Chemo Fog: Cancer Chemotherapy-Related Cognitive Impairment [1 ed.] 1441963057, 9781441963055

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Chemo Fog

ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK, State University of New York at Buffalo IRUN R. COHEN, The Weizmann Institute of Science ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research JOHN D. LAMBRIS, University of Pennsylvania RODOLFO PAOLETTI, University of Milan

Recent Volumes in this Series Volume 670 THERAPEUTIC APPLICATIONS OF CELL MICROENCAPSULATION Edited by José Luis Pedraz and Gorka Orive Volume 671 FRONTIERS IN BRAIN REPAIR Edited by Rahul Jandial Volume 672 BIOSURFACTANTS Edited by Ramkrishna Sen Volume 673 MODELLING PARASITE TRANSMISSION AND CONTROL Edited by Edwin Michael and Robert C. Spear Volume 674 INTEGRINS AND ION CHANNELS: MOLECULAR COMPLEXES AND SIGNALING Edited by Andrea Becchetti and Annarosa Arcangeli Volume 675 RECENT ADVANCES IN PHOTOTROPHIC PROKARYOTES Edited by Patrick C. Hallenbeck Volume 676 POLYPLOIDIZATION AND CANCER Edited by Randy Y.C. Poon Volume 677 PROTEINS: MEMBRANE BINDING AND PORE FORMATION Edited by Gregor Anderluh and Jeremy Lakey Volume 678 CHEMO FOG: CANCER CHEMOTHERAPY-RELATED COGNITIVE IMPAIRMENT Edited by Robert B. Raffa and Ronald J. Tallarida

A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher.

Chemo Fog Cancer Chemotherapy-Related Cognitive Impairment Edited by Robert B. Raffa, PhD Department of Pharmaceutical Sciences Temple University School of Pharmacy Philadelphia, Pennsylvania, USA Ronald J. Tallarida, PhD Department of Pharmacology Temple University School of Medicine Philadelphia, Pennsylvania, USA

Springer Science+Business Media, LLC Landes Bioscience

Springer Science+Business Media, LLC Landes Bioscience Copyright ©2010 Landes Bioscience and Springer Science+Business Media, LLC All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission                    being entered and executed on a computer system; for exclusive use by the Purchaser of the work. Printed in the USA. Springer Science+Business Media, LLC, 233 Spring Street, New York, New York 10013, USA http://www.springer.com Please address all inquiries to the publishers: Landes Bioscience, 1002 West Avenue, Austin, Texas 78701, USA Phone: 512/ 637 6050; FAX: 512/ 637 6079 http://www.landesbioscience.com The chapters in this book are available in the Madame Curie Bioscience Database. http://www.landesbioscience.com/curie Chemo Fog: Cancer Chemotherapy-Related Cognitive Impairment, edited by Robert B. Raffa and Ronald J. Tallarida. Landes Bioscience / Springer Science+Business Media, LLC dual imprint / Springer series: Advances in Experimental Medicine and Biology. ISBN: 978-1-4419-6305-5                     usage of equipment and devices, as set forth in this book, are in accord with current recommendations and practice at the time of publication, they make no warranty, expressed or implied, with respect to material described in this book. In view of the ongoing research, equipment development, changes in governmental regulations and the rapid accumulation of information relating to the biomedical sciences, the reader is urged to carefully review and evaluate the information provided herein.

Library of Congress Cataloging-in-Publication Data Chemo fog : cancer chemotherapy-related cognitive impairment / edited by Robert B. Raffa, Ronald J. Tallarida. p. ; cm. -- (Advances in experimental medicine and biology ; v. 678) Includes bibliographical references and index. ISBN 978-1-4419-6305-5 1. Cancer--Chemotherapy--Complications. 2. Cognition disorders. 3. Antineoplastic agents--Side effects. 4. Neurotoxic agents. I. Raffa, Robert B. II. Tallarida, Ronald J. III. Series: Advances in experimental medicine and biology, v. 678. 0065-2598 ; [DNLM: 1. Cognition Disorders--chemically induced. 2. Neurotoxicity Syndromes. 3. Antineoplastic Agents--pharmacokinetics. 4. Antineoplastic Agents--toxicity. 5. Drug Therapy--adverse effects. 6. Models, Animal. W1 AD559 v. 678 2010 / WL 140 C517 2010] RC271.C5C387 2010 616.99’4061--dc22 2010014177

DEDICATION To our families, with love and gratitude… …and to the patients who speak up about chemo fog/chemo brain and the healthcare providers and researchers who listen to them.

