gms | German Medical Science

81st Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

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

12.05. - 16.05.2010, Wiesbaden

Lapatinib and cisplatin synergise in suppression of head and neck squamous cell carcinoma ex vivo

Meeting Abstract

  • corresponding author Gunnar Wichmann - HNO-Forschungslabor, Universität Leipzig, Deutschland
  • Christoph Schrader - HNO-Forschungslabor, Universität Leipzig, Deutschland
  • Pierre Kruber - HNO-Forschungslabor, Universität Leipzig, Deutschland
  • Andreas Dietz - Klinik und Poliklinik für HNO-Heilkunde, Universitätsklinikum Leipzig, Deutschland
  • Anett Reiche - HNO-Forschungslabor, Universität Leipzig, Deutschland
  • Grit Müller - HNO-Forschungslabor, Universität Leipzig, Deutschland
  • Iris-Susanne Horn - Klinik und Poliklinik für HNO-Heilkunde, Universitätsklinikum Leipzig, Deutschland
  • Christian Mozet - Klinik und Poliklinik für HNO-Heilkunde, Universitätklinikum Leipzig, Deutschland
  • Andreas Boehm - Klinik und Poliklinik für HNO-Heilkunde, Universitätklinikum Leipzig, Deutschland

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. 81. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. Wiesbaden, 12.-16.05.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. Doc10hnod237

DOI: 10.3205/10hnod237, URN: urn:nbn:de:0183-10hnod2378

Published: April 22, 2010

© 2010 Wichmann et al.
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Outline

Text

Introduction: The tyrosine-kinase inhibitor (TKI) lapatinib is introduced into multimodal therapy of advanced head and neck squamous cell carcinoma (HNSCC).

Purpose: To analyze the dose-response curve of lapatinib and whether this TKI combined with cisplatin exerts synergistic suppressive effects on HNSCC in a short-time ex-vivo colony-forming assay – flavin-protecting conditions (FLAVINO).

Methods: Biopsies of 72 HNSCC were taken, minced, collagenase-digested and added into microtiterplates containing serial lapatinib dilutions or medium plus solvent control (DMSO). The same lapatinib concentrations were tested also in combination with cisplatin (1.67, 3.33, or 6.67 µM, corresponding to ¼, ½, or exactly its tolerable plasma level). After 3-d incubation, wells were washed and cells ethanol-fixed. Fluorescent colonies were counted after pan-cytokeratin staining of epithelial cells using a fluorescent-labeled antibody.

Results: 64.7% of HNSCC growing in-vitro showed sufficient colony formation that allows for reliable cut-off detection. Cut-off (complete chemotherapeutical-suppressed colony formation) was achieved either by 6.25 µM lapatinib or 3.33 µM cisplatin alone only in three (9.1%) and in one HNSCC, respectively. The doubled number (eight HNSCC=24.2%) reached cut-off if treated with mixtures of 6.25 µM lapatinib and 3.33 µM cisplatin. The synergism of lapatinib and cisplatin is also reflected by the dose-response curves’ slope and the decreasing IC50 concentrations (50%-inhibition of colony-formation) of lapatinib which were 3.17, 3.21, 0.83, and 0.19 µM in the presence of 0.00, 1.67, 3.33, and 6.67 µM cisplatin.

Conclusions: The ex-vivo results in the FLAVINO assay indicate synergism of lapatinib with cisplatin toward suppressive activity on HNSCC.

This work was supported by GlaxoSmithKline