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Title: Phase II Trial of the Effect of Gemcitabine with Intravenous Omega-3 Fish Oil Infusion in Patients with Unresectable Pancreatic Adenocarcinoma
Authors: Arshad, Ali
Supervisors: Dennison, A.R.
Metcalfe, M
Award date: 15-Jun-2013
Presented at: University of Leicester
Abstract: Introduction Advanced Pancreatic Cancer (APC) has an appalling prognosis characterised by rapidly declining quality of life mediated by circulating pro-inflammatory cytokines and growth factors (CAF). Omega-3 fatty acids (n-3FAs) are proven to have antineoplastic and anti-inflammatory effects. Oral trials of n-3FAs in patients with advanced cancer have shown mixed results due in part to poor bioavailability and compliance with these preparations. Methods A phase II single arm trial was carried out using gemcitabine and intravenous n-3Fas in patients with APC. Primary outcome measure was overall radiological response rate (ORR) with secondary outcome measures of Overall (OS) and Progression-Free Survival (PFS), quality of life using validated questionnaires, Clinical Benefit Response (CBR) rates, adverse events, changes in CAF, complement, uptake of n-3FAs into cell membranes and plasma. Results Twenty nine patients were recruited: 21 were evaluable for ORR which was 3/21 (14.3%). Median OS=4.8 months, median PFS=3.5 months. Improvements and percentage of patients experiencing it in QOL outcomes of at least 10% over baseline was seen in the following domains: Global health- 57%, Summated QOL- 43%, Pain scores- 57%. CBR rates were 38%. PDGF, TRAIL and FGF concentrations reduced significantly with treatment over time. Low baseline IL-6 and IL-8 were correlated with improved OS. PDGF responders showed a tendency towards improved OS and FGF responders a significantly improved PFS. Restoration of hypoactive Mannose Binding Lectin complement activity was associated with improved time to progression. Proportions of n-3FA fractions in cell membranes increased significantly with time. Conclusions Intravenous n-3FAs plus gemcitabine may improve quality of life and provide clinical benefit response in patients with APC. These changes may be mediated by manipulation of CAFs and complement pathways. The independent effect of n-3Fas over gemcitabine warrants further investigation in randomised trials.
Type: Thesis
Level: Doctoral
Qualification: MD
Rights: Copyright © the author. All rights reserved.
Appears in Collections:Theses, Dept. of Cancer Studies & Molecular Medicine
Leicester Theses

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