Scholarlink

Introduction <p>Disulfiram (DSF) is an inhibitor of acetaldehyde dehydrogenase and is currently used for the treatment of alcoholism. Preclinical studies have shown that the DSF metabolite dithiocarbamate, can bind to copper (Cu) and form bis-(diethyldithiocarbamate)-copper (CuET) that has anti-tumor effects. In the present clinical phase Ib study we investigated DSF in combination with Cu and vinorelbine in cancer patients. </p> Patients and method <p>This dose escalating phase 1b trial, registered in EudraCT 2019-001972-12 on 23 Oct 2019, included patients with treatment-refractory advanced solid tumors. The treatment combination consisted of chemotherapy with vinorelbine, DSF and Cu. The primary endpoints were dose limiting toxicity (DLT) and to establish the maximal tolerated dose (MTD) of the treatment combination. </p> Results <p>A total of 16 patients were enrolled in the trial. Two of 16 patients had a dose limiting toxicity (DLT). Three dose levels (DLs) were tested and the MTD was found in DL3: DSF 400 mg once per day (QD) for day 1-7, DSF 200 mg QD day 8-14, Cu 2 mg QD, day 1-15 and vinorelbine (30 mg/m2) day 4 and 11 every third week (Q3W). </p> Conclusion <p>In this phase 1b trial, an MTD for the treatment combination of DSF, Cu and vinorelbine was found. Even though the drug combination DSF, Cu and vinorelbine was safe and an MTD found, further studies are warranted to investigate whether DSF can be used as an anti-neoplastic repurpose drug.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A phase 1b open-label, dose-escalating study of safety and efficacy of disulfiram, copper and vinorelbine in advanced solid tumors

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月16日

查看全文
  • Rikke Løvendahl Eefsen,
  • Jan Stenvang,
  • Jiri Bartek,
  • Per Pfeiffer,
  • Line Tarpgaard,
  • Susann Theile,
  • Nils Brünner,
  • Dorte L. Nielsen

摘要

Introduction

Disulfiram (DSF) is an inhibitor of acetaldehyde dehydrogenase and is currently used for the treatment of alcoholism. Preclinical studies have shown that the DSF metabolite dithiocarbamate, can bind to copper (Cu) and form bis-(diethyldithiocarbamate)-copper (CuET) that has anti-tumor effects. In the present clinical phase Ib study we investigated DSF in combination with Cu and vinorelbine in cancer patients.

Patients and method

This dose escalating phase 1b trial, registered in EudraCT 2019-001972-12 on 23 Oct 2019, included patients with treatment-refractory advanced solid tumors. The treatment combination consisted of chemotherapy with vinorelbine, DSF and Cu. The primary endpoints were dose limiting toxicity (DLT) and to establish the maximal tolerated dose (MTD) of the treatment combination.

Results

A total of 16 patients were enrolled in the trial. Two of 16 patients had a dose limiting toxicity (DLT). Three dose levels (DLs) were tested and the MTD was found in DL3: DSF 400 mg once per day (QD) for day 1-7, DSF 200 mg QD day 8-14, Cu 2 mg QD, day 1-15 and vinorelbine (30 mg/m2) day 4 and 11 every third week (Q3W).

Conclusion

In this phase 1b trial, an MTD for the treatment combination of DSF, Cu and vinorelbine was found. Even though the drug combination DSF, Cu and vinorelbine was safe and an MTD found, further studies are warranted to investigate whether DSF can be used as an anti-neoplastic repurpose drug.