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83rd Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

16.05. - 20.05.2012, Mainz

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Combined effects of Lapatinib and Cisplatin on colony formation of head and neck squamous cell carcinoma

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  • corresponding author Christoph Schrader - Department of Otolaryngology, University Clinic of Leipzig, Leipzig
  • Andreas Boehm - Department of Otolaryngology, University Clinic of Leipzig, Leipzig
  • Christian Mozet - Department of Otolaryngology, University Clinic of Leipzig, Leipzig
  • Andreas Dietz - Department of Otolaryngology, University Clinic of Leipzig, Leipzig
  • Julia Bertolini - Department of Pathology, University Clinic of Leipzig, Leipzig
  • Anette Reiche - Department of Otolaryngology, University Clinic of Leipzig, Leipzig
  • Gunnar Wichmann - Department of Otolaryngology, University Clinic of Leipzig, Leipzig

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. 83. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. Mainz, 16.-20.05.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12hnod301

doi: 10.3205/12hnod301, urn:nbn:de:0183-12hnod3019

Published: April 4, 2012

© 2012 Schrader et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Introduction: Lapatinib (LAP) targets tyrosine-kinases of EGFR/HER2-receptors and hence is under investigation regarding its value within multimodal therapy concepts of advanced head and neck squamous cell carcinoma (HNSCC).

Methods: The potential of LAP alone and combined with cisplatin (CIS) was assessed in short term ex vivo culture assays (FLAVINO assay). Biopsies of HNSCC-specimens were minced, collagenase-digested and exposed to serial LAP dilutions or solvent control (DMSO). Same LAP concentrations were tested in mixture with 6.67 µM, 3.33 or 1.67 µM CIS. After 72-h incubation, wells were washed and cultures ethanol-fixed. Following staining of epithelial cells using a Cy2-labeled pan-cytokeratin antibody, fluorescent colonies formed (CF) were counted (CF≥2 in controls of 33 HNSCC). We tested LAP alone and compared results of the clinically maximum tolerated dose (MTD) of CIS (6.67 µM) with the ability of various combinations of LAP and CIS to suppress CF statistically using the Mann-Whitney U-test.

Results: LAP up from concentrations of 0.39 µM suppressed CF significantly. An increased efficacy to suppress CF of HNSCC was obtained by mixtures of 3.13 µM LAP together with MTD CIS (statistical trend) or up from 6.25 µM LAP (significant). The extent of suppressed CF was decreased significantly at mixtures consisting of 1.67 µM CIS and 3.13 µM LAP compared to those of MTD CIS while LAP concentrations up from 6.25 µM led to no significant differences in suppressive efficacy.

Conclusion: LAP can suppress CF of HNSCC and is able to increase the suppressive activity of CIS towards HNSCC significantly. Reduction of CIS-concentration within combinatorial experiments can lead to a significant loss of antitumor activity towards HNSCC ex vivo compared with MTD CIS alone.