Results of phase II clinical trialsDr. E.D. Michelakis and his team at the University of Manitoba say that
"An ideal therapy should increase GBM [glioblastoma] apoptosis, overcome the molecular heterogeneity, inhibit angiogenesis, and cross the blood-brain barrier while having minimal systemic toxicity. On the basis of our recent findings in animal models [phase I], we hypothesized that the orphan small-molecule dichloroacetate (DCA) fulfills these criteria and may be effective in the treatment of GBM in humans." [18]
Outcomes of the first human clinical trials resulted from Michelakis' in vitro tests from 49 patients whose freshly removed GBM were tested. These tests led researchers to conclude that "DCA ... caused mitochondrial depolarization in GBM but not in normal brain tissue.[19]
In addition to in vitro tests, five palliative patients with DCM were tested. Three had not responded to several chemotherapies; two were newly diagnosed. After surgical removal of tumor mass, they were treated with DCA and chemotherapy.[20]
Dr. Michelakis is hopeful about the results. The in vitro results showed that "DCA ... caused mitochondrial depolarization in GBM but not in normal brain tissue... suggesting that some mitochondrial damage can be reversed."[21]
Of the five patients tested, one died after three months. The surviving four were followed for a total 15 months. Their Karnofsky scores (see Performance status) were unchanged in two cases, and had decreased by only 10 points in two patients.[22]
Dr. Michelakis believes “We have now shown that DCA can be used in patients suffering from GBM... and was associated with... tumor regression and... has an overall good safety profile." DCA side effects were minimal on the four patients, and no apparent effects other than “dose-dependent, reversible nondemyelinating, neurotoxicity that was minimal or absent at 6.25 mg/kg oral, twice-a-day dose.â€[23]
Dr. Michelakis is unable to make any conclusions about these effects because the number of patients treated is too few. He supports further human studies, especially in combination therapies, but is concerned DCA is “vulnerable to other drugs in the emerging family of metabolic modulators†for treating aggressive GBM in humans."[23]
Dr. Michelakis is proceeding with phase three human studies with private funding from philanthropical groups and individuals. DCA's legal status as a discovery is "public doman" because it was made or discovered as far back as 1864[24] and has used been in the treatment of canine and human lactic acidosis, some who presented at the beginning of treatment with cancer.
