Whenever I go away for a conference, things of interest to me that I'd like to blog about start happening fast and furious. Indeed, I could only deal with one of them, and I chose to post my challenge to the Paleyist "intelligent design" creationist surgeon, Dr. William Egnor. Now that I'm back, I'll deal with the other major issue that's been a frequent topic of blogging over the last couple of months and bubbled up again into the blogosphere over the weekend.
Remember all the posts that I did on dichloroacetate (DCA), the small molecule chemotherapeutic agent that targets the Warburg effect and seems to have a wide spectrum of activity against tumors in rat models of human cancer, the report of which back in January triggered a blogospheric meltdown of conspiracy-mongering and credulity about a "cure" for cancer that big pharma is keeping from you, even though only animal data shows promise and the drug has never been tested in humans against cancer? Remember how I wrote about Internet "entrepreneurs" claiming to sell DCA for people to use on their "pets" with advanced cancer and how I demonstrated conclusively that that claim was a lie, that the purveyors of false hope selling DCA at The DCA Site knew damned well that people were primarily buying their "Vet-DCA" for human consumption? Remember how "Heather," the "administrator" of the DCA site changed the site, chameleon-like, in response to my criticisms, something that has occurred yet again, so that the site BuyDCA.com features its prominent (and bogus) disclaimer that DCA is not to be used in humans even more prominently?
The mainstream media is finally noticing, as my blog buddy Abel reports, pointing me in the direction of a story from Friday in the Edmonton Journal about the hype over DCA and the unscrupulous and reckless actions of Jim Tassano, who has been revealed as the person responsible for The DCA Site:
Yet Jim Tassano, a biologist in Sonora, Calif., said he created the DCA website in early February because he doesn't want his ballroom dance instructor to die of cancer. The website, www.thedcasite.com, is a direct result of Michelakis's research, Tassano said.
Tassano and a chemist from the University of California have begun making DCA and selling it over the Internet. The buydca.com site says the compound is for experimental treatment for pets with terminal cancer, but Tassano said he knows people are buying it for themselves or family members as well.
"There are unknowns, but at a low dosage rate, if I were a cancer patient, I would take it," said Tassano, 54. "Are there side-effects? Absolutely, but compare that to radiation."
He said waiting for clinical trials isn't an option for dying people.
"What's the worst that can happen here?" he asked in a telephone interview. "Is it fair to let people die and not do anything about this?"
I've addressed this issue before in detail here and in multiple posts about DCA. Such self-experimentation is not only dangerous, but highly unlikely to produce any useful data, barring the small possibility that DCA is truly the "miracle" cure that it is claimed to be. The bottom line is that this "wild self-medication" represents not only a danger to the desperate patients who have fallen for the sales pitch of people like Jim Tassano and the credulous blogospheric hype over the discovery of DCA. It's good to see that Dr. Evangelos Michelakis, the principal investigator who published his findings on DCA in Cancer Cell in January, is on the same wavelength as I am:
"We are concerned," said Michelakis, who set up a website with the U of A saying he doesn't condone or advise the use of DCA in humans. The site has received more than 141,000 hits and Michelakis has received more than 10,000 e-mails from people eager to become involved in clinical trials.
"We absolutely do not support the use of this drug to patients with cancer any way out of a clinical trial. There are a number of risks associated with it, and unfortunately patients and physicians are exposing each other to these risks."
And, contrary to the message that Jim Tassano is promoting at the DCA Site, DCA is not without a significant risk of complications in adults:
In clinical trials to see how DCA works on metabolic disorders, children took the drug and showed no signs of toxic poisoning.
But when the same trials were done on adults, most had to discontinue using it, since they developed severe peripheral neuropathy, Michelakis said. The damage to the peripheral nerves caused imbalance and finger numbness.
While the effects were reversible, Michelakis said if people take DCA while also undergoing other cancer treatments, the consequences could be lethal.
