MON-P095: The Effect of Fish Oil-Supplemented Gemcitabine Treatment on Leukotriene B4 Levels in Pancreatic Cancer

Pancreatic cancer (PC) is an aggressive cancer and is the 5th leading cause of cancer death in Western Europe and unfavourable prognosis is attributed to advanced disease at diagnosis and lack of effective therapy. The tumour microenvironment is an inflammatory one, and immune-mediators, such as Leukotriene B4 (LTB4), might contribute to the growth and spread of PC. The aim of this study is to determine the potential anti-inflammatory effects of omega-3 fatty acids in patients being treated for PC. Blood samples were taken from PC patients undergoing Gemcitabine treatment (n=8, CON) and from patients undergoing Gemcitabine treatment supplemented (n=17, O-3) with omega-3 fatty acids (Lipidem, BBraun, Germany), for up to a maximum of 6 months where possible. Plasma was isolated from blood and stored at -80⁰C until analysis for baseline LTB4 levels (baseline). A further aliquot of blood was incubated with 1mg/ml Zymosan for 30 min at RT then 30 min at 37⁰C, samples were centrifuged and plasma was collected and stored until analysis (stimulated). All samples were analysed using human LTB4 commercial ELISA kits according to the manufacturers’ instructions (Invitrogen, USA and R&D Systems, UK). There was an overall reduction in plasma LTB4 levels in O-3 patients (CON 3.5±0.3 (mean±SEM) ng/ml vs O-3 2.8±0.1 ng/ml, p=0.02). The stimulated levels of LTB4 in O-3 patients was also significantly reduced (p<0.05). There were no differences in baseline of CON or O-3 patients or stimulated CON patient LTB4 levels of low or high Progression Free Survival (PFS) patients. However, there was a significant reduction in LTB4 levels of stimulated high PFS O-3 patients (O-3 low PFS 4.5±0.3 ng/ml vs O-3 high PFS 3.6±1.1 ng/ml, p=0.01) and in patients at later TNM stage (O-3 stage 3 4.8±0.2 ng/ml vs stage 4 2.9±0.2 ng/ml, p<0.0001). Our results show that although the baseline inflammatory profile of PC patients is unaffected by omega-3 supplementation, the stimulated leukocyte response is reduced and is associated with increased patient PFS and later disease stage. These data indicate that omega-3 supplementation affects an anti-inflammatory profile in these patients, being more effective at later disease stages and may improve survival. Further work is required to assess the effects of omega-3 on the inflammatory profiles in PC.