A PHASE I STUDY OF 2-CHLORODEOXYADENOSINE AND RADIATION FOR THE TREATMENT OF HIGH

放射治疗是高级别胶质瘤最有效的非侵入性治疗方法，但其效果并不令人满意。辐射后死亡的主要方式是继发于DNA损伤的坏死。尽管在临床前和临床环境中已经探索了导致DNA损伤增加的治疗（卤代嘧啶类、缺氧增敏剂），但DNA修复抑制剂是一种新型的、未经测试的能够在体外放射增敏的药物。2-氯脱氧腺苷（2CDA）是一种有效的放射增敏剂，在体外已被证明可以抑制双链断裂的修复。它是一种腺苷类似物，已在I期试验中证明了对复发性恶性胶质瘤的单药活性。在本研究中，我们正在进行I期剂量递增的2CDA的过程中给予加速超分割放射治疗的高级别胶质瘤患者。- 间变性星形细胞瘤，胶质母细胞瘤，2CDA，-人类受试者

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 treatmnets 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 repari 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. - Anaplastic Astrocytoma, Glioblastoma, 2CDA, - Human Subjects