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

Abstract

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.

• Authors: Jakob Schöttle, Sampurna Chatterjee, Caroline Volz, Maike Siobal, Alexandra Florin, Dennis Rokitta, Yvonne Hinze, Felix Dietlein, Dennis Plenker, Katharina König, Kerstin Albus, Johannes M Heuckmann, Daniel Rauh, Thomas Franz, Bernd Neumaier, Uwe Fuhr, Lukas C Heukamp, Roland T Ullrich
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 36 Pg. 38458-68 (Nov 17 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26540572 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Erlotinib Hydrochloride
• EGFR protein, human
• EGFR protein, mouse
• ErbB Receptors

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy, enzymology, genetics, pathology)
• Cell Line, Tumor
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• ErbB Receptors (antagonists & inhibitors, genetics, metabolism)
• Erlotinib Hydrochloride (administration & dosage)
• Humans
• Lung Neoplasms (drug therapy, enzymology, genetics, pathology)
• Male
• Mice
• Mice, Nude
• Protein Kinase Inhibitors (administration & dosage)
• Xenograft Model Antitumor Assays