This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Anaplastic glioma and glioblastoma multiforme (GBM) comprise the most common malignant primary brain tumors and are collectively known as malignant glioma. GBM is the most common subtype. GBM is among the most aggressive tumors known. Despite significant attempts to improve outcome with conventional methods, median survival is still less than one year for GBM and less than 4 yrs for anaplastic glioma. Because these tumors will inevitably recur within the brain despite initial aggressive treatment with surgery and conventional radiation therapy, additional treatment options are sought when recurrence develops. Arsenic Trioxide (ATO) has been shown to have anti-tumor activity and was approved by the FDA for treatment of relapsed acute promyelocytic leukemia. We present preclinical data showing that ATO enhances radiation-induced tumor cell killing in a human malignant brain tumor cell line both in vitro and in vivo. Based on these encouraging results, we have designed a feasibility study using ATO in combination with stereotactic radiosurgery/radiotherapy for the treatment of patients with recurrent malignant glioma. This study is designed as a pilot Phase I dose escalation trial of ATO with stereotactic radiosurgery/radiotherapy for patients with recurrent malignant glioma. Patients will be treated with ATO within 2 hours prior to 1 - 3 daily stereotactic radiation treatments. The starting dose of ATO 0.10mg/kg/dose will be administered to the first cohort of patients. If this dose is tolerable among the first cohort, the dose will be escalated to dose limiting toxicity (DLT).
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