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: Gary Middleton, William Greenhalf, Eithne Costello, Victoria Shaw, Trevor Cox, Paula Ghaneh, Daniel H Palmer, John P Neoptolemos
• Journal: British journal of cancer (Br J Cancer) Vol. 114 Issue 5 Pg. 510-8 (Mar 01 2016) ISSN: 1532-1827 [Electronic] England
• PMID: 26931369 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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, immunology, pathology)
• Cell Proliferation
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Female
• Granulocyte-Macrophage Colony-Stimulating Factor (immunology)
• Humans
• Hypersensitivity, Delayed (immunology)
• Interleukin-6 (immunology)
• Male
• Middle Aged
• Pancreatic Neoplasms (drug therapy, immunology, pathology)
• Peptide Fragments (therapeutic use)
• T-Lymphocytes (immunology)
• Telomerase (therapeutic use)
• Gemcitabine