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J Neurooncol. 2012 Nov;110(2):237-43. doi: 10.1007/s11060-012-0957-6. Epub 2012 Aug 9.

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

Author information

1
Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. SGrimm@nmff.org

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/m(2)/ATO 0.2 mg/kg; (2) TMZ 75 mg/m(2)/ATO 0.2 mg/kg; (3) TMZ 75 mg/m(2)/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.

PMID:
22875709
DOI:
10.1007/s11060-012-0957-6
[Indexed for MEDLINE]

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