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Phase II trial of copper depletion as angiosuppressive treatment in newly diagnosed Glioblastoma Multiforme: Final report.


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Website: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-004316,00.asp

Posted on: 06/08/2004

Phase II trial of copper depletion as angiosuppressive treatment in newly diagnosed Glioblastoma Multiforme: Final report.

Meeting: 2004 ASCO Annual Meeting
Category: Central Nervous System Tumors
SubCategory: CNS Tumors
Abstract No: 1530

Author(s): S. Brem, S. A. Grossman, K. A. Carson, P. New, S. Phuphanich, J. B. Alavi, T. Mikkelsen, R. Priet; NABTT CNS Consortium, Baltimore, MD

Abstract:
Background: Penicillamine is an oral agent used to treat intracerebral copper overload in Wilson's disease. Copper is a known regulator of angiogenesis; copper reduction inhibits experimental glioma growth and invasiveness. This study examined the feasibility, safety, and efficacy of copper deficiency in human glioblastoma multiforme.

Methods: Forty eligible patients with newly diagnosed glioblastoma began concurrent radiation therapy (6000 cGy) in conjunction with a low copper diet and gradual dose escalation of penicillamine. Serum copper was measured at baseline and monthly. The primary endpoint was overall survival compared to controls in the NABTT database.

Results: Twenty-five males and 15 females were enrolled between March 1999 and April 2000. The median age was 54 years, the mean KPS was 88, and 83% received surgical debulking. The mean baseline serum copper level was 138.6 ± 31.6 µg/dL and generally fell to the target range of 50 - 70 µg/dL (57.5 ± 27.5) after two months. Hypocupremia was found to be well tolerated for months. Significant toxicities such as myelosuppression, elevated liver function values, and skin rash were rapidly reversed by copper repletion. The median survival was 11.3 months and the median progression-free survival was 7.1 months. Prolonged survival was related to age and extent of surgical resection, but not hypocupremia.

Conclusions: Although serum copper was effectively reduced by diet and penicillamine in patients with newly diagnosed glioblastoma multiforme who also received radiation, this antiangiogenesis strategy did not improve survival.




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