Concurrent cetuximab, cisplatin, and radiation for squamous cell carcinoma of the head and neck in vitro

Background and purpose: For locoregionally advanced HNSCC, chemoradiotherapy with cisplatin or another platinum compound is considered as one of the standard treatment regimes. Cisplatin has improved the loco-regional control, but also increased especially the acute side effects. Cetuximab blocks ligand binding and receptor activation by binding to the extracellular domain of the EGFR. The blockade of EGFR signaling in combination with cytotoxic drugs or with radiotherapy could be a novel effective management with a relatively favourable toxicity for HNSCC. In the present study we have examined in vitro a potentially novel effective management for HNSCC, cetuximab combined with cisplatin and radiotherapy. Materials and methods: Seven head and neck SCC cell lines were studied. Cetuximab concentrations of 0.22-8.20 nM and cisplatin concentrations of 0.038-0.220 mu g/ml were used. In order to test the concurrent use of cetuximab, cisplatin and radiation, the cells were treated with the desired drug concentrations immediately after irradiation, plated into 96-well culture plates, and incubated for 4 weeks. The number of positive wells was counted. The PE was calculated and fraction survival data were fitted to the LQ model. AUC value was obtained with numerical integration. The types of interaction were analyzed. Results: Cetuximab and cisplatin constantly induced an additive or supra-additive effect when combined with irradiation in the seven HNSCC cell lines tested. Conclusions: We evaluated concurrent cetuximab, cisplatin, and radiation for HNSCC cell lines. Preliminary efficacy results are encouraging, and further development of this targeted combined modality paradigm is warranted. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 92 (2009) 488-392