Razoxane and Dexrazoxane - Two Multifunctional Agents: Experimental and Clinical Results

ISBN-13: 9789401780483 / Angielski / Miękka / 2014 / 243 str.

Walter Rhomberg;Kurt Hellmann

Opis

Razoxane and dexrazoxane are two novel drugs with some uniquely useful features. They block cell division at the G2/M border, but nowhere else, so that they have a low toxicity profile. They suppress tumor metastasis and haemorrhages through normalization of pathological blood vessels. Razoxane potentiates radiotherapy especially in the treatment of soft tissue sarcomas and gastrointestinal neoplasms. They protect normal tissues against toxic chemicals, e.g. the myocardium against anthracyclines or subcutaneous tissue against injuries caused by incidental extravasations of anthracyclines. Dexrazoxane is the only drug approved by the FDA/EMEA for the specific purpose of preventing cardiac damage when giving the widely used and effective antitumor anthracyclines. The reduction of cardiotoxicity is achieved without response reduction or reducing of time to progression of tumors. While the full analysis of their actions at the molecular level is not yet completely understood, it seems most likely that it is via an inhibition on the topoisomerase II a. Moreover, the drugs have the ability to chelate several metals including iron, copper or zinc. The protection of normal tissues is nowhere more important than that of brain, and there are indications that the proteins thought to be responsible for the ravages of Alzheimer's disease could be stabilized by one or both these drugs.

Spis treści

PREFACE 1. INTRODUCTION; Hellmann, K. 1.1 Overview of the development of razoxane and dexrazoxane 2. RAZOXANE 2.1 Preclinical data - in vitro and in vivo; Hellmann, K. 2.2 Modes of action, a brief summary; Rhomberg, W. 2.3 Clinical studies of malignant tumors; Rhomberg, W. 2.3.1 Razoxane as cytotoxic or cytostatic agent 2.3.1.1 Leukaemias and lymphomas 2.3.1.2 Solid tumors, single agent 2.3.1.3 Solid tumors, multiagent therapy 2.3.1.4 Adjuvant use of razoxane 2.3.2 Razoxane as radiosensitizer 2.3.2.1 Soft tissue- and osteosarcomas, chordomas 2.3.2.2 Gastro-intestinal malignancies 2.3.2.3 Lung cancer 2.3.2.4 Other solid tumors 2.3.3 Antimetastatic efficacy 2.3.3.1 Preclinical evidence; Rhomberg, W. 2.3.3.2 Metastasis and the entry of tumor cells into; the vasculature – prevention by razoxane; Hellmann, K. 2.3.3.3 Clinical evidence; Rhomberg, W. 2.3.4 Razoxane - a cytorallentaric drug; Hellmann, K. 2.3.5 Toxicity; Rhomberg, W. 2.4 Studies in non-malignant diseases 2.4.1 Psoriasis and psoriatric arthropathy; Rhomberg, W. 2.4.2 Crohn´s disease and ulcerative colitis; Rhomberg, W. 3. DEXRAZOXANE 3.1 Preface 3.2 The pharmacology of dexrazoxane; Hasinoff, B.B. 3.3 Toxicology and pharmacokinetics; Hellmann, K. 3.4 Identification of dexrazoxane as a cardioprotector; Herman, E. 3.5 Clinical considerations 3.5.1 Dexrazoxane as antitumour agent; Rhomberg, W. 3.5.2 Protection against anthracyclin-induced cardiotoxicity: 3.5.2.1 Two pivotal clinical studies. A report including pharmacology and safety issues; Rubens, R. 3.5.2.2 Comments on study 88001 and 88006; Hellmann, K. 3.5.2.3 Clinical studies on cardioprotection – an update; Jones, R. 3.5.3 Non-cardioprotective efficacy; Langer, S.W. 3.5.4 Neurodegenerative diseases; Greig, N. 4. SUMMARY and OUTLOOK; Hellmann, K. and Rhomberg, W.