Emesis in Anti-cancer Therapy Mechanisms and treatment

Transcription

1 Emesis in Anti-cancer Therapy Mechanisms and treatment Edited by P.L.R. Andrews Reader in Physiology St George's Hospital Medical School London UK and G.J. Sanger Director of Gastrointestinal Research SmithKline Beecham Pharmaceuticals Essex UK CHAPMAN & HALL MEDICAL London Glasgow New York Tokyo Melbourne Madras

2 Contributors Preface ix xi 1 The problem of emesis in anti-cancer therapy: An introduction 1 P.L.R. Andrews and G.J. Sanger 1.1 The size of the problem An introduction to mechanisms and therapy Activation of the emetic reflex by anti-cancer therapy: the impact on the patient Discussion 5 References 6 2 The pharmacokinetics and pharmacodynamics of chemotherapeutic agents 9 M.T. Seymour 2.1 Introduction Pharmacokinetics Pharmacodynamics Anti-cancer cytotoxic chemotherapy Alkylating agents Non-classical alkylators Platinum compounds Anti-tumour antibiotics Plant alkaloids Anti-metabolites Conclusions 38 References 39 3 Toxicology of chemotherapeutic agents 45 I.R. Judson 3.1 Introduction Anti-proliferative side effects Acute non anti-proliferative toxicities Specific organ toxicities 50

3 3.5 Late side effects Conclusions 58 References 58 4 Nausea in anti-cancer therapy: Measurement and mechanisms 61 M. Tonato, F. Roila and A. Del Favero 4.1 Introduction Defining the parameters to be measured The clinical measurement of nausea Choosing the appropriate measurement method Conclusions 68 References 68 5 Changes in gastro-intestinal motility associated with vomiting and nausea 71 H.I.M. Davidson and M.A. Pilot 5.1 Introduction Normal motility patterns of the upper gastro-intestinal tract Motility changes observed in the gastro-intestinal tract during emesis Mechanisms of gastro-intestinal changes occurring during emesis The functions of the motility changes in emesis Motility changes in the gastro-intestinal tract associated with nausea Gastro-intestinal motility effects of chemotherapeutic agents and X-radiation Are motility changes a functional part of emesis? 86 References 87 6 Neurotransmitters and receptors in the emetic pathway 91 R.A. Leslie and D.JM. Reynolds 6.1 Introduction 6.2 CNS structures involved in nausea and emesis 6.3 Clinical strategies for anti-emetic therapy \ 6.4 The neurochemistry of cytotoxic drug-induced vomiting 6.5 Conclusions References 7 The mechanism of emesis induced by anti-cancer therapies P.L.R. Andrews and C.J. Davis 7.1 Introduction 7.2 General mechanisms of emesis 7.3 Cytotoxic drug- and radiation-induced emesis in the animal model 7.4 Pathways involved in acute cytotoxic emesis 7.5 Cellular mechanisms 7.6 The patterns of acute and delayed emesis: is 5-HT the sole mediator? 7.7 The mechanisms of nausea 7.8 Conclusions References vi

4 8 Radiotherapy-induced emesis 163 R.K. Harding, R.W. Young and G.H. Anno 8.1 Introduction Ionizing radiation Radiation lethality Radiotherapy Post-irradiation symptoms Mechanisms of radiation-induced vomiting Future developments 175 References The pharmacology of anti-emetic agents 179 G.J. Sanger 9.1 Introduction Reduction of emesis without the use of drugs Reduction of emesis with the use of natural products Reduction of emesis with the use of pharmaceutical agents The anti-emetic properties of specific drugs Interactions between anti-emetic and cytotoxic drug activity Future developments 199 References Psychological effects of anti-cancer therapy 211, Ann Cull 10.1 Introduction Prevalence Problems of definition Methodological issues Aetiology and prognostic factors Post-treatment nausea and vomiting Prognostic indices Prevention intervention Conclusions 224 References The clinical care of patients receiving chemotherapy 229 A.L. Jones and D. Cunningham 11.1 Introduction Selection of anti-emetic schedules Assessment of response Anti-emetic agents Combination therapy and recommendations The role of the oncology nurse Conclusions 242 References 242 vii

5 Afterword: Unresolved issues and future prospects 247 G.J. Sanger and P.L.R. Andrews Index 251 Vlll