title: Phase II clinical trial of peptide cocktail therapy for patients with advanced pancreatic cancer: VENUS-PC study.
abstract: We previously conducted a phase I clinical trial combining the HLA-A*2402-restricted KIF20A-derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single-armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine. Chemotherapy naïve PC patients were enrolled to evaluate primarily the 1-year survival rate, and secondarily overall survival (OS), progression free survival (PFS), response rate (RR), disease control rate (DCR) and the peptide-specific immune responses. All enrolled patients received therapy without the HLA-A information, and the HLA genotypes were used for classification of the patients. Between June 2012 and May 2013, a total of 68 patients were enrolled. No severe systemic adverse effects of Grade 3 or higher related to these three peptides were observed. The 1-year survival rates between the HLA-A*2402-matched and -unmatched groups were not significantly different. In the HLA-A*2402 matched group, patients showing peptide-specific CTL induction for KIF20A or VEGFR1 showed a better prognosis compared to those without such induction (P = 0.023, P = 0.009, respectively). In the HLA-A*2402-matched group, the patients who showed a strong injection site reaction had a better survival rate (P = 0.017) compared to those with a weak or no injection site reaction. This phase II study demonstrated that this therapeutic peptide cocktail might be effective in patients who demonstrate peptide-specific immune reactions although predictive biomarkers are needed for patient selection in its further clinical application.
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Nobuaki
authors: N
authors: Suzuki
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Shoichi
authors: S
authors: Hazama
authors: Clinical Research Center, Shikoku Cancer Center, NHO, Matsuyama, Japan.
authors: Haruo
authors: H
authors: Iguchi
authors: Clinical Research Center, Shikoku Cancer Center, NHO, Matsuyama, Japan.
authors: Kazuhiro
authors: K
authors: Uesugi
authors: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Hiroaki
authors: H
authors: Tanaka
authors: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Kosei
authors: K
authors: Hirakawa
authors: Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
authors: Atsushi
authors: A
authors: Aruga
authors: Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
authors: Takashi
authors: T
authors: Hatori
authors: Department of Surgical Oncology and Regulation of Organ Function, Miyazaki University School of Medicine, Miyazaki, Japan.
authors: Hidenobu
authors: H
authors: Ishizaki
authors: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan.
authors: Yuzo
authors: Y
authors: Umeda
authors: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan.
authors: Toshiyoshi
authors: T
authors: Fujiwara
authors: Department of Digestive and Transplant Surgery, Tokushima University Graduate School of Medicine, Tokushima, Japan.
authors: Tetsuya
authors: T
authors: Ikemoto
authors: Department of Digestive and Transplant Surgery, Tokushima University Graduate School of Medicine, Tokushima, Japan.
authors: Mitsuo
authors: M
authors: Shimada
authors: Department of Surgery, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.
authors: Kazuhiko
authors: K
authors: Yoshimatsu
authors: Department of Surgery, Ogori Dai-ichi General Hospital, Yamaguchi, Japan.
authors: Ryoichi
authors: R
authors: Shimizu
authors: Department of Surgery, Kanmon Medical Center, NHO, Shimonoseki, Japan.
authors: Hiroto
authors: H
authors: Hayashi
authors: Department of Surgery, Shimonoseki Medical Center, JCHO, Shimonoseki, Japan.
authors: Koichiro
authors: K
authors: Sakata
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Hiroko
authors: H
authors: Takenouchi
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Hiroto
authors: H
authors: Matsui
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Yoshitaro
authors: Y
authors: Shindo
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Michihisa
authors: M
authors: Iida
authors: Department of Pharmacy, Yamaguchi University Hospital, Ube, Japan.
authors: Yasunobu
authors: Y
authors: Koki
authors: Department of Pharmacy, Yamaguchi University Hospital, Ube, Japan.
authors: Hideki
authors: H
authors: Arima
authors: Department of Pharmacy, Yamaguchi University Hospital, Ube, Japan.
authors: Hiroyuki
authors: H
authors: Furukawa
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Tomio
authors: T
authors: Ueno
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Shigefumi
authors: S
authors: Yoshino
authors: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
authors: Yusuke
authors: Y
authors: Nakamura
authors: Yamaguchi University, Yamaguchi, Japan.
authors: Masaaki
authors: M
authors: Oka
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Hiroaki
authors: H
authors: Nagano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D059871:HLA-A24 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D016547:Kinesins / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D011379:Prognosis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000276:immunology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology; D000093542:Gemcitabine
chemical_list: D019496:Cancer Vaccines; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; C410089:KIF20A protein, human; D010455:Peptides; 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: 
  CTL
  ; Advanced pancreatic cancer; immunotherapy; peptide cocktail; phase II