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Optimal dose individualization has become more important in improving clinical efficacy and safety. This is due in part to the variability in drug response. Therefore, the role of optimal dose finding in early clinical drug development so as to maximize successful clinical use is emphasized. This book reviews innovative methods, tools and examples of rational drug development strategies, particularly for novel oncological agents.
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Ernst Schering Research Foundation Workshop 59 Appropriate Dose Selection – How to Optimize Clinical Drug Development Ernst Schering Research Foundation Workshop 59 Appropriate Dose Selection – How to Optimize Clinical Drug Development J. Venitz, W. Sittner Editors With 36 Figures 123 Series Editors: G. Stock and M. Lessl Library of Congress Control Number: 2006928310 ISSN 0947-6075 ISBN-10 3-540-27867-2 Springer Berlin Heidelberg New York ISBN-13 978-3-540-27867-2 Springer Berlin Heidelberg New York This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law. Springer is a part of Springer Science+Business Media springer.com © Springer-Verlag Berlin Heidelberg 2007 The use of general descriptive names, registered names, trademarks, etc. in this publication does not emply, even in the absence of a specific statemant, that such names are exempt from the relevant protective laws and regulations and therefor free for general use. Product liability: The publisher cannot guarantee the accuracy any information about dosage and application contained in this book. In every induvidual case the user must check such information by consulting the relevant literature. Editor: Dr. Ute Heilmann, Heidelberg Desk Editor: Wilma McHugh, Heidelberg Production Editor: Monika Riepl, Leipzig Cover design: WMXDesign GmbH, Heidelberg Typesetting and production: LE-TEX Jelonek, Schmidt & Vöckler GbR, Leipzig 21/3100/YL – 5 4 3 2 1 0 Printed on acid-free paper Preface Cancer has become a chronic disease, often requiring long-term, chronic oncological drug treatment. As a result, the oncological treatment is exposed to a large number of patients who may be on concurrent treatments for other health conditions and/or who may suffer from concomitant illnesses, both of which may affect the efficacy and safety of the oncological treatment by contributing to the increased incidence of adverse events and/or loss of efficacy. VI Preface Newer oncological drugs also have become more targeted to the underlying disease process(es), and their use and dosage regimens may need to be tailored to individual patients. Therefore, as opposed to the older chemotherapeutic drugs, these new agents are usually not dosed to their maximal tolerated dose (MTD), and optimal dose individualization has become more important to improve their clinical efficacy and safety. At the same time, the overall drug development process has become more time-consuming and expensive while more potential biological targets in cancer are being explored. Novel drug candidates are screened in early clinical drug development (ECDD), based on their clinical safety, pharmacokinetic (PK) properties and achievement of desired biological effects; drug candidates surviving this early clinical screen undergo more rigorous and large-scale phase III testing to