title: A randomized, double-blind, placebo-controlled phase II clinical trial of lovastatin for various endpoints of melanoma pathobiology.
abstract: On the basis of large cardiovascular clinical trials of lipid-lowering agents that showed a considerable decrease in the incidence of primary melanomas in the active agent arm, we have carried out a randomized, double-blind clinical trial examining the impact of lovastatin on various biomarkers of melanoma pathogenesis. Subjects with at least two clinically atypical nevi were randomized to receive oral lovastatin or placebo for a 6-month period. Clinical, histopathologic, and molecular biomarkers were evaluated for change in the two groups. Eighty subjects were randomized, evaluable, and included in the analyses. Lovastatin showed no benefit in comparison with placebo in the primary endpoint of decreasing the level of histopathologic atypia, nor in any of the secondary endpoints of decreasing clinical atypia, impact on nevus number, nor in showing significant changes in any of the molecular biomarkers. There were no significant differences in adverse event profiles for lovastatin compared with placebo. The lovastatin arm did show a significant and considerable decrease in total serum cholesterol and serum low-density lipoprotein (LDL) levels compared with placebo, an expected result. This finding bolsters confidence in subject compliance. Given the results of this trial, it is concluded that if lovastatin were to lower the incidence of melanoma, it would appear not to be doing so by reversing atypia of precursor atypical nevi over the 6-month time frame studied. Further research into the pathogenesis of melanoma and in other potential chemopreventive agents is needed.
authors.affiliation: Department of Dermatology and The Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, 101 The City Drive, Orange, CA 92868. kglinden@uci.edu.
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Linden
authors.forename: Sancy A
authors.initials: SA
authors.lastname: Leachman
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Zager
authors.forename: James G
authors.initials: JG
authors.lastname: Jakowatz
authors.forename: Jaye L
authors.initials: JL
authors.lastname: Viner
authors.forename: Christine E
authors.initials: CE
authors.lastname: McLaren
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Barr
authors.forename: Philip M
authors.initials: PM
authors.lastname: Carpenter
authors.forename: Wen-Pin
authors.initials: WP
authors.lastname: Chen
authors.forename: Craig A
authors.initials: CA
authors.lastname: Elmets
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Tangrea
authors.forename: Sung-Jig
authors.initials: SJ
authors.lastname: Lim
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Cochran
authors.forename: Frank L
authors.initials: FL
authors.lastname: Meyskens
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000097:blood*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D008875:Middle Aged; D009506:Nevus / Q000097:blood / Q000473:pathology; D010919:Placebos; D012878:Skin Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology
chemical_list: D000924:Anticholesteremic Agents; D014408:Biomarkers, Tumor; D010919:Placebos; D008148:Lovastatin