A randomized, double-blind, placebo-controlled phase II clinical trial of lovastatin for various endpoints of melanoma pathobiology.
A randomized, double-blind, placebo-controlled phase II clinical trial of lovastatin for various endpoints of melanoma pathobiology.
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DOI：
10.1158/1940-6207.capr-13-0189
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Meyskens FL Jr
中科院分区：
文献类型：
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作者：
Linden KG;Leachman SA;Zager JS;Jakowatz JG;Viner JL;McLaren CE;Barr RJ;Carpenter PM;Chen WP;Elmets CA;Tangrea JA;Lim SJ;Cochran AJ;Meyskens FL Jr
基于降脂药的大型心血管临床试验显示活性药物组中原发性黑色素瘤的发病率显着降低，我们进行了一项随机、双盲临床试验，检查洛伐他汀对黑色素瘤发病机制的各种生物标志物的影响。患有至少两个临床非典型痣的受试者被随机接受口服洛伐他汀或安慰剂为期六个月。对两组的临床、组织病理学和分子生物标志物的变化进行了评估。 80 名受试者被随机化、可评估并纳入分析。与安慰剂相比，洛伐他汀在降低组织病理学异型性水平的主要终点、减少临床异型性、对痣数量的影响的任何次要终点以及任何分子生物标志物的显着变化方面都没有显示出任何益处。与安慰剂相比，洛伐他汀的不良事件特征没有显着差异。与安慰剂相比，洛伐他汀组的血清总胆固醇和血清低密度脂蛋白水平确实显着降低，这是预期的结果。这一发现增强了人们对受试者依从性的信心。鉴于该试验的结果，得出的结论是，如果洛伐他汀要降低黑色素瘤的发病率，那么它似乎并不是通过在研究的六个月时间范围内逆转前体非典型痣的异型性来实现这一目的。需要进一步研究黑色素瘤的发病机制和其他潜在的化学预防剂。
Based on large cardiovascular clinical trials of lipid lowering agents that showed a considerable decrease in 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 six month period. Clinical, histopathologic, and molecular biomarkers were evaluated for change in the two groups. 80 subjects were randomized, evaluable, and included in the analyses. Lovastatin showed no benefit in comparison to 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 to placebo. The lovastatin arm did show a significant and considerable decrease in total serum cholesterol and serum LDL levels compared to 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 six month time frame studied. Further research into the pathogenesis of melanoma and in other potential chemopreventive agents is needed.