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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-02-04

AUTHORS

Gary Middleton, William Greenhalf, Eithne Costello, Victoria Shaw, Trevor Cox, Paula Ghaneh, Daniel H Palmer, John P Neoptolemos

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. More... »

PAGES

510-518

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bjc.2015.468

DOI

http://dx.doi.org/10.1038/bjc.2015.468

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1047785196

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26931369


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34 schema:description 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.
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41 CA19-9
42 GM-CSF
43 IL-6 levels
44 adenocarcinoma
45 advanced pancreatic cancer
46 advanced pancreatic ductal adenocarcinoma
47 antigen 19
48 apoptosis
49 apoptosis induction
50 arm
51 association
52 baseline
53 baseline CA19-9
54 cancer
55 capecitabine chemotherapy
56 capecitabine combination chemotherapy
57 carbohydrate antigen 19
58 changes
59 chemotherapy
60 chemotherapy-induced apoptosis
61 combination chemotherapy
62 combination gemcitabine
63 correlation
64 differences
65 ductal adenocarcinoma
66 effect
67 evidence
68 evidence of apoptosis
69 factors
70 gemcitabine
71 hazard ratio
72 immune response
73 immunobiological effects
74 immunogenicity
75 induction
76 inflammatory markers C-reactive protein
77 interleukin-6
78 levels
79 means
80 pancreatic cancer
81 pancreatic ductal adenocarcinoma
82 patients
83 positive correlation
84 positive immune response
85 post-treatment levels
86 pre
87 preclinical studies
88 protein
89 ratio
90 response
91 study
92 survival
93 total immune response
94 treatment
95 trials
96 vaccine
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