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PREFACE Cancer patients have benefitted greatly from recent advances in the drugs, dose regimens, and combinations used to treat their primary tumor and for the treatment or prevention of spread of their disease. Due to the advances in chemotherapy and other aspects of prevention, early detection, and treatment modalities, an increasing percentage of patients are surviving the disease. For some types of cancer, the majority of patients live decades beyond their diagnosis. For this they are forever thankful and appreciative of the drugs that helped lead to this increased survival rate. But no drug is devoid of adverse effects. This also applies to chemotherapeutic agents. The acute cytotoxic effects of these agents are well known––indeed are often required for their therapeutic benefit. The chronic adverse effects are varied and in some cases less well known. With the increase in survival rates, there has emerged a new awareness of these chronic adverse effects. The adverse effects include pain, visual impairments, anxiety, and impairment of memory and cognition. Not every patient experiences all of these and some, the fortunate ones, experience none of these. But the general problem is real. The editors of this book are professors who are engaged in research on areas that compromise the total healing of body and mind in this patient population. One particular component of the need for survivor care is the memory problems and cognitive deficits experienced by some. The condition has been given a name––actually many names, such as chemo fog, chemo brain, and others. These names reflect the belief that the cause of the problem is the chemotherapy that they received as part of their treatment. In some cases the chemo fog/chemo brain is transient while in others it is of longer duration. Little is known about this problem and that fact peaked our interest and motivated this book. Therefore, this book is devoted to one aspect of survivor care: chemo fog/ chemo brain. The current thinking can be summarized succinctly:  It is not clear that it exists.  If it exists, it is not clear what caused it (the chemotherapy, the disease, or some other factor, such as depression, the onset of menopause, etc.).  If chemotherapy-induced, it is not clear which drug(s) or drug combination(s) are causative.  No ‘prophylactic’ or ‘treatment’ is known.  Most survivors adjust, but some have problems with their jobs or interpersonal relationships. vii

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The material presented here provides background about the historical development of, and insight into, this condition. It also provides the ‘state-of-the-art’ of research (clinical and basic) and direction for future study. As such, the book should be of interest to students and the general reader as well as to patients and healthcare specialists. Toward this end, we have included chapters from a diverse set of authors who approach the subject from different perspectives. Each chapter was written in a way that it can be read independently of the others, but with a uniformity that allows smooth transition from one chapter to the next. It was our fundamental goal that this book provides the reader with an opportunity to quickly get ‘up-to-speed’ on this topic. More in-depth information is available from a variety of sources and so an extensive bibliography is provided. Finally, we wish to point out that the preparation of this book represents a first step by the editors in launching the work of the Forget-Me-Not Foundation, whose mission is fostering improved care for cancer survivors. Robert B. Raffa, PhD Department of Pharmaceutical Sciences Temple University School of Pharmacy Philadelphia, Pennsylvania, USA Ronald J. Tallarida, PhD Department of Pharmacology Temple University School of Medicine Philadelphia, Pennsylvania, USA

ABOUT THE EDITORS...

ROBERT B. RAFFA, PhD, is a Professor of Pharmacology and the Chair of the Department of Pharmaceutical Sciences at Temple University School of Pharmacy in Philadelphia, Pennslyvania. He holds B Chem E and BS degrees in Chemical Engineering and Physiological Psychology, MS degrees in Biomedical Engineering and Toxicology, and a PhD in Pharmacology. He is the co-author or editor of several books on pharmacology and thermodynamics and over 200 articles in refereed journals, and is active in NIH-funded research, editorial, and professional society activities. Dr. Raffa became co-founder and president of the Forget-Me-Not Foundation in 2009.

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ABOUT THE EDITORS...

RONALD J. TALLARIDA, PhD, is a Professor of Pharmacology at Temple University School of Medicine. He received the BS and MS degrees in physics/ mathematics from Drexel University and a PhD in pharmacology. His work, primarily concerned with quantitative aspects of pharmacology, is represented in more than 250 published works that include eight books he has authored or co-authored. Dr. Tallarida currently teaches, serves on editorial advisory boards, conducts NIH-funded research, and is active in professional societies. Dr. Tallarida became co-founder and Vice-president of the Forget-Me-Not Foundation in 2009.

