Terra Sigillata

From the same reporter at the Edmonton Journal who brought us yesterday’s DCA article comes news of a highly-experienced Canadian pharmacist who has been providing patients with physician-prescribed dichloroacetate. Jodie Sinnema reports that a local pharmacist has been selling DCA to patients but their supplier has stopped providing the pharmacy with the compound after intervention by Health Canada, the Canadian equivalent of the US FDA.

Ron Marcinkoski, a pharmacist at Market Drugs Medical at 97th Street and 102nd Avenue, said he was doing what he could to help cancer patients when University of Alberta professor Dr. Evangelos Michelakis phoned the pharmacy to say DCA, which shrank tumours in rats but hasn’t been tested in humans, could be lethal or cause horrible side-effects.

SInce the pharmacist has been practicing for 26 years, it’s clear that he should understand completely the drug approval process and the basic tenets of off-label drug prescribing – but apparently doesn’t:

Although Marcinkoski stopped filling prescriptions before the phone call from Michelakis — his supplier was no longer willing to sell DCA to the pharmacy after supposedly being contacted by Health Canada — Marcinkoski said he doesn’t believe he was doing anything illegal. Doctors routinely write off-label prescriptions, using a drug to treat a different health complication than it was made for.

But Michelakis, whose research was published in the medical journal Cancer Cell in January, said, “The concept of off-label use (in this circumstance) is confusing and dangerous.”

He asked how a doctor can prescribe a drug off-label when it hasn’t been approved by Health Canada for any medical treatment. It’s solely being tested on humans in clinical trials.

However, Sinnema reports that Canadian physician and pharmacy groups are aware of the issue and have taken the appropriate stance that DCA, no matter how promising it may seem from animal studies, is still an investigational drug:

Kelly Eby, spokeswoman for the College of Physicians and Surgeons of Alberta, said since the drug hasn’t been approved in Canada, physicians shouldn’t be prescribing it.

“If we were aware of physicians in particular, we would be telling them it’s inappropriate and this would have to stop,” Eby said. However, the college has no way to find these doctors and Eby said it’s up to Health Canada to decide if prescribing an unapproved drug is illegal.

Greg Eberhart, registrar for the Alberta College of Pharmacists, strongly urged his members not to fill DCA prescriptions outside clinical trials.

Understandably, the pharmacist states that he was trying to be compassionate toward patients, citing that Michelakis knew of his animal results two years ago. However, that stance is indefensible. Literally thousands of anticancer agents prove useful in animal studies, only to be found less effective and/or more toxic in human clinical trials. My oncology colleague, Orac, recently wrote on how DCA might prove ineffective against human cancers.

One would never want to deny a patient a useful anticancer drug but supplying DCA with today’s evidence constitutes giving patients false hope, not to mention that the drug’s safety has not been assessed in cancer patients. I’m also not sure about Canadian pharmacist malpractice guidelines but any pharmacist supplying DCA to patients might care to consult first with their insurance carrier.

Read the entire article by Jodie Sinnema in today’s Edmonton Journal.

Comments

#1 Orac
March 17, 2007

Yeah, I saw this article. I may have to break my rule about serious posts on the weekend again and comment later today or tomorrow…
#2 anon
March 17, 2007

Google “low dose naltrexone” and cancer — for similar hype as DCA
#3 incze
March 17, 2007

“It’s rather disappointing that they didn’t actually test DCA, but, then, the work on this paper and the work on Michelakis’ paper were likely going on at the same time. The drug they did test is 2-deoxyglucose (2-DG) a drug that is being tested because of its ability to inhibit glycolysis and shift the balance of energy production towards aerobic oxidative phosphorylation by a mechanism different from that of DCA.”

This is from Orac’s blog on findings how cancer cells adapted in the brain. But as a matter of fact, the Canadian team did test DCA against brain tumor (it’s included in their patent: “preferably, the cancers treated are non-small cell lung cancer, glioblastoma and breast carcinoma”). So, at least in this case, there is hope, that the mechanisms of DCA are faster than the described adaption mechanism. (Not disputing your points on reponsibility, in general.)
#4 Duxduedx
March 18, 2007

This stuff has been around for decades and has been used to treat people with certain metabolic disorders. It has been shown to be safe. I’m telling you that you have left this information out of your article. Why ? It is no more an experimental drug than is aspirin. If someone has received notice that they will die in X number of days, what possible harm could come by using something already being used in humans for treatment of another illness, regardless of what affect it has on the cancer ? To deny this last hope for recovery is worst than any profiteer trying to make a buck by selling DCA as a pet med. It is like telling people in a burning building to wait for the fire dept. to rescue them instead of telling them to run for their lives !
#5 Abel Pharmboy
March 18, 2007

incze: If I read the patent correctly, the DCA only had activity against brain tumor cells grown in culture (a glioblastoma line, as you note). However, this is many steps removed from even having activity against human brain cancer cells grown in animals. The point I was making in citing Orac’s post is that for those cells that exhibit the Warburg effect, there is a good likelihood of the development of rapid resistance to DCA.

