The quality of evidence is downgraded by study limitations (unclear allocation concealment), and by imprecise results (few patients and otcome events).
A Cochrane review included 14 studies with a total of 909 subjects. The included studies tested a range of medical and complementary treatments: vitamin A and retinoids (4 studies), beta carotene or carotenoids (3 studies), non-steroidal anti-inflammatory drugs (NSAIDs), specifically ketorolac and celecoxib (2 studies), herbal extracts including tea components, a Chinese herbal mixture and freeze-dried black raspberry gel (4 studies), bleomycin (1 study), and Bowman-Birk inhibitor (1 study).
Only 3 studies provided useable data on cancer incidence; active treatment did not reduce the risk of oral cancer more than placebo: systemic vitamin A (RR 0.11, 95% CI 0.01 to 2.05; 1 study, n=85), systemic beta carotene (RR 0.71, 95% CI 0.24 to 2.09; 2 studies, n=132), and topical bleomycin (RR 3.00, 95% CI 0.32 to 27.83; 1 study, n=20). Some individual studies suggested effectiveness of systemic vitamin A, beta carotene and lycopene for achieving clinical resolution of lesions more often than placebo. Similarly, single studies found that systemic retinoic acid and lycopene provided some benefit in terms of improvement in histological features. High rate of relapses was common. Side effects of varying severity were often described, but drop-out rates were similar between treatment and control groups.
A Cochrane reviewAn RCT with a total of 46 patients evaluated the use of low-dose beta-carotene combined with vitamin C supplements for the treatment and to prevent malignant transformation of oral leukoplakia. They were allocated randomly either to an experimental arm (10 mg day of beta-carotene and 500 mg day of vitamin C) or placebo arm (50 mg day of vitamin C) for 1 year. The clinical remission in the experimental arm was 17.4% (4/23) vs. 4.3% (1/23) in the placebo arm (p = 0.346). During the median 60-month follow-up period, 2 subjects in the experimental arm and 3 in the control arm developed oral cancer. RR by supplementing with beta-carotene and vitamin C was 0.77 (95%CI: 0.28-1.89) (p = 0.580).