Terra Sigillata

My blog buddy Orac at Respectful Insolence has a superb post today following up on his continuous coverage of dichloroacetate and two posts I had recently on local coverage in the Edmonton Journal of this unapproved, experimental compound. As an oncologic surgeon, he provides an authoritative rebuttal to the argument that there’s no harm in buying DCA for self-medication by cancer patients whom medicine can no longer help.

As hard as it may be to believe, even if you have a terminal illness with only months to live, things can get worse. One thing worse than dying of cancer is hastening your end in a painful way; i.e., wasting the little time that you have left for a drug that has a low probability of curing you and an only so-so possibility of even helping.

There is, of course, further discussion on how today’s process of drug investigation and regulatory approval was designed precisely to combat “snake-oil” representations of health products during the early to mid-1900s. As I’ll discuss below, DCA falls somewhere between snake oil (due primarily to how it is represented at thedcasite.com) and a regulated drug since it has been and continues to be tested in clinical trials.

But thanks again to readers of ScienceBlogs.com (Edmonton’s Matt the heathen on Respectful Insolence and incze here), we’ve been pointed to two more articles out of the Edmonton Journal regarding dichloroacetate. This time, the articles which appeared Sunday and today, are written by Andrea Sands with one making the nationwide canada.com portal.


The Sunday article brought to my attention an old press release detailing that an Edmonton-based drug company called CardioMetabolics, Inc. (CMI) already has an intravenous form of DCA they call CMI X-11S in Phase III trials for cardiac ischemia/reperfusion injury in geriatric cardiac surgery patients.

To date, CMI has been granted four Patents from the USPTO (United States Patent & Trademark Office) and has several other patent applications pending. Two of the issued patents relate to DCA, while the other two cover related compounds of DCA. CMI’s patent coverage includes the treatment of cardiovascular diseases and metabolic conditions where ischemic [oxygen-deprived] or hypoxic [low-oxygen] conditions present (such as cardiac surgery)…

CMI X-11S (DCA intravenous formulation) is the company’s lead clinical stage drug product. CMI has secured permission from the US Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA) and from the CDN Therapeutic Product Directorate (TPD) to initiate Phase III clinical trials for cardiac surgery in higher risk geriatric patients.

(FYI – A Phase III trial is one that is designed to test a drug’s effectiveness by comparing the responses of patients to the study agent, placebo, and/or standard therapy. The key aspects of a Phase III trials are that patients are randomized to each group (i.e., they cannot pick which treatment they want) and neither the medical investigators nor the patients know who has been assigned to each group until a code is broken by an independent party after completion of the study.)

Huh? DCA being tested in heart surgery? Well, the common thread between some cancers and cardiac surgery is hypoxia; while some cancer cells can happily grow in hypoxic conditions, normal tissues like the heart are damaged by lack of oxygen – that’s what causes a heart attack – and some hypoxia occurs normally during the course of most surgical procedures on the heart. Adding insult to injury, as it were, the reintroduction of oxygen to the heart after ischemia/hypoxia results in a burst of oxygen free radical production that can further damage the heart. Dr Evangelos Michelakis, the University of Alberta physician-scientist whose group published the Cancer Cell paper on the effects of DCA in cancer is first and foremost a cardiologist.

The chief medical officer of the company is a former president of the Canadian Medical Association who carefully explains the quality control differences between patients buying DCA as a “veterinary product” and a carefully formulated and monitored clinical trial material:

Many cancer patients would likely be ingesting chemical-grade rather than pharmaceutical-grade DCA, warned cardiologist Dr. Ruth Collins-Nakai, past president of the Canadian Medical Association and chief medical officer with CardioMetabolics Inc., a U of A spinoff company that is running a DCA study on geriatric open-heart-surgery patients.

“They might be taking contaminated something-or-other, and the contamination may be the thing that’s causing the side effects,” said Collins-Nakai.

“You have to meet stability, purity and temperature standards (to manufacture pharmaceutical-grade drugs). You have to meet concentration standards, efficacy standards. There’s a whole series of things you have to do to make sure it’s safe to be put into the human body.”

Today’s article discusses a 70-year-old cancer patient who appears to have purchased DCA from the California-based buydca.com and has decided not to use take the preparation after discussion with her family and oncologist.

“I spoke to my oncologist. He said he wouldn’t touch it, and I think that’s fair. He’s doing all he can for me.
“It’s grasping at straws and I wouldn’t do it without being supervised (by a physician). I just don’t think that’s sensible. Maybe when it gets closer — maybe I will start grasping at straws.”

Getting back to the sponsorship of clinical trials by CardioMetabolics, Inc., I think we can infer something that supports the contention that DCA’s potential in cancer may be overhyped. A small company will only invest its limited dollars toward indications where it anticipates the highest probability for efficacy. Both Orac and I have noted that perhaps thousands of anticancer compounds show efficacy in animals like DCA, only to crash and burn when they get to human clinical trials. My sense is that the strategists at CMI are aware of this fact and have put their chips on the cardiac surgery market – a Medline search for “dichloroacetate” and “cardiac ischemia” already returns 50 papers, suggesting that far more is known about the utility of DCA in this setting than in cancer and that the probability of clinical success is far greater.

However, I do hope that DCA is ultimately tested in cancer patients in a statistically valid and controlled manner that has the greatest probability of determining whether this agent will be a useful cancer treatment.

The two new articles are:
Experts caution against patients compiling own data on unapproved cancer drug
Dying patient wary of suspect cancer remedy

Finally, as a service to my regular readers and anyone else who might stumble by this post, my colleague Orac has amassed a large number of thoughtful posts on the University of Alberta dichloroacetate repercussions, many of which precede my own interest in this story. As he is a practicing physician who faces daily life and death decisions with his cancer patients, he provides a level of insight into this issue that I cannot:

All Orac posts on DCA:
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

My own posts on dichloroacetate are as follows:

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

Comments

  1. #1 erty
    December 17, 2008

    guys check out this site for more info on dca and other alternative therapies:
    http://forums.cancer.vc

The site is currently under maintenance and will be back shortly. New comments have been disabled during this time, please check back soon.