The controversial drug DCA (dichloroacetate) is in the headlines again, after researchers in Canada carried out a small-scale clinical trial of the drug in five patients with advanced brain tumours.
Over the past year or two there have been several articles in the news and on the internet about DCA, which was claimed to be cheap, safe and “kill most cancers”.
Understandably this caused a great deal of interest, especially as DCA is an off-patent drug and appears to be non-toxic to humans (although it can cause significant side effects, as we’ll see later).
But before we jump to conclusions and hail DCA as a ‘wonder drug’, we need to look at the science behind the headlines.
What is DCA and how does it work?
All our cells need energy to grow and function, including cancer cells. Simply put, our cells usually generate energy by breaking down sugar (glucose). To do this, they use a process known as the Krebs cycle, which takes place in tiny structures within the cell called mitochondria (the ‘power stations’ of the cell).
But cancer cells bypass this cycle and produce energy using a simpler process, known as glycolysis, which takes place outside the mitochondria in the cell’s cytoplasm (the main part of the cell). This was first noticed by Nobel prize-winning German scientist Otto Warburg back in the 1920s.
Mitochondria play a crucial role in cells. As well as generating energy for the cell, they can also trigger the cell to die if it is faulty – a process that helps stop cancers from forming in the first place.
Because cancer cells seem to switch off their mitochondria, scientists think this is one way in which cancer cells are able to evade death and remain immortal.
DCA, or dichloroacetate, is a very simple chemical and is similar to some of the chemicals involved in the Krebs cycle. In 2007, researchers at the University of Alberta (led by Evangelos Michelakis) found that adding DCA to cancer cells grown in the lab kick-starts the Krebs cycle, turning the mitochondria back on again. This caused the cancer cells to stop multiplying and die. The team discovered that DCA didn’t affect healthy cells, because their mitochondria were functioning normally.
DCA has been tested as a treatment for children and adults with certain rare metabolic disorders. This means that, at the doses needed to treat these diseases at least, DCA has been through clinical trials aimed at assessing its safety. Based on their results, the researchers have proposed that DCA could also be useful in treating cancer.
To begin to investigate if this is indeed the case, Michelakis and his team started by carrying out experiments on cancer cells grown in the lab. The team also studied rats that had been injected with cancer cells. They found that DCA could slow the growth of the rats’ tumours, and reduce their size. This did not prove that the cancers were completely cured, or that DCA could prevent cancers from growing.
It is important to stress that DCA had not then been tested as a cancer treatment in humans, despite the implication in news headlines that it “kills most cancers”. There are many research papers produced by scientists around the world every year that reveal potential new treatments for cancer. But it is important that every discovery is carefully investigated to make sure that it is effective and safe for use in patients, and DCA is no exception.
The University of Alberta researchers received approval for a human cancer trial in September 2007, involving 50 patients. Now they have published the first results from five of those patients in the journal Science Translational Medicine.
The new trial
In this study, Michelakis and his team gave DCA to five patients with advanced glioblastoma, a type of brain tumour, in combination with surgery, radiotherapy and a drug called temozolomide. It’s important to point out that the aim of this study was not to find out whether DCA could treat glioblastoma, but to figure out the safest dose to use for cancer patients. We already know that the drug can be safely given to humans – although it can cause side effects – but this is the first time it has been tested in people with cancer.
The study shed light on the dose that could be given to patients without causing nerve problems or other serious side effects. Four patients were still alive after 18 months, and three showed some shrinkage of their tumour, but it is impossible to tell with such a small study whether this is longer than might be expected. And, given that they were also receiving other treatment, it’s hard to know if it was due to DCA at all.
As well as this small trial, the researchers also looked at the effect of DCA on tumour samples from 49 other glioblastoma patients. They found that DCA could switch mitochondria back on in the cancer cells, although – crucially – it’s still not clear exactly how it’s doing this.
Finally, the team looked at tumour samples taken from the five patients on the trial, both before and after treatment with DCA, and found that the drug was again helping to switch mitochondria on. They also discovered other differences in the cancer cells’ metabolism before and after treatment.
A key gap in this trial is that, as we’ve mentioned above, it’s not clear exactly how DCA is working. The researchers suggest that the drug may target cancer stem cells and prevent the growth of blood vessels into tumour, although they didn’t actually prove this.
