Phase I trial of preoperative intratumoral injection of immature dendritic cells and OK-432 for resectable pancreatic cancer patients

J Hepatobiliary Pancreat Sci. 2012 Jul;19(4):465-75. doi: 10.1007/s00534-011-0457-7.

Abstract

Purpose: To determine the feasibility, safety and histological change of preoperative endoscopic ultrasound-guided fine-needle injection (PEU-FNI) of immature DCs (iDCs) with OK-432 in pancreatic cancer patients.

Methods: Nine patients enrolled in the trial (DC group) and were compared with 15 patients operated on without iDC injection (non-DC group). Adverse events of PEU-FNI and postoperative complications were evaluated according to CTC-AE ver.3.0 and the Clavien-Dindo classification/ISGPF definition, respectively. Histological changes within the tumor and lymph nodes were evaluated by immunohistochemical examination of infiltrating inflammatory cells (CD4+, CD8+, Foxp3+ and CD83+).

Results: There were no severe toxicities following PEU-FNI, except for one transient grade 3 fever, and there were no significant differences in the incidence of postoperative complications between the two groups. Colliquative necrosis and diffusely scattered TUNEL-positive cells were observed at the injection sites. CD83+ cells significantly accumulated in the regional lymph nodes of the DC group as well as Foxp3+ cells in the regional and distant lymph nodes. The two DC group patients, one of which was stage IV with distant lymph node metastasis, survived more than 5 years without requiring adjuvant theraphy.

Conclusion: PEU-FNI was feasible and safe, and further study needs to confirm and enhance antitumor responses.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adenocarcinoma / therapy*
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Combined Modality Therapy
  • Dendritic Cells / immunology*
  • Endoscopic Ultrasound-Guided Fine Needle Aspiration*
  • Feasibility Studies
  • Female
  • Humans
  • Immunohistochemistry
  • Injections, Intralesional
  • Lymph Nodes / pathology
  • Lymphocytes, Tumor-Infiltrating
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • Pancreatic Neoplasms / therapy*
  • Picibanil / administration & dosage*
  • Preoperative Period

Substances

  • Antineoplastic Agents
  • Picibanil