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.
Materials and methods: 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.
Results: 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.
Conclusion: 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.
Keywords: Esophageal cancer; gastric cancer; omega-3 fatty acids; omegaven; palliative; polyunsaturated fatty acids.
Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.