Is it safe?
These results show that lower doses of DCA could, at least in theory, be given to cancer patients while avoiding some of the damaging side effects seen at higher doses. For example, a clinical trial of DCA for a childhood disease found that the drug caused significant side effects, affecting the nervous system. It is also known to be an environmental pollutant. And researchers have found that DCA can actually cause cancer in animals.
This is not necessarily a barrier to the use of DCA as a treatment for cancer – there are a number of powerful cancer drugs that are carcinogens themselves. And this is why we need to test them in clinical trials (as Michelakis and his team have begun to do here) to discover how they can be safely used to treat patients while minimising any harmful effects.
Why can’t we use it now?
It is understandable that people with cancer will want to try everything possible to help treat their disease. However, there is still no evidence – yet – to support the immediate use of DCA to treat cancer patients.
The trial in Canada is being conducted under stringent conditions both to ensure the validity of the results and to protect the participants from any unforeseen effects. Further clinical trials of DCA using more patients will help determine whether the treatment is more effective than the cancer therapies that are currently available.
There are reports that people are buying personal supplies of DCA from sources such as the internet. Cancer Research UK would strongly advise against this, as DCA still has not been shown to actually treat tumours successfully in patients. And it may be harmful when given to cancer patients without accurate dosing and medical supervision.
What will happen in the future?
It is clear that DCA is an intriguing drug – one of many currently being investigated by scientists around the world. It will be interesting to see the results of more extensive lab-based experiments and larger clinical trials of DCA. And cancer cell metabolism is certainly a productive area of research that we’re actively funding.
The fact that DCA is off-patent is no barrier to its development as a treatment for cancer. For example, Cancer Research UK has secured a licence for an off-patent drug called fenretinide, which 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 support its widespread use to treat patients.
While these results are intriguing, 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 organisations across the globe – including Cancer Research UK. If anything, these new results show why research is so important in bringing safe and effective treatments to people with cancer – they don’t provide definitive answers, but they support further investigations which may yield benefits for patients in the future.
- A more detailed analysis of the research can be found at Respectful Insolence – DCA and cancer: Deja vu all over again
16th May 2011: Several websites are reporting that last week ‘cancer was cured without anyone reporting on it’. This is not true and seems, we think, to have arisen from a misreading of the date on the most recent paper on DCA (which was published on May 12th 2010 – i.e. this time last year).
Everything we wrote in the post and comments below stands – DCA is still only a ‘potential’ cancer treatment, and more research is needed to find out whether it’s safer or more effective than existing therapies.
17th January 2012/ongoing: A number of scientific papers investigating DCA have been published over the past year or so by researchers around the world – we thought we would highlight some of them here for people who are interested in the current state of DCA research. However, it’s important to remember that most of these studies have only been done using cancer cells grown in the lab, and we still don’t have solid evidence from clinical trials that DCA is effective at treating cancer in patients.
- Lab research on liver cancer cells grown in the lab shows that a combination of DCA and a drug called sorafenib is more effective than DCA alone. (2013)
- Researchers have tested DCA and other inhibitors of cancer cell metabolism in multiple myeloma cells grown in the lab. (2013)
- A combination of DCA and a drug called sulindac can kill non-small cell lung cancer cells and squamous cell cancer cells grown in the lab. (2012)
- DCA can encourage the death of glioma (brain tumour) stem cells grown in the lab. (2012)
- A combination of DCA and the drug omeprazole can slow the growth of bowel cancer cells and fibrosarcoma cells grown in the lab. (2012)
- A combination of omeprazole, tamoxifen and DCA was given to a woman with cholangiocarcinoma that was no longer responding to treatment – it slowed the growth of her cancer for three months. (2012)
- Researchers are testing a new way of delivering DCA more directly to cervical cancer – so far these experiments have only been done using mice. (2012)
- A combination of arsenic trioxide and DCA is more effective than either drug alone at killing cancer cells grown in the lab or slowing their growth. (2011)
- DCA has an effect on aggressive neuroblastoma cells grown in the lab, but not on less aggressive cells. (2012)
- Lab experiments show that DCA can suppress the production of a molecule called HIF1alpha, produced by cancer cells to help them grow a blood supply. Tests in rats show that DCA can reduce the growth of blood vessels in tumours. (2012)
- Cancer Research UK-funded scientists show that combining DCA with a drug called bevacizumab, which blocks the growth of blood vessels into tumours, can have enhanced anti-tumour effects in mice. (2013)
- Scientists in the US are testing a more potent form of DCA, called Mito-DCA, that seems to target mitochondria more effectively. (2014)
- In tests on cells grown in the lab and tumours transplanted into animals, Cancer Research UK-funded scientists show that DCA seems to switch on a response called autophagy in cancer cells, where they start to break down and ‘recycle’ parts of themselves, which could affect how patients respond to DCA treatment. (2014)
- PubMed search for “DCA cancer” – see the latest scientific publications
It’s clear from these papers – and others that we don’t have room to highlight – that DCA and cancer metabolism is an active and exciting research area at the moment. Right now, Cancer Research UK isn’t directly funding research specifically into DCA, but we are funding projects investigating various aspects of cancer metabolism, which may touch on it.
