An uninformative “experiment” on dichloroacetate (DCA) and cancer

I hadn’t planned on writing about dichloroacetate, the inexpensive compound whose success in treating experimental cancer in rats that provoked a blogopheric storm about a “cancer cure” that would supposedly never see the light of day because it’s not patentable. After all, I’ve done about seven posts on the topic, give or take a couple, in the course of the last four weeks or so. That’s saturation blogging, and, really, nothing new has happened on the news front that merits a new post.

Or so I thought.

Then, like Michael Corleone in The Godfather, Part III, just when I thought that I was out they pull me back in. Worse, the one doing the pulling is Dave Springer (a.k.a. DaveScot) who comments:

The guy who started the DCA site discovered DCA by reading my articles on Uncommon Descent so I have a personal interest in how it turns out. There is now one person writing there who obtained a supply of DCA (works in the medical profession so was able to order pharmaceutical grade dichloroacetate acid sodium salt from TCI America), put it into 500mg capsules, and is taking two doses of 1000mg per day for 25mg/kg as used in the congenital lactic acidosis phase 2 trial. He’s also taking 500mg of vitamin B1 to counter possible side-effect neuropathy. He has metastatic prostate cancer. We’ll all know in 60 days or less whether DCA works in humans or not. If not for avarice we could have known two years ago. If it turns out the stuff works I don’t know how the discovers will be able to sleep at night knowing they sat on this for 2 years trying to find a way to profit from it.

Leaving aside DaveScot’s drama queen posturing and conspiracy-mongering (in which, ironically enough, he seems to be turning against Dr. Evangelos Michelakis, the discoverer that DCA can cause apoptosis of tumor cells and shrink experimental tumors in rats, if I’m interpreting his rant about “sitting on this for 2 years trying to find a way to profit from it” correctly), reading this you might think, why not? Despite the fact that DaveScot is inarguably a clueless medical ignoramus (in addition to his more widely known role as an ignoramus about evolution) but doesn’t realize it, maybe this will tell us something.

Maybe, but in reality, contrary to Dave’s bold reality-challenged assertion, it’s almost certain that we won’t “all know in 60 days or less whether DCA works in humans or not” based on a single person taking the drug, assuming what he has obtained is even truly pharmaceutical grade. Single anecdotes only rarely tell us anything definitive (or even anything truly compelling), and the plural of “anecdotes” is not “data.”

To begin with, only if DCA is extremely powerful against prostate cancer will it be likely that any objective evidence of efficacy at all would be seen in just 60 days in just one patient; prostate cancer is often (but not always) a slow-growing cancer. I sincerely hope that, if this guy’s tumor is still androgen-responsive, he isn’t stopping his hormonal therapy. That’s still the single most effective therapy for metastatic prostate cancer and provides excellent palliation. True, nearly all tumors become androgen-independent eventually and stop responding to androgen blockade, but the best prolongation of life in metastatic prostate cancer is generally produced by antiandrogen therapy. (On a side note, a common anti-androgen therapy used in prostate cancer is Lupron, you know, the drug that Mark and David Geier are giving to autistic children to “cure them” based on no good evidence.)

For another thing, even if objective tumor shrinkage were observed, that does not necessarily translate to improved overall survival. I know it’s hard for non-oncologists to understand how that could possibly be (and, indeed, even many oncologists fall into the same trap, given that tumor shrinkage is relatively easy to measure), but it’s true. Initial tumor response to chemotherapy (and, make no mistake about it, DCA is chemotherapy, the claims of one troll in my blog otherwise not withstanding) correlates much less strongly than you might thing with prolonged overall survival. True, observing tumor shrinkage is much better than no tumor shrinkage, but it’s only a marker that the drug could be prolonging life. There have been chemotherapy trials in which impressive initial tumor shrinkage was obtained that either did not translate into prolonged survival or only translated into slightly prolonged survival. That’s the reason why we need clinical trials with a large enough number of patients to determine whether treatment with the new drug actually does result in a prolongation of survival. One patient’s experience, unless it is a truly miraculous apparent “cure,” tells us little or nothing. Worse, on the DCA site, we find patients going through all manner of desperate contortions to try to obtain and use DCA, all before there is clinical evidence of efficacy. It is not hard to imagine these same patients exhausting their saving and remaining energy in search of this drug, particularly patients who were not that well-off to begin with.

