4-Hydroxyphenylretinamide in the Chemoprevention of Cancer

It has been suggested that ultimately half of all cancers might be prevented by early interventions. N-4-hydroxyphenylretinamide (4HPR or fenretinide) has been shown to be an effective and safe agent in various in vivo animal trials and well tolerated in human trials. At present multiple clinical trials are assessing its efficacy in preventing a variety of cancers. Chemoprevention is a term used to describe a novel approach of reducing risk of development of cancer in susceptible individuals by administration of chemical compounds that have the potential to reverse or suppress carcinogenesis. In any chemoprevention, trial toxicity assumes significant importance as the drug is administered to healthy individuals. 4HPR is an attractive chemopreventive agent to study in humans because of its significant activity in in vitro and in vivo preclinical studies with concomitant low toxicity. 4HPR appears to be less toxic than vitamin A. The chapter includes a brief summary of side effects reported from various human studies. In experimental chemoprevention studies, 4HPR has been shown to reduce carcinogen-induced cancers. The chapter summarizes the current status of 4HPR as a chemoprevention agent in cancer.