Related Experiment Videos
Approaches to the development and marketing approval of drugs that prevent cancer
G J Kelloff1, J R Johnson, J A Crowell
1National Cancer Institute, Division of Cancer Prevention and Control, Bethesda, Maryland 20892.
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.
Insights
Chemoprevention uses chemical agents to prevent cancer. This strategy outlines drug development, safety, and efficacy evaluation through clinical trials, focusing on biomarkers for timely approval of cancer-preventing drugs.
Area of Science:
- Oncology
- Pharmacology
- Drug Development
Background:
- Chemoprevention aims to prevent cancer using chemical agents.
- Current drug development and approval pathways for cancer prevention drugs are complex.
Purpose of the Study:
- To present a strategy for identifying and evaluating candidate chemopreventive drugs.
- To outline requirements for safety, efficacy, and biomarker evaluation in clinical trials.
Main Methods:
- Characterization of drug efficacy using in vitro and in vivo models.
- Toxicology testing for safety evaluation.
- Pharmacokinetic, pharmacodynamic, and biomarker analysis in Phase I trials.
Main Results:
- Phase II trials should focus on validated surrogate end points correlated with cancer incidence.
- Phase III trials can use interim analysis of validated surrogate end points for efficient drug marketing.
Conclusions:
- A structured approach to drug development and clinical trial design is crucial for effective chemoprevention.
- Utilizing validated surrogate end points can expedite the availability of cancer prevention drugs.