PHASE-II CHEMOPREVENTION TRIAL OF ORAL FENRETINIDE IN PATIENTS AT RISK FOR ADENOCARCINOMA OF THE PROSTATE

Prostate cancer is the most common cancer diagnosed in American men. T he need to find effective means of preventing this disease is clear. V itamin A and its analogues (retinoids) act as transcriptional regulato rs within the nucleus and have been tested as both preventative and th erapeutic agents in human malignancy. Fenretinide (N-4-hydroxyphenyl r etinamide) (4HPR) has been found to be relatively nontoxic in preclini cal experiments and early clinical trials, Its toxicity and feasibilit y for use as a chemoprevention agent in men at high risk for prostate cancer was evaluated in this study. Twenty-two patients were entered i nto a clinical trial that involved taking 4HPR for twelve 28-day cycle s. Eight patients with negative prestudy biopsies had positive prostat e biopsies prior to or at the time of their 12th cycle evaluation. Thi s led to early closure of the study. 4HPR was well-tolerated, and no m ajor toxicities were associated with its use. The significance of this study is limited due to small sample size. Chemoprevention studies su ch as this can be difficult to complete because of the commitment requ ired of otherwise healthy individuals; nevertheless additional dosages and schedules for 4HPR administration merit further investigation.