As a thought experiment, though, let’s look at some possible outcomes to this uninformative experiment that is being trumpeted and what they may or may not mean:

1. The tumors are larger after 60 days of DCA treatment. This could mean that the drug is ineffective against prostate cancer. It could also mean that the tumors would have grown faster with no treatment, but the drug slowed them down, in which case it could also mean that the treatment wasn’t continued long enough or that the dose of DCA was too low. Those trying to use DCA to treat human cancer are assuming that the dose needed for cancer will be the same as what was effective in the lactic acidosis Phase II trial. There’s no sound justification for that assumption. If DCA is effective at all against cancer, it wouldn’t surprise me if the dose needed for cancer will be much higher than the dose for congenital lactic acidosis. There is no way of knowing, based on one patient, which interpretation is correct. That’s why clinical trials are needed to figure these questions out.

2. The tumors stay the same size after 60 days after 60 days of DCA treatment. In the lingo of cancer clinical trials, this is called “stable disease.” Seeing stable disease could mean that the drug kept the tumors from growing and that it might shrink them if the dose were higher. On the other hand, it might mean nothing at all. Prostate cancer is, as I have pointed out, often a fairly slow-growing tumor; the individual’s tumors may just not have grown enough in 60 days to be detected on imaging. Interpreting this result becomes even more complicated if the individual continues to take other treatments for the cancer. Which one did anything? Did any of them do anything? Did all of them do nothing? Did DCA antagonize the activity of another, effective drug? Did the other drug antagonize the activity of DCA (assuming that DCA has activity alone)? Would DCA have shrunk the tumors if the dose were higher? There’s no way to sort these questions out in a single patient. Again, that’s why we need careful clinical trials.

3. The tumors shrink during the 60 days of DCA treatment. If the individual is taking other drugs, this one would be difficult to interpret as well. (Maybe DCA potentiated the action of the other drug and is useless on its own, or maybe it truly worked, for example.) If he’s taking only DCA, tumor shrinkage would be indicative of a likely effect, but it would not necessarily mean that his life was being prolonged by the drug, although certainly we would hope that that’s what it would mean. Again, that’s why we need clinical trials with a large number of patients. Indeed, unless the tumor shrinkage were truly dramatic, as in “melting away to nothing,” it would be hard to infer from one patient that the treatment is doing what we want; i.e., prolonging life in the case of one patient.

The bottom line is that result #1 is by far the most likely result of this “experiment”; result #2 is the second most likely result; and the likelihood of result #1 or #2 happening is way, way more likely than #3. In either of those first two cases, we would have no idea (1) whether DCA truly doesn’t work against prostate cancer; (2) whether the dose was too low or the treatment too short; or (3) whether DCA might work against other tumors. Even if outcome #3 were to be observed, all we could say is that DCA would appear to have activity against a single patient’s prostate cancer. Response to chemotherapy is a stochastic issue, with a probability distribution of patients responding. Indeed, when looking at chemotherapy against solid tumors, there are numerous trials in which solid tumors respond with significant shrinkage in only 10%-20% of the treated patients. What if DCA were a drug like this and this “experimental subject” just happened to be one of the lucky ones whose tumors responded? As a counterexample, we could just as well turn this around and look at possibility #1, where the tumors don’t respond to DCA. In that case, we could ask: How do we know that DCA doesn’t work for a subset of patients, and this guy just happened to be one of the unlucky ones in which it didn’t work? In fact, we could imagine a scenario where DCA works for, say 75% of patients, but this guy happens to be one of the unlucky 25%. Based on one patient in this case, we would erroneously conclude that the drug “doesn’t work.”

