[Anti-epidermal growth factor receptor treatment: a new paradigm for conducting therapeutic trials]

Agents which modify biological properties of tumour tissue can target many tenths of functions over- or underexpressed in human tumours. In general these agents are cytostatic rather than cytotoxic and will affect only that fraction of human tumours where the target plays and important and unique role for the viability of the tumour tissue. Alternatively it is expected that acute toxicity will not be observed at active dose-time exposure; rather subacute or chronic toxicity can be observed with these agents. Clinical studies will have to follow the following rules: characterisation of the pharmacological target and of its functional role on tumour tissue; definition of an optimal biological dose rather than a maximum tolerated dose; importance of validated pharmacodynamic endpoints; importance and thus need for early studies of combination regimens. It is still too early to define general guidelines for the study of these different therapeutic families. Nevertheless, studies already conducted with agents interfering with EGF mediated signalization have already permitted preliminary indications on pharmacodynamics, target assessment, level of activity and conduct of clinical trials with combination regimens.