As we’ve previously explained, we give out funding in response to applications from researchers, and only fund the very best science that will benefit cancer patients. So if a researcher applied to us for funding to study DCA, their application would be judged on its scientific merits like all the rest.
- P. Kaufmann, et al (2006). Dichloroacetate causes toxic neuropathy in MELAS Neurology, 66, 324-330
- Michelakis ED, et al (2010). Metabolic modulation of glioblastoma with dichloroacetate. Science translational medicine, 2 (31) PMID: 20463368
- S Bonnet et al, (2007). A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth Cancer Cell, 11 (1), 37-51 DOI: 10.1016/j.ccr.2006.10.020
Sophia February 23, 2012
I would like to add that medicor cancer centres in Canada are actually treating people with DCA, in combination with tetrathiomolybdate. The last is a drug that I would not consider administering without medical supervision. They even have a few case studies, but this was not updated since 2009 as far as I could see (a pity). The case studies note the exact treatment as well as side effects (mostly neuropathy, which is also a possible side effect of chemo).
Apparently you can be treated by these centres, even in other countries, cost is about 2000€ for the first four weeks of treatment (rough calculation, do not know in pounds). Some would say that this is another money making thing, but even if they only help 5 people out of a 100, that is better than 0.
Just a note: my husband has small cell lung cancer, standard therapies give him another six months at the most. We were unable to find doctors/oncologists willing to help him with alternative treatment (he is from Italy), the standard answer is: we do not know this drug. But they are willing to treat him with expensive standard therapies, allthough they know that it will not work. We will buy over the internet, allthough we are not sure whether it is a reliable source. And that is the problem: because you are not being helped over the “normal” channels, you end up doing things that you know might be stupid.
Another note: a clinical trial on DCA finished in December 2011, but the results will only be published end of 2012. My husband cannot wait until the end of this year. People with cancer do not have time.
Tom February 3, 2012
Well, Kat, I guess you’re just doing your job answering these posts, but your “Because these trials are already under way, it would not be a good use of our supporters’ money to replicate work being done elsewhere” is not going to wash — of course it’s not. Nobody is asking Cancer Research UK to replicate anyone’s work. As you know and everyone knows, research is a field that contributes very valuably to the field of knowledge in pretty much direct proportion to the number of people, and talentedness of those people, and the equipment available to those people — in other words, the amount of capital — that goes into it. It’s silly to argue that point.
As for this:
— well, how ridiculous. It washes even less.
Tom February 3, 2012
Does all this mean that Cancer Research UK is *not* going to put substantial resources into funding, specifically, trials of DCA? If not, can you explain why not, and assure us that DCA is not going to have the same fate as the anti-cancer drug that was being developed from Vitamin B17 Laetrile, and the work of Raymond Rife (lab smashed up by the FDA, and his notes confisacted, and him dying in mysterious circumstances)?
Kat Arney February 3, 2012
At the moment, early stage trials of DCA are currently being carried out in the US and Canada http://clinicaltrials.gov/ct2/results?term=dichloroacetate+cancer and we look forward to seeing the full results. Because these trials are already under way, it would not be a good use of our supporters’ money to replicate work being done elsewhere.
