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Phase II trial of copper
depletion as angiosuppressive treatment in newly diagnosed Glioblastoma
Multiforme: Final report
S. Brem, S. A. Grossman, K. A. Carson, P. New, S. Phuphanich, J. B. Alavi, T.
Mikkelsen, R. Priet
NABTT CNS Consortium, Baltimore, MD
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.
Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-004316,00.asp
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