Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer

Cancer Sci. 2010 Feb;101(2):433-9. doi: 10.1111/j.1349-7006.2009.01416.x. Epub 2009 Oct 27.


Vascular endothelial growth factor receptor 2 (VEGFR2) is an essential factor in tumor angiogenesis and in the growth of pancreatic cancer. Immunotherapy using epitope peptide for VEGFR2 (VEGFR2-169) that we identified previously is expected to improve the clinical outcome. Therefore, a phase I clinical trial combining of VEGFR2-169 with gemcitabine was conducted for patients with advanced pancreatic cancer. Patients with metastatic and unresectable pancreatic cancer were eligible for the trial. Gemcitabine was administered at a dose of 1000 mg/m(2) on days 1, 8, and 15 in a 28-day cycle. The VEGFR2-169 peptide was subcutaneously injected weekly in a dose-escalation manner (doses of 0.5, 1, and 2 mg/body, six patients/one cohort). Safety and immunological parameters were assessed. No severe adverse effect of grade 4 or higher was observed. Of the 18 patients who completed at least one course of the treatment, 15 (83%) developed immunological reactions at the injection sites. Specific cytotoxic T lymphocytes (CTL) reacting to the VEGFR2-169 peptide were induced in 11 (61%) of the 18 patients. The disease control rate was 67%, and the median overall survival time was 8.7 months. This combination therapy for pancreatic cancer patients was tolerable at all doses. Peptide-specific CTL could be induced by the VEGFR2-169 peptide vaccine at a high rate, even in combination with gemcitabine. From an immunological point of view, the optimal dose for further clinical trials might be 2 mg/body or higher. This trial was registered with (no. NCT 00622622).

Trial registration: NCT00622622.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Cancer Vaccines / therapeutic use*
  • Combined Modality Therapy
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / therapy*
  • Peptide Fragments / immunology*
  • Peptide Fragments / therapeutic use
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Vascular Endothelial Growth Factor Receptor-2 / immunology*
  • Vascular Endothelial Growth Factor Receptor-2 / therapeutic use


  • Cancer Vaccines
  • Peptide Fragments
  • arginyl-phenylalanyl-valyl-prolyl-aspartyl-glycyl-asparagyl-arginyl-isoleucine
  • Deoxycytidine
  • gemcitabine
  • Vascular Endothelial Growth Factor Receptor-2

Associated data