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

Middleton, Gary, Greenhalf, William, Costello, Eithne, Shaw, Victoria ORCID: 0000-0002-0429-0186, Cox, Trevor, Ghaneh, Paula, Palmer, Daniel H ORCID: 0000-0002-7147-5703 and Neoptolemos, John P (2016) Immunobiological effects of gemcitabine and capecitabine combination chemotherapy in advanced pancreatic ductal adenocarcinoma. British Journal of Cancer, 114 (5). pp. 510-518.

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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.

Item Type:	Article
Uncontrolled Keywords:	pancreatic adenocarcinoma, chemotherapy, inflammatory cytokines, apoptosis, immunogenicity
Depositing User:	Symplectic Admin
Date Deposited:	01 Jul 2016 13:26
Last Modified:	19 Jan 2023 07:35
DOI:	10.1038/bjc.2015.468
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3001929