title: Reduction in circulating pro-angiogenic and pro-inflammatory factors is related to improved outcomes in patients with advanced pancreatic cancer treated with gemcitabine and intravenous omega-3 fish oil.
abstract: BACKGROUND
  Pancreatic cancer is a rapidly progressive disease which is often only amenable to palliative treatment. Few patients respond to palliative chemotherapy, so surrogate markers indicating which patients are likely to respond to treatment are required. There is a well-established link between pro-inflammatory circulating cytokines and growth factors (CAF), and the development of neoplasia. Agents that may modulate these factors are of interest in developing potential novel therapeutic applications.
  
  
  METHODS
  As part of a single-arm phase II trial in patients with advanced pancreatic cancer (APC) treated with gemcitabine and intravenous (i.v.) omega-3 rich lipid emulsion (n-3FA), serum samples were analysed for 14 CAF using a multiplex cytokine array. Baseline serum concentrations were correlated with overall (OS) and progression-free survival (PFS), and changes in concentration correlated with time and outcomes for CAF responders were analysed.
  
  
  RESULTS
  Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) concentrations reduced significantly with treatment over time. Low baseline interleukin (IL)-6 and -8 were correlated with improved OS. PDGF responders showed a tendency towards improved OS and FGF responders a significantly improved PFS.
  
  
  CONCLUSIONS
  Treatment with gemcitabine plus i.v. n-3FA may reduce concentrations of CAF which may be associated with an improved outcome. Baseline IL-6 and -8 may be surrogate markers for outcome in patients with APC treated with this regimen.
authors: Department of Hepatobiliary and Department of Pancreatic Surgery, University Hospitals of Leicester, Leicester, UK. ali.arshad@doctors.org.uk
authors: Ali
authors: A
authors: Arshad
authors: Wen Y
authors: WY
authors: Chung
authors: William
authors: W
authors: Steward
authors: Matthew S
authors: MS
authors: Metcalfe
authors: Ashley R
authors: AR
authors: Dennison
mesh_terms: D061605:Administration, Intravenous; D042501:Angiogenic Proteins / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D015536:Down-Regulation; D004739:England; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005346:Fibroblast Growth Factors / Q000097:blood; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D042501:Angiogenic Proteins; D014408:Biomarkers, Tumor; C508606:CXCL8 protein, human; D016207:Cytokines; D015525:Fatty Acids, Omega-3; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D010982:Platelet-Derived Growth Factor; D003841:Deoxycytidine; D005346:Fibroblast Growth Factors; D000093542:Gemcitabine