A multicenter phase II study of temozolomide plus disulfiram and copper for recurrent temozolomide-resistant glioblastoma
| العنوان: | A multicenter phase II study of temozolomide plus disulfiram and copper for recurrent temozolomide-resistant glioblastoma |
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| المؤلفون: | Rekha Chaudhary, Adam L. Cohen, Leping Wan, Stephen Marcus, Prakash Chinnaiyan, Jian Campian, Jiayi Huang, John A. Boockvar, Samuel Goldlust, Karen Fink |
| المصدر: | Journal of Neuro-Oncology. 142:537-544 |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Acetaldehyde Dehydrogenase Inhibitors, Phases of clinical research, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Disulfiram, Temozolomide, medicine, Clinical endpoint, Humans, Antineoplastic Agents, Alkylating, Survival rate, Aged, biology, Brain Neoplasms, business.industry, Prognosis, Trace Elements, Survival Rate, Neurology, Alanine transaminase, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, biology.protein, Drug Therapy, Combination, Female, Neurology (clinical), Neoplasm Recurrence, Local, Glioblastoma, business, Adjuvant, Copper, 030217 neurology & neurosurgery, Chemoradiotherapy, Follow-Up Studies, medicine.drug |
| الوصف: | Preclinical studies have suggested promising activity for the combination of disulfiram and copper (DSF/Cu) against glioblastoma (GBM) including re-sensitization to temozolomide (TMZ). A previous phase I study demonstrated the safety of combining DSF/Cu with adjuvant TMZ for newly diagnosed GBM. This phase II study aimed to estimate the potential effectiveness of DSF/Cu to re-sensitize recurrent GBM to TMZ. This open-label, single-arm phase II study treated recurrent TMZ-resistant GBM patients with standard monthly TMZ plus concurrent daily DSF 80 mg PO TID and Cu 1.5 mg PO TID. Eligible patients must have progressed after standard chemoradiotherapy and within 3 months of the last dose of TMZ. Known isocitrate dehydrogenase (IDH) mutant or secondary GBMs were excluded. The primary endpoint was objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit (response or stable disease for at least 6 months), and safety. From March 2017 to January 2018, 23 recurrent TMZ-resistant GBM patients were enrolled across seven centers, and 21 patients were evaluable for response. The median duration of DSF/Cu was 1.6 cycles (range: 0.1–12.0). The ORR was 0%, but 14% had clinical benefit. Median PFS was 1.7 months, and median OS was 7.1 months. Only one patient (4%) had dose-limiting toxicity (grade three elevated alanine transaminase). Addition of DSF/Cu to TMZ for TMZ-resistant IDH-wild type GBM appears well tolerated but has limited activity for unselected population. |
| تدمد: | 1573-7373 0167-594X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::67dd8cda0c9e9669b8f0ffc9512ca330Test https://doi.org/10.1007/s11060-019-03125-yTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....67dd8cda0c9e9669b8f0ffc9512ca330 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15737373 0167594X |
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