Furthermore, we recently spotted this report that the US company Viral Genetics has been granted a patent for the use of DCA to treat cancer: http://www.businesswire.com/news/home/20111121006368/en/Patent-Licensed-Exclusively-Viral-Genetics-Granted-DCA We are currently investigating what this means in practice.
Research into DCA – as well as many other aspects of tumour metabolism – is ongoing around the world. You may be interested in this recent scientific review from the journal Nature Biotechnology, which talks about several promising approaches in this area, including a detailed discussion of DCA: http://www.nature.com/nbt/journal/v28/n9/full/nbt0910-888.html
Science Information Manager
Mike October 6, 2011
I’m from nigeria and there is a monastry where the monks do alot of research and have so many herbal drugs for a wide range of diseases including cancer, and they Are surprised why the western world has failed to admitt that there is a cure.
tony July 8, 2011
Why do clinical trials? no money can be made on this drug, so $100 million down the toilet.
No major Pharma. will touch it.
Randy M June 13, 2011
For a more balanced perspective, see:
Carine Hartman June 1, 2011
I spoke to Prof. Michelakis this week and just finished doing a story about DCA.The team from the University of Alberta are in Phase 2 with their trials testing it now on more brain cancer sufferers as well as lung and breast cancer patients.
So they tested it on only 49 patients since 2008 – and ALL 49 were healed. And the five terminally ill ones who had at best a year from the worst cancer a human can get? The tumors either shrunk or stopped growing within three months.
I’m sorry. That for me spells a cure: plain and simple. And obviously inexpensive…
Forgive me for being cynical, but money does talk
Tony June 1, 2011
No big bucks to be made = no incentive for either drug companies or researchers = no cure!
Peter May 30, 2011
A good article to read is Cancer as a Metabolic Disease by Prof T Seyfried whose speciality is brain cancer and epilepsy.
Follow on with a web search and the result is interesting for all cancers.
This is therapy you can do yourself and won’t rely on DCA.
Fever / Coley vaccine, if we could get it in the UK would be the cherry on the cake.
Tom Koe May 30, 2011
Dear Cancer Research UK
Please would you (and everyone else) stop confusing the issue around glycolysis and the Krebs cycle by suggesting that they are entirely separate processes! This oversimplifies AND confuses the point due to it’s contradictory, sorry, incorrect status. The end product of glycolysis is pyruvate, the starting point of the Krebs cycle. The point is, without glycolysis there is no Krebs. Glucose is NOT directly fed into the Krebs cycle as some commentators on this topic from around the web appear to believe. If you are in any doubt just look in an A-level textbook…
Regards, a student of biology to degree level.
Bangon Kali May 17, 2011
I hope this will someday be verified in a reasonable degree of certainty.
james March 21, 2011
CRUK and the NHS can carry out a short trial on the safety of dichloroacetate. If no adverse events are reported within a period of six to eight weeks, then DCA can become available for consented use on the NHS. We can put limitations on this type of trial and say that only generic, or already used compounds can be tested in this type of accelerated way. That way there will be no corporate marketing war to push dangerous chemicals through this process. We can test DCA’s compatibility with standard radiotherapy, chemotherapy and surgery, and if there is variation we can do trials involving each (minor) variation of radiotherapy, chemotherapy and surgery.
My idea for this type of trial comes from a clinical trial which is ongoing in the US (Dichloroacetate (DCA) in Patients With Previously Treated Metastatic Breast or Non-Small Cell Lung Cancer (NSCL))* –
‘Patients with HER-2 positive breast cancer will be allowed to continue Herceptin in conjunction with DCA. Given that these two therapies have not been previously evaluated in combination, the first 5 patients assigned to receive Trastuzumab in conjunction with DCA will be monitored for toxicity for 28 days prior to entering further patients with this combination. After the 5th patient receiving DCA and Trastuzumab has been followed for 28 days, further patients will be enrolled with this combination only if there are no grade 3 or 4 toxicities attributed to DCA or the combination of DCA and Trastuzumab.’
