title: Wilms tumor 1 peptide vaccination combined with temozolomide against newly diagnosed glioblastoma: safety and impact on immunological response.
abstract: To investigate the safety of combined Wilms tumor 1 peptide vaccination and temozolomide treatment of glioblastoma, a phase I clinical trial was designed. Seven patients with histological diagnosis of glioblastoma underwent concurrent radiotherapy and temozolomide therapy. Patients first received Wilms tumor 1 peptide vaccination 1 week after the end of combined concurrent radio/temozolomide therapy, and administration was continued once per week for 7 weeks. Temozolomide maintenance was started and performed for up to 24 cycles, and the observation period for safety encompassed 6 weeks from the first administration of maintenance temozolomide. All patients showed good tolerability during the observation period. Skin disorders, such as grade 1/2 injection-site reactions, were observed in all seven patients. Although grade 3 lymphocytopenia potentially due to concurrent radio/temozolomide therapy was observed in five patients (71.4 %), no other grade 3/4 hematological or neurological toxicities were observed. No autoimmune reactions were observed. All patients are still alive, and six are on Wilms tumor 1 peptide vaccination without progression, yielding a progression-free survival from histological diagnosis of 5.2-49.1 months. Wilms tumor 1 peptide vaccination was stopped in one patient after 12 injections by the patient's request. The safety profile of the combined Wilms tumor 1 peptide vaccination and temozolomide therapy approach for treating glioblastoma was confirmed.
authors.affiliation: Department of Neurosurgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan, hashimotonaoya@me.com.
authors.forename: Naoya
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.forename: Naoki
authors.initials: N
authors.lastname: Kagawa
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Chiba
authors.forename: Shuichi
authors.initials: S
authors.lastname: Izumoto
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kijima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.forename: Soyoko
authors.initials: S
authors.lastname: Morimoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakajima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Nishida
authors.forename: Naoki
authors.initials: N
authors.lastname: Hosen
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.forename: Norio
authors.initials: N
authors.lastname: Arita
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yoshimine
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide; D025721:WT1 Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D025721:WT1 Proteins; C583751:WT1 protein, human; D003606:Dacarbazine; D000077204:Temozolomide