title: 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.
abstract: 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 ClinicalTrial.gov (no. NCT 00622622).
authors.affiliation: Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Miyazawa
authors.forename: Ryuji
authors.initials: R
authors.lastname: Ohsawa
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Seiko
authors.initials: S
authors.lastname: Hirono
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawai
authors.forename: Masaji
authors.initials: M
authors.lastname: Tani
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaue
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology* / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology* / Q000627:therapeutic use; D000093542:Gemcitabine
chemical_list: D019496:Cancer Vaccines; D010446:Peptide Fragments; C578462:arginyl-phenylalanyl-valyl-prolyl-aspartyl-glycyl-asparagyl-arginyl-isoleucine; D003841:Deoxycytidine; D040301:Vascular Endothelial Growth Factor Receptor-2; D000093542:Gemcitabine