I would expand this and say – if 28 days is deemed a short enough time for us to know whether further trial subjects can be exposed to DCA (plus herceptin), then can we not say that 28 days with no adverse events is a sufficient time for us to know that DCA is safe to use in the broader (cancer) population with consent?
This type of trial is designed to test acute side effects, not chronic ones. The reason people will, in my opinion, often opt into taking DCA even though the chronic effects for any given period of time will not be known until that period of time elapses is that people with cancer mostly have a terminal disease, and so will be willing to take that risk for themselves.
*Sadly, no such trial is available in the UK, and the trial is set to finish in December 2012. My friend and her family cannot wait that long.
john joe March 16, 2011
what a joke it’s now about 4 years later and we are no further forward with this DCA drug, i just came across this info today and find it unbelievable that clinicastudies or anything hasn’t been done yet.
folk are dying now, they need help now, this a drug that may be able help them, stop the messing about and do something about it!
james March 8, 2011
I’d like to raise a concern here that clinical trials are not being run to best use the chemicals we DO have at our disposal. Also, the process of clinical trials does not cover those who are dying at present. What was heartening about the U of A trials is that the researchers seemed to be adopting as their main aim to keep their trial patients alive – this motive does not seem to be apparent at the moment, since no trials on DCA are actually running* (some which ‘opened’ in 2007 have not even started recruiting yet), and you get the usual ‘we do not have enough resources’ spiel or likewise ‘cancer is a multinational approach etc etc.’
On the resources point, CRUK claimed to spend £334 million on research last year, a small fraction of which could have been used to fund a UK trial of DCA which could have helped UK cancer patients. This is, for me, a huge issue. But even in the long run CRUK are following the wrong approach of getting into the pocket of large pharmaceutical firms. If DCA were discovered in the lab of, say, Novartis, then they would be applying to CRUK to test it, (so they could patent it)and CRUK would be collaborating right now with Novartis. But selling DCA would mean selling in a competitive market, since it can’t be patented (except through a use patent which is impossible to enforce), which means there is no profit to be gained from selling or researching it. It is not their concern that DCA as a treatment could mean people (and states) don’t have to break the bank to get effective treatment.
Many people are running out of time, and it seems inhumane to be doing nothing on this issue. I DO believe that DCA is worth investing in from CRUK’s standpoint, and you can run a trial on this easily available chemical without consulting a third party of academic researchers (given that you have a large amount of researchers working for you, and in universities).
*It is notable that the trials which are in the pipeline (it doesn’t seem as if they have a future) are ‘unmasked’, meaning that patients are not given placebo (so that as many as possible patients can benefit from the new treatment). This, to me, indicates a concern for patients that is lacking in the enormous delays that have lapsed, meaning that many people with Glioblastoma and other cancers will have died by now.
james February 26, 2011
Also, Henry, in answer to your points on corporate sponsorship, it is necessary to make some clarifications.
Obviously, since we are talking about new drugs here, I mean ‘new drug trials’ instead of your broad interpretation of ‘trials.’ I would have thought you inferred that from the context.*
By ‘phase II trials’ if you read the above conversations, I mean ‘phase II or more advanced.’ This is also obvious from the context.
BPA is not a new drug (or drug/procedure). It has been tested since at least 1997. It looks like you’re duplicating studies.
Also the lengthier post is not addressed to you. Most of your comments are irrelevant (given a proper interpretation of the terms I use) and indeed all of the examples you cite are irrelevant, as I have demonstrated above. This is not surprising seeing as you appear not to have paid more than than the scantest attention to my comments (which I assume you are responding to), missing out entirely the section on ‘TKI258’, and not addressing the crucial question as to what deserves funding. More importantly, you do not address the valid concerns of Matthew, Steve or Fiona, or indeed any of the views expressed in this forum. Furthermore, you are rejecting (by ignoring) all constructive proposals suggested here (let alone accepting any criticism), which include funding a phase I trial, funding a phase II trial, or partnering with the Experimental Cancer Medicine centres in the UK to test the drug under monitored conditions, or any other way to expose people with guaranteed safety to this promising drug.
