Copyright
©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Better to be alone than in bad company: The antagonistic effect of cisplatin and crizotinib combination therapy in non-small cell lung cancer
Nele Van Der Steen, Christophe Deben, Vanessa Deschoolmeester, An Wouters, Filip Lardon, Christian Rolfo, Paul Germonpré, Elisa Giovannetti, Godefridus J Peters, Patrick Pauwels
Nele Van Der Steen, Christophe Deben, Vanessa Deschoolmeester, An Wouters, Filip Lardon, Christian Rolfo, Paul Germonpré, Patrick Pauwels, Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium
Nele Van Der Steen, Christophe Deben, Vanessa Deschoolmeester, Patrick Pauwels, Department of Pathology, Antwerp University Hospital, 2650 Edegem, Belgium
Nele Van Der Steen, Elisa Giovannetti, Godefridus J Peters, Department of Medical Oncology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
Christian Rolfo, Department of Oncology, Antwerp University Hospital, 2650 Edegem, Belgium
Paul Germonpré, Department of Pneumology, AZ Maria Middelares, 9000 Ghent, Belgium
Elisa Giovannetti, Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, 56124 Pisa, Italy
Author contributions: All the authors contributed to the manuscript.
Supported by Institute for Innovation, Science and Technology Flanders (IWT), NO: 121114.
Institutional review board statement: Not applicable.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Elisa Giovannetti, MD, PhD, Department of Medical Oncology, VU University Medical Center, room 1.53, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
elisa.giovannetti@gmail.com
Telephone: +31-20-4442630
Received: June 20, 2016
Peer-review started: June 20, 2016
First decision: August 11, 2016
Revised: September 29, 2016
Accepted: October 25, 2016
Article in press: October 27, 2016
Published online: December 10, 2016
Processing time: 162 Days and 15.5 Hours
AIM
To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies.
METHODS
We tested three different treatment schemes in four non-small cell lung cancer (NSCLC) cell lines with a different cMET/epidermal growth factor receptor genetic background by means of the sulforhodamine B assay and performed analysis with Calcusyn.
RESULTS
All treatment schemes showed an antagonistic effect in all cell lines, independent of the cMET status. Despite their different genetic backgrounds, all cell lines (EBC-1, HCC827, H1975 and LUDLU-1) showed antagonistic combination indexes ranging from 1.3-2.7. These results were independent of the treatment schedule.
CONCLUSION
These results discourage further efforts to combine cMET inhibition with cisplatin chemotherapy in NSCLC.
Core tip: Targeted therapies are a valuable treatment option in non-small cell lung cancer. Several therapies have now been approved like erlotinib and gefitinib for epidermal growth factor receptor - mutant patients and crizotinib for Anaplastic Lymphoma Kinase-rearranged patients. However, resistance against these therapies eventually occurs. Combination therapy might be able to overcome or delay this resistance. Here we investigate the combination of the cMET inhibitor crizotinib with cisplatin in a panel of non-small cell lung cancer (NSCLC) cell lines with different histological and genetic backgrounds. We show that this leads to strong antagonism in all of the used cell lines. Furthermore we also link these results to the earlier in vitro and clinical results of the combination of erlotinib/gefitinib with cisplatin based chemotherapy in NSCLC.
