title: Phase I/IIa trial of autologous formalin-fixed tumor vaccine concomitant with fractionated radiotherapy for newly diagnosed glioblastoma. Clinical article.
abstract: OBJECTIVE
  The objective of the present study was analysis of results of the prospective clinical trial directed toward the evaluation of therapeutic efficacy of the administration of autologous formalin-fixed tumor vaccine (AFTV) concomitant with fractionated radiotherapy in cases of newly diagnosed glioblastoma multiforme.
  
  
  METHODS
  Twenty-four patients were enrolled into the clinical trial, while 2 cases were excluded from the final analysis of results. The treatment protocol included aggressive tumor resection, fractionated radiotherapy up to a total dose of 60 Gy, and 3 concomitant courses of AFTV administered with an interval of one week at the late stage of irradiation. Two delayed-type hypersensitivity (DTH) tests were done--one 48 hours before the initial course of vaccination (DTH-1) and one 2 weeks after the third (DTH-2). All but one of the patients received salvage therapy at the time of tumor progression. The defined primary end point was overall survival; secondary end points were progression-free survival and safety of concomitant treatment.
  
  
  RESULTS
  The median duration of overall survival was 19.8 [corrected] months (95% CI 13.8-31.3 months). The actuarial 2-year survival rate was 40%. The median duration of progression-free survival was 7.6 months (95% CI 4.3-13.6 months). Overall survival showed a statistically significant association with recursive partitioning analysis class (p < 0.05); progression-free survival showed a statistically significant association with p53 staining index (p < 0.05) and size of DTH-2 response (p < 0.001). AFTV injection concomitant with fractionated radiotherapy was well tolerated by all patients and in no case did treatment-related adverse effects exceed Grade 1 toxicity; adverse effects were limited to local erythema, induration, and swelling at the site of injection.
  
  
  CONCLUSIONS
  The results of this study demonstrate that AFTV treatment concomitant with fractionated radiotherapy may be effective in patients with newly diagnosed glioblastoma. Further clinical testing is warranted.
authors.affiliation: Faculty of Advanced Techno-Surgery, Graduate School of Medicine, Tokyo Women's Medical University, Tokyo, Japan. ymuragaki@abmes.twmu.ac.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Muragaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Maruyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iseki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tanaka
authors.forename: Chie
authors.initials: C
authors.lastname: Shinohara
authors.forename: Kintomo
authors.initials: K
authors.lastname: Takakura
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumura
authors.forename: Masao
authors.initials: M
authors.lastname: Matsutani
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Karasawa
authors.forename: Katsunori
authors.initials: K
authors.lastname: Shimada
authors.forename: Naohito
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
authors.forename: Keiki
authors.initials: K
authors.lastname: Sato
authors.forename: Youji
authors.initials: Y
authors.lastname: Uemae
authors.forename: Tadao
authors.initials: T
authors.lastname: Ohno
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Okada
authors.forename: Tomokatsu
authors.initials: T
authors.lastname: Hori
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000401:mortality / Q000628:therapy*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines