Chemo Fog (eBook)

Cancer Chemotherapy-Related Cognitive Impairment

Robert B. Raffa, Ronald J. Tallarida (Herausgeber)

eBook Download: PDF

2011 | 2010
XXI, 216 Seiten
Springer New York (Verlag)
978-1-4419-6306-2 (ISBN)

Infos

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.

ROBERT B. RAFFA, PhD, is Professor of Pharmacology and 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. RONALD J. TALLAR IDA, PhD, is a Professor of Pharmacology at Temple University School of Medicine. He has 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.

Inhalt

Title Page 3
Copyright Page 4
DEDICATION 5
PREFACE 6
ABOUT THE EDITORS... 8
ABOUT THE EDITORS... 9
PARTICIPANTS 10
Table of Contents 12
ACKNOWLEDGEMENTS 18
Chapter 1. SHORT INTRODUCTION AND HISTORY 19
Introduction and History 19
Conclusion 26
References 27
Chapter 2. PATIENT’S PERSPECTIVE 29
Conclusion 30
Chapter 3. ONCOLOGY NURSE’S PERSPECTIVE 31
Introduction: Personal Reflections of an Oncology Nurse 31
Chemotherapy-Related Cognitive Impairment: The Oncology Nurse Perspective 32
Oncology Nursing Research 32
Oncology Nursing Society Research Agenda 32
Selected Research Conducted by Oncology Nurses 33
Oncology Nursing Education 35
Conclusion 35
References 35
Chapter 4 Oncology Pharmacist’s Perspective 37
Conclusion 38
Reference 38
Chapter 5. THE IMPACT OF CHEMO BRAIN ON THE PATIENT WITH A HIGH GRADE GLIOMA 39
Background 39
Brain Cancer 40
Impact of Chemo Brain on the Patient 41
Impact of Chemo Brain on the Family 42
Impact of Chemo Brain on Society 42
Conclusion 43
Bibliography 43
Chapter 6. NEUROCOGNITIVE EFFECTS OF CHILDHOOD CANCER TREATMENT 44
Background 44
Identified Risk Factors 45
Treatment of Childhood Leukemia: Past and Present 46
Treatment of Childhood Brain Tumors: Past and Present 46
Neurocognitive Effects of Chemotherapy 47
Cognitive Remediation 48
Pharmacological Intervention: Methylphenidate 49
Conclusion 49
References 50
Chapter 7. THE ECONOMIC BURDEN 51
Epidemiology of Chemo Fog 51
Disease Impact 52
Economic Burden of Chemo Fog 52
Direct Costs 53
Indirect Costs 53
Total Burden 54
Conclusion 54
References 54
Chapter 8. DESIGNING CONCEPTUAL MODEL-BASED RESEARCH IN CHEMOTHERAPY-RELATED CHANGES IN COGNITIVE FUNCTION 55
Understanding the Issue 55
Defining the Problem 55
Terminology 58
Conceptual Models 59
Designing Research Trials 61
Study Design 64
Experimental and Non-Experimental Designs 67
Phases of Research 69
Outcomes Assessment 71
Conclusion 71
References 71
Chapter 9. NEUROPSYCHOLOGIC TESTING FOR CHEMOTHERAPY-RELATED COGNITIVE IMPAIRMENT 73
Introduction 73
Neuropsychologic Test Overview 73
Issues Related to Neurocognitive Testing for CRCI 76
Conclusion 85
References 86
Chapter 10. IMAGING AS A MEANS OF STUDYING CHEMOTHERAPY-RELATED COGNITIVE IMPAIRMENT 88
Introduction 88
Electrophysiological Studies 88
Neuroimaging Studies 89
Conclusion 91
References 93
Chapter 11. CHEMOTHERAPY ASSOCIATED CENTRAL NERVOUS SYSTEM DAMAGE 95
Introduction 95
Stem Cells, Progenitor Cells and Lineage Systems within the Central Nervous System 96
Cell-Biological Analysis of Chemotherapy Associated Brain Damage 97
Conclusion 100
References 100
Chapter 12. IS SYSTEMIC ANTI-CANCER THERAPY NEUROTOXIC? DOES CHEMO BRAIN EXIST? AND SHOULD WE RENAME IT? 104
Introduction 104
Towards a Better Definition of Chemo Brain 105
Self-Reported Cognitive Problems 105
Objective Cognitive Impairment and Its Duration 105
Objective Cognitive Impairment 105
Duration of Symptoms and Clinical Signs 105
Towards a Better Understanding of Chemo Brain 106
Can Chemo Brain Occur without Chemotherapy? 106
Before Chemotherapy 106
Role of Hormonal Therapy (HT) 106
Understanding Chemo Brain through Its Physiopathology and Preclinical Studies 107
Understanding Chemo Brain through ElectrophysiologicalTechniques and Imaging 109
Does Chemo Brain Exist? 110
A New Name for a New Concept 110
New Techniques Bringing an Evolving Concept 110
New Markers and Future Directions 110
Conclusion 110
References 111
Chapter 13. EVALUATION OF MULTIPLE NEUROTOXIC OUTCOMES IN CANCER CHEMOTHERAPY 114
