دورية أكاديمية
أعرض في EDS

A phase I study to repurpose disulfiram in combination with temozolomide to treat newly diagnosed glioblastoma after chemoradiotherapy.

التفاصيل البيبلوغرافية
العنوان: A phase I study to repurpose disulfiram in combination with temozolomide to treat newly diagnosed glioblastoma after chemoradiotherapy.
المؤلفون: Huang J; Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO, 63110, USA. jhuang@radonc.wustl.edu.; Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, 63110, USA. jhuang@radonc.wustl.edu., Campian JL; Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, 63110, USA.; Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO, 63110, USA., Gujar AD; Department of Neurosurgery, Washington University School of Medicine, St Louis, MO, 63110, USA., Tran DD; Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO, 63110, USA.; Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, 63110, USA.; Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO, 63110, USA., Lockhart AC; Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, 63110, USA.; Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO, 63110, USA., DeWees TA; Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO, 63110, USA., Tsien CI; Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO, 63110, USA.; Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, 63110, USA., Kim AH; Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, 63110, USA.; Department of Neurosurgery, Washington University School of Medicine, St Louis, MO, 63110, USA.
المصدر: Journal of neuro-oncology [J Neurooncol] 2016 Jun; Vol. 128 (2), pp. 259-66. Date of Electronic Publication: 2016 Mar 10.
نوع المنشور: Clinical Trial, Phase I; Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: United States NLM ID: 8309335 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7373 (Electronic) Linking ISSN: 0167594X NLM ISO Abbreviation: J Neurooncol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2005- : New York : Springer
Original Publication: Boston : M. Nijhoff, 1983-
مواضيع طبية MeSH: Antineoplastic Agents/*therapeutic use , Dacarbazine/*analogs & derivatives , Disulfiram/*therapeutic use , Glioblastoma/*therapy , Supratentorial Neoplasms/*therapy, Administration, Oral ; Adult ; Aged ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/pharmacokinetics ; Chemoradiotherapy ; Dacarbazine/therapeutic use ; Disulfiram/adverse effects ; Disulfiram/pharmacokinetics ; Dose-Response Relationship, Drug ; Drug Repositioning ; Drug Therapy, Combination ; Female ; Glioblastoma/blood ; Humans ; Male ; Middle Aged ; Proteasome Endopeptidase Complex/blood ; Proteasome Endopeptidase Complex/drug effects ; Proteasome Inhibitors/adverse effects ; Proteasome Inhibitors/pharmacokinetics ; Proteasome Inhibitors/therapeutic use ; Supratentorial Neoplasms/blood ; Temozolomide ; Treatment Outcome ; Young Adult
مستخلص: Disulfiram, a generic alcohol aversion drug, has promising preclinical activity against glioblastoma (GBM). This phase I study aims to evaluate its safety, maximum tolerated dose (MTD), pharmacodynamic effect, and preliminary efficacy when combined with adjuvant temozolomide in GBM patients after standard chemoradiotherapy. Patients received disulfiram 500-1000 mg once daily, in combination with 150-200 mg/m(2) temozolomide. A modified 3 + 3 dose-escalation design was used to determine the MTD. The pharmacodynamic effect of proteasome inhibition was assessed using fluorometric 20S proteasome assay on peripheral blood cells. The MTD was determined based on the dose-limiting toxicities (DLTs) within the first month of therapy. Twelve patients were enrolled to two dose levels: 500 and 1000 mg. Two DLTs of grade 3 delirium occurred after 15 days of administration at 1000 mg per day. Other possible grade 2-3 DSF-related toxicities included fatigue, ataxia, dizziness, and peripheral neuropathy. The toxicities were self-limiting or resolved after discontinuing DSF. The MTD was determined to be 500 mg per day. Limited proteasome inhibition was observed at week 4 and showed an increased trend with escalated disulfiram. Median progression-free survival with 500 mg of DSF was 5.4 months from the start of disulfiram and 8.1 months from the start of chemoradiotherapy. Disulfiram can be safely combined with temozolomide but can cause reversible neurological toxicities. The MTD of disulfiram with adjuvant temozolomide appears to produce limited proteasome inhibition on peripheral blood cells.
References: PLoS One. 2013 Oct 23;8(10):e78130. (PMID: 24194908)
N Engl J Med. 2014 Feb 20;370(8):699-708. (PMID: 24552317)
J Pharm Bioallied Sci. 2010 Oct;2(4):290-9. (PMID: 21180460)
Clin Pharmacol Ther. 1984 Oct;36(4):520-6. (PMID: 6090051)
Prostate Cancer Prostatic Dis. 2013 Dec;16(4):357-61. (PMID: 23958896)
J Clin Oncol. 2002 Nov 15;20(22):4420-7. (PMID: 12431963)
Lancet Oncol. 2011 May;12(5):431-40. (PMID: 21507715)
J Clin Oncol. 2013 Nov 10;31(32):4085-91. (PMID: 24101040)
Am J Clin Oncol. 1987 Dec;10(6):517-9. (PMID: 3687835)
Carcinogenesis. 2014 Mar;35(3):692-702. (PMID: 24193513)
J Clin Oncol. 2010 Apr 10;28(11):1963-72. (PMID: 20231676)
J Clin Oncol. 2007 Jan 10;25(2):209-16. (PMID: 17210942)
Brain Res. 1987 Apr 21;409(2):265-74. (PMID: 2438009)
J Clin Psychopharmacol. 2006 Jun;26(3):290-302. (PMID: 16702894)
Br J Cancer. 2012 Oct 23;107(9):1488-97. (PMID: 23033007)
Res Commun Chem Pathol Pharmacol. 1978 Sep;21(3):543-67. (PMID: 705029)
Ecancermedicalscience. 2014 Jul 10;8:442. (PMID: 25075216)
Neuro Oncol. 2015 Jun;17(6):810-21. (PMID: 25378634)
Cancer Res. 2006 Nov 1;66(21):10425-33. (PMID: 17079463)
J Neurooncol. 2012 Apr;107(2):359-64. (PMID: 22045118)
Nature. 2006 Dec 7;444(7120):756-60. (PMID: 17051156)
Biol Psychiatry. 1979 Apr;14(2):337-44. (PMID: 476222)
Oncotarget. 2012 Oct;3(10):1124-36. (PMID: 23165409)
J Med Chem. 2008 Oct 23;51(20):6256-8. (PMID: 18816109)
Stem Cells. 2015 Apr;33(4):1042-6. (PMID: 25588723)
N Engl J Med. 2005 Mar 10;352(10 ):987-96. (PMID: 15758009)
Oncotarget. 2012 Oct;3(10 ):1112-23. (PMID: 23047041)
Clin Chem. 2000 May;46(5):673-83. (PMID: 10794750)
Oncotarget. 2013 Apr;4(4):502-30. (PMID: 23594434)
فهرسة مساهمة: Keywords: Disulfiram; Glioblastoma; Phase I clinical trial; Proteasome inhibition; Temozolomide
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Proteasome Inhibitors)
7GR28W0FJI (Dacarbazine)
EC 3.4.25.1 (Proteasome Endopeptidase Complex)
TR3MLJ1UAI (Disulfiram)
YF1K15M17Y (Temozolomide)
تواريخ الأحداث: Date Created: 20160312 Date Completed: 20171127 Latest Revision: 20220408
رمز التحديث: 20240829
DOI: 10.1007/s11060-016-2104-2
PMID: 26966095
قاعدة البيانات: MEDLINE
الوصف
تدمد:1573-7373
DOI:10.1007/s11060-016-2104-2