Phase 2 trial of copper depletion and penicillamine as antiangiogenesis therapy of glioblastoma

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2005-07, Vol.7 (3), p.246-253
• Main Authors: Brem, Steven, Grossman, Stuart A, Carson, Kathryn A, New, Pamela, Phuphanich, Surasak, Alavi, Jane B, Mikkelsen, Tom, Fisher, Joy D
• Format: Article
• Language: English
• Subjects: Brain Neoplasms - mortality; Brain Neoplasms - therapy; Chelating Agents - toxicity; Clinical Investigations; Copper - blood; Diet Therapy; Female; Glioblastoma - mortality; Glioblastoma - therapy; Humans; Male; Middle Aged; Neovascularization, Pathologic - drug therapy; Penicillamine - toxicity; Survival Analysis
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1215/S1152851704000869

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 creating a copper deficiency in human glioblastoma multiforme. Forty eligible patients with newly diagnosed glioblastoma multiforme began radiation therapy (6000 cGy in 30 fractions) in conjunction with a low-copper diet and escalating doses of penicillamine. Serum copper was measured at baseline and monthly. The primary end point of this study was overall survival compared to historical controls within the NABTT CNS Consortium database. The 25 males and 15 females who were enrolled had a median age of 54 years and a median Karnofsky performance status of 90. Surgical resection was performed in 83% of these patients. Normal serum copper levels at baseline (median, 130 microg/dl; range, 50-227 microg/dl) fell to the target range of