title: Phase I/II clinical trial of carbon ion radiotherapy for malignant gliomas: combined X-ray radiotherapy, chemotherapy, and carbon ion radiotherapy.
abstract: OBJECTIVE
  To report the results of a Phase I/II clinical trial for patients with malignant gliomas, treated with combined X-ray radiotherapy (XRT), chemotherapy, and carbon ion radiotherapy (CRT).
  
  
  METHODS
  Between October 1994 and February 2002, 48 patients with histologically confirmed malignant gliomas (16 anaplastic astrocytoma (AA) and 32 glioblastoma multiforme (GBM) were enrolled in a Phase I/II clinical study. The treatment involved the application of 50 Gy/25 fractions/5 weeks of XRT, followed by CRT at 8 fractions/2 weeks. Nimustine hydrochloride (ACNU) were administered at a dose of 100 mg/m(2) concurrently in weeks 1, 4, or 5 of XRT. The carbon ion dose was increased from 16.8 to 24.8 Gray equivalent (GyE) in 10% incremental steps (16.8, 18.4, 20.0, 22.4, and 24.8 GyE, respectively).
  
  
  RESULTS
  There was no Grade 3 or higher acute reaction in the brain. The late reactions included four cases of Grade 2 brain morbidity and four cases of Grade 2 brain reaction among 48 cases. The median survival time (MST) of AA patients was 35 months and that of GBM patients 17 months (p = 0.0035). The median progression-free survival and MST of GBM showed 4 and 7 months for the low-dose group, 7 and 19 months for the middle-dose group, and 14 and 26 months for the high-dose group.
  
  
  CONCLUSIONS
  The results of combined therapy using XRT, ACNU chemotherapy, and CRT showed the potential efficacy of CRT for malignant gliomas in terms of the improved survival rate in those patients who received higher carbon doses.
authors: Hospital, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan. j_mizoe@nirs.go.jp
authors: Jun-Etsu
authors: JE
authors: Mizoe
authors: Hirohiko
authors: H
authors: Tsujii
authors: Azusa
authors: A
authors: Hasegawa
authors: Tsuyoshi
authors: T
authors: Yanagi
authors: Ryo
authors: R
authors: Takagi
authors: Tadashi
authors: T
authors: Kamada
authors: Hiroshi
authors: H
authors: Tsuji
authors: Kintomo
authors: K
authors: Takakura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001254:Astrocytoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D002250:Carbon Radioisotopes / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015376:Nimustine / Q000627:therapeutic use; D011879:Radiotherapy Dosage
chemical_list: D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D015376:Nimustine