"Most of the anti-cancer drugs that we currently use are neurotoxic themselves," he said. "So a patient who has been exposed to these drugs and now tries DCA might have a severe form of peripheral neuropathy. This patient might have severe problems that he cannot walk or he cannot touch or feel."
Even for those who say they have only six months to live and nothing to lose, Michelakis said it's not worth the risk.
"Of course you have things to lose, because you can die earlier and in much worse shape," he said.
He said self-medicating without proper supervision has broader implications.
"It's a public health threat if you start using on your own and acting out of your own desperate situation," he said, noting that people taking DCA have no mechanism to formally report side-effects and complications. Nor can they know if the compound is pure.
"That's the worst nightmare in medicine, to start making judgments on whether a drug is good or bad based on what any patient will post on a blog. This is the death of medicine and organized research as we know it."
Indeed it is. It's a throwback to the era before the FDA, where snake oil peddlers could sell any "remedies" they wanted and make any claims for those remedies that they wanted, all without any regulation. Patients had no idea what they were getting or whether it would be safe and effective, and the only recourse they had would occur when enough problems cropped up from a patent medicine seller's wares to result in his being run out of town on a rail. But it's worse than that. The Internet and the blogosphere amplify a million-fold the ability of people supporting or selling unproven "cancer cures" by providing a world-wide reach that 19th century hucksters could only dream about.
Michelakis sounds like a good man. He seems reasonable, and he knows what the issues are. 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. Indeed, one reason that we as surgeons are often reluctant to do palliative operations for some forms of abdominal malignancy is because the recovery time could well be a significant proportion of the little time the patient has left, and, if there's a significant complication, the patient could well spend his or her remaining days in the hospital. We try to avoid that and give the patient as much time at home before the end as is possible. In any case, coming back to DCA, peripheral neuropathy can be a particularly nasty complication of some chemotherapy drugs, particularly drugs that block microtubule activity or assembly. Just ask any medical oncologist. It's a dose-limiting toxicity of certain chemotherapeutic drugs like Taxol that can have a severe impact on the quality of life of cancer patients. Dr. Michelakis is absolutely correct: If a cancer patient is already on one or more of the chemotherapeutic agents that can cause peripheral neuropathy as a side effect and takes DCA without telling his or her oncologist, it's entirely possible that the toxicities of the drugs (the chemotherapy and the DCA) to nerves could very well be synergistic.
Unfortunately, Dr. Michelakis has no control over the misguided and ethically very dubious actions of Jim Tassano, the owner of Foothill Sierra Pest Control in Sonora, California, who, while donning the mantle of the patient advocate who is bucking the system to save lives, is even now trying to drum up business by soliciting testimonials on his website from people who have used DCA, all the while regularly altering the content of his site to try to stay one step ahead of the FDA. I definitely feel for Dr. Michelakis. I'm guessing that his conscience is bothering him, even though he's done nothing wrong and has no control over how the story of his discovery has been spun. He's quite correct; if patients can start taking various experimental drugs outside the context of clinical trials, it could indeed mean the death of organized research as we know it. There'd never be a way to definitively find out if new drugs worked because no one would want to sign up for clinical trials. Why should they if they could get the drug outside the context of a clinical trial? Nobody wants to deny dying patients what they perceive to be a shot at a "cure," but, n the end, such an outcome would end up harming far more cancer patients than it would help and, in fact, would be quite unlikely to help even a few.
