A multicenter phase II study of temozolomide plus disulfiram and copper for recurrent temozolomide-resistant glioblastoma

Jiayi Huang, Rekha Chaudhary, Adam L. Cohen, Karen Fink, Samuel Goldlust, John Boockvar, Prakash Chinnaiyan, Leping Wan, Stephen Marcus, Jian L. Campian

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Purpose: Preclinical studies have suggested promising activity for the combination of disulfiram and copper (DSF/Cu) against glioblastoma (GBM) including re-sensitization to temozolomide (TMZ). A previous phase I study demonstrated the safety of combining DSF/Cu with adjuvant TMZ for newly diagnosed GBM. This phase II study aimed to estimate the potential effectiveness of DSF/Cu to re-sensitize recurrent GBM to TMZ. Methods: This open-label, single-arm phase II study treated recurrent TMZ-resistant GBM patients with standard monthly TMZ plus concurrent daily DSF 80 mg PO TID and Cu 1.5 mg PO TID. Eligible patients must have progressed after standard chemoradiotherapy and within 3 months of the last dose of TMZ. Known isocitrate dehydrogenase (IDH) mutant or secondary GBMs were excluded. The primary endpoint was objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit (response or stable disease for at least 6 months), and safety. Results: From March 2017 to January 2018, 23 recurrent TMZ-resistant GBM patients were enrolled across seven centers, and 21 patients were evaluable for response. The median duration of DSF/Cu was 1.6 cycles (range: 0.1–12.0). The ORR was 0%, but 14% had clinical benefit. Median PFS was 1.7 months, and median OS was 7.1 months. Only one patient (4%) had dose-limiting toxicity (grade three elevated alanine transaminase). Conclusions: Addition of DSF/Cu to TMZ for TMZ-resistant IDH-wild type GBM appears well tolerated but has limited activity for unselected population.

Original languageEnglish
Pages (from-to)537-544
Number of pages8
JournalJournal of Neuro-Oncology
Volume142
Issue number3
DOIs
StatePublished - May 1 2019

Keywords

  • Clinical trial
  • Copper
  • Disulfiram
  • Recurrent glioblastoma
  • Temozolomide

Fingerprint Dive into the research topics of 'A multicenter phase II study of temozolomide plus disulfiram and copper for recurrent temozolomide-resistant glioblastoma'. Together they form a unique fingerprint.

  • Cite this