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PARTICIPANTS Christopher D. Aluise University of Kentucky Lexington, Kentucky USA

Maha El-Beltagy Queen’s Medical Centre Nottingham, England UK

Geoff Bennett Queen’s Medical Centre Nottingham, England UK

Lisa M. Hess School of Medicine Indiana University Indianapolis, Indiana USA

!   University of Kentucky Lexington, Kentucky USA Rachel Clark-Vetri Department of Pharmacy Practice Temple University School of Pharmacy Philadelphia, Pennsylvania USA Jennifer Costa Uuniversity of Massachusettes Memorial Children’s Medical Center Worcester, Massachusetts USA Jörg Dietrich Harvard Medical School Boston, Massachusetts USA

Michele R. Lucas Stephen E. and Catherine Pappas Center for Neuro-Oncology Massachusetts General Hospital Boston, Massachusetts USA Laura Lyons Queen’s Medical Centre Nottingham, England UK Kathleen J. Martin New Holland, Pennsylvania USA Jeffrey A. Moscow University of Kentucky Lexington, Kentucky USA

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Sarah Mustafa University of Aberdeen Aberdeen, Scotland UK Jamie S. Myers School of Nursing University of Kansas Kansas City, Kansas USA Swati Nagar Temple University School of Pharmacy Philadelphia, Pennsylvania USA Robert B. Raffa Department of Pharmaceutical Sciences Temple University School of Pharmacy Philadelphia, Pennsylvania USA Daret St. Clair University of Kentucky Lexington, Kentucky USA Rukhsana Sultana University of Kentucky Lexington, Kentucky USA Sophie Taillibert Groupe Hospitalier Pitie-Salpetriere Paris France Ronald J. Tallarida Department of Pharmacology Temple University School of Medicine Philadelphia, Pennsylvania USA

Participants

Jitbangjong Tangpong Walaikak University Nakhon Si Thammarat Thailand and University of Kentucky Lexington, Kentucky USA Jariya Umka Queen’s Medical Centre Nottingham, England UK Mary Vore University of Kentucky Lexington, Kentucky USA Ellen A. Walker Temple University School of Pharmacy Philadelphia, Pennsylvania USA Bernard Weiss University of Rochester School of Medicine and Dentistry Rochester, New York USA Albert I. Wertheimer Temple University School of Pharmacy Philadelphia, Pennsylvania USA Peter M. Wigmore Queen’s Medical Centre Nottingham, England UK

CONTENTS 1. SHORT INTRODUCTION AND HISTORY ................................................. 1 Robert B. Raffa Abstract................................................................................................................................. 1 Introduction and History .................................................................................................... 1 Conclusion ............................................................................................................................ 8

2. PATIENT’S PERSPECTIVE ..........................................................................11 Robert B. Raffa and Kathleen J. Martin Abstract............................................................................................................................... 11 Conclusion .......................................................................................................................... 12

3. ONCOLOGY NURSE’S PERSPECTIVE .................................................... 13 Jamie S. Myers Abstract............................................................................................................................... 13             ............................................. 13 Chemotherapy-Related Cognitive Impairment: The Oncology Nurse Perspective..... 14 Oncology Nursing Research .............................................................................................. 14 Oncology Nursing Education ............................................................................................ 17 Conclusion .......................................................................................................................... 17

4. ONCOLOGY PHARMACIST’S PERSPECTIVE ...................................... 19 Rachel Clark-Vetri Abstract............................................................................................................................... 19 Conclusion .......................................................................................................................... 20

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5. THE IMPACT OF CHEMO BRAIN ON THE PATIENT WITH A HIGH GRADE GLIOMA....................................................... 21 Michele R. Lucas Abstract............................................................................................................................... 21 Background ........................................................................................................................ 21 Brain Cancer ...................................................................................................................... 22 Impact of Chemo Brain on the Patient ............................................................................ 23 Impact of Chemo Brain on the Family ............................................................................ 24 Impact of Chemo Brain on Society................................................................................... 24 Conclusion .......................................................................................................................... 25

6. NEUROCOGNITIVE EFFECTS OF CHILDHOOD CANCER TREATMENT ......................................................................................... 26 Jennifer Costa Abstract............................................................................................................................... 26 Background ........................................................................................................................ 26       ...................................................................................................... 27 Treatment of Childhood Leukemia: Past and Present ................................................... 28 Treatment of Childhood Brain Tumors: Past and Present............................................. 28 Neurocognitive Effects of Chemotherapy ........................................................................ 29 Cognitive Remediation ...................................................................................................... 30 Pharmacological Intervention: Methylphenidate ........................................................... 31 Conclusion .......................................................................................................................... 31

7. THE ECONOMIC BURDEN ........................................................................ 33 Albert I. Wertheimer Abstract............................................................................................................................... 33 Epidemiology of Chemo Fog ............................................................................................. 33 Disease Impact.................................................................................................................... 34 Economic Burden of Chemo Fog ...................................................................................... 34 Conclusion .......................................................................................................................... 36

