Journal of Neuro-Oncology

, Volume 110, Issue 2, pp 237–243 | Cite as

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
Clinical Study

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/m2/ATO 0.2 mg/kg was safe and well tolerated. A phase II study evaluating the efficacy of this combination is underway.

Keywords

Glioblastoma Malignant glioma Chemoradiation Arsenic trioxide Central nervous system tumor 

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Sean A. Grimm
    • 1
  • Maryanne Marymont
    • 2
  • James P. Chandler
    • 3
  • Kenji Muro
    • 3
  • Steven B. Newman
    • 4
  • Robert M. Levy
    • 3
  • Borko Jovanovic
    • 5
  • Katie McCarthy
    • 6
  • Jeffrey J. Raizer
    • 6
  1. 1.Department of NeurologyFeinberg School of Medicine, Northwestern UniversityChicagoUSA
  2. 2.Department of Radiation OncologyFeinberg School of Medicine, Northwestern UniversityChicagoUSA
  3. 3.Department of NeurosurgeryFeinberg School of Medicine, Northwestern UniversityChicagoUSA
  4. 4.Department of MedicineFeinberg School of Medicine, Northwestern UniversityChicagoUSA
  5. 5.Department of Preventative MedicineFeinberg School of Medicine, Northwestern UniversityChicagoUSA
  6. 6.Department of NeurologyFeinberg School of Medicine, Northwestern UniversityChicagoUSA

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