Potential cancer drug DCA tested in early trials

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).
http://www.medicorcancer.com/dca-reports.html
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.

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:
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— well, how ridiculous. It washes even less.

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)?

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.

Why do clinical trials? no money can be made on this drug, so $100 million down the toilet.
No major Pharma. will touch it.

For a more balanced perspective, see:

http://scienceblogs.com/pharyngula/2011/05/dichloroacetate_and_cancer.php

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

No big bucks to be made = no incentive for either drug companies or researchers = no cure!

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.

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.

I hope this will someday be verified in a reasonable degree of certainty.

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.’

(clinicaltrials.gov)

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.

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!

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.

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.

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.

James,

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:

http://cancerhelp.cancerresearchuk.org/trials/AdvancedSearch/

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.

Henry

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.

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.

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.

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!

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.

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.

all at present going well will be having ca125 marker test next week

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.

matthew is saying every thing that needs to be said well done matthew all we hope is that the people that could help us do and that would put a stop to the likes of us trying to make it work by trial / error

Kat your article winds me up. It’s written with a negative and cynical undertone.

Let’s summarise..

• 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 (FANTASTIC NEWS!)
• The team discovered that DCA didn’t affect healthy cells, because their mitochondria were functioning normally (BRILLIANT).
• DCA has been tested as a treatment for children and adults with certain rare metabolic disorders (SO ALREADY BEEN USED SUCCESSSFULLY).
• This means that, at the doses needed to treat these diseases at least, DCA has been through clinical trials aimed at assessing its safety (GREAT).
• Based on their results, the researchers have proposed that DCA could also be useful in treating cancer (GOOD NEWS).
• The University of Alberta researchers received approval for a human cancer trial in September 2007, involving 50 patients. FOUR patients were still alive after 18 months (SO DCA WONT NECESSARLY KILL YOU QUICKLY), and THREE showed some shrinkage of their tumour (THAT’S A 75% SUCCESS RATE, IF YOU CAN LIVE LONG ENOUGH).
• 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! (IT JUST KEEPS GOING!!).
• A key gap in this trial is that, as we’ve mentioned above, it’s not clear exactly how DCA is working (SO WHAT! IT WASN’T UNTIL THE 1600’S THAT SCIENCE ANSWERED EVEN SOME OF THE MOST BASIC QUESTIONS).

We don’t need comments like… “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”. That just has the undercurrent of modern day culture of ‘don’t sue us’.

OK – SO LET’S START. Peter has the right idea, get on with it. If I’m reading that Pancreatic cancer (which has metastasized) has a life expectancy of 4-6 months of course you should try! And why the hell not! I agree with Fiona, give people in these situations the choice! Get off your backsides Cancer Research UK and start really helping people. The results show that there was a 75% success rate, providing you LIVE LONG ENOUGH. So let’s not waste any more time. After all this drug is free and available. However that in my opinion is the problem… how can any one make any money out of a free ‘cure’? So why bother promoting it and destroying a multi-billion pound industry? Prove me wrong Cancer Research UK!! If DCA didn’t kill the other 46 patients in the Alberta trials and it has already been tested on children, surely this is just a matter of dosage?? This won’t cost millions of pounds, so come on Cancer Research UK, do some research.

Be strong everyone, have hope and fight on!

I am UK orthodox medically qualified. I have colon cancer. I have metastases. Over the last 18 months standard chemotherapy almost killed me but I am alive because of it and I wouldn’t have refused it for DCA or anything else.
But now:
My options are very limited in view of side effects from oxaliplatin and 5FU.
Don’t tell me about the safety of DCA. I take it and gladly.
Artemisinin is also worth a look and I take it too.
I can’t wait for controlled trials. I would be happy to be included in one but am now doing my own.
On for one month now and trying to avoid liver resection. We’ll see.

The median survival for a Glioblastoma patient is 11 months with current standard treatment(source cancer research UK). Though a trial of 5 patients is small, 4 patients surviving to 18 months is a good improvement on standard treatment. The worst thing that can happen you if you have this disease (my husband has GBM) is that you can die after losing all your functions slowly.

The idea that because DCA or other drugs mechanisims of working are not fully understood they should not be tried in terminally ill patients is just not fair to the patient. Similarly the idea of the side effects being a reason not to try them out in Patients who have no other hope, and have already endured horrible side effects from standard evidence based medcine is not balanced. Terminally ill patients don’t want guaranteed winners, they want to be allowed to buy lottery tickets from reputable sources.

Tell the patients the risks then let them choose. Option 1 you will die (probably horribly) option 2 you might still die horribly but you might live, but its not proven. I know from speaking to them what most GBM patients would choose.

This is why people buy unlicenced drugs over the internet. Because they are not being supported by mainstream medcine in their desire to identify and participate in the most promising experimental treatments.

My family cannot wait 5 years, we cannot even wait 11 months, so we will try for ourselves to find the best options.

Hi Kat,

Thanks for the info, you kinda forget about all the other impacting variables involved wih something like this. Will take a look at the info you suggested.

Cheers

Karl

Do they have any idea how long it will take the Canadian clinical trials to produce results worthy of warrenting major interest?

Karl