title: Long-term administration of Wilms tumor-1 peptide vaccine in combination with gemcitabine causes severe local skin inflammation at injection sites.
abstract: The skin toxicity of vaccine therapy at injection sites is generally limited to Grades 1-2 due to the nature of their function. We experienced two cases of severe and prolonged local adverse effects in 25 patients following a Phase I study of gemcitabine and Wilms tumor-1 peptide vaccine mixed with incomplete Freund's adjuvant for inoperable pancreatic or biliary tract cancer. These patients requested to continue the treatment after the study period; however, in the course of compassionate use, they developed unacceptable local skin reactions and terminated their vaccine treatment. One patient (human leukocyte antigen, A0201, 3 mg) developed Grade 3 ulceration at the 10th vaccination and another (human leukocyte antigen, A2402, 1 mg) developed Grade 2 indulation and fibrosis at the 16th vaccination. Skin toxicity occurred at 6.4-8.4 months and continued for several months after the final vaccination during gemcitabine treatment. In these cases, activation or induction of Wilms tumor-1-specific T lymphocytes was not apparent in the peripheral blood despite their severe local reactions. Therefore, we need to monitor patients for late-onset, severe and long-lasting skin reactions at injection sites in Wilms tumor-1 cancer vaccine therapy, particularly for combination treatment with gemcitabine.
authors.affiliation: Department of Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Soeda
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Morita-Hoshi
authors.forename: Miho
authors.initials: M
authors.lastname: Kaida
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: Yuji
authors.initials: Y
authors.lastname: Heike
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000556:secondary; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D018797:Cell Cycle Proteins; D017024:Chemotherapy, Adjuvant; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000556:secondary; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003872:Dermatitis / Q000209:etiology* / Q000276:immunology; D004334:Drug Administration Schedule; D005260:Female; D005706:Gallbladder Neoplasms / Q000473:pathology; D006801:Humans; D007271:Injections, Intradermal / Q000009:adverse effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008214:Lymphocytes / Q000276:immunology; D009687:Nuclear Proteins / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D010166:Palliative Care / Q000379:methods; D000072260:RNA Splicing Factors; D018714:Radiotherapy, Adjuvant; D012867:Skin / Q000187:drug effects* / Q000276:immunology; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D019496:Cancer Vaccines; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; C419554:WTAP protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine