Eltweri Amar M, Thomas Anne L, Chung Wen Y, Morgan Bruno, Thompson John, Dennison Ashley R, Bowrey David J
Department of Surgery, University Hospitals of Leicester NHS Trust, Leicester, U.K.
Department of Cancer Studies, University of Leicester, Leicester, U.K.
Anticancer Res. 2019 Feb;39(2):853-861. doi: 10.21873/anticanres.13185.
BACKGROUND/AIM: Previous studies have shown anti-proliferative and anti-apoptotic effects of omega-3 fatty acids (Omegaven®) in vitro and in vivo. Whether this effect can be exploited in patients with advanced esophago-gastric adenocarcinoma is unknown. The present study intended to determine the tumour radiological response and toxicity profile of intravenous omega-3 fish oil infusion when combined with standard palliative chemotherapy, and present the effects of this treatment on plasma cytokine biomarkers.
Participants with advanced esophago-gastric adenocarcinoma were enrolled in a phase II single-arm clinical trial of palliative chemotherapy (epirubicin, oxaliplatin, and capecitabine; EOX) coupled with weekly infusion of Omegaven®. Outcomes were compared to those observed in 37 historical control patients who had received EOX alone. Toxicity was graded using the CTCAE v4.03 and radiological response was assessed using RECIST v1.1. Plasma cytokine levels of IL-1, IL-2, IL-6, TNF-α, and VEGF were evaluated by ELISA.
Twenty participants were included in the analysis. Radiological responses were as follows: partial response (EOX plus omega-3 group 73% vs. EOX alone 39%, p=0.03), stable disease (EOX plus omega-3 21% vs. EOX alone 39%, p=0.24), and progressive disease (EOX plus omega-3 7% vs. EOX alone 18%, p=0.34). Grade 3 or 4 toxicity was less common (thromboembolism & gastrointestinal) in those who received EOX plus omega-3. This translated into fewer hospital admissions. There were significant reductions in the concentrations of IL-2 (p=0.009), TNF-α (p<0.0001) and VEGF (p=0.002) following each treatment.
The treatment with supplementary omega-3 fatty acids reduced chemotherapy-related toxicity and resulted in better radiological responses. The combination treatment resulted in a shift towards a favourable anti-inflammatory cytokine profile. These findings should be evaluated in a randomised clinical trial.
背景/目的：既往研究已表明ω-3脂肪酸（Omegaven®）在体外和体内具有抗增殖和抗凋亡作用。这种作用能否应用于晚期食管胃腺癌患者尚不清楚。本研究旨在确定静脉输注ω-3鱼油联合标准姑息化疗时的肿瘤放射学反应和毒性特征，并呈现该治疗对血浆细胞因子生物标志物的影响。
晚期食管胃腺癌患者参加了一项姑息化疗（表柔比星、奥沙利铂和卡培他滨；EOX）联合每周输注Omegaven®的II期单臂临床试验。将结果与37例仅接受EOX治疗的历史对照患者的结果进行比较。使用CTCAE v4.03对毒性进行分级，使用RECIST v1.1评估放射学反应。通过ELISA评估血浆中IL-1、IL-2、IL-6、TNF-α和VEGF的细胞因子水平。
20名参与者纳入分析。放射学反应如下：部分缓解（EOX加ω-3组73% vs. 仅EOX组39%，p = 0.03），疾病稳定（EOX加ω-3组21% vs. 仅EOX组39%，p = 0.24），疾病进展（EOX加ω-3组7% vs. 仅EOX组18%，p = 0.34）。接受EOX加ω-3治疗的患者中3级或4级毒性（血栓栓塞和胃肠道毒性）较少见。这导致住院次数减少。每次治疗后IL-2（p = 0.009）、TNF-α（p < 0.0001）和VEGF（p = 0.002）的浓度均显著降低。
补充ω-3脂肪酸治疗可降低化疗相关毒性，并产生更好的放射学反应。联合治疗导致向有利的抗炎细胞因子谱转变。这些发现应在随机临床试验中进行评估。