Of course, it’s hard to tell a dying patient that he shouldn’t grasp at what he perceives to be his last chance at life, no matter how unlikely. I can’t even fault this patient with prostate cancer too much; he’s trying to save his life, not answer the definitive question of whether DCA works against cancer; it is DaveScot who is claiming his little “trial” will do that. I can’t even guarantee that, were I to develop metastatic cancer at my current (relatively) young age, I wouldn’t be highly tempted to use my status as a physician to pursue any option, including something like DCA. And that’s perhaps the biggest reason why the hype over DCA is so harmful, other than the misleading and ignorant claims made by DaveScot and his ilk. The harm, I would argue, is twofold. First, as I mentioned before, it sells false hope to desperate patients, some of whom may forgo effective palliative therapies seeking after this unproven drug. This is not unlike patients going to Tijuana for quackery, the only difference being that DCA might ultimately be proven to have efficacy. For example, look at this other “testimonial” from the DCA site:

We hope to help people in the same situation by shearing our experience with DCA.
We prepared a 12.5 gr Sodium dichloroacteta/100ml in pure water.
My wive (with metastasized colon cancer) took 4.5 ml (in a glas of water) twice daily (25 mg/kg/day). After 4 days she feels nauseous and she stopped after 6 days due to bad feeling. Now I think the problem was first due to the bad constitution of my wife (45 kg) and second we didn’t take care of vitamines and carbonhydrates. Both are very important by the fact that DCA stimulates the pyruvat dehydrogenase complex and by this a lot of vitamin B1 is used. We will try to give glucose as a carbonhydrat source half an our before DCA and daily vitamine B1 (thiamin).

Could measuring of lactate in blood be a good marker to find the best dose for DCA?

We are hopeful to that last chance and hope!

It’s heart-wrenching to see a woman who is dying of metastatic colon cancer, apparently to the point of being emaciated (her weight is around 99 lbs.), trying an unproven drug (DCA) as her last hope. Worse, this excessive hype of DCA by people like DaveScot and others opens the door to quacks to prey on desperate patients just like this woman. How long, do you think, will it be before quacks start selling DCA that is either sloppily synthesized and laden with possibly harmful impurities or isn’t even DCA at all? How long, do you think, will it be before quack clinics in Tijuana begin advertising that they have DCA, leading to another migration south of cancer patients, much like what we saw during the 1970’s and 1980’s with Laetrile? I wouldn’t be surprised if it’s already happening, and we have credulous and irresponsible bloggers like DaveScot and others to thank for stoking the demand.

The other pernicious effect is on the cancer patients themselves. Imagine yourself as dying of cancer. Now imagine that you see stories all over the Internet about a “cure” for cancer that is being kept from you because “big pharma” doesn’t find it “profitable enough” to pursue. Never mind that it’s only been tested in cell culture and animals. Never mind that it’s completely unknown whether it will even work in humans. It’s a cure! And, you’re told, it’s being kept from you by greed! You’re going to die unnecessarily because “they’re” keeping the cure for cancer from you!

Imagine how you would feel. It’s irrelevant that the true situation is that, although its preclinical activity looks promising, we have no idea whether DCA will work against cancer in humans. Also irrelevant is that, based on the history of drugs with anticancer activity in animals, it’s highly unlikely that DCA will be any sort of “cure.” Ditto that the true story of why drug companies appear uninterested in the drug is a more complicated story and is more indicative of systemic defects in our system of drug development and incentives for research and development of unpatented and unpatentable compounds than any malice. You would wonder if you were dying unnecessarily, whether drug companies are “denying you the cure“!

