Guidance for development of chemopreventive agents

✍ Scribed by Gary J. Kelloff; John R. Johnson; James A. Crowell; Charles W. Boone; Joseph J. DeGeorge; Vernon E. Steele; Menul U. Mehta; Jean W. Temeck; Wendelyn J. Schmidt; Gregory Burke; Peter Greenwald; Robert J. Temple

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 381 KB
• Volume: 56
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240560904

✦ Synopsis

Approaches to the development and marketing approval of cancer chemopreventive agents have been described by a Working Group from the National Cancer Institute and the Food and Drug Administration in a recent publication [l]. The approaches described do not constitute regulatory requirements, but rather are a summary of the participants' consensus views. It was noted that each potential chemopreventive drug will present unique characteristics such that the fine points of development must be considered on a case-by-case basis. The examples of chemopreventive approaches given primarily involve intraepithelial neoplasia (dysplasia), since the majority of human cancers are epithelial in origin. However, in the future, the approaches may be applied to dysplasia in mesenchymal tissue as well, such as in premalignant lesions of connective and hematopoietic tissues leading to sarcomas, leukemias, and lymphomas.

A strategy was developed to identify candidate drugs, with examples that illustrate how drugs can be characterized for efficacy through in vitro transformation modulation and mechanistic assays, and animal tumor modulation models of carcinogenesis. To qualify an agent for clinical study, sufficient evidence was recommended as follows: (1) one or more animal tumor modulation efficacy studies with statistically significant reduced tumor incidences, reduced