title: 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.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Köln-Bonn, University of Cologne, Germany and Center of Molecular Medicine Cologne (ZMMK), University of Cologne, Cologne, Germany.|Max-Planck-Institute for Metabolism, with Klaus-Joachim-Zülch Laboratories of The Max Planck Society and The Medical Faculty of The University of Cologne, Cologne, Germany.|Department of Translational Genomics, University of Cologne, Medical Faculty, Weyertal, Cologne, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Schöttle
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Köln-Bonn, University of Cologne, Germany and Center of Molecular Medicine Cologne (ZMMK), University of Cologne, Cologne, Germany.|Max-Planck-Institute for Metabolism, with Klaus-Joachim-Zülch Laboratories of The Max Planck Society and The Medical Faculty of The University of Cologne, Cologne, Germany.|Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Sampurna
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Köln-Bonn, University of Cologne, Germany and Center of Molecular Medicine Cologne (ZMMK), University of Cologne, Cologne, Germany.|Max-Planck-Institute for Metabolism, with Klaus-Joachim-Zülch Laboratories of The Max Planck Society and The Medical Faculty of The University of Cologne, Cologne, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Volz
authors.affiliation: Max-Planck-Institute for Metabolism, with Klaus-Joachim-Zülch Laboratories of The Max Planck Society and The Medical Faculty of The University of Cologne, Cologne, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Siobal
authors.affiliation: Department of Pathology, University Hospital Medical Center, University of Cologne, Cologne, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Florin
authors.affiliation: Department of Pharmacology, University Hospital Medical Center, University of Cologne, Cologne, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Rokitta
authors.affiliation: Max-Planck-Institute for Ageing, Cologne, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Hinze
authors.affiliation: Department of Translational Genomics, University of Cologne, Medical Faculty, Weyertal, Cologne, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Dietlein
authors.affiliation: Department of Translational Genomics, University of Cologne, Medical Faculty, Weyertal, Cologne, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Plenker
authors.affiliation: Department of Pathology, University Hospital Medical Center, University of Cologne, Cologne, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: König
authors.affiliation: Department of Pathology, University Hospital Medical Center, University of Cologne, Cologne, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Albus
authors.affiliation: NEO New Oncology AG, Cologne, Germany.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Heuckmann
authors.affiliation: Technical University Dortmund, Dortmund, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rauh
authors.affiliation: Max-Planck-Institute for Ageing, Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Franz
authors.affiliation: Max-Planck-Institute for Metabolism, with Klaus-Joachim-Zülch Laboratories of The Max Planck Society and The Medical Faculty of The University of Cologne, Cologne, Germany.|Institut für Radiochemie und Experimentelle Molekulare Bildgebung (IREMB), University Hospital Medical Center, University of Cologne, Cologne, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Neumaier
authors.affiliation: Department of Pharmacology, University Hospital Medical Center, University of Cologne, Cologne, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Fuhr
authors.affiliation: Department of Pathology, University Hospital Medical Center, University of Cologne, Cologne, Germany.|NEO New Oncology AG, Cologne, Germany.
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Heukamp
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology Köln-Bonn, University of Cologne, Germany and Center of Molecular Medicine Cologne (ZMMK), University of Cologne, Cologne, Germany.|Max-Planck-Institute for Metabolism, with Klaus-Joachim-Zülch Laboratories of The Max Planck Society and The Medical Faculty of The University of Cologne, Cologne, Germany.
authors.forename: Roland T
authors.initials: RT
authors.lastname: Ullrich
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; C541485:EGFR protein, mouse; D066246:ErbB Receptors
keywords: EGFR; NSCLC; PET; erlotinib; high-dose scheduling