Phase 1 study of topical perillyl alcohol cream for chemoprevention of skin cancer.

Perillyl alcohol (POH) is a natural product derived from plants such as cherry and lavendin. Previous studies have indicated that topical POH inhibits ultraviolet (UV) B-induced skin carcinogenesis in vivo, and it may be an effective chemopreventive agent for skin cancer. We performed a 1-mo, first-in-man, Phase 1 trial of topically administered POH cream in human subjects.

Reproducibility and expression of skin biomarkers in sun-damaged skin and actinic keratoses.

Objectives: To explore p53 and proliferating cell nuclear antigen (PCNA) expression and polyamine content as biomarkers in skin cancer chemoprevention trials, we evaluated their expression in early stages of UV-induced squamous cell tumorigenesis.

Methods: Biopsies were collected from three groups: 78 subjects with sun damage on forearms, 33 with actinic keratosis (AK) on forearms, and 32 with previous squamous cell carcinoma. Participants with sun damage were randomized to sunscreen or no sunscreen.

Karyometric analysis of actinic damage in unexposed and sun-exposed skin and in actinic keratoses in untreated individuals.

Objective: To assess the ability of karyometric analysis to demonstrate progression of actinic damage as a function of sun exposure in individuals with actinic keratoses (AKs) and to evaluate the stability of that assessment over a 3-month period.

Study Design: Biopsies from subjects with AKs were obtained from unexposed skin, sun-exposed skin and AK lesions. Subjects used an SPF 50 sunscreen, and 3 months later additional biopsies were taken from sun-exposed and AK sites.

Safety and efficacy of dose-intensive oral vitamin A in subjects with sun-damaged skin.

Purpose: 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.

Experimental Design: 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.

Karyometry of nuclei from actinic keratosis and squamous cell cancer of the skin.

Objective: To use karyometric analysis methods to compare actinic keratoses (AKs) to squamous cell carcinomas (SCCs) to determine if SCCs showed a logical progression beyond that seen in AKs and to explore variability within and between lesion types to better understand distinctions between the 2.

Study Design: Biopsies from 31 subjects with AKs were obtained from upper inner arm skin, forearm skin and AK lesions. Biopsies from 23 different subjects in a related subproject provided SCC biopsies for comparison.

Reliability and validity of a histologic score as a marker for skin cancer chemoprevention studies.

Objective: To develop a reliable and valid scoring system for grading skin biopsies from actinic keratosis (AK) and sun-damaged skin for use in evaluating the efficacy of skin cancer chemopreventive agents.

Study Design: A panel of dermatopathologists developed histologic criteria and diagnostic definitions for the progression of lesions from early AK to AK. The criteria were then applied to a sample of 335 histologic slides from an ongoing chemoprevention study.

Statistical analysis of chemopreventive efficacy of vitamin A in sun-exposed, normal skin.

Objective: To develop numeric, statistically secured measures of chemopreventive efficacy and to derive procedures with high sensitivity of detection.

Study Design: Karyometric features were computed for nuclei from the basal cell layer of biopsies taken from sun-exposed but histologically "normal" skin. Biopsies were collected from placebo-treated subjects and subjects treated for one year with daily, oral doses of 25,000, 50,000 and 75,000 IU of vitamin A.