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Updated: Sep 6, 2025
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Phase II study of Disulfiram and Cisplatin in Refractory Germ Cell Tumors. The GCT-SK-006 phase II trial
M Mego1,2,3, D Svetlovska4,5, De Angelis V5
1Translational Research Unit, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia. misomego@gmail.com.
Background:
Multiple relapsed/refractory germ cell tumor (GCT) patients have extremely poor prognosis. Cisplatin resistant testicular GCTs overexpress aldehyde-dehydrogenase (ALDH) isoforms and inhibition of ALDH activity by disulfiram is associated with reconstitution of cisplatin sensitivity in vitro as well as in animal model. This study aimed to determine the efficacy and toxicity of ALDH inhibitor disulfiram in combination with cisplatin in patients with multiple relapsed/refractory GCTs.
Methods:
Disulfiram was administered at a dose of 400 mg daily until progression or unacceptable toxicity, cisplatin was administered at dose 50 mg/m2 day 1 and 2, every 3 weeks. Twelve evaluable patients had to be enrolled into the first cohort, and if 0 of 12 patients had treatment response, the study was to be terminated. The results of the first stage of the trial are presented in this report.
Results:
Twelve patients with multiple relapsed/refractory GCTs were enrolled in the phase II study from May 2019 to September 2021. Median number of treatment cycles was 2 (range 1-6). None of patients achieved objective response to treatment, therefore the study was terminated in first stage. Median progression-free survival was 1.4 months, 95% CI (0.7-1.5 months), and median overall survival was 2.9 months 95% CI (1.5-4.7 months). Disease stabilization for at least 3 months was observed in 2 (16.7%) patients. Treatment was well tolerated, however, 5 (41.7%) of patients experienced grade 3/4 fatigue, 4 (33.3%) thrombocytopenia, 3 (25.0%) anemia, while 2 (16.7%) experienced neutropenia, nausea and infection.
Conclusions:
This study failed to achieve its primary endpoint and our data suggest limited efficacy of disulfiram in restoring sensitivity to cisplatin in multiple relapsed/refractory GCTs.
Insights
This study investigated disulfiram combined with cisplatin for relapsed germ cell tumors (GCTs). The combination therapy showed limited efficacy and did not meet its primary endpoint in patients with refractory GCTs.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Germ cell tumors (GCTs) with multiple relapses or refractory disease have a poor prognosis.
- Cisplatin-resistant GCTs often overexpress aldehyde dehydrogenase (ALDH) isoforms.
- Disulfiram inhibits ALDH activity, potentially restoring cisplatin sensitivity in vitro and in animal models.
Purpose of the Study:
- To evaluate the efficacy and toxicity of disulfiram in combination with cisplatin.
- To determine if ALDH inhibition can re-sensitize refractory GCTs to cisplatin.
Main Methods:
- A Phase II study enrolled twelve patients with multiple relapsed/refractory GCTs.
- Disulfiram (400 mg daily) and cisplatin (50 mg/m² on days 1-2 every 3 weeks) were administered.
- The study was designed to terminate if no objective response was observed in the first 12 patients.
Main Results:
- None of the twelve enrolled patients achieved an objective response, leading to early study termination.
- Median progression-free survival was 1.4 months, and median overall survival was 2.9 months.
- While generally well-tolerated, significant toxicities included fatigue (41.7%), thrombocytopenia (33.3%), and anemia (25.0%).
Conclusions:
- The combination of disulfiram and cisplatin did not achieve the primary endpoint.
- Limited efficacy was observed in restoring cisplatin sensitivity in patients with multiple relapsed/refractory GCTs.
