Dichloroacetate and The DCA Site: A low bar for "success" (part 2)

Be careful what you ask for; you just might get it.

I say this in light of a commenter, who decided to show up in one of my old posts to claim "positive results" from dichloroacetate (DCA), the small molecule experimental cancer drug that has shown promising activity in rat models of cancer but has not yet been subjected to testing in human trials, and invite me to check out new testimonials. Because DCA is a small molecule that is inexpensive to produce and can't itself be patented (although a patent for its use in treating cancer, a weaker form of patent, is possible), pharmaceutical companies have been reluctant to fund clinical trials to determine whether this promising new chemotherapy has activity in humans. The result has been a perfect storm of blogospheric hype over this drug as being a "cancer cure" that "big pharma is ignoring" (or even "suppressing"). Back in January, I tried, apparently in vain, to explain that DCA, although promising, is almost certainly not a "cure" and that, although it does show promise in animals, other than its novel mechanism of action there is really not much to distinguish it from the other promising anticancer compounds that show promise in animal models but then fail when tested in humans.

Since then, fueled by bloggers who obviously know nothing about cancer research and spearheaded by an "entrepreneur" and pesticide seller named Jim Tassano, who decided to hire a chemist and start synthesizing "PetDCA" to sell for use in "pets," even though it was abundantly clear that he was really marketing it to desperate cancer patients, a cottage industry to sell unregulated and unapproved DCA to cancer patients has popped up. Recently, this selling of an untested (in humans against cancer, at least) cancer chemotherapeutic and self-experimentation outside the auspices of a well-designed clinical trial has made it into the mainstream media more and more. Most recently, Abel Pharmboy has pointed out that there was a segment on a Canadian radio show called The Current (audio clip here) about DCA, which included interviews with "Sandra" (whom we've met before making newbie mistakes in interpreting cancer growth kinetics) and Jim Tassano himself.

The last time I examined the claims about DCA from its boosters and found them to be primarily wishful thinking was over a month ago; so I figured it might be time to see if anything new has happened. Remember, I like the concept behind DCA. I really hope that it works. My problem is with this unsupervised, unorganized self-experimentation by people who clearly don't have the first clue about running a clinical trail for a new cancer chemotherapy, an activity that not only is unlikely to help more people than it hurts but may contaminate a potentially promising new chemotherapeutic drug with the taint of quackery, à la Laetrile. Here's what our commenter said:

You should check out www.thedcasite.com for more recent testimonials. Some of them are highly positive. If you are going to be objective, you must also count the positive reports along with the negative one.

The DCA Site itself boasts:

Please note that DCA is not active against all cancers. An excellent analysis by "Willis", which is supported by the limited feedback we are getting, indicates that sarcomas, for example, are not controlled by DCA. However, many cancers are definitely responding to DCA. Non small cell lung cancer patients, even in Stage 4 are recovering. We are seeing lymphatic, mammary, bladder and other cancers responding very well to DCA.

Finally, not surprisingly, everybody's favorite credulous "intelligent design" creationist, global warming denialist, and, apparently, self-styled cancer "expert," while thinking he's applying a "cluestick" to me makes six claims:

Highlights of the past month:

1. Most cancer sufferers report almost immediate recovery of energy, appetite, and mobility upon taking DCA. Best efficaciousness seems to be at the lower end of the recommended dosage range (10mg/kg).
2. Some tumors die so fast that tumor lysis syndrome (poisoning the body from dead tissue cells) is problematic. Dosing schedules are being experimented with to moderate it.
3. Some cancers start shrinking in days while sarcoma and possibly small cell lung cancer exhibit resistance.
4. Reversible peripheral neuropathy (tingling in the extremities that goes away after ceasing DCA) is reported by a few people taking higher dosages (25mg/kg) after several weeks. Managing blood pH so it stays neutral to alkaline seems to be a key for both making DCA more effectacious against cancer and eliminating the reversable neuropathy. DCA is an acid and tends to lower blood pH. The myelin sheath around nerves is compromised by the high acid level. Managing diet by eating high alkaline foods or supplementation with things like milk of magnesia and monitoring blood pH through inexpensive home testing of urine and saliva seems to be working.
5. Temporary dizziness and disorientation from low glucose after some time at higher dosages is reported by a few. DCA alters glucose metabolism. This side effect is successfully managed by snacking between regular meals to keep a constant supply of glucose.
6. Perhaps oddest of all is a few people reporting that slow growing moles they've had most of their lives are shrinking and disappearing. No one expected that but it makes sense as DCA use restores mitochondrial activity so that malfunctioning cells are given a suicide order (apoptosis). Moles are typically non-cancerous but are still malfunctioning cells that refuse to die. One person reported that topical application of DCA eliminated an unknown surface skin growth he'd had for years that had become painful.

