Prospective clinical trial of disulfiram plus copper in men with metastatic castration‐resistant prostate cancer

Autor: Tian Zhang, Julie Kephart, Elizabeth Bronson, Monika Anand, Christine Daly, Ivan Spasojevic, Subha Bakthavatsalam, Katherine Franz, Hannah Berg, Georgia S. Karachaliou, Olga G. James, Lauren Howard, Susan Halabi, Michael R. Harrison, Andrew J. Armstrong, Daniel J. George
Rok vydání: 2022
Předmět:
Zdroj: The Prostate. 82:858-866
ISSN: 1097-0045
0270-4137
Popis: In preclinical models of prostate cancer (PC), disulfiram (DSF) reduced tumor growth only when co-administered with copper (Cu), and Cu uptake in tumors is partially regulated by androgen-receptor signaling. However, prior trials of DSF in PC used DSF as monotherapy.To assess the safety and efficacy of concurrent administration of DSF with Cu, we conducted a phase 1b clinical trial of patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Cu with DSF.Patients with mCRPC were treated in two cohorts: mCRPC with nonliver/peritoneal metastases (A), and mCRPC with liver and/or peritoneal metastases (B). Baseline Cu avidity was measured byWe treated nine patients with mCRPC (six on cohort A and three on cohort B). Bone and nodal metastases showed differential and heterogeneous Cu uptake onOral DSF is not an effective treatment for mCRPC due to rapid metabolism into an inactive metabolite, Me-DDC. This trial has stopped enrollment and further work is needed to identify a stable DSF formulation for treatment of mCRPC.
Databáze: OpenAIRE
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