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

David S Alberts, James Ranger-Moore, Janine G Einspahr, Kathylynn Saboda, Paul Bozzo, Yun Liu, Xiao Chun Xu, Reuben Lotan, James A Warneke, Stuart Salasche, Suzanne Stratton, Norman Levine, Rayna Goldman, Marcy Islas, Laura Duckett, Deborah Thompson, Peter Bartels

Research output: Contribution to journalArticle

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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 α, retinoic acid receptor β, and retinoid X receptor α 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.

Original languageEnglish (US)
Pages (from-to)1875-1880
Number of pages6
JournalClinical Cancer Research
Volume10
Issue number6
DOIs
StatePublished - Mar 15 2004

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Solar System
Vitamin A
Safety
Skin
Skin Neoplasms
Retinoic Acid Receptors
Placebos
Chemoprevention
Karyometry
Actinic Keratosis
Retinoid X Receptors
Squamous Cell Neoplasms
Retinoids
Risk Reduction Behavior
Forearm
Research Design
Biopsy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Safety and Efficacy of Dose-Intensive Oral Vitamin A in Subjects with Sun-Damaged Skin. / Alberts, David S; Ranger-Moore, James; Einspahr, Janine G; Saboda, Kathylynn; Bozzo, Paul; Liu, Yun; Xu, Xiao Chun; Lotan, Reuben; Warneke, James A; Salasche, Stuart; Stratton, Suzanne; Levine, Norman; Goldman, Rayna; Islas, Marcy; Duckett, Laura; Thompson, Deborah; Bartels, Peter.

In: Clinical Cancer Research, Vol. 10, No. 6, 15.03.2004, p. 1875-1880.

Research output: Contribution to journalArticle

Alberts, DS, Ranger-Moore, J, Einspahr, JG, Saboda, K, Bozzo, P, Liu, Y, Xu, XC, Lotan, R, Warneke, JA, Salasche, S, Stratton, S, Levine, N, Goldman, R, Islas, M, Duckett, L, Thompson, D & Bartels, P 2004, 'Safety and Efficacy of Dose-Intensive Oral Vitamin A in Subjects with Sun-Damaged Skin', Clinical Cancer Research, vol. 10, no. 6, pp. 1875-1880. https://doi.org/10.1158/1078-0432.CCR-03-0188
Alberts, David S ; Ranger-Moore, James ; Einspahr, Janine G ; Saboda, Kathylynn ; Bozzo, Paul ; Liu, Yun ; Xu, Xiao Chun ; Lotan, Reuben ; Warneke, James A ; Salasche, Stuart ; Stratton, Suzanne ; Levine, Norman ; Goldman, Rayna ; Islas, Marcy ; Duckett, Laura ; Thompson, Deborah ; Bartels, Peter. / Safety and Efficacy of Dose-Intensive Oral Vitamin A in Subjects with Sun-Damaged Skin. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 6. pp. 1875-1880.
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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 α, retinoic acid receptor β, and retinoid X receptor α 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.",
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AU - Ranger-Moore, James

AU - Einspahr, Janine G

AU - Saboda, Kathylynn

AU - Bozzo, Paul

AU - Liu, Yun

AU - Xu, Xiao Chun

AU - Lotan, Reuben

AU - Warneke, James A

AU - Salasche, Stuart

AU - Stratton, Suzanne

AU - Levine, Norman

AU - Goldman, Rayna

AU - Islas, Marcy

AU - Duckett, Laura

AU - Thompson, Deborah

AU - Bartels, Peter

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N2 - 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 α, retinoic acid receptor β, and retinoid X receptor α 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.

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