Curiosity piqued, I decided it was time to dive back into The DCA Site one more time to see if maybe, just maybe, there were any actual positive results. Certainly, it's possible, but sadly, the testimonials at The DCA Site turned out to be quite disappointing. Out of all them, I could only find one case that might--I repeat, might--represent an objective antitumor effect, and even that is not particularly good evidence. I'll look at the claims in light of my browsing the discussion and testimonials last night and then conclude this post with a brief commentary on the interview that Abel turned up.

First, I'll deal with the items that can be handled briefly. For example, the "immediate recovery of energy" (#1) described might indicate an anti-tumor effect, but more likely it's nothing other than the placebo effect. When a patient decides to undertake a treatment, particularly one in which he is so emotionally invested, as is the case here, it's not surprising that they report feeling better. Also, the people posting to The DCA Site discussion boards are a highly self-selected group that mutually support each other's decisions. In fact, I'd have been surprised if most patients didn't report feeling better after starting DCA. Remember, to control for the placebo effect is one of the many reasons why randomized clinical trials are so important.

Next, the report of "moles" that supposedly regressed on DCA means relatively little. He appears to be referring to this anecdote:

There has been this growth on the inside of one of my nostrils for quite a while (like, years). I had tried all sorts of self medication but the thing never responded and/or went away. In the last 3 months, it had become painful, especially if I pulled off a piece of the hardened/scabby tissue that forms on top if it. After a little research, I finally (and with great reluctance) concluded that the growth/tumor could be cancerous. After reading that one of the chemicals that I regularly was exposed to at a prior job could cause such a cancer, my concerns were heightened.

About the time I was ready to give in and make a doctor's appointment, I heard about DCA. Hey, I figured, I'll give it a shot and if nothing good happens then there will probably still be time to make that appointment. Making a long story shorter here, I got some DCA (from buydca.com)and began applying it topically. Sure enough, there seems to be a significant shrinkage and the pain is gone. To apply the DCA, I wet a Qtip with water and dip it into some of the DCA powder. Then, I just kind of rub it on/in at the tumor site for a few minutes. It makes a kind of a paste which can sting for a while but nothing too terrible at all.

This could be due to the much higher local concentration of DCA that is likely achievable by topical application, a common characteristic of many drugs. Alternatively, this was on a mucous membrane and could very well have been something as trivial as a caustic effect from DCA dissolving in the mucus membranes and releasing dichloroacetic acid. Either way, it's a lot less impressive than it's made to sound. Similarly, this story of warts lightening is also similarly underwhelming, as far as being an indication that DCA is effective.

Next, the whole claim that the peripheral neuropathy can be controlled by keeping the "blood pH" neutral by keeping saliva and urine pH higher than 6.8 is implausible in the extreme. For one thing, the blanket claim is made that "in layman's term's DCA under acidic conditions reduces the Electrical Insulating properties of Myelin creating nerve malfunctions," but it's far more likely that it is the manner in which DCA interferes with the energetics of cells that is responsible for neuropathy, as explained here, where it is pointed out that "nerve tissues are highly vulnerable to damage from diseases that impair the body's ability to transform nutrients into energy." Moreover, peripheral neuropathy from DCA is not entirely unexpected based on the study of Kaufmann et al, who even went so far as to question whether this complication outweighs the therapeutic benefit in the MELAS syndrome. As I've explained facetiously before, blood pH is controlled very tightly within a very narrow range. In the presence of reasonably normal renal, metabolic, and respiratory function, it is very difficult to change the blood pH by very much. In essence, by taking various bases to "alkalinize the blood," all a patient is doing is alkalinizing his urine. There are conditions where alkalinizing the urine is therapeutic, but this isn't one of them.

