Radiotherapy is the most effective non-invasive treatment of high grade gliomas, however the results are far from satisfactory. The predominant mode of death following radiation is necrosis secondary to DNA damage. Although treatments which result in the increase in DNA damage (halogenated pyrimidines, hypoxic sensitizers) have been explored in the pre-clinical and clinical setting, inhibitors of DNA repair are a novel, untested class of agents capable of radiosensitization in vitro. 2-Chlorodeoxyadenosine (2CDA) is a potent radiosensitizer which has been shown to inhibit repair of double strand breaks in vitro. It is an adenosine analog which has demonstrated single agent activity against recurrent malignant gliomas in a phase I setting. In the present study, we are conducting a phase I dose escalation of 2CDA given during the course of accelerated hyperfractionated radiotherapy for patients with high grade glioma.
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