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

作者：Gurtner Kristin; Deuse Yvonne; Buetof Rebecca; Schaal Katja; Eicheler Wolfgang; Oertel Reinhard; Grenman Reidar; Thames Howard; Yaromina Ala; Baumann Michael; Krause Mechthild^*

来源：Radiotherapy and Oncology, 2011, 99(3): 323-330.

DOI：10.1016/j.radonc.2011.05.035

• Radiotherapy
• Head and neck cancer
• EGFR inhibition
• Cetuximab
• Erlotinib
• Combined treatment
• Prediction

Purpose: 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.
Material and methods: 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).
Results: 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.
Conclusion: 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.

• 出版日期2011-6