Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, USA.
J Natl Cancer Inst. 2011 Oct 19;103(20):1540-51. doi: 10.1093/jnci/djr307. Epub 2011 Aug 17.
Although preclinical and epidemiological data suggest that statins may have antineoplastic properties, the impact of statin use on patient survival after a curative resection of stage III colon cancer is unknown.
We conducted a prospective observational study of 842 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial from April 1999 to May 2001 to investigate the relationship between statin use and survival. Disease-free survival (DFS), recurrence-free survival (RFS), and overall survival (OS) were investigated by Kaplan-Meier curves and log-rank tests in the overall study population and in a subset of patients stratified by KRAS mutation status (n = 394), and Cox proportional hazards regression was used to assess the simultaneous impact of confounding variables. All statistical tests were two-sided.
Among 842 patients, 134 (15.9%) reported statin use after completing adjuvant chemotherapy. DFS among statin users and nonusers was similar (hazard ratio [HR] of cancer recurrence or death = 1.04, 95% confidence interval [CI] = 0.73 to 1.49). RFS and OS were also similar between statin users and nonusers (adjusted HR of cancer recurrence = 1.14, 95% CI = 0.77 to 1.69; adjusted HR of death = 1.15, 95% CI = 0.77 to 1.71). Survival outcomes were similar regardless of increasing duration of statin use before cancer diagnosis (P(trend) = .63, .63, and .59 for DFS, RFS, and OS, respectively). The impact of statin use did not differ by tumor KRAS mutation status, with similar DFS, RFS, and OS for statin use among mutant and wild-type subgroups (P(interaction) = .84, .67, and .98 for DFS, RFS, and OS, respectively).
Statin use during and after adjuvant chemotherapy was not associated with improved DFS, RFS, or OS in patients with stage III colon cancer, regardless of KRAS mutation status.
尽管临床前和流行病学数据表明他汀类药物可能具有抗肿瘤特性,但他汀类药物的使用对接受根治性 III 期结肠癌切除术的患者的生存影响尚不清楚。
我们对 1999 年 4 月至 2001 年 5 月参加随机辅助化疗试验的 842 例 III 期结肠癌患者进行了前瞻性观察性研究,以调查他汀类药物使用与生存之间的关系。在整个研究人群和按 KRAS 突变状态分层的亚组(n=394)中,通过 Kaplan-Meier 曲线和对数秩检验研究了他汀类药物使用与无病生存(DFS)、无复发生存(RFS)和总生存(OS)的关系,并使用 Cox 比例风险回归评估混杂变量的同时影响。所有统计检验均为双侧。
在 842 例患者中,有 134 例(15.9%)在完成辅助化疗后报告使用了他汀类药物。使用他汀类药物和未使用者的 DFS 相似(癌症复发或死亡的风险比[HR] = 1.04,95%置信区间[CI] = 0.73 至 1.49)。RFS 和 OS 也在他汀类药物使用者和未使用者之间相似(癌症复发的调整 HR = 1.14,95%CI = 0.77 至 1.69;死亡的调整 HR = 1.15,95%CI = 0.77 至 1.71)。无论癌症诊断前他汀类药物使用时间的长短如何,生存结果均相似(DFS、RFS 和 OS 的 P(趋势)分别为.63、.63 和.59)。他汀类药物使用的影响与肿瘤 KRAS 突变状态无关,在突变和野生型亚组中,他汀类药物使用的 DFS、RFS 和 OS 相似(DFS、RFS 和 OS 的 P(交互作用)分别为.84、.67 和.98)。
无论 KRAS 突变状态如何,在接受 III 期结肠癌辅助化疗期间和之后使用他汀类药物均不能改善 DFS、RFS 或 OS。