Abstract

The prognosis for most patients with high grade gliomas remains poor. Local progression remains the predominate mode of treatment failure. Resistance to radiotherapy is largely due to DNA repair, ultimately resulting recurrence and death. We are exploring the use of DNA repair inhibiting compounds as radiosensitizers for the treatment of primary brain tumors. 2-Chlorodeoxyadenosine (2CDA) is an adenosine analog which resists deamination, inhibits DNA repair, and is a potent radiosensitizer of tumor cells in vitro. 2CDA has also demonstrated single agent activity against recurrent gliomas in a phase 1 study of non-hematologic malignancies. Thus, in the present study we are conducting a phase 1 dose escalation of 2CDA given during the course of acelerated hyperfractionated radiotherapy for patients with high grade glioma or glioblastoma.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01SC010065-01
Application #
2464555
Study Section
Special Emphasis Panel (RO)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1996
Total Cost
Indirect Cost

  Institution

Name
National Cancer Institute Division of 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
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
Trotti, Andy; Colevas, A Dimitrios; Setser, Ann et al. (2003) CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 13:176-81
Camphausen, Kevin; Sproull, Mary; Tantama, Steve et al. (2003) Evaluation of copper chelation agents as anti-angiogenic therapy. Bioorg Med Chem 11:4287-93
Coleman, C Norman (2003) Linking radiation oncology and imaging through molecular biology (or now that therapy and diagnosis have separated, it's time to get together again!). Radiology 228:29-35
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

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