Abstract
In the preface of this text, the editors state that the book was written “…with the objective of having a single reference on clinical pharmacology to serve as a guide to drug development with a focus on cancer therapy.” Accordingly, the structure of the text, which comprises 34 chapters in 622 pages, follows, in general, the path of drug development of anticancer drugs beginning with the identification of susceptible molecular targets and culminating with 2 chapters on clinical trials of promising anticancer agents. Actually, the final chapter discusses pharmacogenetic counseling which, although a topic of growing importance, somehow does not fit the original asserted book plan.
Thus, early chapters explore preclinical screening of putative compounds and the use of mouse models as a guide to determine the initial dose in man. The latter calculation repeats arguments for dosage based on body surface area. The design of Phase I trials is addressed, and there is a courageous inclusion of bioanalytical methods that incorporate validation of assay methods. Having established a validated drug assay, the editors are now freed to present chapters on clinical pharmacology and pharmacokinetics and pharmacodynamic modeling, plus an additional chapter on pharmacometrics. The last appears to incorporate the previous topics with the addition of further population pharmacokinetics and pharmacodynamics.
Following these chapters, the editors provide reviews of more basic science topics a propos to the clinical pharmacology of anticancer drugs. These chapters include protein binding of anticancer drugs, drug metabolism, polymorphism in the genes of drug targets and metabolizing enzymes, drug interactions, and transporters, such as the ABC transporters. A chapter on the application of microdialysis to measure drug concentrations within tumors is also included. Next is a section focusing on regional delivery of drug therapy. These chapters include continuous hyperthermic peritoneal perfusion, as well as vascular isolation and perfusion techniques, isolated lung perfusion, and targeting drugs to the brain.
A useful section of the book is devoted to more novel and, in particular, biological approaches to treating cancer. Specifically, this includes the combination of angiogenesis inhibitors coupled with radiation, gene therapy, vaccines, antibodies, and immunotoxins, as well as the use of other biological agents, such as interferons. The final section of the book addresses regulatory issues and cancer drug clinical trials, with a very thorough presentation by Bruce Chabner and colleagues.
Overall, this is an excellent book providing an overview of the issues involved in the conception of a new anticancer agent or a novel delivery method, evaluating its therapeutic efficacy, and ultimately confirming its suitability as a significant contribution and advance to the current anticancer armory.
If there is to be a complaint, it would be minor grumbling at the presence of spelling errors in the text. I identified 19 such errors on first reading, which is modest, yet somewhat surprising with computerized typesetting.
This book is, in many ways, unique in the field of texts on anticancer drugs in that it is an encyclopedia of techniques and methods essential to optimizing current and emerging active anticancer agents and associated therapies. It will be a particularly useful resource for individuals involved in both the basic and clinical pharmacology of anticancer drugs. In most cases, the authors are well published and internationally recognized for work in their respective areas. The book is an excellent companion to the several texts describing the basic and clinical pharmacology of individual anticancer drugs or drug classes.