Oncotarget

Priority Research Papers:

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

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 and Roland T. Ullrich _

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Oncotarget. 2015; 6:38458-38468. https://doi.org/10.18632/oncotarget.6276

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Abstract

Jakob Schöttle1,2,3, Sampurna Chatterjee1,2,10, Caroline Volz1,2, Maike Siobal2, Alexandra Florin4, Dennis Rokitta5, Yvonne Hinze6, Felix Dietlein3, Dennis Plenker3, Katharina König4, Kerstin Albus4, Johannes M. Heuckmann7, Daniel Rauh8, Thomas Franz6, Bernd Neumaier2,9, Uwe Fuhr5, Lukas C. Heukamp4,7 and Roland T. Ullrich1,2

1 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

2 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

3 Department of Translational Genomics, University of Cologne, Medical Faculty, Weyertal, Cologne, Germany

4 Department of Pathology, University Hospital Medical Center, University of Cologne, Cologne, Germany

5 Department of Pharmacology, University Hospital Medical Center, University of Cologne, Cologne, Germany

6 Max-Planck-Institute for Ageing, Cologne, Germany

7 NEO New Oncology AG, Cologne, Germany

8 Technical University Dortmund, Dortmund, Germany

9 Institut für Radiochemie und Experimentelle Molekulare Bildgebung (IREMB), University Hospital Medical Center, University of Cologne, Cologne, Germany

10 Department of Radiation Oncology, Cox-7, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA

Correspondence to:

Roland T. Ullrich, email:

Keywords: lung cancer, NSCLC, EGFR, erlotinib, high-dose scheduling, PET

Received: July 09, 2015 Accepted: October 01, 2015 Published: November 02, 2015

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.


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