A randomized, double-blind, placebo-controlled phase II clinical trial of lovastatin for various endpoints of melanoma pathobiology

Kenneth G. Linden, Sancy Leachman, Jonathan S. Zager, James G. Jakowatz, Jaye L. Viner, Christine E. McLaren, Ronald J. Barr, Philip M. Carpenter, Wen Pin Chen, Craig A. Elmets, Joseph A. Tangrea, Sung Jig Lim, Alistair J. Cochran, Frank L. Meyskens

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)496-504
Number of pages9
JournalCancer Prevention Research
Volume7
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

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Lovastatin
Phase II Clinical Trials
Controlled Clinical Trials
Melanoma
Placebos
Nevus
Biomarkers
Clinical Trials
Incidence
Serum
LDL Cholesterol
Lipids
Research

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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A randomized, double-blind, placebo-controlled phase II clinical trial of lovastatin for various endpoints of melanoma pathobiology. / Linden, Kenneth G.; Leachman, Sancy; Zager, Jonathan S.; Jakowatz, James G.; Viner, Jaye L.; McLaren, Christine E.; Barr, Ronald J.; Carpenter, Philip M.; Chen, Wen Pin; Elmets, Craig A.; Tangrea, Joseph A.; Lim, Sung Jig; Cochran, Alistair J.; Meyskens, Frank L.

In: Cancer Prevention Research, Vol. 7, No. 5, 2014, p. 496-504.

Research output: Contribution to journalArticle

Linden, KG, Leachman, S, Zager, JS, Jakowatz, JG, Viner, JL, McLaren, CE, Barr, RJ, Carpenter, PM, Chen, WP, Elmets, CA, Tangrea, JA, Lim, SJ, Cochran, AJ & Meyskens, FL 2014, 'A randomized, double-blind, placebo-controlled phase II clinical trial of lovastatin for various endpoints of melanoma pathobiology', Cancer Prevention Research, vol. 7, no. 5, pp. 496-504. https://doi.org/10.1158/1940-6207.CAPR-13-0189
Linden, Kenneth G. ; Leachman, Sancy ; Zager, Jonathan S. ; Jakowatz, James G. ; Viner, Jaye L. ; McLaren, Christine E. ; Barr, Ronald J. ; Carpenter, Philip M. ; Chen, Wen Pin ; Elmets, Craig A. ; Tangrea, Joseph A. ; Lim, Sung Jig ; Cochran, Alistair J. ; Meyskens, Frank L. / A randomized, double-blind, placebo-controlled phase II clinical trial of lovastatin for various endpoints of melanoma pathobiology. In: Cancer Prevention Research. 2014 ; Vol. 7, No. 5. pp. 496-504.
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