Alberts David, Ranger-Moore James, Einspahr Janine, Saboda Kathylynn, Bozzo Paul, Liu Yun, Xu Xiao-Chun, Lotan Reuben, Warneke James, Salasche Stuart, Stratton Suzanne, Levine Norman, Goldman Rayna, Islas Marcy, Duckett Laura, Thompson Deborah, Bartels Peter, Foote Janet
Department of Medicine, Arizona Cancer Center, College of Medicine, College of Public Health, University of Arizona, Tucson, Arizona 85724-05024, USA.
Clin Cancer Res. 2004 Mar 15;10(6):1875-80. doi: 10.1158/1078-0432.ccr-03-0188.
Previously, we reported the results of a Phase III, placebo-controlled trial in 2297 randomized participants with moderately severe actinic keratoses wherein 25000 IU/day vitamin A caused a 32% risk reduction in squamous cell skin cancers. We hypothesized that dose escalation of vitamin A to 50000 or 75000 IU/day would be both safe and more efficacious in skin cancer chemoprevention.
One hundred and twenty-nine participants with severely sun-damaged skin on their lateral forearms were randomized to receive placebo or 25000, 50000, or 75000 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.
There were no significant differences in expected clinical and laboratory toxicities between the groups of participants randomized to placebo, 25000 IU/day, 50000 IU/day, and 75000 IU/day. Karyometric features were computed from the basal cell layer of skin biopsies, and a total of 22600 nuclei from 113 participants were examined, showing statistically significant, dose-response effects for vitamin A at the 25000 and 50000 IU/day doses. These karyometric changes correlated with increases in retinoic acid receptor alpha, retinoic acid receptor beta, and retinoid X receptor alpha at the 50000 IU/day vitamin A dose.
The vitamin A doses of 50000 and 75000 IU/day for 1 year proved safe and equally more efficacious than the 25000 IU/day dose and can be recommended for future skin cancer chemoprevention studies.
此前，我们报告了一项针对2297名中度严重光化性角化病随机参与者的III期安慰剂对照试验结果，其中每天25000国际单位维生素A使皮肤鳞状细胞癌风险降低了32%。我们假设将维生素A剂量增至每天50000或75000国际单位在皮肤癌化学预防中既安全又更有效。
129名前臂外侧皮肤严重晒伤的参与者被随机分配接受安慰剂或每天25000、50000或75000国际单位维生素A，为期12个月。主要研究终点是维生素A的临床和实验室安全性，次要终点包括对晒伤皮肤中类视黄醇和类视黄醇X受体的定量、核测量图像分析和评估。
随机接受安慰剂、每天25000国际单位、50000国际单位和75000国际单位的参与者组之间，预期的临床和实验室毒性无显著差异。从皮肤活检的基底细胞层计算核测量特征，共检查了113名参与者的22600个细胞核，结果显示，每天25000和50000国际单位剂量的维生素A具有统计学显著的剂量反应效应。这些核测量变化与每天50000国际单位维生素A剂量下视黄酸受体α、视黄酸受体β和类视黄醇X受体α的增加相关。
为期1年、每天50000和75000国际单位的维生素A剂量被证明是安全的，且比每天25000国际单位的剂量同样更有效，可推荐用于未来的皮肤癌化学预防研究。
