Chemoprevention: will it work?

Cancer chemoprevention has been a major area of inquiry in the United States for over a decade. The field originated from the confluence of developments in laboratory carcinogenesis and nutritional epidemiology. Although still owing much to other research disciplines, chemoprevention researchers have developed models and methodologies specific to the topic. Of particular importance has been the search for intermediate endpoints which might provide valid indications of cancer prevention effectiveness. Intermediate endpoints, however, suffer the limitations of the extrapolation required to the prevention of cancer per se. More direct evidence of chemoprevention effectiveness may come from trials that use actual reduction of cancer incidence as the primary endpoint. Several trials of potential chemopreventive agents are underway or have been completed in the United States or elsewhere with U.S. investigator participation. The results to date have been mixed, and unanticipated findings have raised doubts about the probability of success of primary prevention of cancer by chemoprevention. Future prospects for success may depend upon development of a better understanding of biological mechanisms before progressing to large, long-duration human population trials.