title: The advancement of cancer chemoprevention by revision of clinical trial strategies.
abstract: After a quarter of a century of rapid advances in cancer research, the focus of oncological drug development has shifted from cytotoxic chemotherapy to rationally designed agents that target specific molecules associated with malignant cells or their environment. As a consequence of greater public awareness of health related issues and population screening, the detection of early cancer or premalignant lesions has demonstrated the potential that exists for targeting the same molecules during carcinogenesis. One method of such intervention is chemoprevention, the inhibition, retardation or reversal of carcinogenic processes by chemical means. Tamoxifen and celecoxib have been licensed in the USA for the chemoprevention of breast and colorectal cancers respectively in certain well-defined "at risk" individuals. Unfortunately, many large-scale cancer chemoprevention trials have yielded negative results, and a few may even have caused harm to healthy individuals considered at risk of developing cancer. In this article, the importance of not putting the cart before the horse is argued. In particular, two factors in chemopreventive agent development will be emphasised: phase I/II studies in patients with cancer or patients at risk of second primary tumors and the validation and incorporation of biomarkers of carcinogenesis from the earliest phases of clinical development. This structured approach currently emerging is providing pharmacological and mechanistic data on novel agents which will prove essential in the planning of larger-scale commitments.
authors.affiliation: Cancer Biomarkers and Prevention Group, Oncology Department, University of Leicester, Leicester, UK. ras20@le.ac.uk
authors.forename: R A
authors.initials: RA
authors.lastname: Sharma
mesh_terms: D018890:Chemoprevention; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000517:prevention & control*; D012107:Research Design