I looked for examples of all the other claims, and, quite frankly, I had a hard time finding anything on the discussion boards that supports the grandiose claims of tumor responses to DCA. I could find no unequivocal evidence to back up Tassano's claim that "many cancers are definitely responding to DCA" or of tumors starting to "shrink within days." (I can't help but note than no direct links are provided anywhere to the anecdotes that supposedly support these claims.) Indeed, I'm not the only one who's noticed this. A site regular going under the 'nym the oracle has noticed too:

Some news here would sure be great but NO ONE who has been CT scanned after using DCA for a couple months is talking or coming back except for squareb who gave us bad news. What is going on here? are we participating in a venting session where these folks are linked with those folks selling us DCA? what exactly is going on - our lives and our loved ones lives are on the line and not ONE CT SCAN in 4 months!!!! or the TRUTH is being removed from the site and people who had scans did post bad results so it was also removed like my questions are.

I am not happy about this admin - gee sorry I lost everything sorry - what? didn't this happen last month on another persons testimony who DIED!! while using DCA. Something is definitely missing here and I am starting to think its THE TRUTH.

I believe in DCA but I am starting to think these admins are manipulating the information to suit them which is pretty typical for us trying to survive to run into. Sorry but these admins need to either post it ALL or explain why they are not allowing CT scan results to be listed on this site. Folks just think about it - Jan, Feb, March, April and now May - 4 months and nothing - come on folks lets get real here - do you really think its a coincidence?

An excellent question, although in fairness I will note that it's only been two to three months that Tassano's been selling his home brew DCA and it turns out that his other comments probably were not deleted. Even so, I note that Tassano has been forced to admit that at least one patient trying DCA has died. As time marches on, it's becoming increasingly hard for Tassano's defenders to gloss over the oracle's observation, and it's really depressing to me to read members on the forums grasping at increasingly thin straws to try to reassure themselves that DCA is working for each other. The lack of any real objective response thus far is the elephant in the room. In fact, the closest thing I could find to a story that might--I repeat, might--indicate a weak response was the story of a woman with a brain tumor whose tumor growth appears not to have progressed on DCA, although it could simply be another example of Gompertzian growth kinetics.

Perhaps the most ridiculous claim on the site is that some side effects of visual disturbances due to DCA are due to tumor lysis syndrome. First off, tumor lysis syndrome only occurs when rapid and dramatic tumor shrinkage in response to chemotherapy occurs, most commonly with lymphomas and leukemias. It results from the potassium and cellular debris from rapidly dying tumors released into the blood stream, where they cause metabolic derangements and damage to organs. It may start with no symptoms but can rapidly progress to cause mental status changes, renal failure, heart arrhythmias, vomiting, fluid overload and edema, and joint pain, among others. In fact, though, tumor lysis syndrome is uncommon in tumors other than lymphomas or leukemias, and, in the absence of rapid tumor shrinkage, it's not appropriate to make this diagnosis. Moreover, there's not a single case of tumor shrinkage on the entire DCA Site dramatic enough to be plausibly accompanied by tumor lysis syndrome.

Even worse, the purveyors of The DCA Site make proclamations about what tumors DCA does not work for. For example, based on (apparently) one case, Tassano declares that "sarcomas are not controlled by DCA." It's utterly idiotic and ludicrous to make such a pronouncement based on one patient, or even a handful of patients! Yet, the sole evidence for this generalization seems to be based on the experience of one patient with metastatic sarcoma, SquareB, for whom DCA clearly didn't work. Just as we can't properly judge the effectiveness of a treatment by only one or two patients, we can't judge the ineffectiveness of a treatment on the basis of one patient. In reality, we have no idea whether DCA works in sarcoma or not. Just because DCA clearly didn't work for SquareB doesn't mean that it might not work for other patients.

