title: Phase 1 trial of Wilms tumor 1 (WT1) peptide vaccine and gemcitabine combination therapy in patients with advanced pancreatic or biliary tract cancer.
abstract: An open-labeled, dose-escalation phase 1 trial of Wilms tumor 1 (WT1) vaccine and gemcitabine (GEM) combination therapy for patients with advanced pancreatic cancer or biliary tract cancer was performed. The primary end point was evaluation of toxicity, safety, and optimal immunologic dose of vaccine. Human leukocyte antigen (HLA)-A 0201, HLA-A 0206, and/or HLA-A 2402-positive patients with inoperable advanced pancreatic or biliary tract cancer who had not previously been treated with GEM were eligible for this study. Six doses of GEM and 4 doses of WT1 peptide (1 or 3 mg) emulsified in Montanide adjuvant were administered over 2 months. Twenty-five patients (13 male and 12 female) were enrolled. Nine patients had inoperable advanced pancreatic cancer, 8 had gallbladder cancer, 4 had intrahepatic, and 4 had extrahepatic bile duct cancer. The adverse events were comparable to those with GEM alone. Delayed-type hypersensitivity test was positive after vaccination in 2 patients, and WT1-specific T cells in peptide-stimulated culture were detected by tetramer assay in 59% (13 of 22) of patients. The disease control rate at 2 months was 89% for pancreatic cancer and 50% for biliary tract cancer. With a median follow-up time of 259 days, the median survival time for biliary tract cancer was 288 days, and that for pancreatic cancer was 259 days. Although objective clinical efficacy was not apparent, the safety of WT1 vaccine and GEM combination therapy was confirmed in this study.
authors.affiliation: Department of Medical Oncology, National Cancer Research Center Hospital, Chuo-ku, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Kaida
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Morita-Hoshi
authors.forename: Atsuko
authors.initials: A
authors.lastname: Soeda
authors.forename: Takako
authors.initials: T
authors.lastname: Wakeda
authors.forename: Yuni
authors.initials: Y
authors.lastname: Yamaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kojima
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kondo
authors.forename: Chigusa
authors.initials: C
authors.lastname: Morizane
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takaue
authors.forename: Yuji
authors.initials: Y
authors.lastname: Heike
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy / Q000628:therapy*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D018797:Cell Cycle Proteins; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000628:therapy*; D000072260:RNA Splicing Factors; D022223:Vaccines, Subunit / Q000009:adverse effects / Q000627:therapeutic use*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D019496:Cancer Vaccines; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D022223:Vaccines, Subunit; C419554:WTAP protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine