title: Approaches to the development and marketing approval of drugs that prevent cancer.
abstract: The broad concept of chemoprevention applies to the prevention of clinical cancer by the administration of chemical agents. Current approaches to the development and marketing approval of drugs to prevent cancer are described by a Working Group from the National Cancer Institute and the Food and Drug Administration. A strategy is presented that identifies candidate drugs, with examples that illustrate how drugs are characterized for efficacy through in vitro transformation modulation and mechanistic assays, and in vivo tumor modulation models of carcinogenesis. Requirements and recommendations for safety evaluation in toxicology testing are given, and the evaluation of pharmacokinetic and pharmacodynamic drug effects and potential surrogate end point biomarkers in Phase I trials are discussed. Appropriate subject populations are identified. Phase II trials should emphasize the evaluation of surrogate end point biomarkers that are highly correlated with cancer incidence and may serve as an estimate of cancer incidence reduction. In Phase III trials the interim analysis of a validated surrogate end point of cancer incidence may facilitate timely and cost-effective marketing of efficacious drugs.
authors.affiliation: National Cancer Institute, Division of Cancer Prevention and Control, Bethesda, Maryland 20892.
authors.forename: G J
authors.initials: GJ
authors.lastname: Kelloff
authors.forename: J R
authors.initials: JR
authors.lastname: Johnson
authors.forename: J A
authors.initials: JA
authors.lastname: Crowell
authors.forename: C W
authors.initials: CW
authors.lastname: Boone
authors.forename: J J
authors.initials: JJ
authors.lastname: DeGeorge
authors.forename: V E
authors.initials: VE
authors.lastname: Steele
authors.forename: M U
authors.initials: MU
authors.lastname: Mehta
authors.forename: J W
authors.initials: JW
authors.lastname: Temeck
authors.forename: W J
authors.initials: WJ
authors.lastname: Schmidt
authors.forename: G
authors.initials: G
authors.lastname: Burke
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D017277:Drug Approval; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009316:National Institutes of Health (U.S.); D009369:Neoplasms / Q000517:prevention & control*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents