This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Alberts, D. Articles by Bartels, P. Search for Related Content PubMed PubMed Citation Articles by Alberts, D. Articles by Bartels, P.

Safety and Efficacy of Dose-Intensive Oral Vitamin A in Subjects with Sun-Damaged Skin

¹ Department of Medicine, ² Arizona Cancer Center, ³ College of Medicine, ⁴ College of Public Health, ⁵ Department of Surgery, ⁶ Section of Dermatology, and ⁷ Optical Sciences Center, University of Arizona, Tucson, Arizona, and ⁸ University of Texas M. D. Anderson Cancer Center, Houston, Texas

ABSTRACT

Purpose: Previously, we reported the results of a Phase III, placebo-controlled trial in 2,297 randomized participants with moderately severe actinic keratoses wherein 25,000 IU/day vitamin A caused a 32% risk reduction in squamous cell skin cancers. We hypothesized that dose escalation of vitamin A to 50,000 or 75,000 IU/day would be both safe and more efficacious in skin cancer chemoprevention.

Experimental Design: One hundred and twenty-nine participants with severely sun-damaged skin on their lateral forearms were randomized to receive placebo or 25,000, 50,000, or 75,000 IU/day vitamin A for 12 months. The primary study end points were the clinical and laboratory safety of vitamin A, and the secondary end points included quantitative, karyometric image analysis and assessment of retinoid and rexinoid receptors in sun-damaged skin.

Results: There were no significant differences in expected clinical and laboratory toxicities between the groups of participants randomized to placebo, 25,000 IU/day, 50,000 IU/day, and 75,000 IU/day. Karyometric features were computed from the basal cell layer of skin biopsies, and a total of 22,600 nuclei from 113 participants were examined, showing statistically significant, dose-response effects for vitamin A at the 25,000 and 50,000 IU/day doses. These karyometric changes correlated with increases in retinoic acid receptor , retinoic acid receptor ß, and retinoid X receptor at the 50,000 IU/day vitamin A dose.

Conclusions: The vitamin A doses of 50,000 and 75,000 IU/day for 1 year proved safe and equally more efficacious than the 25,000 IU/day dose and can be recommended for future skin cancer chemoprevention studies.

This article has been cited by other articles:

				J. G. Einspahr, M.-J. Xu, J. Warneke, K. Saboda, J. Ranger-Moore, P. Bozzo, L. Duckett, R. Goldman, P. Lin, J. Buckmeier, et al. Reproducibility and Expression of Skin Biomarkers in Sun-Damaged Skin and Actinic Keratoses Cancer Epidemiol. Biomarkers Prev., October 1, 2006; 15(10): 1841 - 1848. [Abstract] [Full Text] [PDF]

				R. L. Sedjo, J. Ranger-Moore, J. Foote, N. E. Craft, D. S. Alberts, M.-J. Xu, and A. R. Giuliano Circulating Endogenous Retinoic Acid Concentrations among Participants Enrolled in a Randomized Placebo-Controlled Clinical Trial of Retinyl Palmitate Cancer Epidemiol. Biomarkers Prev., November 1, 2004; 13(11): 1687 - 1692. [Abstract] [Full Text] [PDF]