Published online Dec 10, 2016. doi: 10.5306/wjco.v7.i6.425
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
To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies.
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.
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.
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.