Introduction 114
Two Contrasting Views of Neurotoxicity 116
Dimensions of Neurotoxicity 117
Lessons Learned from Studies of Cognitive Dysfunction 117
Cognitive Function Approaches 118
Sensory Function 120
Vision 120
Hearing 121
Somatosensory Function 122
Olfactory Discrimination 123
Motor Function 123
Animal Models 123
Purpose of Animal Models 123
Procedures 124
Choice of Doses 124
Choice of Endpoints 125
Schedule-Controlled Operant Behavior 125
Alternative Approaches 128
Conclusion 128
Acknowledgements 128
References 128
Chapter 14. CHEMOTHERAPY-RELATED VISUAL SYSTEM TOXICITY 131
Introduction 131
Visual-System Deficits in Chemo Fog/Chemo Brain 131
Chemotherapeutic Agent Toxicity on the Visual System 132
Conclusion 134
Acknowledgement 134
References 134
Chapter 15. THE POSSIBLE ROLE OF CYTOKINES IN CHEMOTHERAPY-INDUCED COGNITIVE DEFICITS 137
The Role of Proinflammatory Cytokines 137
Overview of Cytokines 137
The Immune Response 137
Proinflammatory Cytokines and Cancer 138
Proinflammatory Cytokines and Antineoplastic Agents 139
Proinflammatory Cytokines and Sickness Behavior 139
Proinflammatory Cytokines and Other Symptoms 140
Future Implications 140
Conclusion 140
References 140
Chapter 16. PHARMACOKINETICS OF ANTI-CANCER DRUGS USED IN BREAST CANCER CHEMOTHERAPY 142
Introduction 142
Pharmacokinetics of Anticancer Drugs Used in Breast Cancer Chemotherapy 142
Cyclophosphamide 142
Docetaxel 145
Doxorubicin 145
5-Fluorouracil 146
Methotrexate 146
Tamoxifen 146
Pharmacokinetics in Special Populations: Age and Menopause Status 147
Pharmacokinetics of Anticancer Drugs and Memory Deficit as a Pharmacodynamic Endpoint 148
Conclusion 148
References 148
Chapter 17. COMBINATION ANALYSIS 151
Introduction 151
Drug Additivity 151
Tests of Drug Combinations and the Isobole 153
Error Estimates 154
Dose-Effect Relation of the Drug Combination 154
Variable Potency Ratio 154
Conclusion 155
References 155
Chapter 18. ANIMAL MODELS 156
Introduction 156
Effects of Cancer Chemotherapeutic Agents on the Disruption of Sensory Processing in Animal Models 158
Effects of Cancer Chemotherapeutic Agents on the Disruption of Motor and Spontaneous Behavior in Animal Models 158
Effects of Cancer Chemotherapeutic Agents on Motivational Behavior in Animal Models 159
Acute Effects of Cancer Chemotherapeutic Agents on Learning and Memory in Animal Models 159
Repeated Treatment of Cancer Chemotherapeutics in Animal Models 161
Potential Neural Mechanisms of Chemotherapy-Induced Learning and Memory Impairments 162
Conclusion 163
Acknowledgements 163
References 163
Chapter 19. CHEMO BRAIN (CHEMO FOG) AS A POTENTIAL SIDE EFFECT OF DOXORUBICIN ADMINISTRATION: ROLE OF CYTOKINE-INDUCED,OXIDATIVE/NITROSATIVE STRESS IN COGNITIVE DYSFUNCTION 165
Introduction 165
Description of DOX and Mechanisms of Action 166
Toxicity of DOX 167
Peripheral Oxidative Stress 167
DOX and Central Nervous System Oxidative Stress 168
Role of Cytokines on Doxorubicin-Induced CNS Toxicity 169
Evidence of Cell Death in Brain with DOX 170
Description of Chemo Fog in Context of DOX 170
Conclusion 171
Acknowledgements 171
References 171
Chapter 20. EFFECTS OF 5-FU 175
Introduction 175
Drug Action 175
Clinical Usage 176
Cognitive Effects 177
Animal Models 178
Brain Regions Associated with the Behavioral Effects of 5-FU 179
Biochemical and Cellular Markers of the Effects of 5-FU Chemotherapy 179
Conclusion 180
References 180
Chapter 21. FUTURE DIRECTIONS 183
Background 183
‘Chemo Fog’/Chemo Brain: Current 183
Chemo Fog/Chemo Brain: Future 184
Conclusion 185
SUGGESTED READING 186
INDEX 229

Produkt-Details

• Erscheint lt. Verlag: 11.1.2011
• Reihe/Serie: Advances in Experimental Medicine and Biology
• Reihe/Serie: Advances in Experimental Medicine and Biology
• Zusatzinfo: XXI, 216 p.
• Verlagsort: New York
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Onkologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Schlagworte: Cancer • Chemo • Fog • Imaging • Raffa • Tallarida
• ISBN-10: 1-4419-6306-5 / 1441963065
• ISBN-13: 978-1-4419-6306-2 / 9781441963062