Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Clinical Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01SC010065-05
Application #
6435315
Study Section
(RO)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2000
Total Cost
Indirect Cost

  Institution

Name
Clinical Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Chan, Linda W; Moses, Marsha A; Goley, Elizabeth et al. (2004) Urinary VEGF and MMP levels as predictive markers of 1-year progression-free survival in cancer patients treated with radiation therapy: a longitudinal study of protein kinetics throughout tumor progression and therapy. J Clin Oncol 22:499-506
Coleman, C Norman; Blakely, William F; Fike, John R et al. (2003) Molecular and cellular biology of moderate-dose (1-10 Gy) radiation and potential mechanisms of radiation protection: report of a workshop at Bethesda, Maryland, December 17-18, 2001. Radiat Res 159:812-34
Chakraborty, Mala; Abrams, Scott I; Camphausen, Kevin et al. (2003) Irradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and CTL adoptive immunotherapy. J Immunol 170:6338-47
Marcus, Karen J; Dutton, Sharon C; Barnes, Patrick et al. (2003) A phase I trial of etanidazole and hyperfractionated radiotherapy in children with diffuse brainstem glioma. Int J Radiat Oncol Biol Phys 55:1182-5
Colevas, A Dimitrios; Brown, J Martin; Hahn, Stephen et al. (2003) Development of investigational radiation modifiers. J Natl Cancer Inst 95:646-51
Tofilon, Philip J; Saxman, Scott; Coleman, C Norman (2003) Molecular targets for radiation therapy: bringing preclinical data into clinical trials. Clin Cancer Res 9:3518-20
Menard, Cynthia; Camphausen, Kevin; Muanza, Thierry et al. (2003) Clinical trial of endorectal amifostine for radioprotection in patients with prostate cancer: rationale and early results. Semin Oncol 30:63-7
Palayoor, Sanjeewani T; Tofilon, Philip J; Coleman, C Norman (2003) Ibuprofen-mediated reduction of hypoxia-inducible factors HIF-1alpha and HIF-2alpha in prostate cancer cells. Clin Cancer Res 9:3150-7
Stone, Helen B; Coleman, C Norman; Anscher, Mitchell S et al. (2003) Effects of radiation on normal tissue: consequences and mechanisms. Lancet Oncol 4:529-36
Coleman, C Norman; Wallner, Paul E; Abrams, Jeffrey S (2003) Inflammatory breast issue. J Natl Cancer Inst 95:1182-3

Showing the most recent 10 out of 13 publications