Disulfiram and Copper Plus Chemotherapy Not Effective for Glioblastoma

Adding disulfiram and copper to chemotherapy increases toxic effects, not survival outcomes, compared with chemotherapy alone among patients with recurrent glioblastoma. These are the findings of a study published in JAMA Network Open.

The drug disulfiram, which is used to treat alcohol dependency, has gained attention as a potential anticancer drug.

Researchers designed an open-label, randomized, controlled, parallel group phase II/III trial (ClinicalTrials.gov Identifier: NCT02678975), conducted at 7 sites in Sweden and 2 in Norway between 2017 and 2020, to investigate the potential utility of disulfiram for the treatment of glioblastoma. Patients (N=88) with a first recurrence of glioblastoma were randomly assigned in a 1:1 ratio to receive standard of care (SOC) of any alkylating chemotherapy (n=45) or SOC plus 400 mg daily disulfiram and 2.5 mg elementary copper (n=43). The primary outcome was survival at 6 months.

The patients were mean age, 55.4 (SD, 11.5) years, 72% were men, 90% had undergone initial resection, 93% had undergone initial radiotherapy with temozolomide, and 49% used steroids at baseline.

The chemotherapy regimens received by the SOC and disulfiram cohorts were lomustine (64% vs 51%), temozolomide (27% vs 32%), and procarbazine (27% vs 32%), respectively. The SOC group received a longer duration of chemotherapy than the disulfiram group (median, 93.5 vs 60 days; P =.007), respectively.

Survival rates at 6 months were 62% for the SOC group and 44% for the disulfiram group (P =.10). No significant differences in survival were observed at 9, 12, or 24 months between groups.

Similarly, no group differences in secondary efficacy outcomes were observed. Median progression-free survival was 77 and 68 days (P =.07), 76% and 81% had progression at 6 months (P =.56), and the mean daily change in tumor volume was 12% and 3% (P =.19) for the SOC and disulfiram cohorts, respectively.

The disulfiram recipients did, however, have a significantly increased rate of adverse events of grade 3 or higher severity (34% vs 11%; P =.02) as well as any serious adverse events (41% vs 16%; P =.02) compared with SOC, respectively. Overall, 22% of the disulfiram group experienced at least 1 serious adverse event that was deemed as probably, possibly, or definitely related to the intervention.

The limitations of this study included the fact that it was an interim analysis and the open-label design.

These data did not support the use of disulfiram for the treatment of glioblastoma. The researchers concluded, “This randomized clinical trial found that the addition of disulfiram and copper to alkylating chemotherapy did not improve survival in patients with recurrent glioblastoma. Instead, the treatment regimen of 400 mg disulfiram daily resulted in significantly more toxic effects. These results suggest that disulfiram and copper is not of benefit in patients with recurrent glioblastoma.”

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.