Similarly, contrary to the claims of Jim Tassano and his supporters on the discussion boards at the DCA Site, a "database" consisting of a bunch of desperately ill self-medicating cancer patients will not produce much, if any, useful data. There are now several examples on these discussion boards of desperate patients are looking at any blips in blood values, regardless of whether the "markers" they are looking at have ever been shown to correlate reliably with tumor burden. In fact, there are very few blood markers that do correlate with tumor burden reliably (CEA and PSA, for example) and even these are subject to many confounding factors and variables. I noted with dismay at least one example of using useless "tumor markers" as "evidence" that DCA is "working," specifically this man, who is looking at upward blips in his serum copper and concluding that his tumor is dying, even though serum copper is such a nonspecific marker that making such a conclusion is unwarranted. There's a reason that clinical trials have such complex and detailed reporting requirements, and there's a reason for double-blinding the trial groups. For one thing, the placebo effect, selective thinking, and confirmation bias will guarantee that most patients self-medicating with DCA will claim to feel better, whether or not there is any objective anti-tumor affect attributable to DCA. Similarly, those who do feel better, whether through placebo effect or not, will be far more likely to report it than those who notice no effect, thanks to the communal reinforcement that is clearly going on in these discussions. Meanwhile, patients measure blood markers that are very nonspecific and view any little glitch in a favorable direction as "evidence" that DCA is working. Well, it may be, or it may not be. Trends are what is important, and an objective observer is needed to determine whether there has been any objective evidence of antitumor activity. The plural of "anecdotes" is not "data," and this is even more true for testimonials, which is all the information in this "database" is. The very reason for the existence of such formalized, randomized, double-blind clinical trials is the realization of how easily humans' thinking goes wrong and to minimize the possibility of these errors producing an apparently positive result when in reality there is none.
Also, not suprisingly, in a case of the classic "pharma shill" gambit, the denizens of The DCA Site's discussion boards are accusing the journalist who wrote the article, of being in the pocket of big pharma. Indeed, they're turning on Dr. Michelakis because he has urged a Canadian pharmacy not to fill prescriptions for DCA for cancer and complaining without justification that they were being quoted without permission. (People, if you post to a public discussion board on the Internet, I have news for you: The newspaper probably doesn't need your permission to publish your words.) It's not an unexpected reaction; they simply don't want to hear the message that this sort of unregulated experimentation is potentially dangerous, almost certainly won't produce any useful data, and is very unlikely to help the very cancer patients engaging in it--a trifecta of reasons why it shouldn't be permitted.
Given this article, I'm hoping that other major news outlets pick up on this story in order to expose the reckless and ill-advised activities of Mr. Tassano. However, I do realize that such publicity could backfire and stoke the demand for DCA all the more, even though more likely than not it will not be anything like a "miracle cure." What people don't seem to realize is that, had DCA been developed by big pharma soup to nuts and shown to have a comparable level of activity against tumors in rat models, it would have been a promising, but utterly unremarkable anticancer drug, at least compared to all the other anticancer drugs that make it as far in the pipeline as animal studies demonstrating tumor growth delay. Lots of drugs cause significant tumor growth delay in animals, as DCA did. Sadly, most drugs that show promise against cancer in animal trials ultimately fail to show comparable activity in human trials. That is a simple fact. Were it not for the whole "cure for cancer" that "big pharma" doesn't want you to know about (or, as Kevin Trudeau would put it, "they" don't want you to know about) angle, few outside of the scientists involved in DCA research and interested insiders would be likely to care that much about it. Certainly, no one would be trying to make home brew DCA to treat their friends with. There's no doubt that DCA is a promising agent that needs to be studied in Phase II trials to determine if it works against common human cancers, but it's not unique and it's almost certainly not a cure.
The bottom line is that the only reason DCA is being represented as a "cure" for cancer by misguided and ethically dubious "entrepreneurs" like Jim Tassano, idiotic pseudoscientists like DaveScot, and a number of alties who seem to think that it is not chemotherapy (it is chemotherapy, by the way) is because DCA wasn't developed by big pharma and big pharma has shown little interest in funding its further development. It makes a great story that alties just love: an abandoned drug that shows promise against cancer in animal experiments but is having difficulty attracting investment dollars from pharmaceutical companies, allowing full expression of their conspiracy theories. Even though it's systemic defect in how drugs are developed and marketed in this country and not any sort of conspiracy, promising preclinical results in rats, coupled with its "unpatentability," coupled with the understandable reluctance of big pharma to spend a lot of money to get it approved, have all combined into a perfect storm, leading to travesties like Jim Tassano's "Vet-DCA" and the even more distressing spectacle of dying cancer patients influenced by Tassano's delusion go to great lengths to buy his DCA.