* This is not a trivial point. It appears that CRUK does not have any new drugs in the pipeline which are not sponsored by large pharmaceutical firms.
james February 26, 2011
No, you mean IF the application is of an appropriate standard (without any other conditions), because DCA already HAS sufficient preclinical work done on it. The TRIAL is the thing which gives the ‘positive result’ – you said you run phase I trials – this is the NEXT STEP on the road.*
Let’s get this clear once and for all. ‘A positive result’ comes from a trial. YOU are the ones who run trials. ‘A positive result’ cannot happen until someone like you RUNS a trial. So the ‘positive result’ you claim to need does not, in your terms, come from preclinical work. It comes from a charity or government-sponsored trial. So you cannot claim you need a ‘positive result’ BEFORE you run a trial.
Another thing we need to get clear: the University of Alberta team HAS FINISHED THEIR TRIAL. Its results were published in MAY 2010. You can read this by doing the most basic search on the internet. Please don’t tell me you are not aware of this.
If any one else is reading on this forum, I think we should all lobby the University of Alberta team to apply for funding from Cancer Research UK and other charities/government agents, then see what happens next. If they say they need funding, where better to get it than a charity?
*NB you could argue that you could go straight to phase II, but this is a SEPARATE debate, so please do not pick me up on it. I am happy to drop this point and let the rest stand, so please do not base your response (if you do respond) around this tangential issue.
Henry Scowcroft February 25, 2011
It’s not true to say we “only carry out phase II trials” nor that we “only carry out trials if they are supported by industry”. For example, we’re helping to fund the NEO EXCEL trial, a phase 3 trial looking at improving drug therapy before surgery for women with breast cancer. Our partners in this trial are the National Cancer Research Network (NCRN), the University Hospital Birmingham NHS Foundation Trust, and the University of Birmingham.
Or this phase 1 trial looking at a drug called boron phenylalanine (BPA) affects people with a form of brain cancer, which we’re funding in partnership with the Experimental Cancer Medicine Centre (ECMC) network.
And we don’t just fund trials of chemotherapy and cancer drugs – for example, we’re supporting CHART-ED, a phase 1 trial looking at lung cancer radiotherapy, along with the Cancer Clinical Trials Unit Scotland (CaCTUS), the Experimental Cancer Medicine Centre (ECMC), the National Cancer Research Network (NCRN) and Sheffield Teaching Hospitals NHS Foundation Trust.
You can find out more about UK clinical trials, including those that we’re supporting, by searching our Clinical Trials database – the Advanced Search lets you look specifically for trials of different phases:
But it’s also true that we partner with the pharmaceutical industry on other trials. This is often absolutely crucial, for example to ensure that the researchers running the trial can have access to the drug they want to test. It’s important to point out that when we partner with industry in this way, the trials are run to the highest academic standards, and the data they generate remain the property of the academic institution running the trial.
Regarding your point about how decisions are made on which agents to fund – Cancer Research UK currently operates via a type of funding often described as ‘response-mode’ funding. As we’ve said elsewhere, this means that academics and other researchers submit proposals to us for funding, which we have reviewed by a panel of experts and allocate funds according to each proposal’s merit. We don’t actively commission specific research projects ourselves.
We have not, to date, received an application to carry out any human trials on DCA.
Although we cannot predict the future, it is reasonable to assume that if the Canadian trials yield a positive result, and if an application of the appropriate standard was made to our clinical trials funding board, then we would of course consider this application on its scientific and clinical merit. Indeed, under such circumstances, we would welcome such an application.
We hope this addresses your points. You might also be interested in reading about our Clinical Developments Partnership initiative, which aims to target funding to older and deprioritsed experimental drugs to try to bring them to cancer patients.
james February 23, 2011
OK I’ve looked at the section of your website on clinical trials. It looks like you are carrying out a few phase II clinical trials with industry support (not on DCA). There are two possibilities, as it seems to me. One, you only carry out phase II trials (which, incidentally are more expensive per patient and in total). Two, you only carry out trials if they are supported by industry (eg. Astra Zeneca, Novartis – I checked the breast cancer trials). If it is the first reason, then I suggest you make a slight break and carry out a phase I trial on DCA (about 96 patients at 13700 dollars per head). If it is the second reason, then I suggest to others in the population and to government bodies like the MRC, NICE etc. that we fundamentally restructure the way we fund research. If I were CRUK, I would follow this path without prompting, because, otherwise, it would look like you were callously following the whims of industry.
