Livingstone Elisabeth, Hollestein Loes M, van Herk-Sukel Myrthe P P, van de Poll-Franse Lonneke, Joosse Arjen, Schilling Bastian, Nijsten Tamar, Schadendorf Dirk, de Vries Esther
Department of Dermatology, University Hospital Duisburg-Essen, Essen, Germany.
Cancer Med. 2014 Oct;3(5):1284-93. doi: 10.1002/cam4.285. Epub 2014 Jun 17.
Preclinical data showed anticancer effects of statins in melanoma, but meta-analyses could not demonstrate a reduced melanoma incidence in statin users. Rather than preventing occurrence, statins might reduce growth and metastatic spread of melanomas and ultimately improve survival. In this population-based study, we investigated the relationship between statin use and survival of melanoma patients. Patients ≥18 years who were diagnosed with cutaneous melanoma (Breslow thickness >1 mm) and registered in the Eindhoven Cancer Registry and in PHARMO Database Network between 1 January 1998 and 31 December 2010 were eligible. The hazard ratio (HR) of all-cause mortality was calculated by employing adjusted time-dependent and time-fixed Cox proportional hazard models. Disease-specific survival was estimated by means of 3-year relative survival rates (RSR). A control cohort of randomly selected patients using statins from PHARMO Database Network matched on age and gender was used to compare RSR of statin users to the general population. After melanoma diagnosis, 171 of 709 patients used statins. Use of statins showed a nonsignificantly decreased hazard of death (adjusted HR 0.76, 95% confidence interval [CI] 0.50-1.61). After stratification for gender, male but not female statin users showed a favorable outcome compared to nonusers (HR 0.57, 95% CI 0.32-0.99; HR 1.22, 95% CI 0.62-2.38, respectively). Three-year RSR for male statin users tended to be higher than for nonusers (91% vs. 80.5%, P = 0.06), no differences were observed in women (87.1% vs. 92.5%, P = 0.76). Statin use was not associated with an improved survival of melanoma patients. The trend for better survival of male in contrast to female statin users warrants further research.
临床前数据显示他汀类药物对黑色素瘤具有抗癌作用，但荟萃分析未能证明他汀类药物使用者的黑色素瘤发病率有所降低。他汀类药物可能无法预防黑色素瘤的发生，而是会减少其生长和转移扩散，并最终提高生存率。在这项基于人群的研究中，我们调查了他汀类药物的使用与黑色素瘤患者生存率之间的关系。纳入标准为1998年1月1日至2010年12月31日期间在埃因霍温癌症登记处和PHARMO数据库网络中登记的、年龄≥18岁且被诊断为皮肤黑色素瘤（Breslow厚度>1mm）的患者。采用调整后的时间依赖性和时间固定的Cox比例风险模型计算全因死亡率的风险比（HR）。通过3年相对生存率（RSR）估计疾病特异性生存率。使用来自PHARMO数据库网络的按年龄和性别匹配的随机选择的使用他汀类药物的患者作为对照队列，以比较他汀类药物使用者与一般人群的RSR。黑色素瘤诊断后，709例患者中有171例使用他汀类药物。使用他汀类药物显示死亡风险有非显著性降低（调整后HR 0.76，95%置信区间[CI] 0.50 - 1.61）。按性别分层后，男性他汀类药物使用者与未使用者相比显示出较好的结果（HR 0.57，95% CI 0.32 - 0.99；女性分别为HR 1.22，95% CI 0.62 - 2.38）。男性他汀类药物使用者的3年RSR倾向于高于未使用者（91%对80.5%，P = 0.06），女性未观察到差异（87.1%对92.5%，P = 0.76）。使用他汀类药物与黑色素瘤患者生存率的改善无关。与女性他汀类药物使用者相比，男性生存率更好的趋势值得进一步研究。
