Immunobiological effects of gemcitabine and capecitabine combination chemotherapy in advanced pancreatic ductal adenocarcinoma

Br J Cancer. 2016 Mar 1;114(5):510-8. doi: 10.1038/bjc.2015.468. Epub 2016 Feb 4.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / immunology
  • C-Reactive Protein / immunology
  • CA-19-9 Antigen / metabolism
  • Cancer Vaccines / therapeutic use*
  • Capecitabine / administration & dosage
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Proliferation
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Gemcitabine
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Humans
  • Hypersensitivity, Delayed / immunology
  • Interleukin-6 / immunology
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / pathology
  • Peptide Fragments / therapeutic use*
  • T-Lymphocytes / immunology
  • Telomerase / therapeutic use*


  • CA-19-9 Antigen
  • Cancer Vaccines
  • IL6 protein, human
  • Interleukin-6
  • Peptide Fragments
  • Deoxycytidine
  • Capecitabine
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • C-Reactive Protein
  • GV1001 peptide
  • Telomerase
  • Gemcitabine