Duxduedx: As you note, DCA has indeed been used in humans but never tested directly in patients with end-stage cancer. Many of these patients are indeed very sick, with compromised liver and or kidney function that can render them far more sensitive to the toxic effects of DCA than in the metabolic disorder trials done a number of years ago. So, I still consider safety in cancer patients to be an issue that requires careful investigation. That’s the harm that worries me: that indiscriminant use of DCA outside of a monitored clinical trial may accelerate the demise of very sick folks.
#6 incze
March 19, 2007

“incze: If I read the patent correctly, the DCA only had activity against brain tumor cells grown in culture (a glioblastoma line, as you note).”

Yes, indeed, in culture: more or less the same environment as the tests described by Orac were going on. (Even, in the Orac mentioned experiment the metabolic adaptation of cancer cell’s were somewhat speeded up by directed selection, if I understand well.)
—

There is another story you may be interested in (the “database”): Experts caution against patients compiling own data on unapproved cancer drug (http://www.canada.com/topics/news/national/story.html?id=80b15f9d-cb4a-46a0-a4bc-f1a4ddea60d3&k=56245)
#7 Duxdudex
March 19, 2007

Isn’t it interesting how the AIDS drugs were allowed out without testing in order to save lives. It was the AIDS activist and lobbyist that made AIDS a political issue and got the AMA and the FDA and whoever else off of that high horse. We need someone with political muscle to get involved with this issue as well. There are a hell of a lot more people with terminal cancer than there are with AIDS.

This is more a money issue than a medical issue. Glaxo Smith Cline just recently issued a press release stating that their new cancer drug would add 7 or 8 months to the lives of breast cancer patents at a cost of $2600 per month and went on to say how many billions the drug would earn over the years. This is the Cancer industry at work. Do you honestly believe any investor would want to see this disease cured and to see all of those dollars lost ? I think not ! There is far too much money to be made slowly ushering these poor unfortunate people into the next world. At best they would like to see cancer as a chronic disease which would require treatment for the balance of the patents life and of course only if they could afford the cost of living. Can’t you see what’s going on here ?
#8 Duxdudex
March 22, 2007

Well, I guess that’s the end of this debate.
#9 Abel Pharmboy
March 23, 2007

Duxdudex: No, not the end of the debate but one where I question the argument. Firstly, I will be very interested to learn how DCA performs against cancers in the clinic compared with other drugs of known efficacy – we just don’t know how the current animal studies will translate to human cancer patients.

Let me make one thing clear: All of us involved in cancer research would gladly give anything to have an actual cure for all cancers. However, this will be unlikely in my lifetime at least for many reasons that are biological, not financial. The GlaxoSmithKline’s of the world will do just fine if cancer were cured because they can sell other drugs for more truly chronic diseases like heart disease, diabetes, obesity, depression, and anxiety, to name a few. Cancer drugs only comprise 20-25% of worldwide drug spending and if all cancers were cured, drug companies would simply increase the price of all other drugs to compensate for the lost revenue.

The early AIDS drugs were the stimulus for the accelerated IND process but they were not exactly “allowed out without testing.” The likely reason that there is no “political muscle” behind DCA is that those with such influence realize that it is very, very early to consider DCA a treatment for human cancer.

You do raise a very good question, however, about how much we as a society are willing to pay for what health economists call the incremental cost of a quality-adjusted life year (QALY). In the United Kingdom, the National Institute for Clinical Evaluation of the British National Health Service has defined the each QALY paid for by tax funds will be limited to 30,000 pounds/~$50,000. Individuals can choose to pay more out-of-pocket for better drugs or services, but the British have put a top value on the government’s responsibility for an additional life year. We are starting to do that in the US indirectly via group/private health insurance, Medicare, and Medicaid, but we as a society have been reluctant to put a precise value on a drug’s ability to extend life. The market will continue to support high drug prices, especially for cancer drugs that may only increase survival by months, as long as someone will pay them.
#10 Duxdudex
March 23, 2007

Abel Pharmboy,

I would love to see clinical trials on humans, but, I doubt it will ever happen. Just answer this one question for me, If a cancer patient is terminal and all other treatments have failed, What is the problem with using DCA “Right Now” ?
#11 Abel Pharmboy
March 25, 2007

Duxdudex, if a patient’s cancer has progressed to the point that only palliative care is offered, there are still reasons not to use any therapy that has not yet been tested in human cancer patients: an agent can actually hasten one’s death and/or reduce the remaining quality of one’s life.

