title: Beta-carotene produces sustained remissions in patients with oral leukoplakia: results of a multicenter prospective trial.
abstract: BACKGROUND
  Beta-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 beta-carotene.
  
  
  METHODS
  In this multicenter, double-blind, placebo-controlled trial, subjects were given beta-carotene, 60 mg/d, for 6 months. At 6 months, responders were randomized to continue beta-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 beta-carotene arm and 2 (17%) of 12 in the placebo arm relapsed. Baseline biopsies were performed in all patients, with dysplasia 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. Beta-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 beta-carotene therapy.
  
  
  CONCLUSIONS
  The activity of beta-carotene in patients with oral leukoplakia was confirmed. The responses produced were durable for 1 year.
authors.affiliation: Arizona Cancer Center, University of Arizona, Southern Arizona Veterans' Affairs Healthcare System, Tucson 85723, USA. hgarewal@azcc.arizona.edu
authors.forename: H S
authors.initials: HS
authors.lastname: Garewal
authors.forename: R V
authors.initials: RV
authors.lastname: Katz
authors.forename: F
authors.initials: F
authors.lastname: Meyskens
authors.forename: J
authors.initials: J
authors.lastname: Pitcock
authors.forename: D
authors.initials: D
authors.lastname: Morse
authors.forename: S
authors.initials: S
authors.lastname: Friedman
authors.forename: Y
authors.initials: Y
authors.lastname: Peng
authors.forename: D G
authors.initials: DG
authors.lastname: Pendrys
authors.forename: S
authors.initials: S
authors.lastname: Mayne
authors.forename: D
authors.initials: D
authors.lastname: Alberts
authors.forename: T
authors.initials: T
authors.lastname: Kiersch
authors.forename: E
authors.initials: E
authors.lastname: Graver
mesh_terms: D000368:Aged; D000428:Alcohol Drinking; D000975:Antioxidants / Q000627:therapeutic use*; D004032:Diet; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007972:Leukoplakia, Oral / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012907:Smoking; D016896:Treatment Outcome; D019207:beta Carotene / Q000097:blood / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D019207:beta Carotene