Praeklinische Daten als Grundlage fuer die Konzeption klinischer Studien [Preclinical data as basis for the design of clinical studies]

Preclinical Data as Basis for the Design of Clinical Studies. The preclinical development of novel anticancer compounds mainly resembles the same principle as valid for other drug classes. New target structures on tumors are identified within academic or industrial fundamental research groups enabling a selective attack of cancerostatics. After the proof of principle in molecular or cellular systems, substance candidates are selected which undergo a stepwise preclinical testing. This procedure consists of cell culture models (in vitro) and animal experiments (in vivo) using suitable tumor models. With selected lead compounds the pharmaceutical formulation is prepared, and the legally required preclinical toxicological investigations are performed before initiation of clinical phase I studies. There is one special feature distinguishing cytostatics from all other drugs - their narrow therapeutic index. This constraint is to be considered already in early phases of anticancer drug development, and a special focus should be given to the revealing of potential side effects. This contribution especially gives attention to this aspect of preclinical anticancer drug development. Further on, focus is put on target-oriented compounds, whose preclinical development generates special challenges