8. DESIGNING CONCEPTUAL MODEL-BASED RESEARCH IN CHEMOTHERAPY-RELATED CHANGES IN COGNITIVE FUNCTION ............................................................... 37 Lisa M. Hess Abstract .............................................................................................................................. 37 Understanding the Issue .................................................................................................... 37 Designing Research Trials ................................................................................................. 43 Conclusion .......................................................................................................................... 53

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9. NEUROPSYCHOLOGIC TESTING FOR CHEMOTHERAPYRELATED COGNITIVE IMPAIRMENT ........................................... 55 Jamie S. Myers Abstract............................................................................................................................... 55 Introduction ........................................................................................................................ 55 Neuropsychologic Test Overview ...................................................................................... 55 Issues Related to Neurocognitive Testing for CRCI ....................................................... 58 Conclusion .......................................................................................................................... 67

10. IMAGING AS A MEANS OF STUDYING CHEMOTHERAPYRELATED COGNITIVE IMPAIRMENT ........................................... 70 Robert B. Raffa Abstract............................................................................................................................... 70 Introduction ........................................................................................................................ 70 Electrophysiological Studies.............................................................................................. 70 Neuroimaging Studies ........................................................................................................ 71 Conclusion .......................................................................................................................... 73

11. CHEMOTHERAPY ASSOCIATED CENTRAL NERVOUS SYSTEM DAMAGE ............................................................................... 77 Jörg Dietrich Abstract............................................................................................................................... 77 Introduction ........................................................................................................................ 77 Stem Cells, Progenitor Cells and Lineage Systems within the Central Nervous System .......................................................................................................... 78 Cell-Biological Analysis of Chemotherapy Associated Brain Damage.......................... 79 Conclusion .......................................................................................................................... 82

12. IS SYSTEMIC ANTI-CANCER THERAPY NEUROTOXIC? DOES CHEMO BRAIN EXIST? AND SHOULD WE RENAME IT? .................................................................................. 86 Sophie Taillibert Abstract............................................................................................................................... 86 Introduction ........................................................................................................................ 86        !"#   .................................................................. 87 Towards a Better Understanding of Chemo Brain ......................................................... 88 Does Chemo Brain Exist?.................................................................................................. 92 Conclusion .......................................................................................................................... 92

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13. EVALUATION OF MULTIPLE NEUROTOXIC OUTCOMES IN CANCER CHEMOTHERAPY ........................................................ 96 Bernard Weiss Abstract............................................................................................................................... 96 Introduction ........................................................................................................................ 96 Two Contrasting Views of Neurotoxicity ......................................................................... 98 Dimensions of Neurotoxicity ............................................................................................. 99 Lessons Learned from Studies of Cognitive Dysfunction............................................... 99 Cognitive Function Approaches...................................................................................... 100 Sensory Function.............................................................................................................. 102 Motor Function ................................................................................................................ 105 Animal Models ................................................................................................................. 105 Alternative Approaches ................................................................................................... 110 Conclusion ........................................................................................................................ 110

14. CHEMOTHERAPY-RELATED VISUAL SYSTEM TOXICITY ..........113 Robert B. Raffa Abstract............................................................................................................................. 113 Introduction ...................................................................................................................... 113 $ %&#    !"# '(!"#  ) .................................................. 113 Chemotherapeutic Agent Toxicity on the Visual System .............................................. 114 Conclusion ........................................................................................................................ 116

15. THE POSSIBLE ROLE OF CYTOKINES IN CHEMOTHERAPY-INDUCED COGNITIVE DEFICITS .........119 Jamie S. Myers Abstract............................................................................................................................. 119 "    ## !  ....................................................................... 119 Overview of Cytokines..................................................................................................... 119 The Immune Response .................................................................................................... 119

 ## !   !  ....................................................................... 120

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 ## !   " &#/# ...................................................... 122 Future Implications.......................................................................................................... 122 Conclusion ........................................................................................................................ 122

16. PHARMACOKINETICS OF ANTI-CANCER DRUGS USED IN BREAST CANCER CHEMOTHERAPY ..................................... 124 Swati Nagar Abstract............................................................................................................................. 124 Introduction ...................................................................................................................... 124 Pharmacokinetics of Anticancer Drugs Used in Breast Cancer Chemotherapy ........ 124 Pharmacokinetics in Special Populations: Age and Menopause Status...................... 129

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