Ionizing radiation produces cancer cell death by creating high levels of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, in irradiated cells. Cancer cells are preferentially affected by ROS. The investigators, therefore, propose that interfering with the detoxification of ROS will make radiation more toxic to cancer cells. Several cellular mechanisms exist to detoxify ROS, and glucose metabolism plays an important role in many of these mechanisms. The investigators propose that interfering with glucose metabolism will sensitize cancer cells to radiation. The investigators' central hypothesis is that 2DG will sensitize cancer cells to ionizing radiation by inhibiting the use of glucose to detoxify reactive oxygen species produced by radiation. As an initial step to evaluate this hypothesis, the investigators have designed this phase I study.
Radiosurgery is a proven treatment option for intracranial metastases. This trial is an initial effort to potentiate the therapeutic effect of single dose stereotactic radiosurgery by combining a radiation sensitizing agent, 2DG, with radiosurgery in the treatment of intracranial metastases. Our preclinical studies indicate the degree of cancer cell radiosensitization using 2DG increases with increasing radiation dose. We therefore are interested to use 2DG with radiosurgery, since this technique allows for delivery of a large single dose of radiation. This trial seeks to determine the maximum tolerable one time dose of 2DG that can be delivered to subjects receiving stereotactic radiosurgery. We will also measure the physiologic effects of 2DG on glucose and reactive oxygen species metabolism.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Addition of 2DG to stereotactic radiosurgery. Dose escalation study.
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Safety
Time frame: During treatment and 30 days post-treatment
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