Cancer Clinical Pharmacology

by Schellens, Jan H. M.; McLeod, Howard L.; Newell, David R.

• ISBN13: 9780192629661
• ISBN10: 0192629662
• Format: Hardcover
• Copyright: 2005-06-23
• Publisher: Oxford University Press

Summary

'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.

Table of Contents

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