ADDENDUM: Hot off the presses this morning, a story about a patient who bought DCA but has since decided it's not a good idea to use it. (Hat tip: Matt the Heathen.)
ADDENDUM: Walnut has posted his critique on Daily Kos as well.
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
- Dichloroacetate (DCA) and cancer: Magical thinking versus Tumor Biology 101
- Checking in with The DCA Site
- Dichloroacetate and The DCA Site: A low bar for "success"
- Dichloroacetate (DCA): A scientist's worst nightmare?
- Dichloroacetate and The DCA Site: A low bar for "success" (part 2)
- "Clinical research" on dichloroacetate by TheDCASite.com: A travesty of science
- A family practitioner and epidemiologist are prescribing dichloracetate (DCA) in Canada
- An "arrogant medico" makes one last comment on dichloroacetate (DCA)
Posts by fellow ScienceBlogger Abel Pharmboy:
- 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
- Perversion of good science
- CBC's 'The Current' on dichloroacetate (DCA)
"When all else fails, panic".
I don't have any comment on the main post, but on that video....
*thumps head on desk repeatedly*
"Today on Science Stories, DuPont engineers have created a record-breaking 7 torr vacumn, whatever a 'torr' is, inside my head! They did it by connecting my skull to the only harder vacumn in the universe, the skulls of our Marketing Department!"
Orac, I would like to first apologize for my last post; you do cover this story in a much more detailed and even-handed manner than I gave you credit for. Onto my new points, I generally agree with you that people shouldn't be self-medicating with anything. Having said that, I think that it is not reasonable to expect people with no other options not to try everything they can - especially one based on completely novel results reported in a journal like Cancer Cell. Moreover, as I mentioned in my first post on your blog, the Cancer Cell article was not really about dichloroacetate, but about a more fundamental understanding of cancer qua cancer (hence the title: "A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth"). As you mentioned in one of your posts there is still some debate regarding the relative priority of the metabolic and genetic derangement of cancer cells. I would suggest that the Michelakis, et al. paper, together with other recent papers seem to indicate a more important role for metabolic derangement. I am referring to the paper by Pelicano, et al. regarding the connection between mitochondrial respiratory defects and activation of the Akt pathway. In addition, two recent papers by German (and I think Swiss) investigators report important role for voltage-gated potassium channels in carcinogenesis and tumor proliferation. I have attached the PubMed links to these papers. I understand the concern about anyone trying to self-medicate with anything, but I think that in the fixation on dichloroacetate, you are missing the implication of the Michelakis paper. If they are correct, then I don't think this is like the normal "cancer cure" story that we see all of the time. To the extent there are any unscrupulous entrepreneurs and religious nuts associated with this, let me ask who are the first to latch onto any "cancer cure" story? As you think about that, I would ask that you keep in mind what they say about broken clocks.
Very nice comprehensive post. I'm glad you commented on your rationale about palliative surgery in the end-stage cancer patient. I was visited by a commenter who asked similarly how DCA could be of any harm. While I neglected to note your point about additive peripheral neuropathy with chemo drugs, I did respond that cancer patients often have compromised hepatic and renal function. DCA has the potential for toxicity in both organ sites and I'd predict that phase I trials show that DCA is not exactly as safe as it appeared for other indications (remember readers, while DCA has been in clinical trials, it has never been studied systematically in cancer patients.)
The pharma shill accusations toward this award-winning health and education reporter defy logic. As you point out, there are laws and processes to protect people as a result of deadly drug misadventures in our history; Jodie Sinnema's consultation with regulatory and professional authorities illustrates that she understands unapproved drugs far better than the Edmonton docs prescribing DCA or the pharmacist who was filling the orders.
Orac - Thanks for staying on top of this, and keeping us in the loop.
