Cancer Clinical Pharmacology

'Cancer Clinical Pharmacology' provides a comprehensive account of the scientific basis of anti-cancer therapy in patients with solid tumours and haematological malignancies. An international group of experts have brought together information on the basic principles of pharmacology and tumour biology, bioanalytical aspects, pharmacokinetics, and the pharmacodynamics of anti-cancer agents. The clinical pharmacology of individual anti-cancer agents are covered, including the most important recently registered novel anti-cancer drugs. This book will prove an invaluable source of information for all trainees in oncology, haematology and internal medicine. Since cancer clinical pharmacology is a vast subject this book will be useful for all individuals involved in cancer pharmacology such as nurses, pharmacists, general pharmacologists, and cancer scientists.

Bioanalytical methods for anticancer drugs

1

(17)

Jos H. Beijnen

Hilde Rosing

Introduction

1

(1)

Analytical methods

2

(1)

High-performance liquid chromatography (HPLC)

3

(9)

Samples and sampling

12

(1)

Conclusions

13

(1)

References

13

(5)

Principles of pharmacokinetics

18

(12)

Etienne Chatelut

Introduction

18

(4)

Pharmacokinetic parameters

22

(4)

Pharmacokinetic analysis of plasma concentration versus time data

26

(3)

Non-linear pharmacokinetics

29

(1)

Bibliography

29

(1)

Clinical implications and mechanisms of variability in the response to anticancer agents

30

(11)

Jan H.M. Schellens

Introduction

30

(1)

Variability in pharmacokinetics

30

(7)

Variability in pharmacodynamics

37

(2)

Conclusions

39

(1)

References

39

(2)

Drug development and study design

41

(10)

Jim Cassidy

Introduction

41

(1)

Preclinical phase

41

(3)

Phase I trials

44

(2)

Phase II trials

46

(2)

Phase III trials

48

(1)

General and ethical issues

49

(1)

Conclusions

49

(1)

References

49

(2)

Pyrimidine antimetabolites

51

(12)

Gerard Milano

Jan H.M. Schellens

Summary

51

(1)

Introduction

51

(1)

5-Fluorouracil (5FU)

52

(3)

Capecitabine

55

(4)

Cytosine arabinoside (ara-C)

59

(1)

References

60

(3)

Purine analogs and antifolates

63

(21)

Jan Liliemark

Curt Peterson

Purine nucleoside analogues

63

(8)

Thiopurines

71

(4)

Antifolates

75

(3)

References

78

(6)

Alkylating agents

84

(20)

Alan V. Boddy

Summary

84

(1)

Introduction

84

(1)

Cyclophosphamide and ifosfamide

85

(5)

Melphalan

90

(1)

Nitrosoureas

91

(1)

Busulphan

92

(2)

Chlorambucil

94

(1)

Thiotepa

95

(1)

Temozolomide

96

(2)

References

98

(6)

Epipodophyllotoxins

104

(13)

Howard L. McLeod

Summary

104

Introduction

102

(3)

Clinical use

105

(1)

Mechanism of action

106

(1)

Mechanisms of resistance

106

(1)

Chemistry

107

(1)

Pharmacokinetics and pharmacokinetic models

107

(5)

Pharmacodynamics

112

(3)

References

115

(2)

Anthracyclines

117

(17)

Jacques Robert

Summary

117

(1)

Introduction

117

(1)

Chemistry

117

(2)

Mechanism of action

119

(2)

Mechanisms of resistance

121

(1)

Clinical use

121

(1)

Analytical methodology

122

(1)

Metabolism

122

(1)

Pharmacokinetics

122

(5)

Pharmacodynamics

127

(1)

Loco-regional administration of anthracyclines

128

(1)

New and potent anthracyclines

129

(1)

Anthracycline carriers and vehicles

129

(1)

References

130

(4)

Taxanes

134

(16)

Lucia Vigano

Alberta Locatelli

Luca Gianni

Summary

134

(1)

Introduction

134

Clinical use

133

(2)

Chemistry

135

(2)

Mechanism of action

137

(2)

Mechanism of resistance

139

(1)

Analytical methodology

139

(1)

Pharmacokinetics and protein binding

139

(4)

Pharmacodynamics

143

(1)

Toxicity

144

(1)

References

145

(5)

Vinca alkaloids

150

(14)

Timothy W. Synold

Summary

150

(1)

Introduction

150

(1)

Clinical use

151

(1)

Mechanism of action

151

(1)

Mechanisms of resistance

152

(1)

Chemistry

152

(1)

Analytical methodology

152

(2)

Pharmacokinetics

154

(5)

Pharmacokinetic models

159

(1)

Pharmacodynamics

160

(1)

References

160

(4)

Topoisomerase I targeting agents

164

(21)

Eric K. Rowinsky

Sharyn D. Baker

Introduction and historical survey

164

(1)

Chemistry and structure-activity relationships of CPT analogues

164

(3)

Mechanisms of action

167

(1)

Mechanisms of resistance

167

(1)

Topoisomerase I targeting agents approved as cancer therapeutics

168

(7)

References

175

(10)

Platinum agents

185

(13)

Steven W. Johnson

James P. Stevenson

Peter J. O'Dwyer

Summary

185

(1)

Introduction

185

(1)

Clinical use

186

(2)

Mechanism of action

188

(1)

Mechanisms of resistance

188

(2)

Chemistry

190

(1)

Analytical methodology

190

(1)

Pharmacokinetics

190

(2)

Toxicity

192

(1)

Pharmacodynamics

193

(1)

Future directions

194

(1)

References

194

(4)

Novel tyrosine kinase inhibitors: focus on imatinib and gefitinib

198

(18)

Wandena S. Lakhai

Jos H. Beijnen

Jan H.M. Schellens

Summary

198

(1)

Introduction

198

(3)

Imatinib (Glivec, STI571)

201

(7)

Gefitinib (Iressa, ZD 1839)

208

(3)

Future perspectives

211

(1)

References

212

(4)

Anti-endocrine drugs used in cancer treatment

216

(22)

Per Eystein Lonning

Summary

216

(1)

Introduction

216

(1)

Different drugs and their clinical uses

217

(5)

Anti-oestrogens

222

(3)

Aromatase inhibitors

225

(2)

Luteinizing hormone-releasing hormone analogues

227

(1)

Progestins

228

(1)

Non-steroidal anti-androgens

229

(1)

References

230

(8)

The clinical application of tumour biology

238

(22)

D. Paul Harkin

Patrick G. Johnston

Introduction

238

(1)

Molecular basis of cancer

238

(1)

Clinical implications and the way forward

239

(10)

Conclusions

249

(7)

References

256

(4)

Index

260

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Cancer Clinical Pharmacology

Summary

Table of Contents

Supplemental Materials