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Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors
Open accessAbstract
Background Recurrent malignant brain tumors (RMBTs) carry a poor prognosis. Dichloroacetate (DCA) activates mitochondrial oxidative metabolism and has shown activity against several human cancers. Design We conducted an open-label study of oral DCA in 15 adults with recurrent WHO grade III - IV gliomas or metastases from a primary cancer outside the central nervous system. The primary objective was detection of a dose limiting toxicity for RMBTs at 4 weeks of treatment, defined as any grade 4 or 5 toxicity, or grade 3 toxicity directly attributable to DCA, based on the National Cancer Institute's Common Toxicity Criteria for Adverse Events, version 4.0. Secondary objectives involved safety, tolerability and hypothesis-generating data on disease status. Dosing was based on haplotype variation in glutathione transferase zeta 1/maleylacetoacetate isomerase (GSTZ1/MAAI), which participates in DCA and tyrosine catabolism. Results Eight patients completed at least 1 four week cycle. During this time, no dose-limiting toxicities occurred. No patient withdrew because of lack of tolerance to DCA, although 2 subjects experienced grade 0-1 distal parasthesias that led to elective withdrawal and/or dose-adjustment. All subjects completing at least 1 four week cycle remained clinically stable during this time and remained on DCA for an average of 75.5 days (range 26-312). Conclusions Chronic, oral DCA is feasible and well-tolerated in patients with recurrent malignant gliomas and other tumors metastatic to the brain using the dose range established for metabolic diseases. The importance of genetic-based dosing is confirmed and should be incorporated into future trials of chronic DCA administration.
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“This knowledge has led to the testing of drugs that inhibit glycolysis such as dichloroacetic acid (DCA), which inhibits PDK activity (Dunbar et al., 2014).”
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Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B., Belanger, K., Brandes, A. A., Marosi, C., Bogdahn, U., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043330 · Cited by 21,807
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
Toxicity and response criteria of the Eastern Cooperative Oncology Group
Oken, M. M., Creech, R. H., Tormey, D. C., Horton, J., Davis, T. E., Mcfadden, E. T., & Carbone, P. P. (1982) · American Journal of Clinical Oncology · doi:10.1097/00000421-198212000-00014 · Cited by 11,686
A New Statistical Method for Haplotype Reconstruction from Population Data
Stephens, M., Smith, N. J. C., & Donnelly, P. (2001) · The American Journal of Human Genetics · doi:10.1086/319501 · Cited by 7,512
Wen, P. Y., Macdonald, D. R., Reardon, D. A., Cloughesy, T. F., Sorensen, A. G., Galanis, E., DeGroot, J. F., Wick, W., Gilbert, M. R., Lassman, A. B., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.3541 · Cited by 3,890
The clinical evaluation of chemotherapeutic agents in cancer
Karnofsky, D. A. (1949) · Medical Entomology and Zoology · Cited by 2,933
Response criteria for phase II studies of supratentorial malignant glioma.
Macdonald, D. R., Cascino, T. L., Schold, S. C., & Cairncross, J. G. (1990) · Journal of Clinical Oncology · doi:10.1200/jco.1990.8.7.1277 · Cited by 2,409
Bonnet, S., Archer, S. L., Allalunis‐Turner, J., Haromy, A., Beaulieu, C., Thompson, R. B., Lee, C. T., Lopaschuk, G. D., Puttagunta, L., Bonnet, S. B., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2006.10.020 · Cited by 1,552
Yung, W. K. A., Albright, R. E., Olson, J., Fredericks, R., Fink, K., Prados, M. D., Brada, M., Spence, A., Hohl, R. J., Shapiro, W., et al. (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1316 · Cited by 929 · cited 1×
“Recurrent malignant brain tumors (RMBTs), whether from primary malignant gliomas, or from metastasis to the central nervous system (CNS), have a poor prognosis [1, 2].”
Metabolic Modulation of Glioblastoma with Dichloroacetate
Michelakis, E. D., Sutendra, G., Dromparis, P., Webster, L., Haromy, A., Niven, E. B., Maguire, C., Gammer, T.-L., Mackey, J. R., Fulton, D. S., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3000677 · Cited by 744
Research works printed but not linked: 1
- Mitchell G, Lambert M, Tanguay R. Hypertyrosinemia (1995) In Schriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, Inc., Health Professions Division, New York, pp. 1077–106
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Sun, L., Zhang, H., & Gao, P. (2021) · Protein & Cell · doi:10.1007/s13238-021-00846-7 · Cited by 818
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“This knowledge has led to the testing of drugs that inhibit glycolysis such as dichloroacetic acid (DCA), which inhibits PDK activity (Dunbar et al., 2014).”
BackgroundMetabolic reprogramming in macrophage responses
Liu, Y., Xu, R., Gu, H., Zhang, E., Qu, J., Cao, W., Huang, X., Yan, H., He, J., & Cai, Z. (2021) · Biomarker Research · doi:10.1186/s40364-020-00251-y · Cited by 680
Metadata
- Authors
- Dunbar, E. M., Coats, B. S., Shroads, A. L., Langaee, T., Lew, A., Forder, J. R., Shuster, J. J., Wagner, D. A., & Stacpoole, P. W.
- Affiliations
- University of Florida Health (US)
- University of Florida (US)
- Metabolic Solutions (US)
- Corresponding author
- Stacpoole, P. W.
- Venue
- Investigational New Drugs
- Published
- 2013-12-03
- Volume
- 32
- Issue
- 3
- Pages
- 452-464
- ISSN
- 0167-6997 (ISSN-L)
- 1573-0646
- PMC
- PMC4455946
- OpenAlex
- W2017529554
- Cited by
- 241
- References
- 50
- Citations by year
- 2026: 30 · 2025: 18 · 2024: 17 · 2023: 15 · 2022: 16 · 2021: 18 · 2020: 18 · 2019: 29 · 2018: 20 · 2017: 17 · 2016: 15 · 2015: 19 · 2014: 9
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Investigational New Drugs (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000064)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
- Keywords
- dichloroacetate, glioma, brain metastases, dose-limiting toxicity, drug safety and tolerability, mitochondrial oxidative metabolism
- MeSH terms
- Acetone, Adult, Aged, Alanine Transaminase, Antineoplastic Agents, Aspartate Aminotransferases, Brain Neoplasms, Breath Tests, Dichloroacetic Acid, Female, Glutathione Transferase, Haplotypes, Humans, Male, Maleates, Middle Aged, Pyruvic Acid
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