Phase I/II Study of Temozolomide Plus Nimustine Chemotherapy for Recurrent Malignant Gliomas: Kyoto Neuro-oncology Group

• AOKI Tomokazu

  Department of Neurosurgery, National Hospital Organization, Kyoto Medical Center

• ARAKAWA Yoshiki

  Department of Neurosurgery, Graduate School of Medicine, Kyoto University

• UEBA Tetsuya

  Department of Neurosurgery, Kochi Medical School, Kochi University

• ODA Masashi

  Department of Neurosurgery, National Hospital Organization, Himeji Medical Center

• NISHIDA Namiko

  Department of Neurosurgery, Kitano Hospital Medical Research Institute

• AKIYAMA Yukinori

  Department of Neurosurgery, Sapporo Medical University

• TSUKAHARA Tetsuya

  Department of Neurosurgery, National Hospital Organization, Kyoto Medical Center

• IWASAKI Koichi

  Department of Neurosurgery, Kitano Hospital Medical Research Institute

• MIKUNI Nobuhiro

  Department of Neurosurgery, Sapporo Medical University

• MIYAMOTO Susumu

  Department of Neurosurgery, Graduate School of Medicine, Kyoto University

Abstract

The objective of this phase I/II study was to examine the efficacy and toxicity profile of temozolomide (TMZ) plus nimustine (ACNU). Patients who had received a standard radiotherapy with one or two previous chemo-regimens were enrolled. In phase I, the maximum-tolerated dose (MTD) by TMZ (150 mg/m²/day) (Day 1-5) plus various doses of ACNU (30, 35, 40, 45 mg/m²/day) (Day 15) per 4 weeks was defined on a standard 3 + 3 design. In phase II, these therapeutic activity and safety of this regimen were evaluated. Forty-nine eligible patients were enrolled. The median age was 50 years-old. Eighty percent had a KPS of 70–100. Histologies were glioblastoma (73%), anaplastic astrocytoma (22%), anaplastic oligodendroglioma (4%). In phase I, 15 patients were treated at four cohorts by TMZ plus ACNU. MTD was TMZ (150 mg/m²) plus ACNU (40 mg/m²). In phase II, 40 patients were treated at the dose of cohort 3 (MTD). Thirty-five percent of patients experienced grade 3 or 4 toxicities, mainly hematologic. The overall response rate was 11% (4/37). Sixty-eight percent (25/37) had stable disease. Twenty-two percent (8/37) showed progression. Progression-free survival (PFS) rates at 6 and 12 months were 24% (95% CI, 12–35%) and 8% (95% CI, 4–15%). Median PFS was 13 months (95% CI, 9.2–17.2 months). Overall survival (OS) at 6 and 12 were 78% (95% CI, 67–89%) and 49% (95% CI, 33–57%). Median OS was 11.8 months (95% CI, 8.2–14.5 months). This phase I/II study showed a moderate toxicity in hematology and may has a promising efficacy in OS, without inferiority in PFS.

Journal

• Neurologia medico-chirurgica

  Neurologia medico-chirurgica 57 (1), 17-27, 2017

  The Japan Neurosurgical Society

Keywords

• temozolomide
• nimustine
• recurrent malignant gliomas
• phase I/II study

Details

• CRID: 1390282680034744960
• NII Article ID: 120006335651
• NII Article ID: 130005290679
• DOI: 10.2176/nmc.oa.2016-0162
• ISSN: 13498029
• ISSN: 04708105
• HANDLE: 2433/226823
• PubMed: 27725524
• Web Site: https://www.jstage.jst.go.jp/article/nmc/57/1/57_oa.2016-0162/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2017229238
• Text Lang: en
• Data Source:
  • JaLC
  • IRDB
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed