Concomitant chemoirradiation with vinorelbine and gefitinib induces additive effect in head and neck squamous cell carcinoma cell lines in vitro

Background and purpose: The study was performed to measure the radiosensitizing effect of vinorelbine together with gefitinib in head and neck squamous cell carcinoma (HNSCC) cell lines in vitro. Materials and methods: Three recently established HNSCC cell lines, originating from larynx and oral cavity tumors, were tested in this study. Vinorelbine concentration of 0.5 nM was used, corresponding to the IC70 value of cell lines. Gefitinib concentrations of 0.10-0.35 mu M were used, corresponding to IC70- and IC50-values of each cell line, causing 30% and 50% inhibition in clonogenic survival, respectively. Vinorelbine was added to the medium and the cells were plated in 96-well culture plates in this solution. 24 h later the cells were irradiated in plates with 4 MeV photons generated by a linear accelerator, producing radiation doses 0.75-7.5 Gy. Immediately after irradiation the desired concentrations of gefitinib were added, whereafter the plates were incubated at 37 degrees C with 5% CO2. After four weeks, the number of wells containing coherent living colonies, consisting of 32 cells or more, was counted. The plating efficiency was calculated and the fraction survival data were fitted to the linear quadratic model, F = exp[-(alpha D + beta D-2)]. The area under the survival curve (AUC) value was obtained with numerical integration. ErbB receptor expression of the HNSCC cell lines was analyzed by Western blotting. Results: The growth-inhibitory effect of simultaneous vinorelbine and gefitinib concomitant with radiation was supra-additive in cell line UT-SCC-33 and additive in cell lines UT-SCC-19A and -34. Conclusions: HNSCC is in vitro constantly sensitive to the combination of vinorelbine and gefitinib, which have together an additive effect in concomitant use with irradiation. Further studies are warranted to evaluate the concomitant use of vinorelbine and gefitinib with irradiation in clinical studies. In addition, both drugs are available in an oral formulation allowing effortless administration schedules. (c) 2007 Published by Elsevier Ireland Ltd. Radiotherapy and Oncology 85 (2007) 138-145.