ArticleInvestigational new drugs2015
A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate (DCA) in patients with advanced solid tumors.
Article in Investigational new drugs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- Rewriting the vascular script: epigenetic modifiers as scribes of metabolic reprogramming in pulmonary hypertension.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Multi-Step Synthesis of Chimeric Nutlin-DCA Compounds Targeting Dual Pathways for Treatment of Cancer.Molecules (Basel, Switzerland) · 2025Article
- Dendritic cells: understanding ontogeny, subsets, functions, and their clinical applications.Molecular biomedicine · 2025Review
- Reprogramming of glucose metabolism in pancreatic cancer: mechanisms, implications, and therapeutic perspectives.Frontiers in immunology · 2025Review
- The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities.Neoplasia (New York, N.Y.) · 2024Review
- Targeting mitochondria: restoring the antitumor efficacy of exhausted T cells.Molecular cancer · 2024Review
- Metabolic reprogramming in the tumor microenvironment of liver cancer.Journal of hematology & oncology · 2024Review
- Stem Cell Theory of Cancer: Clinical Implications for Cellular Metabolism and Anti-Cancer Metabolomics.Cancers · 2024Article
- The role of metabolic reprogramming in liver cancer and its clinical perspectives.Frontiers in oncology · 2024Review
- From signalling pathways to targeted therapies: unravelling glioblastoma's secrets and harnessing two decades of progress.Signal transduction and targeted therapy · 2023Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose Preclinical evidence suggests dichloroacetate (DCA) can reverse the Warburg effect and inhibit growth in cancer models. This phase 1 study was undertaken to assess the safety, recommended phase 2 dose (RP2D), and pharmacokinetic (PK) profile of oral DCA in patients with advanced solid tumors. Patients and Methods Twenty-four patients with advanced solid malignancies were enrolled using a standard 3 + 3 protocol at a starting dose of 6.25 mg/kg twice daily (BID). Treatment on 28 days cycles was continued until progression, toxicity, or consent withdrawal. PK samples were collected on days 1 and 15 of cycle 1, and day 1 of subsequent cycles. PET imaging ((18) F-FDG uptake) was investigated as a potential biomarker of response. Results Twenty-three evaluable patients were treated with DCA at two doses: 6.25 mg/kg and 12.5 mg/kg BID (median of 2 cycles each). No DLTs occurred in the 6.25 mg/kg BID cohort so the dose was escalated. Three of seven patients had DLTs (fatigue, vomiting, diarrhea) at 12.5 mg/kg BID. Thirteen additional patients were treated at 6.25 mg/kg BID. Most toxicities were grade 1-2 with the most common being fatigue, neuropathy and nausea. No responses were observed and eight patients had stable disease. The DCA PK profile in cancer patients was consistent with previously published data. There was high variability in PK values and neuropathy among patients. Progressive increase in DCA trough levels and a trend towards decreased (18) F-FDG uptake with length of DCA therapy was observed. Conclusions The RP2D of oral DCA is 6.25 mg/kg BID. Toxicities will require careful monitoring in future trials.
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