title: Randomized trial of chemoradiotherapy and adjuvant chemotherapy with nimustine (ACNU) versus nimustine plus procarbazine for newly diagnosed anaplastic astrocytoma and glioblastoma (JCOG0305).
abstract: OBJECTIVE
  Glioblastoma (GBM) is one of the worst cancers in terms of prognosis. Standard therapy consists of resection with concomitant chemoradiotherapy. Resistance to nimustine hydrochloride (ACNU), an alkylating agent, has been linked to methylguanine DNA methyltransferase (MGMT). Daily administration of procarbazine (PCZ) has been reported to decrease MGMT activity. This study investigated the efficacy of ACNU + PCZ compared to ACNU alone for GBM and anaplastic astrocytoma (AA).
  
  
  METHODS
  Patients (20-69 years) who had newly diagnosed AA and GBM were randomly assigned to receive radiotherapy with ACNU alone or with ACNU + PCZ. The primary endpoint was overall survival (OS). This was designed as a phase II/III trial with a total sample size of 310 patients and was registered as UMIN-CTR C000000108.
  
  
  RESULTS
  After 111 patients from 19 centers in Japan were enrolled, this study was terminated early because temozolomide was newly approved in Japan. The median OS and median progression-free survival (PFS) with ACNU alone (n = 55) or ACNU + PCZ (n = 56) in the intention-to-treat population were 27.4 and 22.4 months (p = 0.75), and 8.6 and 6.9 months, respectively. The median OS and median PFS of the GBM subgroup treated with ACNU alone (n = 40) or ACNU + PCZ (n = 41) were 19.0 and 19.5 months, and 6.2 and 6.3 months, respectively. Grade 3/4 hematologic adverse events occurred in more than 40 % of patients in both arms, and 27 % of patients discontinued treatment because of adverse events.
  
  
  CONCLUSIONS
  The addition of PCZ to ACNU was not beneficial, in comparison with ACNU alone, for patients with newly diagnosed AA and GBM.
authors.affiliation: Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. sshibui@ncc.go.jp
authors.forename: Soichiro
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authors.lastname: Shibui
authors.forename: Yoshitaka
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authors.forename: Junki
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authors.lastname: Mizusawa
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authors.lastname: Minamida
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authors.lastname: Yamaki
authors.forename: Toshihiro
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authors.lastname: Kumabe
authors.forename: Teiji
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authors.lastname: Tominaga
authors.forename: Takamasa
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authors.lastname: Kayama
authors.forename: Kaori
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authors.lastname: Sakurada
authors.forename: Motoo
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authors.lastname: Nagane
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Nakamura
authors.forename: Tamio
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authors.lastname: Ito
authors.forename: Takahito
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authors.lastname: Yazaki
authors.forename: Hikaru
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authors.lastname: Sasaki
authors.forename: Katsuyuki
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authors.lastname: Tanaka
authors.forename: Hideaki
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authors.lastname: Takahashi
authors.forename: Akio
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authors.lastname: Asai
authors.forename: Tomoki
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authors.lastname: Todo
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Wakabayashi
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
authors.forename: Shingo
authors.initials: S
authors.lastname: Takano
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Fujimaki
authors.forename: Minako
authors.initials: M
authors.lastname: Sumi
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Miyakita
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sato
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Fukuda
authors.forename: Kazuhiro
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authors.lastname: Nomura
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001254:Astrocytoma / Q000401:mortality / Q000628:therapy*; D001932:Brain Neoplasms / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D015376:Nimustine / Q000008:administration & dosage / Q000627:therapeutic use*; D011344:Procarbazine / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D015376:Nimustine; D011344:Procarbazine