All of this brings us back to the radio segment mentioned by Abel. Having listened to the segment, I definitely agree that Jim Tassano does not come off sounding very good; he seems quite disingenuous, particularly the part where he oh-so-piously claims that it would be wrong not to be up front about what he is doing. Compare this to his previous disingenuous insistence that he was selling DCA only for use in pets and how he started altering and changing parts of his website after I pointed out his disingenuousness. Tassanno also seems to have oddly forgotten the story of wanting to help his dance instructor friend with cancer, too. Funny, but it played such a big role in his earlier justifications for what he is doing.

More disturbing is the interview with "Sandra," who's all over The DCA Site forums. Apparently, after she was diagnosed with breast cancer but before she discovered DCA, Sandra had chosen naturopathy to treat her cancer in lieu of conventional therapy. From her interview I could not tell whether she had advanced cancer at the time of diagnosis or whether she had an operable, treatable cancer. If the latter case, she was potentially curable by surgery, chemotherapy, and radiation therapy. Forgoing those modalities for naturopathy was in essence choosing death, which is why it always pains me greatly to hear of cases like this. Even if Sandra has metastatic cancer, present treatments offer good palliation. In any case, in the interview, making the repeated point that she is an engineer, Sandra claims that her tumor became softer and shrank by 1 cm. Whether this is an accurate assessment or is significant or not depends a lot on how large her tumor is. Large tumors not infrequently outgrow their blood supply and shrink somewhat during their course; that doesn't mean they won't metastasize or start to invade surrounding structures. Without better data, it's impossible to know whether this is what's happening or whether DCA is having an effect. Moreover, as hard as it is for a non-oncologist to grasp, although it's a promising sign when it happens and we do look at it as indication that a therapy is working, initial tumor shrinkage does not necessarily translate into prolonged survival. Again, only well-designed clinical trials can determine the magnitude of survival benefit conferred by a treatment or if there even is one.

I can understand why patients with terminal cancer might be tempted to try home brew DCA under uncontrolled conditions. I still don't think it's a good idea, but I can understand why they might do it. What I do have trouble understanding is why patients for whom conventional therapy offers real benefits choose a therapy of unknown effectiveness over those of known effectiveness. That being said, one thing I can say with a fair amount of confidence from reading the accounts on The DCA Site is that DCA is certainly not the "miracle cure" for cancer that some bloggers were ignorantly calling it in January. If it were such a powerful, miraculous cure, there would very likely be unequivocal reports of dramatic objective tumor responses by now. There aren't. This observation doesn't mean that DCA is ineffective or that it won't ultimately be found to be useful against cancer, most likely as new ingredient in combination chemotherapy. However, it does bring DCA down to earth, down to the realm of lots of other experimental chemotherapeutics, which often demonstrate no obvious responses in Phase I trials.

The difference between Tassano's "self-experimenting" trial is that there are no controls for other drugs or supplements the patients are taking or even just to compare the treatment group to. There's also no objective data, making the anecdotes I'm hearing well nigh uninterpretable. Worse, as I've said before, Jim Tassano's whole project, egged on by Internet hype, has caused the whiff of quackery to apply itself to this promising new chemotherapeutic drug, conceivably jeopardizing the real clinical trials that will be needed to establish the efficacy, or lack thereof, of DCA. Given that DCA now appears no more "amazing" than any of a lot of other experimental chemotherapeutic drugs presently being tested in clinical trials, it's hard to understand why patients are still so interested in going to such lengths to try it, rather then going to Clinicaltrials.gov and looking for clinical trials of drugs appropriate to their cancer. There are lots of experimental chemotherapeutics that, if made and sold by hucksters like Jim Tassano, would produce results just as disappointing under uncontrolled conditions. In the face of these stories, the mystique of DCA seems to be maintained solely from the glamor of having become known as the cheap "cure" rejected by big pharma.

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)