title: Treatment of oral leukoplakia with a low-dose of beta-carotene and vitamin C supplements: a randomized controlled trial.
abstract: Management of oral leukoplakia-a potentially malignant disorder-is currently not evidence-based. Of the few randomized trials that have been reported, most have negative data. Therefore, a multi-centre, randomized, double-blind controlled trial (RCT) was undertaken to evaluate the use of low-dose beta-carotene combined with vitamin C supplements for the treatment and to prevent malignant transformation of oral leukoplakia. 46 Japanese participants with oral leukoplakia were allocated randomly either to an experimental arm (10 mg day(-1) of beta-carotene and 500 mg day(-1) of vitamin C) or placebo arm (50 mg day(-1) of vitamin C). Current or ex-smokers within 3 months of cessation were excluded. The supplements were continued over a period of 1 year. The primary endpoint was clinical remission at 1-year and the likelihood of malignant transformation during a 5-year follow-up period as a secondary endpoint. The overall clinical response rate in the experimental arm was 17.4% (4/23) and 4.3% (1/23) in the placebo arm (p = 0.346). During the median 60-month follow-up period, two subjects in the experimental arm and three in the control arm developed oral cancer. Under the intention-to-treat principle, relative risk by supplementing with beta-carotene and vitamin C was 0.77 (95%CI: 0.28-1.89) (p = 0.580) by the Cox proportional hazards model. No unfavorable side-effects were noted. Beta-carotene (10 mg day(-1) ) and vitamin C were neither effective for clinical remission, nor for protection against the development of cancer. Data from this RCT does not support the hypothesis that chemoprevention with this treatment is effective for oral leukoplakia.
authors.affiliation: Department of Oral and Maxillofacial Surgery and Stomatology, Okazaki City Hospital, Okazaki, Japan; Department of Oral Medicine, WHO Collaborating Centre for Oral Cancer/Precancer, King's, College London Dental Institute at Guy's, King's & St. Thomas' Hospitals, London, United Kingdom; Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan; Department of Hygiene, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nagao
authors.forename: Saman
authors.initials: S
authors.lastname: Warnakulasuriya
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kato
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hideo
authors.initials: H
authors.lastname: Fukano
authors.forename: Koji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shimozato
authors.forename: Shuji
authors.initials: S
authors.lastname: Hashimoto
mesh_terms: D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D002471:Cell Transformation, Neoplastic; D019587:Dietary Supplements; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007972:Leukoplakia, Oral / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome; D019207:beta Carotene / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D019207:beta Carotene; D001205:Ascorbic Acid
keywords: beta-carotene; chemoprevention; clinical trial; malignant transformation; oral leukoplakia; vitamin C