Phase i study of arsenic trioxide and temozolomide in combination with radiation therapy in patients with malignant gliomas

Sean A. Grimm*, Maryanne Marymont, James P. Chandler, Kenji Muro, Steven B. Newman, Robert M. Levy, Borko Jovanovic, Katie McCarthy, Jeffrey J. Raizer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

To evaluate the toxicity and maximum tolerated dose (MTD) of arsenic trioxide (ATO) in combination with temozolomide (TMZ) and radiation therapy (RT) in malignant gliomas. A 3 + 3 dose escalation study was performed in patients with newly diagnosed glioblastoma, anaplastic astrocytoma (AA), and anaplastic oligoastrocytoma (AOA). All patients received RT 59-61 Gy in 28-33 fractions, TMZ for 42 days, and ATO 1-2 h prior to RT for 5 days during the first week, then twice weekly until completing RT. Dose levels (DL) were: (1) TMZ 60 mg/m2/ATO 0.2 mg/kg; (2) TMZ 75 mg/m2/ATO 0.2 mg/kg; (3) TMZ 75 mg/m2/ATO 0.25 mg/kg. Dose-limiting toxicity (DLT) was defined as grade 3 non-hematologic toxicity or grade 4 toxicity of any type from enrollment until 3 weeks after finishing RT. 17 patients (13 glioblastoma, 4 AA/AOA) were accrued. Median age was 52 (range 25-80). Median KPS was 90 %. DLT's occurred at DL 2 (grade 4 transaminase elevation) and DL 3 (grade 4 neutropenia and grade 3 QTc prolongation). The MTD of TMZ 75 mg/m 2/ATO 0.2 mg/kg was safe and well tolerated. A phase II study evaluating the efficacy of this combination is underway.

Original languageEnglish (US)
Pages (from-to)237-243
Number of pages7
JournalJournal of Neuro-Oncology
Volume110
Issue number2
DOIs
StatePublished - Nov 2012

Keywords

  • Arsenic trioxide
  • Central nervous system tumor
  • Chemoradiation
  • Glioblastoma
  • Malignant glioma

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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