If they are correct, then I don't think this is like the normal "cancer cure" story that we see all of the time.
See this, for example, in which I describe how, not only are there cancer cells that are immune to the Warburg effect, but whose ability to metastasize to the brain might be dependent upon their losing the Warburg effect.
The Warburg effect is no different than activated oncogenes, angiogenesis, etc. It's another mechanism behind tumor cell malignancy that can be exploited and that, I predict, tumor cells will be able to evolve resistance to. A mere eight years ago, we thought that targeting tumor angiogenesis would be the "magic bullet" against cancer. Now we know better.
Once again, my prediction is that DCA and other drugs targeting the Warburg effect will be useful against some tumors, but that none of them will be a "cure."
I agree with everything you say (about stupid conspiracy theories, the distance to go with DCA as a possible chemotherapeutic agent, toxicity etc etc).
I have widely metastatic (although indolent) breast cancer. I recently finished 6 months of palliative Taxol (and have been lucky enough not to get peripheral neuropathy, btw). I note your two reasons againts self-experimentation; that it is "not only dangerous, but highly unlikely to produce any useful data".
Do you believe that these (or another reason) provide sufficient philosophical justification for preventing patients - including me - from self-experimenting? And if the answer is "no", do you believe that regulations should prevent people like Tassano from making the wherewithal for self-experimentation available?
I don't see how you can answer "yes" to the first question without also claiming that the majority (perhaps even the vast majority, given that it can't possibly be ALL) of patients are too stupid or too credulous to be able to make such a risk decision for themselves. That may be so. But it's a big big claim.
(No, I'm not goinmg to self-experiment, BTW).
There is an additional article in the Edmonton Journal this morning.
DCA is getting a lot of coverage here in Edmonton. It is a strange phenomenon. There will always be the snake-oil peddlers, and there will always be those who believe the snake-oil is the cure "they don't want you to know about". I'm sure that after DCA, there will be others.
I really feel the desperation of Michelakis here. What approach do you take to convince patients to wait for a trail, when their own doctors and pharmacists are telling them otherwise? How can you warn people about the dangers of DCA without fanning the flames of hysteria further?
Philosophically, it is very difficult to argue against a patient's right to experiment with anything that may prevent of delay his/her fast-approaching death. However, the main argument against Tassano, who takes advantage of the patient's misfortune to profit, is that he is pushing a product that no one tested to verify its identity or purity. Such action is reprehensible.
I'm sad to report that the DCA craze has now struck home, showing up in the "Science" section of my campus newspaper. The article wasn't quite as bad as some of the ones I've seen (no accusals of a big conspiracy, but it did imply that the reason it wasn't being picked up was because it wasn't patentable), but it still had its fair share of flaws.
I sent them in a letter to the editor about it, explaining how the situation really was (I have you to thank for most of the info on it. If I hadn't have been reading your blog, I wouldn't have known there was any real problem). Unfortunately, they didn't publish the letter this last week, so I'm not really sure where they stand. Sometimes it takes them an extra week to fit letters in, or it could be they just didn't want to publish my dissenting view.
But unfortunately, even if my letter does get published, it's possible that it's too late and the damage has been done; not everyone who read the initial article is likely to read my letter, and even for those that do, I fear some might have already bought their own DCA (not too likely; universities aren't known for having a high number of desperate cancer patients, but there could be some).
I had seen the breast cancer brain metastasis article when you posted it before, and I understand your point in that regard. However, I think that that point seems to depend on the mitochondrial function being an all or nothing proposition. I refer you to page 1474 of the brain metastases immediately under the header regarding oxidative phosphorylation where they state "BCM2 brain-derived
cells seem to use primarily aerobic glycolysis, coupled to the TCA
cycle and oxidative phosphorylation, to generate energy for cell
growth." That is, oxidative phosphorylation, etc. was upregulated, but the cells still relied on aerobic glycolysis (the so-called Warburg effect) for most of their energy. I think that the question would be: does any mitochondrial respiratory activity (which you correctly note the brain metastases paper reported) imply that the mitochondria in such cells will not be susceptible to the effects described by Michelakis, et al. regarding the Kv1.5 channel, etc. Put another way, could mitochondria in cancer cells engage in oxidative phosphorylation without normalizing the Kv1.5 channel discussed by Michelakis, et al. As I said, I think I understand your point regarding the breast cancer brain metastases, but I don't think that that paper is decisive, even in the case of breast cancer brain metastases.
