retinol-acetate and Leukoplakia--Oral

We conducted a double-blind placebo-controlled trial to evaluate the chemopreventive potential of either vitamin A alone or beta carotene alone in subjects with oral leukoplakia in Kerala, India. We randomised 160 fishermen and women with oral precancerous lesions to receive oral vitamin A (retinyl acetate 300,000 IU/week x 12 months, n = 50), or beta carotene (360 mg/week x 12 months, n = 55), or placebo (n = 55). Blood, saliva and urine samples were collected at baseline and at exit to study serum micronutrients and mutagenicity assays. Biopsies of the mucosal lesions at entry were performed for histopathological exclusion of malignancy. The subjects were examined once every 2 months to establish clinical response of lesions and toxicity, if any. The results are based on 43 complaint subjects on placebo, 42 on vitamin A and 46 on beta carotene. The complete regression rates were: 10% in the placebo arm, 52% with vitamin A and 33% with beta carotene (P < 0.0001). Homogeneous leukoplakias and smaller lesions responded better than non-homogeneous and larger lesions. No major toxicities were observed. Half of the responders with beta carotene and two thirds with vitamin A relapsed after stopping supplementation. Serum beta carotene concentration increased substantially with beta carotene administration while with vitamin A supplementation there was no change in serum retinol levels. In the vitamin A treated group there was a significant decrease in serum alpha tocopherol. Vitamin A administration resulted in a significant remission of oral leukoplakia without any side effects of prolonged vitamin A supplementation. The results of this study, as well as those from previous studies, appear to provide strong supporting evidence to justify long term trials with vitamin A in subjects with high-risk leukoplakias with oral cancer as an endpoint.

Topics: Adult; Anticarcinogenic Agents; beta Carotene; Diterpenes; Double-Blind Method; Female; Humans; Leukoplakia, Oral; Male; Micronutrients; Middle Aged; Mouth Neoplasms; Mutagenicity Tests; Retinyl Esters; Treatment Outcome; Vitamin A

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Diterpenes; Humans; Leukoplakia, Oral; Retinyl Esters; Vitamin A

Sixty young adult Syrian hamsters were divided into five groups. Group 1 and Group 2 animals were treated with 0.25% dimethylbenz(a)anthracene (DMBA), painted on their left buccal pouches thrice weekly for 20 weeks. Starting at 12 weeks, at which time there was clinical evidence of leukoplakia and initial tumor formation, Group 2 animals received 10 mg retinyl acetate 3 times/week in a 5% solution in peanut oil, while Group 1 animals received only peanut oil. Two animals in Group 1 and two animals in Group 2 were sacrificed weekly from week 12 to week 20. Left buccal pouches were examined, tumors were counted, and tumor size was measured. Group 3 animals were untreated controls, Group 4 animals were retinyl acetate controls, and Group 5 animals received only peanut oil. It was found that DMBA-treated animals receiving retinyl acetate from week 12 to week 20 developed fewer tumors, and their average tumor size was less than that in DMBA-treated animals not receiving retinyl acetate. It appears that retinyl acetate, administered systemically, can retard tumor development even after leukoplakia has been established and tumors have begun to develop.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma, Squamous Cell; Cheek; Cricetinae; Diterpenes; Leukoplakia, Oral; Mesocricetus; Mouth Neoplasms; Retinyl Esters; Vitamin A