13-cis-Retinoic Acid in the Treatment of Oral Leukoplakia

13- cis -Retinoic acid has been reported to be effective in treating oral leukoplakia. We randomly assigned 44 patients with this disease to receive 13- cis -retinoic acid (24 patients) or placebo (20), 1 to 2 mg per kilogram of body weight per day for three months, and followed them for six months. There were major decreases in the size of the lesions in 67 percent (16 patients) of those given the drug and in 10 percent (2 patients) of those given placebo (P = 0.0002); dysplasia was reversed in 54 percent (13 patients) of the drug group and in 10 percent (2 patients) of the placebo group (P = 0.01). The clinical response to the drug correlated with the histologic response in 56 percent (9 of 16) of the patients evaluated. Relapse occurred in 9 of 16 patients two to three months after treatment ended. The toxic effects of the drug were acceptable in all but two patients. Cheilitis, facial erythema, and dryness and peeling of the skin were common; conjunctivitis and hypertriglyceridemia also occurred. All adverse reactions could be reversed by reducing the dose or temporarily discontinuing the drug. We conclude that 13- cis -retinoic acid, even in short-term use, appears to be an effective treatment for oral leukoplakia and has an acceptable level of toxicity. (N Engl J Med 1986;315:1501–5.) BECAUSE leukoplakia may precede invasive carcinoma by months or years or may accompany overt carcinomas, it is assumed to be etiologically associated with oral cancer as a premalignant lesion. 1 2 3 4 5 6 Malignant transformation occurs in as many as 3 to 6 percent of lesions evaluated. 1 2 3 4 5 The treatment of choice for localized leukoplakia is surgical removal, but a wide distribution of mucosal lesions precludes excision. 1 2 3 4 5 6 Recent reports from several nonrandomized studies, however, suggest that oral leukoplakia can be reversed by systemic or local administration of retinoids. 7 8 9 Such an approach is based on findings that vitamin A deficiency in rodents leads to squamous metaplasia, . . .