Randomized trial of fenretinide (4-HPR) to prevent recurrences, new localizations and carcinomas in patients operated on for oral leukoplakia: long-term results.

We assessed the efficacy of fenretinide at preventing relapses, new lesions and carcinomas after surgical excision of oral leukoplakia. In a controlled multicenter study, 170 patients operated on for oral leukoplakias with benign postoperative histology were randomized to 200 mg fenretinide daily for 1 year vs. no intervention. Preliminary analysis indicated that fenretinide had good tolerability and was effective at preventing relapses and new lesions during treatment. Analysis after 5-year follow-up suggested that fenretinide protected against relapses and new lesions up to 19 months after randomization, with both limits of the 95% hazard ratio CI for fenretinide vs. control below 1 for 7 months after randomization. There was also a protective effect against all first events, including cancer, for 25 months, with both limits of the 95% CI below 1 up to 11 months after randomization. Subsequently, risk ratio estimates were unstable. Fenretinide was well tolerated and effective at preventing relapses and new leukoplakias during treatment and after. The trial had to be stopped prematurely for very low recruitment and had insufficient power to reveal any protective effect against oral carcinoma; nevertheless, continuing studies on this promising chemopreventive are justified.