β-Carotene produces sustained remissions in patients with oral leukoplakia. Results of a multicenter prospective trial

Background: β-Carotene has been reported to produce regressions in patients with oral leukoplakia, a premalignant lesion. However, previous studies have all been of short duration, with clinical response as the end point. Objective: To evaluate the duration of response and the need for maintenance therapy in subjects who respond to β-carotene. Methods: In this multicenter, double-blind, placebo- controlled trial, subjects were given β- carotene, 60 mg/d, for 6 months. At 6 months, responders were randomized to continue β-carotene or placebo therapy for 12 additional months. Results: Fifty-four subjects were enrolled in the trial, with 50 being evaluable. At 6 months, 26 subjects (52%) had a clinical response. Twenty-three of the 26 responders completed the second, randomized phase. Only 2 (18%) of 11 in the β-carotene arm and 2 (17%) of 12 in the placebo arm relapsed. Baseline biopsies were per- formed in all patients, with displasia being present in 19 (38%) of the 50 evaluable patients. A second biopsy was obtained at 6 months in 23 subjects who consented to this procedure. There was improvement of at least 1 grade of dysplasia in 9 (39%), with no change in 14 (61%). Nutritional intake was assessed using food frequency questionnaires. There was no change in carotenoid intake during the trial. Responders had a lower intake of dietary fiber, fruits, folate, and vitamin E supplements than did nonresponders. β-Carotene levels were measured in plasma and oral cavity cells. Marked increases occurred during the 6-month induction. However, baseline levels were not restored in subjects taking placebo for 6 to 9 months after-discontinuation of β-carotene therapy. Conclusions: The activity of β-carotene in patients with oral leukoplakia was confirmed. The responses produced were durable for 1 year.