Diverse effects of combined radiotherapy and EGFR inhibition with antibodies or TK inhibitors on local tumour control and correlation with EGFR gene expression.

Abstract

To compare functional effects of combined irradiation and EGFR inhibition in different HNSCC tumour models in vivo with the results of molecular evaluations, aiming to set a basis for the development of potential biomarkers for local tumour control. In five HNSCC tumour models, all wild-type for EGFR and KRAS, the effect of radiotherapy alone (30 fractions/6 weeks) and with simultaneous cetuximab or erlotinib treatment on local tumour control were evaluated and compared with molecular data on western blot, immunohistochemistry and fluorescence-in situ-hybridisation (FISH). Erlotinib and cetuximab alone significantly prolonged tumour growth time in 4/5 tumour models. Combined irradiation and cetuximab treatment significantly improved local tumour control in 3/5 tumour models, whereas erlotinib did not alter local tumour control in any of the tumour models. The amount of the cetuximab-effect on local tumour control significantly correlated with the EGFR/CEP-7 ratios obtained by FISH. Both drugs prolonged growth time in most tumour models, but only application of cetuximab during irradiation significantly improved local tumour control in 3/5 tumour models. The significant correlation of this curative effect with the genetic EGFR expression measured by FISH will be further validated in preclinical and clinical studies.