Add-on disulfiram, copper not recommended for patients with recurrent glioblastoma

When added to chemotherapy, disulfiram and copper do not appear to yield survival benefits in patients with recurrent glioblastoma, even leading to an increased frequency of adverse events, as shown in the results of an open-label, randomized phase II/III study.

The study involved adult patients who had a first recurrence of glioblastoma and an indication for treatment with alkylating chemotherapy, recruited at seven study sites in Sweden and two sites in Norway. They were randomly assigned to receive either standard-of-care (SOC) alkylating chemotherapy alone or SOC combined with disulfiram (400 mg daily) and copper (2.5 mg daily).

Survival at 6 months was the primary endpoint. Secondary endpoints included overall survival, progression-free survival, adverse events, and patient-reported quality of life.

A total of 88 patients (mean age 55.4 years, 72 percent men) were included in the analysis, among whom 45 were in the SOC group and 43 were in the SOC plus disulfiram and copper group. The 6-month survival rate was similar in the two treatment groups (62 percent vs 44 percent; p=0.10).

Median overall survival was 8.2 months (95 percent confidence interval [CI], 5.4–10.2) with SOC and 5.5 months (95 percent CI, 3.9–9.3) with SOC plus disulfiram and copper. The respective median progression-free survival was 2.6 months (95 percent CI, 2.4–4.6) and 2.3 months (95 percent CI, 1.7–2.6).

Grade 3 or higher adverse events occurred more frequently among patients in the SOC plus disulfiram and copper group than in the SOC alone group (34 percent vs 11 percent; p=0.02), as did serious adverse events (41 percent vs 16 percent; p=0.02). Adverse event led to discontinuation of disulfiram in 10 patients.

The present data suggest that disulfiram and copper are not recommended in patients with recurrent glioblastoma.