The strain that cancer itself and previous chemotherapy puts on the liver, kidneys, and nervous system could cause DCA to further damage one or more of these systems. Therefore, if patients choose to self-experiment with DCA, they should advise their doctors they are doing so in the event of untoward side effects.

If a patient wants to try an experimental therapy and is still mobile and healthy enough to meet inclusion criteria, there are hundreds of phase I clinical trials ongoing for agents that hold more promise than DCA. However, note that phase I trials are only designed to pick doses for efficacy trials (phase 2 and 3) by understanding any dose-related side effects of a drug. US patients can search for registered trials in their geographical area and by cancer type at clinicaltrials.gov.
#12 Duxdudex
March 26, 2007

Abel Pharmboy,

You, my friend, are one of many medical professionals who blindly pledge allegiance to a flawed system, a system, which, in my opinion, was created to better serve the system itself rather than the patient. A system which, by the way, kills thousands of trusting people every year with so called approved drugs and treatments and just shrugs its shoulders and says �That�s to be expected, when so many are cured�. What exactly are we fighting for here, to save lives or to save a system ?

I�ll say this once more then I�m done, if a person knows for certain that he is going to succumb to a disease and all other �Approved� treatments have failed, he should be able to exercise his God given right to choose his next step, be it no additional treatments or a treatment which is untested but showing promise. It shouldn�t matter to anyone else what that �Free� individual chooses to do with the remainder of his life. Whether the treatment hastens his death or cures him, it is his prerogative and no one else�s, to make that decision.
#13 Abel Pharmboy
March 27, 2007

Duxdudex, you asked me what harm could be done by use of an untested remedy in end-stage cancer and I gave you the serious and objective answer. You’re making a straw man argument that has nothing to do with my response to you. Federally-approved treatments certainly do have their risks and the public needs to understand that such approval does not equate to absolute safety; instead, it means that the benefits to many outweigh the risks to some and as much effort as possible is taken to minimize those risks.

I support patient autonomy but I also hope that patients educate themselves about the risks and benefits of any approach they take, approved or otherwise. My argument through all of these threads has been that such information is not yet known for the use of DCA by cancer patients.
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January 15, 2008

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#15 timothy mcgough
September 16, 2008

From reading the responses of Abel Pharmboy, there will be a time in his life where cancer will either visit him, his mother or father, brother or sister, or close loved one.

I have lived with cancer for 2 years now. I’ve received chemo, and all the great drugs associated with it.

Let me just tell you from looking through the eyes of someone that has experienced the worse that cancer can through at you. You need to open your eyes and grasp some reality, because that day that Cancer visit’s you, it will change your life. And nothing that the FDA, or the government approves or supports will make one difference in your life. And when death is staring you in the face from your cancer, do you really believe you’ll hold to your beliefs of not reaching out for a cure ?

God help you when you are faced with that situation.

Timothy J. McGough
#16 Matt Helm
February 6, 2009

For you that support the idea that people should get what they want regardless. What do you think ethics and the long and many trials(including Court)of the Medical World were
all about? We live in a society. Each of us is dependant in one way or another on each other and nothing could be truer than in protecting society on the whole from as many dangers as possible. When people can do anything they want regardless of the situation it can affect a great many. The use of DCA off label is Not going to help the Researcher at all, it will hinder him if not in fact prevent him from from finding out whether his trial drug is of any real use. Why? Because It Is about money! It takes money to do clinical trials. Now when people act outside of this even thru certain unethical doctors say in Toronto vicinity who “don’t care that they are wrecking a clinical trial” ,Don’t care? About who? the Reaseacher or Us? This spreads bad news when they get piss poor results. This means it gets out that there is no sense in supporting a clinical trial. Now how Much Money do you all have to pay for all this unfounded cure or the next one you Will try? This again is the source of of the real thing thats going on! Un-ethical peole taking advantage of desperate individuals. How many invalid drugs and programs will you be able to buy into if you had a terminal disease? That ladys and Gentleman is why we have worked to have a system. There is no conspiracy except in the minds of people who can’t seem to fit in and work with a system that is there to protect the society. If I am not mistaken I believe selfless acts are considered Good and selfish acts are considered Evil. When a society by majority act in a selfish way, that society will soon fall apart. I believe this applies to all things in our society from finances to medical situations. Stop believing anything as true on this internet. Help the researcher find out if this drug will be of value, don’t hinder him. One more thing Marijauna does not cure cancer. Will not shrink tumours. It has great value in dealing with side affects and a huge plus for opiate intolerant patients. (Yes there is such a thing.) There is as of this date NO CURE FOR ANY CANCER. This is another reason to support the reseachers. As for other cancer doctors they are just doing what they can with the best tools availble.