title: Phase II clinical trial using novel peptide cocktail vaccine as a postoperative adjuvant treatment for surgically resected pancreatic cancer patients.
abstract: We investigated peptide cocktail vaccine OCV-C01 containing epitope peptides derived from KIF20A, vascular endothelial growth factor receptor (VEGFR)1 and VEGFR2 combined with gemcitabine in the adjuvant treatment for resected pancreatic cancer patients. A single-arm multicenter phase II study was performed on 30 patients with pancreatic ductal carcinoma who underwent pancreatectomy. At each 28-day treatment cycle, patients received weekly subcutaneous injection of OCV-C01 for 48 weeks and gemcitabine was administered intravenously at 1,000 mg/m2on days 1, 8 and 15 for 24 weeks. Patients were followed for 18 months. The primary endpoint was disease-free survival (DFS) and secondary endpoints included safety, overall survival (OS) and immunological assays on peptide-specific cytotoxic T lymphocyte (CTL) activity and KIF20A expression in resected pancreatic cancer. The median DFS was 15.8 months [95% confidence interval (CI), 11.1-20.6] and the DFS rate at 18 months was 34.6% (95% CI, 18.3-51.6). The median OS was not reached and the OS rate at 18 months was 69.0% (95% CI, 48.8-82.5). The administration of OCV-C01 was well tolerated. In the per protocol set, there were significant differences in DFS between patients with KIF20A-specific CTL responses and without (p = 0.027), and between patients with KIF20A expression and without (p = 0.014). In addition, all four patients who underwent R0 resection with KIF20A expression had no recurrence of pancreatic cancer with KIF20A-specific CTL responses. OCV-C01 combined with gemcitabine was tolerable with a median DFS of 15.8 months, which was favorable compared with previous data for resected pancreatic cancer.
authors.affiliation: Second Department of Surgery, Wakayama Medical University School of Medicine, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Miyazawa
authors.affiliation: Second Department of Surgery, Wakayama Medical University School of Medicine, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Katsuda
authors.affiliation: Center for Gastroenterology, Teine-Keijinkai Hospital, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Maguchi
authors.affiliation: Center for Gastroenterology, Teine-Keijinkai Hospital, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Katanuma
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Ozaka
authors.affiliation: Department of Gastroenterology, Aichi Cancer Center Hospital, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamao
authors.affiliation: Department of Gastroenterology, Aichi Cancer Center Hospital, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imaoka
authors.affiliation: Second Department of Surgery, Wakayama Medical University School of Medicine, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawai
authors.affiliation: Second Department of Surgery, Wakayama Medical University School of Medicine, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Hirono
authors.affiliation: Second Department of Surgery, Wakayama Medical University School of Medicine, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Okada
authors.affiliation: Second Department of Surgery, Wakayama Medical University School of Medicine, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaue
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D000939:Epitopes / Q000276:immunology; D005260:Female; D059871:HLA-A24 Antigen / Q000276:immunology*; D006801:Humans; D016233:Immunotherapy, Active; D053208:Kaplan-Meier Estimate; D016547:Kinesins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D022223:Vaccines, Subunit / Q000627:therapeutic use*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000276:immunology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D019496:Cancer Vaccines; D000939:Epitopes; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; C410089:KIF20A protein, human; D009363:Neoplasm Proteins; C000620786:OCV-C01; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D003841:Deoxycytidine; C000588866:KDR protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D016547:Kinesins; D000093542:Gemcitabine
keywords: KIF20A; adjuvant therapy; pancreatic cancer; peptide vaccine; predictive marker