title: Gastrointestinal bleeding during anti-angiogenic peptide vaccination in combination with gemcitabine for advanced pancreatic cancer.
abstract: Most pancreatic cancer patients are diagnosed at the advanced stages, and no therapy is superior to gemcitabine alone. To confirm the feasibility and efficacy of a novel clinical intervention using tumor vessel-specific anti-angiogenic peptide vaccination, we conducted a clinical phase I/II trial using HLA-A*2402/A*0201-restricted vascular endothelial growth factor receptor type 1 (VEGFR1)-derived peptide vaccination in combination with gemcitabine for advanced pancreatic cancer (http://www.clinical-trials.gov; NCT00683358 and NCT00683085). Four of the enrolled patients (n = 2 for HLA-A*2402 and n = 2 for HLA-A*0201 protocol, respectively), defined as having progressive disease according to the Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v.1.0), failed to respond to the therapy. Another two patients enrolled in HLA-A*2402 protocol dropped out of the study due to rapid disease progression. Grade 2-3 hematologic toxicities were observed in all cases, but the treatment was well tolerated with minimal systemic adverse events. One case in HLA-A*2402 protocol and another case in HLA-A*0201 protocol suffered complicated gastrointestinal (GI) bleeding during vaccination. The causal relationship between GI bleeding and VEGFR1-peptide vaccination is unclear according to the pathologic examination. These studies terminated prematurely because of the advanced stage of the disease in the enrolled patients on entry to the study. Despite GI bleeding, peptide vaccination provides a feasible treatment option for many advanced pancreatic cancer patients.
authors.affiliation: Division of Advanced Medical Science, Research Hospital, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. zephyrus@ims.u-tokyo.ac.jp.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nagayama
authors.affiliation: Department of Clinical Trial Safety Management, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Division of Advanced Medical Science, Research Hospital, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Isoo
authors.affiliation: Division of Advanced Medical Science, Research Hospital, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Division of Advanced Medical Science, Research Hospital, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Division of Advanced Medical Science, Research Hospital, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakaoka
authors.affiliation: Department of Surgery, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Shinozaki
authors.affiliation: Division of Radiology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Division of Radiology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Clinical Trial Safety Management, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Nagamura
authors.affiliation: Division of Pathology, Research Hospital, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Oyaizu
authors.affiliation: Division of Advanced Medical Science, Research Hospital, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Naohide
authors.initials: N
authors.lastname: Yamashita
keywords: GI bleeding; Gemcitabine; Pancreatic cancer; Peptide vaccination; VEGFR1