Randomized double-blinded, placebo-controlled phase II trial of simvastatin and gemcitabine in advanced pancreatic cancer patients
Randomized double-blinded, placebo-controlled phase II trial of simvastatin and gemcitabine in advanced pancreatic cancer patients
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DOI：
10.1007/s00280-013-2328-1
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发表时间：
2014-01-01
影响因子：
3
通讯作者：
Park, Young Suk
中科院分区：
文献类型：
--
作者：
Hong, Jung Yong;Nam, Eun Mi;Park, Young Suk
他汀类药物通过阻止细胞周期进程和诱导细胞凋亡而具有潜在的抗肿瘤特性。先前的一项研究证明了他汀类药物和吉西他滨之间的体外和体内抗肿瘤协同作用。本随机、双盲、II 期试验比较了吉西他滨加辛伐他汀 (GS) 与吉西他滨加安慰剂 (GP) 在局部晚期和转移性胰腺癌患者中的疗效和安全性。患者被随机分配接受为期 3 周的 GS 治疗方案（第 1、8 和 15 天吉西他滨 1,000 mg/m(2) 加辛伐他汀 40 mg 每天一次）或 GP（吉西他滨 1,000 mg/m(2)，第 1、8 和 15 天加安慰剂）。主要终点是疾病进展时间（TTP）。2008 年 12 月至 2012 年 4 月期间，共有 114 名患者入组。两组之间的中位 TTP 无显着差异，GS 组和 GP 组分别为 2.4 个月（95% CI 0.7-4.1 个月）和 3.6 个月（95% CI 3.1-4.1 个月）（P = 0.903）。 GS 组和 GP 组的总体疾病控制率分别为 39.7% (95% CI 12.2-33.8%) 和 57.1% (95% CI 19.8-44.2%) (P = 0.09)。 1 年预期生存率相似（GS 组和 GP 组分别为 27.7% 和 31.7%；P = 0.654）。两组中 3 级或 4 级不良事件的发生率相似，并且没有患者出现横纹肌溶解症。在晚期胰腺癌中，在吉西他滨中添加低剂量辛伐他汀不会带来临床益处，但也不会导致毒性增加。鉴于他汀类药物在克服抗 EGFR 治疗耐药性方面的新作用，有必要进行进一步的研究来评估联合使用辛伐他汀和抗 EGFR 药物（如厄洛替尼或西妥昔单抗）以及吉西他滨治疗晚期胰腺癌的疗效和安全性。
Statins have potential antineoplastic properties via arrest of cell-cycle progression and induction of apoptosis. A previous study demonstrated in vitro and in vivo antineoplastic synergism between statins and gemcitabine. The present randomized, double-blinded, phase II trial compared the efficacy and safety of gemcitabine plus simvastatin (GS) with those of gemcitabine plus placebo (GP) in patients with locally advanced and metastatic pancreatic cancer.Patients were randomly assigned to receive a 3-week regimen with GS (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus simvastatin 40 mg once daily) or GP (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus placebo). The primary end point was time to progression (TTP).Between December 2008 and April 2012, 114 patients were enrolled. The median TTP was not significantly different between the two arms, being 2.4 months (95 % CI 0.7-4.1 months) and 3.6 months (95 % CI 3.1-4.1 months) in the GS and GP arms, respectively (P = 0.903). The overall disease control rate was 39.7 % (95 % CI 12.2-33.8 %) and 57.1 % (95 % CI 19.8-44.2 %) in the GS and GP arms, respectively (P = 0.09). The 1-year expected survival rates were similar (27.7 and 31.7 % in the GS and GP arms, respectively; P = 0.654). Occurrence of grade 3 or 4 adverse events was similar in both arms, and no patients had rhabdomyolysis.Adding low-dose simvastatin to gemcitabine in advanced pancreatic cancer does not provide clinical benefit, although it also does not result in increased toxicity. Given the emerging role of statins in overcoming resistance to anti-EGFR treatment, further studies are justified to evaluate the efficacy and safety of combined simvastatin and anti-EGFR agents, such as erlotinib or cetuximab, plus gemcitabine for treating advanced pancreatic cancer.