Chemo Fog. Cancer Chemotherapy-Related Cognitive Impairment. Springer Science+Business Media, LLC Landes Bioscience. Edited by

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1 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

2 CONTENTS SHORT INTRODUCTION AND HISTORY 1 Robert Raffa Abstract 1 and History 1 Conclusion 8 2. PATIENT'S PERSPECTIVE 11 Robert Raffa and Kathleen J. Martin Abstract 11 Conclusion ONCOLOGY NURSE'S PERSPECTIVE 13 Jamie S. Myers Abstract 13 Introduction: personal Reflections of an Oncology Nurse 13 Chemotherapy-Related Cognitive Impairment: The Oncology Nurse Perspective 14 Oncology Nursing Research 14 Oncology Nursing Education 17 Conclusion ONCOLOGY PHARMACIST'S PERSPECTIVE 19 Rachel Abstract 20

3 xvi Contents 5. THE IMPACT OF CHEMO BRAIN ON THE PATIENT WITH HIGH GRADE 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 NEUROCOGNITIVE EFFECTS OF CHILDHOOD CANCER TREATMENT 26 Jennifer Costa Abstract 26 Background 26 Identified Risk Factors Treatment of Childhood Leukemia: Past and Present Treatment of Childhood Brain Tumors: Past and Present ~ 28 Neurocognitive Effects of Chemotherapy 29 Cognitive Remediation 30 Pharmacological Intervention: Methylphenidate Conclusion THE ECONOMIC BURDEN 33 Albert I. Abstract 33 Epidemiology of Chemo Fog 33 Disease Impact 34 Economic Burden of Chemo Fog 34 Conclusion 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

4 Contents xvii 9. NEUROPSYCHOLOGIC TESTING FOR CHEMOTHERAPY- RELATED COGNITIVE IMPAIRMENT 55 Jamie S. Myers Abstract 55 Introduction 55 Neuropsychologic Test Overview 55 Issues Related to Neurocognitive Testing for 58 Conclusion IMAGING AS A MEANS OF STUDYING CHEMOTHERAPY- RELATED COGNITIVE IMPAIRMENT 70 Robert B. Raffa Abstract 70 Introduction 70 Electrophysiological Studies 70 Neuroimaging Studies 71 Conclusion CHEMOTHERAPY ASSOCIATED CENTRAL NERVOUS SYSTEM DAMAGE 77 Jorg 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 IS SYSTEMIC ANTI-CANCER THERAPY NEUROTOXIC? DOES CHEMO BRAIN EXIST? AND SHOULD WE RENAME IT? 86 Sophie Taillibert Abstract 86 Introduction 86 Towards a Better Definition of Chemo Brain 87 Towards a Better Understanding of Chemo Brain 88 Does Chemo Brain Exist? 92 Conclusion 92

5 xviii Contents 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 HO 14. CHEMOTHERAPY-RELATED VISUAL SYSTEM TOXICITY 113 Robert B. Raffa Abstract 113 Introduction 113 Visual-System Deficits in Chemo Brain' 113 Chemotherapeutic Agent Toxicity on the Visual System 114 Conclusion THE POSSIBLE ROLE OF CYTOKINES IN CHEMOTHERAPY-INDUCED COGNITIVE DEFICITS 119 Jamie S. Myers Abstract 119 The Role of Proinflammatory Cytokines 119 Overview of Cytokines 119 The Immune Response 119 Proinflammatory Cytokines and Cancer 120 Proinflammatory Cytokines and Antineoplastic Agents 121 Proinflammatory Cytokines and Sickness Behavior 121 Proinflammatory Cytokines and Other Symptoms 122 Future Implications 122 Conclusion PHARMACOKINETICS OF 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

6 Contents Pharmacokinetics of Anticancer Drugs and Memory Deficit as a Pharmacodynamic Endpoint 130 Conclusion COMBINATION ANALYSIS 133 Ronald J. Tallarida Abstract 133 Introduction 133 Additivity 133 Tests of Drug Combinations and the Isobole 135 Error Estimates 136 Dose-Effect Relation of the Drug Combination 136 Variable Potency Ratio 136 Conclusion ANIMAL MODELS 138 Ellen A. Walker Abstract 138 Introduction 138 Effects of Cancer Chemotherapeutic Agents on the Disruption of Sensory Processing in Animal Models 140 Effects of Cancer Chemotherapeutic Agents on the Disruption of Motor and Spontaneous Behavior in Animal Models 140 Effects of Cancer Chemotherapeutic Agents on Motivational Behavior in Animal Models 141 Acute Effects of Cancer Chemotherapeutic Agents on Learning and Memory in Animal Models 141 Repeated Treatment of Cancer Chemotherapeutics in Animal Models 143 Potential Neural Mechanisms of Chemotherapy-Induced Learning and Memory Impairments 144 Conclusion.' CHEMO BRAIN (CHEMO FOG) AS A POTENTIAL SIDE EFFECT OF DOXORUBICIN ADMINISTRATION: ROLE CYTOKINE STRESS IN COGNITIVE DYSFUNCTION 147 Christopher D. Aluise, Rukhsana Sultana, Jitbangjong Daret St. Clair, Jeffrey A. Moscow and D. Allan Mary Vore, Abstract 147 Introduction 147 Description of DOX and Mechanisms of Action 148 Toxicity DOX 149 Description of Chemo Fog in Context of DOX 152 Conclusion 153 xix

7 xx Contents 20. EFFECTS OF 5-FU 157 Peter M. Sarah Mustafa, Maha Laura Lyons, Jariya and Geoff Bennett Abstract 157 Introduction 157 Animal Models 159 Conclusion FUTURE DIRECTIONS Robert B. Raffa and Ronald J. Tallarida Abstract 165 Background 165 Chemo Brain: Current 165 Chemo Brain: Future 166 Conclusion, 167 SUGGESTED INDEX 213