That’s the most pernicious effect of the bloviations of idiots like DaveScot of all. He’s already roped at least one into publicizing the drug before it’s ready for prime time. One result is this uninformative experiment, which is already influencing others, including the administrator of the DCA Site (Heather Nordstrom), who, in an action that is breathtaking in its level of utter irresponsibility and cluelessness, is promising in the near future to publicize information about where to obtain DCA. If you think that the purveyors of The DCA Site are doing this all out of the goodness of their hearts, think again. While poking around on the site, I noticed that the contact information is info@buydca.com. (“BuyDCA.com”?) Curious, I checked out whether there was a website to go with the domain, wondering: If you go to the BuyDCA.com website, what do you find?

Surprise, surprise! As one might expect from a name like BuyDCA.com, the website’s owners are selling DCA. Indeed, they’re selling it as a “cancer treatment for pets.” Gee, you don’t think they’re doing that to avoid the FDA scrutiny and potential liability, do you? Perish the thought, O cynical ones! How dare you doubt Heather? She’s doing it to help people! Of course, she and whoever else is responsible for running these websites will try to make sure that patients who buy DCA are only planning on treating a pet with cancer and aren’t planning on using on humans, right?

Yeah, right.

In other words, from my observations and reading, The DCA Site appears to be nothing more than an advertising site for BuyDCA.com. Does that make DaveScot a DCA shill?

I leave my readers to answer that question for themselves.

No one wants to tell cancer patients that they can’t have a promising experimental drug. No physician wants to tell dying patients that there is no longer anything modern medicine can do that will prevent their cancer from killing them and that all that can be offered is palliation. We don’t withhold experimental treatments from all but enrollees in clinical trials because we’re callous, cold, and don’t care. We do it because letting such medicines out prematurely has the potential to harm far, far more patients than it would help. Sanctioning the widespread use of an unproven drug like DCA is a recipe for disaster; like the recent well-intentioned but badly misguided movement to allow patients to have access to experimental drugs that have only passed Phase I studies, it could jeopardize the very science that would tell us whether it truly has any anticancer activity or not.

ADDENDUM: Walnut has posted his critique on Daily Kos as well.

All Orac posts on DCA:

  1. In which my words will be misinterpreted as “proof” that I am a “pharma shill”
  2. Will donations fund dichloroacetate (DCA) clinical trials?
  3. Too fast to label others as “conspiracy-mongers”?
  4. Dichloroacetate: One more time…
  5. Laying the cluestick on DaveScot over dichloroacetate (DCA) and cancer
  6. A couple of more cluesticks on dichloroacetate (DCA) and cancer
  7. Where to buy dichloroacetate (DCA)? Dichloroacetate suppliers, even?
  8. An uninformative “experiment” on dichloroacetate
  9. Slumming around The DCA Site (TheDCASite.com), appalled at what I’m finding
  10. Slumming around The DCA Site (TheDCASite.com), the finale (for now)
  11. It’s nice to be noticed
  12. The deadly deviousness of the cancer cell, or how dichloroacetate (DCA) might fail
  13. The dichloroacetate (DCA) self-medication phenomenon hits the mainstream media
  14. Dichloroacetate (DCA) and cancer: Magical thinking versus Tumor Biology 101
  15. Checking in with The DCA Site
  16. Dichloroacetate and The DCA Site: A low bar for “success”
  17. Dichloroacetate (DCA): A scientist’s worst nightmare?
  18. Dichloroacetate and The DCA Site: A low bar for “success” (part 2)
  19. “Clinical research” on dichloroacetate by TheDCASite.com: A travesty of science
  20. A family practitioner and epidemiologist are prescribing dichloracetate (DCA) in Canada
  21. An “arrogant medico” makes one last comment on dichloroacetate (DCA)

Posts by fellow ScienceBlogger Abel Pharmboy:

  1. The dichloroacetate (DCA) cancer kerfuffle
  2. Where to buy dichloroacetate…
  3. Local look at dichloroacetate (DCA) hysteria
  4. Edmonton pharmacist asked to stop selling dichloroacetate (DCA)
  5. Four days, four dichloroacetate (DCA) newspaper articles
  6. Perversion of good science
  7. CBC’s ‘The Current’ on dichloroacetate (DCA)