On a separate note, it would be good to have an open debate on why certain chemicals are given priority over others. So why does ‘TKI258’ (‘a new biological therapy called a tyrosine kinase inhibitor’ -CRUK) deserve funding whereas DCA does not?
From the CRUK clinical trials website: ‘We know from laboratory studies that ‘TKI258′ may shrink or slow the growth of many different types of cancers.’ But this is the same as DCA. On the one hand, you are recommending DCA’s promising lab results do not mean that further testing is warranted:
‘there is not enough scientific evidence currently available to support testing DCA in large scale clinical trials.’ (CRUK)
And on the other, you are recommending that TKI258’s laboratory tests be used to justify further testing. Furthermore, ‘TKI258’ is a new chemical (whereas DCA is not – it has a detailed American EPA assessment compiled on it) and ‘TKI258’ will clearly interfere with normal cellular function (whereas DCA will apparently not). A small factor in the discrepancy in treatment of two similar chemicals may be that Novartis, a multinational pharmaceutical company, has given the OK and probably financial support to this trial.
Finally, I suggest in your execution of your trial on DCA that you follow the model of Kenn Petruk, and Evangelos Michelakis at the University of Alberta. They administered DCA at therapeutic doses, and monitored the patients after a six week period for evidence of efficacy. That way, if it doesn’t work, you will know it’s not working, and you can abort the trial to save money. If it does work, you will be able to help people with cancer.
“This is a very quick way to monitor whether or not there is going to be therapeutic efficacy so we should know within one month to six weeks after the patients begin their DCA trial if the drug will work,” he said. “If it is not working, these patients will be cycled into existing therapies such as radiation therapy and chemotherapy, so they won’t be denied current therapies.”
(of PET technology)
So, patients will not risk missing out on known, effective (but not sufficient) therapies.
According to cancer research UK, PET scans are used to ‘Show how well cancer drug treatment is working’. Since we are looking at glucose metabolism (which PET scans track) then this should be ideal.
james February 14, 2011
With respect to dca, you are refusing to test in it in humans because you don’t know how effective it will be in humans. But we do have indications that it will be effective.
“DCA has anti-proliferative properties in addition to pro-apoptotic properties, and can be effective against highly metastatic disease in vivo, highlighting its potential for clinical use”
(Journal Breast Cancer Research and Treatment)
surely this is the basis on which we test any compound. I would also take issue with your insinuation that ‘the canadian team’ are conducting trials on this compound. They have finished their trials. It is up to you and other institutions like yours to continue this process. If we leave it to the market nothing will happen.
NB. posting on the patients board would have no consequence. Except, it would probably serve the purpose of making people take it off-label, which you are supposedly against.
Peter February 2, 2011
Well, Mathew, I had to stop the DCA because of other problems but I have been investigating multibacterial vaccine, MBVax.com.
Most of the ‘spontaneous recovery’ cases in cancer followed a febrile illness.
Look up Coley toxin, fever therapy, Uwe Hobohm and Stephen Hoption Caan.
I now think this is a better bet than targeted things like DCA.
Can’t get it in UK though; we are protected by MHRA. The makers are a serious Canadian company and will only deal with pharmaceutical import companies with proper paperwork. They have standardised the product but it needs tailoring to the patient.
In UK you might get it as a ‘named patient’ but that is difficult and the immune system is seriously compromised by that time. It is something that CRUK might trial. I would have no second thoughts about it.
Kat Arney February 2, 2011
Thanks for your comments. There are several issues here that we’d like to clarify.
Firstly, there is not enough scientific evidence currently available to support testing DCA in large scale clinical trials. Early stage, small scale trials are currently being carried out by the Canadian team, and we need to see the full results from these before any decision can be made to run a larger study in the UK. At the moment, the early results from the DCA trial are relatively modest, and only involve five patients. As we point out in the post above:
Cancer research is an international, collaborative effort, and DCA is being investigated in a similar way to most new treatments. In order to make the most appropriate use of all the cancer research resources around the world, small scale trials (known as Phase 1 and phase 2 trials) will usually be carried out in just one or two centres. If the results of the small trials are promising, then larger (phase 3) studies will be run at many more centres in a larger number of countries for drugs that show promise. The current results from the DCA trial in Canada simply don’t provide enough evidence to support the case for a UK trial right now.
