Section of Molecular Gastroenterology, Leeds Institute of Biomedical & Clinical Sciences, St James's University Hospital, Leeds, UK Department of Hepatobiliary Surgery, Leeds Teaching Hospitals NHS Trust, St James's University Hospital, Leeds, UK.
Section of Molecular Gastroenterology, Leeds Institute of Biomedical & Clinical Sciences, St James's University Hospital, Leeds, UK.
Gut. 2014 Nov;63(11):1760-8. doi: 10.1136/gutjnl-2013-306445. Epub 2014 Jan 27.
Oral administration of the omega-3 fatty acid eicosapentaenoic acid (EPA), as the free fatty acid (FFA), leads to EPA incorporation into, and reduced growth of, experimental colorectal cancer liver metastases (CRCLM).
We performed a Phase II double-blind, randomised, placebo-controlled trial of EPA-FFA 2 g daily in patients undergoing liver resection surgery for CRCLM. The patients took EPA-FFA (n=43) or placebo (n=45) prior to surgery. The primary end-point was the CRCLM Ki67 proliferation index (PI). Secondary end-points included safety and tolerability of EPA-FFA, tumour fatty acid content and CD31-positive vascularity. We also analysed overall survival (OS) and disease-free survival (DFS).
The median (range) duration of EPA-FFA treatment was 30 (12-65) days. Treatment groups were well matched with no significant difference in disease burden at surgery or preoperative chemotherapy. EPA-FFA treatment was well tolerated with no excess of postoperative complications. Tumour tissue from EPA-FFA-treated patients demonstrated a 40% increase in EPA content (p=0.0008), no difference in Ki67 PI, but reduced vascularity in 'EPA-naïve' individuals (p=0.075). EPA-FFA also demonstrated antiangiogenic activity in vitro. In the first 18 months after CRCLM resection, EPA-FFA-treated individuals obtained OS benefit compared with placebo, although early CRC recurrence rates were similar.
EPA-FFA therapy is safe and well tolerated in patients with advanced CRC undergoing liver surgery. EPA-FFA may have antiangiogenic properties. Remarkably, limited preoperative treatment may provide postoperative OS benefit. Phase III clinical evaluation of prolonged EPA-FFA treatment in CRCLM patients is warranted.
ClinicalTrials.gov NCT01070355.
口服欧米伽-3 脂肪酸二十碳五烯酸（EPA）作为游离脂肪酸（FFA），可导致 EPA 掺入并抑制实验性结直肠癌肝转移（CRCLM）的生长。
我们对接受结直肠癌肝转移切除术的患者进行了一项 II 期双盲、随机、安慰剂对照的 EPA-FFA 每日 2g 试验。患者在术前服用 EPA-FFA（n=43）或安慰剂（n=45）。主要终点是 CRCLM Ki67 增殖指数（PI）。次要终点包括 EPA-FFA 的安全性和耐受性、肿瘤脂肪酸含量和 CD31 阳性血管密度。我们还分析了总生存期（OS）和无病生存期（DFS）。
EPA-FFA 治疗的中位（范围）时间为 30（12-65）天。治疗组在手术时的疾病负担或术前化疗方面无显著差异，匹配良好。EPA-FFA 治疗耐受性良好，术后并发症无增加。接受 EPA-FFA 治疗的患者的肿瘤组织 EPA 含量增加了 40%（p=0.0008），Ki67 PI 无差异，但在“EPA 初治”个体中血管密度降低（p=0.075）。EPA-FFA 还在体外显示出抗血管生成活性。在结直肠癌肝转移切除后的前 18 个月，EPA-FFA 治疗组与安慰剂组相比获得了 OS 获益，尽管早期 CRC 复发率相似。
在接受肝脏手术的晚期 CRC 患者中，EPA-FFA 治疗安全且耐受良好。EPA-FFA 可能具有抗血管生成特性。值得注意的是，有限的术前治疗可能提供术后 OS 获益。需要进行 III 期临床试验评估 EPA-FFA 治疗结直肠癌肝转移患者的疗效。
ClinicalTrials.gov NCT01070355。
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