title: Regulatory considerations for preclinical development of anticancer drugs.
abstract: 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.
authors.affiliation: Division of Oncology Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20857, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: DeGeorge
authors.forename: C H
authors.initials: CH
authors.lastname: Ahn
authors.forename: P A
authors.initials: PA
authors.lastname: Andrews
authors.forename: M E
authors.initials: ME
authors.lastname: Brower
authors.forename: D W
authors.initials: DW
authors.lastname: Giorgio
authors.forename: M A
authors.initials: MA
authors.lastname: Goheer
authors.forename: D Y
authors.initials: DY
authors.lastname: Lee-Ham
authors.forename: W D
authors.initials: WD
authors.lastname: McGuinn
authors.forename: W
authors.initials: W
authors.lastname: Schmidt
authors.forename: C J
authors.initials: CJ
authors.lastname: Sun
authors.forename: S C
authors.initials: SC
authors.lastname: Tripathi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D017321:Clinical Trials, Phase I as Topic; D017277:Drug Approval; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000592:standards; D015507:Drugs, Investigational / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational