Epidermal growth factor receptor/angiogenesis dual targeting: preclinical experience

This review aims to critically examine the preclinical background regarding the combination of drugs targeting the epidermal growth factor receptor and anti-angiogenic compounds.

There are studies exploring the anti-tumor efficacy of dual inhibitors, such as the compound ZD6474, which combines in the same molecule an anti-tyrosine kinase activity against the epidermal growth factor receptor and the vascular endothelial growth factor receptor. In addition, several studies have investigated the anti-tumor effects of combinations of an anti-epidermal growth factor receptor agent and a vascular endothelial growth factor receptor inhibitor. In general, in these studies, supra-additive anti-tumor efficacy was apparent when combining anti-epidermal growth factor receptor and anti-angiogenic treatments. Beneficial effects were also observed when combining this dual targeted therapy with either conventional chemotherapy or irradiation.

Early clinical trials combining the anti-epidermal growth factor receptor drug erlotinib (Tarceva) and the anti-angiogenic agent bevacizumab (Avastin) show acceptable toxicity and promising anti-tumor activity (lung cancer), which need to be confirmed in randomized trials.