title: Immunobiological effects of gemcitabine and capecitabine combination chemotherapy in advanced pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  Preclinical studies suggest that chemotherapy may enhance the immune response against pancreatic cancer.
  
  
  METHODS
  The levels of granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) and the associated inflammatory marker C-reactive protein (CRP) were assessed in 38 patients receiving gemcitabine and capecitabine combination chemotherapy for advanced pancreatic cancer within the TeloVac trial. Apoptosis (M30) and total immune response (delayed-type hypersensitivity and/or T-cell response) were also assessed and levels of apoptosis induction correlated with immune response. The telomerase GV1001 vaccine was given either sequentially (n=18) or concomitantly (n=24) with the combination chemotherapy.
  
  
  RESULTS
  There were no differences between baseline and post-treatment levels of CRP (P=0.19), IL-6 (P=0.19) and GM-CSF (P=0.71). There was a positive correlation between post-chemotherapy CRP and IL-6 levels (r=0.45, P=0.005) and between CRP with carbohydrate antigen-19-9 (CA19-9) levels at baseline (r=0.45, P=0.015) and post treatment (r=0.40, P=0.015). The change in CRP and IL-6 levels was positively correlated (r=0.40, P=0.012). Hazard ratios (95% CI) for baseline CA19-9 (1.30 (1.07-1.59), P=0.009) and CRP (1.55 (1.00-2.39), P=0.049) levels were each independently predictive of survival. The M30 mean matched differences between pre- and post-chemotherapy showed evidence of apoptosis in both the sequential (P=0.058) and concurrent (P=0.0018) chemoimmunotherapy arms. Respectively, 5 of 10 and 9 of 20 patients had a positive immune response but there was no association with apoptosis.
  
  
  CONCLUSIONS
  Combination gemcitabine and capecitabine chemotherapy did not affect circulating levels of GM-CSF, IL-6 and CRP. Chemotherapy-induced apoptosis was not associated with the immunogenicity induced by the GV1001 vaccine in advanced pancreatic cancer.
authors.affiliation: Institute of Immunology and Immunotherapy, University of Birmingham B15 2TT and University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham B15 2TH, UK.
authors.forename: Gary
authors.initials: G
authors.lastname: Middleton
authors.affiliation: National Institutes of Health Research Liverpool Pancreas Biomedical Research Unit and Clinical Directorate of General Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust and the University of Liverpool, Liverpool L69 3GA, UK.|Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Block C Waterhouse Building, 1-3 Brownlow Street, Liverpool L69 3GA, UK.
authors.forename: William
authors.initials: W
authors.lastname: Greenhalf
authors.affiliation: National Institutes of Health Research Liverpool Pancreas Biomedical Research Unit and Clinical Directorate of General Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust and the University of Liverpool, Liverpool L69 3GA, UK.|Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Block C Waterhouse Building, 1-3 Brownlow Street, Liverpool L69 3GA, UK.
authors.forename: Eithne
authors.initials: E
authors.lastname: Costello
authors.affiliation: National Institutes of Health Research Liverpool Pancreas Biomedical Research Unit and Clinical Directorate of General Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust and the University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Shaw
authors.affiliation: Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Block C Waterhouse Building, 1-3 Brownlow Street, Liverpool L69 3GA, UK.
authors.forename: Trevor
authors.initials: T
authors.lastname: Cox
authors.affiliation: National Institutes of Health Research Liverpool Pancreas Biomedical Research Unit and Clinical Directorate of General Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust and the University of Liverpool, Liverpool L69 3GA, UK.|Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Block C Waterhouse Building, 1-3 Brownlow Street, Liverpool L69 3GA, UK.
authors.forename: Paula
authors.initials: P
authors.lastname: Ghaneh
authors.affiliation: National Institutes of Health Research Liverpool Pancreas Biomedical Research Unit and Clinical Directorate of General Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust and the University of Liverpool, Liverpool L69 3GA, UK.|Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Block C Waterhouse Building, 1-3 Brownlow Street, Liverpool L69 3GA, UK.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Palmer
authors.affiliation: National Institutes of Health Research Liverpool Pancreas Biomedical Research Unit and Clinical Directorate of General Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust and the University of Liverpool, Liverpool L69 3GA, UK.|Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Block C Waterhouse Building, 1-3 Brownlow Street, Liverpool L69 3GA, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Neoptolemos
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000276:immunology; D002097:C-Reactive Protein / Q000276:immunology; D018395:CA-19-9 Antigen / Q000378:metabolism; D019496:Cancer Vaccines / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D019098:Telomerase / Q000627:therapeutic use*; D000093542:Gemcitabine
chemical_list: D018395:CA-19-9 Antigen; D019496:Cancer Vaccines; C508600:IL6 protein, human; D015850:Interleukin-6; D010446:Peptide Fragments; D003841:Deoxycytidine; D000069287:Capecitabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002097:C-Reactive Protein; C514987:GV1001 peptide; D019098:Telomerase; D000093542:Gemcitabine