Investigational New Drugs

, Volume 33, Issue 3, pp 603–610 | Cite as

A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate (DCA) in patients with advanced solid tumors

  • Quincy Siu-Chung ChuEmail author
  • Randeep Sangha
  • Jennifer Spratlin
  • Larissa J. Vos
  • John R. Mackey
  • Alexander J. B. McEwan
  • Peter Venner
  • Evangelos D. MichelakisEmail author


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.


Dichloroacetate Phase 1 Cancer Recommended phase 2 dose 



We would like to thank the Clinical Research Coordinator Bonnie Chalmers, the Clinical Research Nurse Diane Arndt, and the Medical Physicist Terence Riauka.

We would also like to thank the Hecht Memorial Foundation (Vancouver, Canada) and the Alberta Cancer Foundation (Edmonton, Canada) for financial support of this clinical trial.

Research support

The study was funded in part by the Hecht Memorial Foundation (Vancouver, Canada) and the Alberta Cancer Foundation (Edmonton, Canada). The funding agencies had no role in study design, data analysis, or preparation of the manuscript for publication.


The authors have nothing to disclose. The study has been previously presented in part as a poster presentation at the European Society for Medical Oncology Conference, 2014.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Quincy Siu-Chung Chu
    • 1
    Email author
  • Randeep Sangha
    • 1
  • Jennifer Spratlin
    • 1
  • Larissa J. Vos
    • 1
  • John R. Mackey
    • 1
  • Alexander J. B. McEwan
    • 2
  • Peter Venner
    • 1
  • Evangelos D. Michelakis
    • 3
    Email author
  1. 1.Department of OncologyUniversity of Alberta and Division of Medical Oncology, Cross Cancer InstituteEdmontonCanada
  2. 2.Department of OncologyUniversity of AlbertaEdmontonCanada
  3. 3.Department of MedicineUniversity of AlbertaEdmontonCanada

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