In this thoroughly updated and expanded second edition of Beverly Teicher's widely used classic survey, Anticancer Drug Development Guide: Preclinical Screening, Clinical Trials, and Approval, leading cancer researchers from pharmaceutical companies, government laboratories, and academia provide a step-by-step guide to anticancer drug development from initial design through FDA approval. The authors have included new material on the use of high-throughput screening in industry, on specialized in vitro/in vivo procedures employed by the National Cancer Institute (NCI) in preclinical drug evaluations, and on nonclinical testing to support both human clinical trials, as well as trials of biologic oncology products. There are also new chapters on health-related quality of life (HRQL) issues in cancer clinical trials, and FDA review and requirements for approval of oncologic products. The chapters on phase I, II, and III clinical trials and on novel phase II clinical trial designs for targeted therapies have been significantly updated, along with those on cancer drug development in Europe, on working with the NCI, as well as on the FDA's role in cancer drug development and in setting requirements for approval.
Authoritative and up-to-date, Anticancer Drug Development Guide: Preclinical Screening, Clinical Trials, and Approval takes oncologists, pharmacologists, medicinal chemists, and other cancer researchers on an encyclopedic tour of the cancer drug development and approval process, moving from the design and execution of high-throughput screens, to preclinical testing, to safety and toxicity testing under FDA requirements, to early clinical trials, and on to final FDA approval.

Klappentext

This unique volume traces the critically important pathway by which a "molecule" becomes an "anticancer agent. " The recognition following World War I that the administration of toxic chemicals such as nitrogen mustards in a controlled manner could shrink malignant tumor masses for relatively substantial periods of time gave great impetus to the search for molecules that would be lethal to specific cancer cells. Weare still actively engaged in that search today. The question is how to discover these "anticancer" molecules. Anticancer Drug Development Guide: Preclinical Screening, Clinical Trials, and Approval, Second Edition describes the evolution to the present of preclinical screening methods. The National Cancer Institute's high-throughput, in vitro disease-specific screen with 60 or more human tumor cell lines is used to search for molecules with novel mechanisms of action or activity against specific phenotypes. The Human Tumor Colony-Forming Assay (HTCA) uses fresh tumor biopsies as sources of cells that more nearly resemble the human disease. There is no doubt that the greatest successes of traditional chemotherapy have been in the leukemias and lymphomas. Since the earliest widely used in vivo drug screening models were the murine L 1210 and P388 leukemias, the community came to assume that these murine tumor models were appropriate to the discovery of "antileukemia" agents, but that other tumor models would be needed to discover drugs active against solid tumors.

Inhalt

Part I: In Vitro Methods High-Volume Screening Michel Pagé High-Throughput Screening in Industry Michael D. Boisclair, David A. Egan, Kety Huberman, and Ralph Infantino The NCI Human Tumor Cell Line (60-Cell) Screen: Concept, Implementation, and Applications Michael R. Boyd Human Tumor Screening Axel-R. Hanauske, Susan G. Hilsenbeck, and Daniel D. Von Hoff Part II: In Vivo Methods Murine L1210 and P388 Leukemias William R. Waud In Vivo Methods for Screening and Preclinical Testing: Use of Rodent Solid Tumors for Drug Discovery Thomas Corbett, Lisa Polin, Patricia LoRusso, Fred Valeriote, Chiab Panchapor, Susan Pugh, Kathryn White, Juiwanna Knight, Lisa Demchik, Julie Jones, Lynne Jones, and Loretta Lisow Human Tumor Xenograft Models in NCI Drug Development Michael C. Alley, Melinda G. Hollingshead, Donald J. Dykes, and William R. Waud NCI Specialized Procedures in Preclinical Drug Evaluations Melinda G. Hollingshead, Michael C. Alley, Gurmeet Kaur, Christine M. Pacula-Cox, and Sherman F. Stinson Patient-Like Orthotopic Metastatic Models of Human Cancer Robert M. Hoffman Preclinical Models for Combination Therapy Beverly A. Teicher Models for Biomarkers and Minimal Residual Tumor Beverly A. Teicher Spontaneously Occurring Tumors in Companion Animals As Models for Drug Development David M. Vail and Douglas H. Thamm Part III: Nonclinical Testing to Support Human Trials Nonclinical Testing: From Theory to Practice Denis Roy and Paul A. Andrews Nonclinical Testing for Oncology Drug Products Paul A. Andrews and Denis Roy Nonclinical Testing for Oncology Biologic Products Carolyn M. Laurençot, Denis Roy, and Paul A. Andrews Part IV: Clinical Testing Working With the National CancerInstitute Paul Thambi and Edward A. Sausville Phase I Trial Design and Methodology for Anticancer Drugs Patrick V. Acevedo, Deborah L. Toppmeyer, and Eric H. Rubin Phase II Trials: Conventional Design and Novel Strategies in the Era of Targeted Therapies Keith T. Flaherty and Peter J. O'Dwyer Drug Development in Europe: The Academic Perspective Chris Twelves, Mike Bibby, Denis Lacombe, and Sally Burtles The Phase III Clinical Cancer Trial Ramzi N. Dagher and Richard Pazdur Assessing Tumor-Related Symptoms and Health-Related Quality of Life in Cancer Clinical Trials: A Regulatory Perspective Judy H. Chiao, Grant Williams, and Donna Griebel The Role of the Oncology Drug Advisory Committee in the FDA Review Process for Oncologic Products Leslie A. Vaccari FDA Role in Cancer Drug Development and Requirements for Approval Susan Flamm Honig Index