeted high-dose schedules induce more profound as well as sustained target inhibition and may afford enhanced therapeutic efficacy.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.6276