Pharmacologic aspects of new classes of anti-cancer agents: inhibitors of topoisomerase I or tubulin

Abstract

Many processes involved in unregulated proliferation of cells are subject to antitumor therapy, inhibition of the nucleair enzyme topoisomerase I and protein tubulin being two of them. Important (pre-)clinical observations, such as synergism with other cytotoxic agents, the benefices of oral therapy as a means of prolonged exposure and the crucial role of the solubilization agent Cremophor EL, are involved in their further clinical development and in refinement of existing therapies. Given the narrow therapeutic window, means to improve the individual dosing precision need to be studied. Clinical pharmacological studies, as described in this thesis, are intended to serve as a guide to better chemotherapy schedules for the individual cancer patient