title: Phase 1 study of topical perillyl alcohol cream for chemoprevention of skin cancer.
abstract: 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. Endpoints included safety and evaluation of any histopathological changes in skin after 1 mo use of POH cream. We randomized 25 subjects with normal, healthy skin with little or no sun damage and no history of skin cancer in a double-blind fashion to receive topical POH (0.76% wt/wt) on 1 forearm with placebo cream applied to the other forearm twice daily for 30 days. Subjects were monitored for toxicity, and a 4 mm punch biopsy in the treated area was performed at the end of study for histopathological evaluation. The topical cream was well tolerated. No serious cutaneous toxicities, systemic toxicities, or histopathological abnormalities were observed. A total of 8 subjects (32%) reported mild adverse events possibly or probably related to use of cream including reversible appearance of 1 to 2 small papules. However, there was no significant difference between lesions appearing on the POH treated forearm vs. the placebo-treated forearm.
authors.affiliation: Arizona Cancer Center and Department of Medicine, College of Medicine, University of Arizona, Tucson, Arizona 85724, USA. sstratton@azcc.arizona.edu
authors.forename: Steven P
authors.initials: SP
authors.lastname: Stratton
authors.forename: Kathy Lynn
authors.initials: KL
authors.lastname: Saboda
authors.forename: Paul B
authors.initials: PB
authors.lastname: Myrdal
authors.forename: Abhishek
authors.initials: A
authors.lastname: Gupta
authors.forename: Naja E
authors.initials: NE
authors.lastname: McKenzie
authors.forename: Chris
authors.initials: C
authors.lastname: Brooks
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Salasche
authors.forename: James A
authors.initials: JA
authors.lastname: Warneke
authors.forename: James
authors.initials: J
authors.lastname: Ranger-Moore
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bozzo
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.forename: Janine G
authors.initials: JG
authors.lastname: Einspahr
authors.forename: Robert T
authors.initials: RT
authors.lastname: Dorr
authors.forename: Norman
authors.initials: N
authors.lastname: Levine
authors.forename: David S
authors.initials: DS
authors.lastname: Alberts
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005542:Forearm; D006801:Humans; D008297:Male; D008875:Middle Aged; D039821:Monoterpenes / Q000008:administration & dosage* / Q000009:adverse effects; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D012878:Skin Neoplasms / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D039821:Monoterpenes; C032208:perillyl alcohol