Chemotherapy for Leukemia Takanori Ueda Editor

Chemotherapy for Leukemia Novel Drugs and Treatment Editor Takanori Ueda Vice-President, University of Fukui Fukui, Japan

ISBN 978-981-10-3330-8 ISBN 978-981-10-3332-2 (eBook) DOI 10.1007/978-981-10-3332-2

Library of Congress Control Number: 2017939138

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This Springer imprint is published by Springer Nature The registered company is Springer Nature Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore Preface

Chemotherapy for Leukemia: Novel Drugs and Treatment covers the most recent progress in chemotherapy for leukemia and related diseases, including promising studies that are still in progress. The book consists of three parts:

1. Molecular targeted therapy 2. Novel chemotherapeutic agents, including analogues 3. Therapy targeting leukemic stem cells

Every drug presented will be of great interest to hemato-oncologists. The focus is on the drug and not treatment protocols. The book is designed to be a practical guide for drug selection decisions, and drugs are described basically, ­pharmacokinetically, and clinically by leading experts in each field. I will be very happy if this book helps hemato-oncologists to cure, or improve the outcomes of, leukemia patients. I would like to thank very much the contributing authors from many countries for providing their input despite their busy schedules and Dr. Takahiro Yamauchi for his excellent scientific advice. Thanks are also due to Ms. Yoko Arai for the proposal to publish this book and her editorial advice, Ms. Tamaki Yamamoto and Ms. Makie Kambara for the editorial assistance, and Ms. Juri Hashimoto, Ms. Rie Yamagishi, and Ms. Hitomi Takeuchi for the excellent secretarial assistance. Finally, I owe much to my wife, children, and grandchildren, who have provided invaluable support.

Fukui, Japan Takanori Ueda November 2016

v Contents

1 An Overview...... 1 Takanori Ueda

Part I Bcr-Abl Tyrosine Kinase Inhibitors (TKIs) 2 Imatinib: Basic Results...... 11 Fujiko Tsukahara and Yoshiro Maru 3 Imatinib: Clinical Pharmacology and Therapeutic Results...... 33 Kazunori Ohnishi 4 Dasatinib, Nilotinib, Bosutinib, Ponatinib, and Other TKIs...... 55 Shinya Kimura

Part II New Antibodies for Leukemia 5 Rituximab and Alemtuzumab for Chronic Lymphocytic Leukemia: Basic Results and Pharmacokinetics...... 79 Katsuki Sugiyama 6 Rituximab and Alemtuzumab for Chronic Lymphocytic Leukemia: Clinical Pharmacology and Therapeutic Results...... 99 Suguru Fukuhara and Kensei Tobinai 7 Inotuzumab Ozogamicin for Acute Lymphoblastic Leukemia: Clinical Pharmacology and Therapeutic Results...... 123 Noriko Usui 8 Blinatumomab for Acute Lymphoblastic Leukemia: Clinical Pharmacology and Therapeutic Results...... 137 Satoru Takada 9 Mogamulizumab in Adult T-Cell Leukemia/Lymphoma...... 151 Michinori Ogura

vii viii Contents

Part III Signaling Inhibitors 10 FLT3 Inhibitors...... 167 Hitoshi Kiyoi

Part IV Differentiating Agents 11 Retinoic Acid, All-trans Retinoic Acid (ATRA), and Tamibarotene...... 183 Norio Asou 12 The Molecular Basis of Treatment for Acute Promyelocytic Leukemia (APL)...... 213 Masahiro Kizaki 13 Arsenic Trioxide: Clinical Pharmacology and Therapeutic Results...... 221 Nobuhiko Emi

Part V New Chemotherapeutic Agents Including Antimetabolite 14 ...... 241 Takahiro Yamauchi and Takanori Ueda 15 Forodesine ...... 251 Takahiro Yamauchi and Takanori Ueda 16 : Structure, Mechanism of Action, and Clinical Pharmacology...... 261 William B. Parker and Varsha Gandhi 17 Clinical Use of Clofarabine for Adults and Children with Leukemia...... 287 James McCloskey, Jamie Koprivnikar, Stefan Faderl, Dirk Reinhardt, and Nobuko Hijiya 18 Re-emerging with Novel Mechanism of Action with Respect to Epigenetic Regulation: Basic Aspects...... 311 Dzjemma Sarkisjan, Renske D.M. Steenbergen, Jacqueline Cloos, and Godefridus J. Peters 19 Epigenetic Regulator, Re-emerging Antimetabolites with Novel Mechanism of Action ( and ): Clinical Pharmacology and Therapeutic Results...... 327 Shinya Sato and Yasushi Miyazaki

Part VI Therapy Targeting Leukemic Stem Cells 20 Therapies Targeting Leukemic Stem Cells...... 343 Taira Maekawa