Regulatory considerations for preclinical development of anticancer drugs

• Published in: Cancer chemotherapy and pharmacology Vol. 41; no. 3; pp. 173 - 185
• Main Authors: DEGEORGE, J. J, AHN, C.-H, TRIPATHI, S. C, ANDREWS, P. A, BROWER, M. E, GIORGIO, D. W, GOHEER, M. A, LEE-HAM, D. Y, MCGUINN, W. D, SCHMIDT, W, SUN, C. J
• Format: Journal Article
• Language: English
• Published: Berlin Springer 1998
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Antineoplastic Agents - toxicity; Biological and medical sciences; Clinical Trials, Phase I as Topic; Drug Approval; Drug Evaluation, Preclinical - methods; Drug Evaluation, Preclinical - standards; Drugs, Investigational - pharmacokinetics; Drugs, Investigational - therapeutic use; Drugs, Investigational - toxicity; General aspects; Humans; Medical sciences; Pharmacology. Drug treatments; United States; United States Food and Drug Administration; United States; Antineoplastic agent; Human; Toxicity; Preclinical trial; Cytotoxicity; Review; Malignant tumor; In vitro; Recommendation; In vivo; Chemotherapy; Treatment; Animal; Immunotherapy; Targeted drug; Phase I trial; Combined treatment
• ISSN: 0344-5704; 1432-0843

The entry of new anticancer treatments into phase I clinical trials is ordinarily based on relatively modest preclinical data. This report defines the battery of preclinical tests important for assessing safety under an Investigational New Drug application (IND) and outlines a basis for extrapolating starting doses of investigational anticancer drugs in phase I clinical trials from animal toxicity studies. Types of preclinical studies for the support of marketing of a new anticancer drug are also discussed. This report addresses differences and similarities in the preclinical development of cytotoxic drugs (including photosensitizers and targeted delivery products), drugs used chronically (chemopreventive drugs, hormonal drugs, immunomodulators), and drugs intended to enhance the efficacy (MDR-reversing agents and radiation/chemotherapy sensitizers) or diminish the toxicity of currently used anticancer therapies. Factors to consider in the design of preclinical studies of combination therapies, alternative therapies, and adjuvant therapies in the treatment of cancer, and to support changes in clinical formulations or route of administration, are also discussed.