Disulfiram and copper ‘should not be recommended’ for patients with recurrent glioblastoma
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Key takeaways:
- Results showed no significant difference in 6-month survival with disulfiram and copper plus standard-of-care chemotherapy vs. chemotherapy alone.
- The combination appeared associated with higher toxicity rates.
The addition of disulfiram and copper to chemotherapy did not result in a significant survival benefit for patients with recurrent glioblastoma, according to data published in JAMA Network Open.
Moreover, the combination appeared associated with significantly increased toxic effects compared with chemotherapy alone, researchers wrote.
“Unfortunately, I was not so surprised by the results, as many of my patients on treatment in the study had difficulties tolerating the disulfiram treatment, even after lowering the dose,” Katja Werlenius, MD, research student in the department of oncology at Sahlgrenska University Hospital in Gothenburg, Sweden, told Healio. “However, I was surprised and sad to see that [disulfiram] might even have had a negative impact in this setting.”
Background and methodology
Disulfiram, which has been used to treat alcoholism since the 1940s, has shown broad antitumoral effects in several preclinical studies. Werlenius and colleagues sought to evaluate the efficacy and safety of disulfiram and copper plus alkylating chemotherapy in patients with recurrent glioblastoma, one of the proposed indications for the agent.
The open-label, randomized phase 2/phase 3 trial included 88 adults (72% male) who had a first recurrence of glioblastoma and an indication for treatment with alkylating chemotherapy. Researchers assigned patients in a 1:1 ratio to receive standard-of-care alkylating chemotherapy with or without disulfiram and copper at seven study sites in Sweden and two in Norway between January 2017 and November 2020.
Patients in the investigational group (n = 43) received 400 mg disulfiram and 2.5 mg copper daily.
Follow-up occurred until death or for a maximum of 24 months.
Survival at 6 months served as the primary endpoint. Secondary endpoints included OS, PFS, adverse events and patient-reported quality of life.
Results
Researchers noted no significant difference in 6 months survival rates between the groups (62% for standard of care chemotherapy vs. 44% for chemotherapy plus disulfiram and copper). Results showed median OS of 8.2 months (95% CI, 5.4-10.2 months) with standard-of-care chemotherapy and 5.5 months (95% CI, 3.9-9.3 months) with chemotherapy plus disulfiram and copper, and median PFS of 2.6 months (95% CI, 2.4-4.6) vs. 2.3 months (95% CI, 1.7-2.6).
More patients in the disulfiram and copper group reported grade 3 or higher adverse events (34% vs. 11%; P = .02) and serious adverse events (41% vs. 16%; P = .02) than in the chemotherapy-alone group. Ten patients discontinued disulfiram treatment due to adverse events.
Next steps
Werlenius plans to investigate the potential of other novel treatment strategies to assist patients with recurrent glioblastoma.
“It has never been our clinical practice to use disulfiram in the treatment of patients with cancer; now we know that disulfiram should not be recommended outside clinical trials,” Werlenius said. “I will not continue to study this topic, but I will continue to try to find better ways of treating patients with brain tumors.”
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