Do you remember dicholoroacetate (DCA)?
In a letter dated 24 September (PDF here), Dr Evangelos Michelakis of the University of Alberta announced that his group had received approval from Health Canada and U of A’s institutional review board to begin a Phase II clinical trial of dichloroacetate (DCA). The trial will enroll 50 patients with astrocytomas or glioblastomas, two classes of malignant brain tumors, who have either been newly diagnosed or have not responded to previous therapies. The purpose of a Phase II trial is to provide an initial assessment of drug efficacy in a small population of diseased subjects and to provide further information on the safety of the drug in this patient population. Approval is still pending for a Phase I trial that will be designed to determine the maximally tolerated dose of DCA in cancer patients and what side effects are likely to be observed.
Like hundreds (if not, thousands) of compounds being tested to treat cancer, DCA was shown by Michelakis’ group earlier this year to slow the growth of human lung tumors in a preclinical rodent model.
So, what is so special about DCA?
DCA is conceptually interesting because, unlike most anticancer drugs, it appears to inhibit aerobic glycolysis, an unusual energy-generating pathway used by some cancers. However, media reports at the time focused on that fact that DCA is in the public domain (i.e., the molecule itself cannot be patented) and that it is unlikely that a corporate sponsor would be found to sponsor further development of this agent. The Alberta group began accepting donations to support clinical studies of DCA and have collected over $800,000 so far; these funds will support the recently-announced trial – $1.5 million is anticipated to be required to complete both the Phase I and II trials.
More problematic, and sensationalist, was that DCA was portrayed as a cure for cancer that was being ignored by evil drug companies who only wanted to make profits and cancer patients began searching for where to buy DCA to self-medicate for their disease.
Seizing upon these misperceptions and the desperation of many cancer patients, an operator of a pest control firm in California teamed up with a chemist and began selling DCA on the web at BuyDCA.com and encouraged patients to report their “results” on discussion forums at TheDCAsite.com. In July, the US Food and Drug Administration shut down BuyDCA.com, leading to further discussion of a conspiracy by drug companies to keep the cure for cancer unaccessible to patients.
What these portrayals did not do was properly represent that DCA is just one of a multitude of experimental drugs that only exhibit cancer cell killing effects at very high doses in cell culture and slow, but do not stop, the growth of human tumors grown in rodent models. BuyDCA.com was selling false hope to patients by neglecting to note the fact that a great many drugs show promise like DCA in animal studies, only to fall by the wayside due to lack of effectiveness in humans. And if the Google search terms that have led people to Terra Sigillata over the last week are any indication, patients are still looking for where to buy DCA, likely spurred by last week’s news reports on the Alberta trial.
I’ve contended all along that DCA should be tested in clinical trials but that patients should be realistic about the chances of a positive outcome. Even with this Phase II trial, only 50 patients will be evaluated and the choice of brain cancers sets an extremely high bar for DCA to meet. In addition, DCA is likely to have minimal activity on its own and will probably have to be combined with other chemotherapeutic drugs, as is common with many cancer drugs.
In the meantime, self-medicating with DCA is ill-advised, because we still don’t know what side effects might occur in cancer patients (peripheral neuropathy and electrolyte disturbances are known from DCA’s use in patients with a rare inherited mitochondrial disease). I know that this won’t stop some people from trying but they should have a sober and realistic sense that the promise of DCA may not match the hype.
For more DCA information:
A more lengthy overview of the DCA story is available at The New Scientist, making up for their original article that propagated the hype.
An excellent patient information sheet on DCA can be found at the site of Cancer Research UK. The final three paragraphs concisely puts DCA in proper perspective:
The fact that DCA is off-patent is no barrier to its development as a treatment for cancer. For example, Cancer Research UK recently secured a licence for an off-patent drug that could be used to treat rare childhood cancers. And there is certainly no “conspiracy” by pharmaceutical companies to prevent research into DCA – there is just not enough evidence at the moment to start using it in the clinic.
However, it is unlikely that this one compound represents “the cure” for cancer – and it is also unlikely that DCA is the “wonder drug” that the headlines portray. Cancer is a complex and multi-faceted disease, and it can be caused by a range of different faults within the cell. It is unlikely that any single drug could ever treat all forms of the disease.
There are many promising new treatments for cancer currently in development, funded by Cancer Research UK and other organisations. It is important to carry out research into all aspects of cancer, to develop new and effective ways to diagnose, prevent and treat the disease. This is why Cancer Research UK funds such a wide range of research.
Other DCA posts at Terra Sigillata:
- The dichloroacetate (DCA) cancer kerfuffle
- Where to buy dichloroacetate…
- Local look at dichloroacetate (DCA) hysteria
- Edmonton pharmacist asked to stop selling dichloroacetate (DCA)
- Four days, four dichloroacetate (DCA) newspaper articles
- Perversion of good science
- CBC’s ‘The Current’ on dichloroacetate (DCA)
Other DCA posts by fellow ScienceBlogger, Orac, at Respectful Insolence:
- In which my words will be misinterpreted as “proof” that I am a “pharma shill”
- Will donations fund dichloroacetate (DCA) clinical trials?
- Too fast to label others as “conspiracy-mongers”?
- Dichloroacetate: One more time…
- Laying the cluestick on DaveScot over dichloroacetate (DCA) and cancer
- A couple of more cluesticks on dichloroacetate (DCA) and cancer
- Where to buy dichloroacetate (DCA)? Dichloroacetate suppliers, even?
- An uninformative “experiment” on dichloroacetate
- Slumming around The DCA Site (TheDCASite.com), appalled at what I’m finding
- Slumming around The DCA Site (TheDCASite.com), the finale (for now)
- It’s nice to be noticed
- The deadly deviousness of the cancer cell, or how dichloroacetate (DCA) might fail
- The dichloroacetate (DCA) self-medication phenomenon hits the mainstream media
- Dichloroacetate (DCA) and cancer: Magical thinking versus Tumor Biology 101
- Checking in with The DCA Site
- Dichloroacetate and The DCA Site: A low bar for “success”
- Dichloroacetate (DCA): A scientist’s worst nightmare?
- Dichloroacetate and The DCA Site: A low bar for “success” (part 2)
- “Clinical research” on dichloroacetate by TheDCASite.com: A travesty of science
- A family practitioner and epidemiologist are prescribing dichloracetate (DCA) in Canada
- An “arrogant medico” makes one last comment on dichloroacetate (DCA)
- Finally, the FDA acts on TheDCASite.com