Categories: Articles

Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors

Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors

  • M. Dunbar
  • S. Coats
  • L. Shroads
  • Langaee
  • Lew
  • R. Forder
  • J. Shuster
  • A. Wagner
  • W. Stacpoole

Summary

Background Recurrent malignant brain tumors (RMBTs) carry a poor prognosis. Dichloroacetate (DCA) activates mitochondrial oxidative metabolism and has shown activity against several human cancers. DesignWe 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.

suzzy

Share
Published by
suzzy

Recent Posts

DCA Papers and Clinical Trials

DCA papers and clinical trials For almost a decade there has been a growing interest in Dichloroacetate potential to successfully…

3 weeks ago

DCA History

DCA history Since 1973 Sodium Dichloroacetate (DCA) was used to treat various mitochondrial disorders. It inhibits the activity of pyruvate dehydrogenase kinase,…

3 weeks ago

Methods and Supplements for Preventing DCA Side Effects

Methods and supplements for preventing DCA side effects When you begin your Sodium dichloroacetate regimen, it is crucial that you take supplementation…

3 weeks ago

DCA Safety and Side Effects

DCA safety and side effects Sodium dichloroacetate is considered to be a fairly safe alternative cancer treatment. There have been no…

3 weeks ago

How DCA Works

For almost half a century, DCA has been a relatively basic substance used for treating people with congenital mitochondrial diseases.…

3 weeks ago

DCA and Cancer: Non-Hodgkin’s lymphoma cured in 4 months (Case presentation)

Today we would like to present you our first article based on Dichloroacetate usage benefits as described in case series.…

3 weeks ago