[edit] Potential cancer applications
Cancer cells generally use glycolysis rather than respiration (oxidative phosphorylation) for energy (the Warburg effect), as a result of hypoxia that exists in tumors and damaged mitochondria.[12] Usually dangerously damaged cells kill themselves via apoptosis, a mechanism of self-destruction that involves mitochondria, but this mechanism fails in cancer cells.
A study published in January 2007 by researchers at the University of Alberta,[13] testing DCA on in vitro cancer cell lines and a rat model, found that DCA restored mitochondrial function, thus restoring apoptosis, killing cancer cells in vitro, and shrinking the tumors in the rats.[14]
These results received extensive media attention, beginning with an article in New Scientist titled "Cheap, ‘safe’ drug kills most cancers".[15] Subsequently, the American Cancer Society and other medical organizations have received a large volume of public interest and questions regarding DCA.[16] Reports have since pointed out that although the study results are promising, no formal clinical trials in humans with cancer have yet been conducted in the USA and are not yet final in Canada, emphasizing the need for caution in interpreting the preliminary results.[16][17]
Some doctors are treating cancer using DCA "off-label",[18][19] which generates controversy in some circles.[18] The off-label use of prescription drugs is common practice for cancer patients at the most prestigious medical institutions in the world, especially those diagnosed with cancers designated as orphan diseases, for which very few government-approved therapies are available.
Akbar and Humaira Khan have since March 2007 treated cancer patients using DCA off-label at their private clinic, Medicor Cancer Centres, in Toronto.[20] They have treated several types of cancer and said on their web site that some patients "are showing varied positive responses to DCA including tumour shrinkage, reduction in tumour markers, symptom control, and improvement in lab tests".[19] Although, they have not published their results nor reported it at medical conferences, they have uploaded details of patient responses and overall statistics on their web site.[21]
Terry Polevoy, of Kitchener, Ontario, called on the College of Physicians and Surgeons of Ontario to take away the Khans' licences for offering a compound that hasn't been proven to shrink tumours in humans. "They are not oncologists. They should not be making these decisions. I think they should be disciplined for using this stuff. That, to me, is unethical, to use something that has never been proved to do anything." But the College said that it was not their role to say which therapies a doctor can use.[22] Dr. Polevoy himself is not an oncologist, but a medical doctor who runs an acne clinic in Kitchener, Ontario, as well as a web site devoted to exposing what he considers self-promotion and self-described "quack remedies" called Healthwatcher.net.[23]
The New Scientist later editorialized, "The drug may yet live up to its promise as an anti-cancer agent – clinical trials are expected to start soon. It may even spawn an entirely new class of anti-cancer drugs. For now, however, it remains experimental, never yet properly tested in a person with cancer. People who self-administer the drug are taking a very long shot and, unlikely as it may sound, could even make their health worse."[24]
DCA has been used historically to treat patients with lactic acidosis, and therefore could arguably enter phase 2 trials in patients with cancer.[25]
DCA is non-patentable as a compound, though a patent has been filed for its use in cancer treatment.[26] Research by Dr. Evangelos Michelakis has received no support from the pharmaceutical industry. Concerns have been raised that without strong intellectual property protection, the financial incentive for drug development is reduced, and therefore clinical trials of DCA may not be funded.[15][16][17][27] However, other sources of funding exist; previous studies of DCA have been funded by government organizations such as the National Institutes of Health, the Food and Drug Administration, the Canadian Institutes of Health Research and by private charities (e.g. the Muscular Dystrophy Association). Recognizing anticipated funding challenges, Dr Michelakis's lab took the unorthodox step of directly soliciting online donations to fund the research.[28] After 6 months, his lab had raised over $800,000, enough to fund a small Clinical Phase 2 study. Dr. Michelakis and Dr. Archer have applied for a patent on the use of DCA in the treatment of cancer.[29][30]
On 24 September 2007, the Department of Medicine of Alberta University reported that after the trial funding was secured, both the Alberta local ethics committee and Health Canada approved the first DCA clinical trial for cancer.[31] This initial trial is relatively small with enrollment of up to 50 patients.
The promise of DCA as a cheap, effective and safe treatment for cancer generated a great deal of public interest. Many people turned to self-medication.[32][33]
When faced with the high costs of getting Food and Drug Administration approval, estimated by Tufts University to exceed one billion dollars [34], the chance of getting DCA approved for the treatment of cancer in the United States is extremely low. This problem is highlighted in the 2007 New York Times article by Ralph Moss titled "Patents over Patients" [35].
[edit] Side effects
Reports in the lay press after the 2007 University of Alberta announcement claim that dichloroacetate "has actually been used safely in humans for decades",[36] but the limited scholarly literature suggests side effects of pain, numbness and gait disturbances in some patients.[36] A clinical trial where DCA was given to patients of MELAS (a form of genetically inherited lactic acidosis) at 25 mg/kg/day was ended prematurely due to excessive peripheral nerve toxicity.[37] Dichloroacetate can also have anxiolytic or sedative effects.[6]
Doses of 5 mg/kg every three days limits effects from toxicity while maintaining adequate progress.[38]
Animal studies suggest that the neuropathy and neurotoxicity during chronic dichloroacetate treatment may be partly due to depletion of thiamine, and thiamine supplementation in rats reduced these effects.[39] However, more recent studies in humans suggest that peripheral neuropathy is a common side effect during chronic DCA treatment, even with coadministration of oral thiamine.[40][41] An additional study reported that 50 mg/kg/day DCA treatment resulted in unsteady gait and lethargy in two patients, with symptoms occurring after one month for one patient and two months for the second. Gait disturbance and consciousness were recovered with cessation of DCA, however sensory nerve action potentials did not recover in one month.[42]
Studies of the trichloroethylene (TCE) metabolites dichloroacetic acid (DCA), trichloroacetic acid (TCA), and chloral hydrate suggest that both DCA and TCA are involved in TCE-induced liver tumorigenesis and that many DCA effects are consistent with conditions that increase the risk of liver cancer in humans at dosages much higher than used for cancer therapy.[43]
It has been reported that animals and patients treated with DCA have elevated levels of delta-aminolevulinic acid (delta-ALA) in the urine. A study published in 2008 suggests that this product may be the cause of the neurotoxic side-effect of DCA by blocking peripheral myelin formation. ([1])
