Arshad Ali, Chung Wen, Isherwood John, Steward William, Metcalfe Matthew, Dennison Ashley
Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Leicester, UK.
JPEN J Parenter Enteral Nutr. 2014 Feb;38(2):214-9. doi: 10.1177/0148607113476304. Epub 2013 Feb 19.
Pancreatic cancer has an extremely poor clinical outcome. Surrogate biomarkers for outcome are scarce. There is mixed evidence for the association of high mannose-binding lectin (MBL) complement activity with cancer outcomes, including reduced survival and increased infectious complications. ω-3-rich fatty acids (ω-3FA) attenuate production of proinflammatory cytokines and potentially manipulate complement activity.
As part of a single-arm phase II trial in a university hospital, patients with advanced pancreatic adenocarcinoma were treated with weekly ω-3FA-rich intravenous infusion (Lipidem [B. Braun Melsungen AG, Melsungen, Germany]: up to 100 g/wk) plus gemcitabine chemotherapy until withdrawal or tumor progression. Primary outcome measure was objective response rate. Changes in complement activity, which were a secondary outcome measure, were analyzed and relation to clinical outcome determined.
Twenty-three patients were assessable for time to progression (TTP), overall survival (OS), and complement activity. No hypoactivity in alternative and classical pathways was demonstrated. Baseline MBL was low in 10 of 23 patients (43.5%). There was no difference in OS or TTP between low- and high-baseline MBL patients. Of these 10 patients, 5 were classified as MBL responders. MBL responders had a tendency toward improved OS over nonresponders (8.9 vs 4.4 months, P = .07). MBL responders had significantly improved ttp over nonresponders (10.6 VS 5.3 MONTHS, P = .03).
MBL restoration had an association with improved outcome in the cohort of patients with low MBL activity at baseline. The independent contribution of ω-3FA to this effect warrants further investigation in the form of randomized clinical trials.
胰腺癌的临床预后极差。用于评估预后的替代生物标志物很少。关于高甘露糖结合凝集素（MBL）补体活性与癌症预后的关联，包括生存率降低和感染并发症增加，证据不一。富含ω-3的脂肪酸（ω-3FA）可减弱促炎细胞因子的产生，并可能调节补体活性。
作为大学医院一项单臂II期试验的一部分，晚期胰腺腺癌患者接受每周一次富含ω-3FA的静脉输注（Lipidem [德国美因茨市贝朗医疗公司]：最高100 g/周）加吉西他滨化疗，直至停药或肿瘤进展。主要结局指标是客观缓解率。分析作为次要结局指标的补体活性变化，并确定其与临床结局的关系。
23例患者可评估疾病进展时间（TTP）、总生存期（OS）和补体活性。未发现替代途径和经典途径存在低活性。23例患者中有10例（43.5%）基线MBL水平较低。基线MBL水平低的患者与高的患者在OS或TTP方面无差异。在这10例患者中，5例被归类为MBL反应者。MBL反应者的OS有优于无反应者的趋势（8.9个月对4.4个月，P = 0.07）。MBL反应者的TTP显著优于无反应者（10.6个月对5.3个月，P = 0.03）。
在基线MBL活性低的患者队列中，MBL恢复与预后改善相关。ω-3FA对这一效应的独立作用值得通过随机临床试验进一步研究。
