Exploring novel formulations and new classes of anticancer drugs in solid tumors

Abstract

Many current anticancer drugs have non-ideal pharmaceutical and pharmacological properties, which can lead to adverse consequences, including lack of or suboptimal therapeutic activity, dose-limiting side effects and poor patient quality of life. In this thesis we focused on some novel formulations, especially camptothecin glycoconjugate BAY 56-3722 and liposomal drug formulations, hoping to overcome some of these problems. We also focused on __old drugs__ for new indications, as an example HDAC inhibitors and cardiac glycosides. Unfortunately, the outcomes of some of the presented studies were disappointing: a clinical hold during the phase II study of BAY 56-3722, no benefit of LiPlaCis over standard cisplatin formulations and a non-completed clinical phase I trial with UNBS1450. Besides the disappointing outcomes of some of the presented studies, we demonstrated that LEP-ETU and Taxol_ met the required 80-125% bioequivalence criteria and we showed that patients with mild or moderate hepatic function could be safely treated with the same dose of panobinostat as patients with normal hepatic function. The reviews of liposomal anticancer drugs, HDAC inhibitors and cardiac glycosides all showed that to fulfill the high expectations of all these formulations and new drugs and to overcome the existing problems much research is still necessary