title: A phase I/II trial of a WT1 (Wilms' tumor gene) peptide vaccine in patients with solid malignancy: safety assessment based on the phase I data.
abstract: OBJECTIVE
  We conducted a phase I study to investigate the safety of a weekly WT1 tumor vaccine therapy in patients with solid tumors that had been refractory to all other anti-cancer therapies.
  
  
  METHODS
  Skin-test-negative patients were intradermally injected weekly for 12 weeks with 3.0 mg of an HLA-A*2402-restricted modified 9-mer WT1 peptide emulsified in Montanide ISA51 adjuvant. We estimated the Bayesian posterior probability of the occurrence of grade 3 or 4 toxicity when receiving the weekly WT1 vaccination. This analysis provided the basis for making a decision to terminate the phase I study and switch to phase II. Moreover, we performed an exploratory assessment of the anti-tumor effects of WT1 treatment.
  
  
  RESULTS
  Ten patients received 114 vaccinations with WT1 on a weekly schedule. No grade 3 or 4 toxicities were observed. Based on the Bayesian approach, it was highly likely that the probability of grade 3 or 4 toxicity was below 20% (the posterior probability = 0.914). Fifteen grade 2 and two grade 1 toxicities were observed; all of these incidents, however, were determined by the Independent Data and Safety Monitoring Committee to be unrelated to the WT1 treatment. One patient exhibited a partial response; five additional patients had stable disease while receiving weekly WT1 treatment.
  
  
  CONCLUSIONS
  This paper confirms that the potential toxicities of the treatment schedule of weekly WT1 vaccination are acceptable and suggested a potential anti-tumor effect. Consequently, we validated the decision to continue to the phase II trial.
authors.affiliation: Department of Epidemiology and Health care Research, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. satoshi_morita@pbh.med.kyoto-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawakami
authors.forename: Motohiko
authors.initials: M
authors.lastname: Maruno
authors.forename: Shuichi
authors.initials: S
authors.lastname: Izumoto
authors.forename: Tadashi
authors.initials: T
authors.lastname: Osaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taguchi
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ueda
authors.forename: Akira
authors.initials: A
authors.lastname: Myoui
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Nishida
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shirakata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohno
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Aozasa
authors.forename: Jun
authors.initials: J
authors.lastname: Hatazawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Udaka
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yoshimine
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Nakatsuka
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001499:Bayes Theorem; D001943:Breast Neoplasms / Q000628:therapy*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000628:therapy*; D005260:Female; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D007271:Injections, Intradermal; D008297:Male; D008875:Middle Aged; D014611:Vaccination; D025721:WT1 Proteins / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D025721:WT1 Proteins