It could be potentially hazardous to embark on a large scale clinical trial of any untested drug on a large scale, before its benefits and potential side effects are known. This is why small scale trials, such as the Canadian study, are vital to establish the correct dose of any treatment, check that it actually works, and monitor side effects. Furthermore, investing money in clinical trials of untested drugs – which can cost hundreds of thousands of pounds – means that research organisations with limited funds might not be able to invest in trials of other, more promising, drugs that are coming through the system.
Of course we understand that people with cancer may want to try anything to treat their disease. But we urge people to talk to their own doctors before trying any unlicensed or untested treatment. Taking untested drugs without medical supervision can be dangerous, and it’s important for doctors to know if patients are taking anything alongside their prescribed medical treatment. On a broader level, large scale use of untested drugs can also cause problems for scientific research, as it can complicate the results of clinical trials and may even end up hindering research into new treatments for cancer in the long run.
Finally, the blog isn’t really the best place to discuss medical issues and cancer treatment. If you would like to talk with people affected by cancer, please visit our CancerChat forum: http://cancerchat.cancerresearchuk.org/index.jspa
Matthew February 1, 2011
Hello, I think James is right.
I do find it strange what little effort is going into DCA research on a World Wide basis. Why are we all waiting on one small study??
I can understand why the Universities and big pharmaceuticals have zero interest in a non patented, non profit making drug!
However, CRUK is funded by donations so should have no hidden agenda or profit making requirements. Indeed there must be many such charitable organisations world wide all fighting the same cause. How about a concerted group effort? CRUK could at the very least start that going.
What we really need is a dedicated DCA UK trial, testing, the full works.
Whilst we are at it, how about looking at Trimetazidine (TMZ) as well?
Fiona, how did your family get on?
Peter and Steve how are you both doing?
Be strong and fight on!
james January 30, 2011
I still think you should use what capital and influence you have to help dca become developed into a cancer treatment. You have 19 experimental cancer centres in the UK, which supposedly offer experimental treatments – why don’t you suggest that dca be included in one or more of these programs? Or start a clinical trial of dca in the UK? Your organisation can make a difference, you are not just passive actors.
james January 15, 2011
Hi Kat I looked at the fenretidine report – it looks like fenretidine has the same efficacy profile as dca. Given this is the case, I suggest CRUK use the same approach and secure a license to administer dca, with outside collaboration or without. If you don’t do this, your claim to be concerned with developing orphan drugs will seem disingenuous, so I suggest you do so and provide the public with news as you have done in the case of fenretidine.
Kat Arney January 17, 2011
Thanks for your comment. There is a big difference between fenretinide and DCA. Fenretinide has already been relatively well-tested in cancer patients (for example, this study of nearly 3,000 women with breast cancer http://220.127.116.11/content/19/6/1664.full) The orphan drug licence allows us to investigate its effectiveness for treating cancer in children, as opposed to adults.
In contrast, DCA is still at an early stage of testing – for any type of cancer – and there’s not yet enough evidence to draw any scientifically solid conclusions about its effectiveness. The Canadian trial we wrote about above may provide some answers but there’s a long way to go before we can properly compare DCA to other, well-tested and established treatments.
steve August 28, 2010
all at present going well will be having ca125 marker test next week
Peter July 26, 2010
Good 20 page article on mitochondria in Nature in June: Nature Volume 9 p447ff
which mentions dichloroacetate, among many other substances manufactured and natural, and how it works.
I’m not sure DCA will mediate the eradication of cancers but even if it stops it regenerating and makes immortal cells mortal it may well help if combined with cell killers.
Artemisinin is worth a look for killing cancer cells.
To add DCA to a standard chemo regime would be the way forward and shouldn’t cost too much, I think.
Another good article on mitochondria in inflammation is in the New England Journal of Medicine June 3rd p2132
Dr David Servan-Schreiber 58 minute lecture
http://www.youtube.com/watch?v=XaDt3AJQ98c is well worth paying attention to.