As I noted earlier, you had mentioned the long-standing debate of which comes first the metabolic or genetic derangement of cancer cells. I would appreciate hearing your thoughts on this in light of the Michelakis, Pelicano, and the two German papers. While certainly not conclusive of anything, this does seem like a recent accumulation of evidence pointing in the direction of a more fundamental role for metabolism/mitochondrial function than had previously been suspected.
"not only dangerous, but highly unlikely to produce any useful data". Do you believe that these (or another reason) provide sufficient philosophical justification for preventing patients - including me - from self-experimenting?
It's not just that it's unlikely to produce useful data, it's that it's unlikely to work. Even if DCA really works, before clinical trials it's impossible to know what the proper dosage is to actually have a positive effect in humans.
"...provide sufficient philosophical justification for preventing patients - including me - from self-experimenting?"
Because if it works, we can't tell that it worked. Because if it doesn't work, we can't tell that it didn't work. Because if it's toxic, we can't tell if it's toxic. Philosophically that means that the patient after you is in the same information vacuum that you are in. That next patient has gained absolutely nothing from your experience. Nor have all the patients that come after.
That second and subsequent person/s may in turn pay forward the 'favour' by self-experimenting rather than entering a proper clinical trial. And the cycle perpetuates. In the long run this causes direct pain and suffering to many thousands of people REGARDLESS of whether DCA works or not. The only people who win are the peddlers. They get rich. Everybody else gets nothing or loses from the deal.
And Coin made a good point about the dose- even if it does work.
The big problem I see with self-experimentation is, who is going to be responsible for, and support, those patients who decide to take DCA before the clinical trials are out? Who is going to take demographic/pathological data on who it succeeds and fails in? If it fails for a patient and they die of their disease, who is going to assess what (if any) effect the stuff had on their tumour? If a subset of patients fails, who is going to identify the confounding factors that might have interfered with the DCA? Because if nobody gains any information out of this, the risks those patients took and the deaths they died will have been wasted.
Who is going to determine just how much you should take?
Who is going to take responsibility to assess you and ensure that your tumour burden really is shrinking? Or is the fact that you simply feel better good enough for the person who sold it to you?
If the person who provides it to you and the person who looks after you while you take it are two different people, I'd question the ethics of the provider. If Mr Tassano wants to sell you this stuff, he should also wear the legal and moral responsibility if something goes wrong. Has he undertaken to do this? Or will he wash his hands of you and say that you knew the risk you were taking? Has he even admitted to you that there could be side-effects, and made at least an attempt to explain what these are?
Just some food for thought.
But if you're going to die anyway ... well I understand why some people would go ahead and take the risk."
Abel brings up an interesting point:
Has anyone even mapped the hepatic metabolic pathways of DCA? Might it inhibit or oversaturate any CYP enzymes, especially ones that might play a role in the metabolism of chemotherapeutic drugs? Granted, I doubt that many chemotherapeutic drugs work via active metabolites...but on the other hand, many opioid painkillers do (codeine to morphine, hydrcodone to hydromorphone, etc), and cancer patients are likely to be taking these drugs. Imagine the problems caused if DCA were to inhibit the main pathways necessary to create the active metabolites for these drugs, and patients were unable to control their pain symptoms? Or it could prevent the active substances from being metabolized and excreted, resulting in risk of overdose.
All possible ways that DCA could make things worse, even for the most desperate patients.
Granted, I doubt that many chemotherapeutic drugs work via active metabolites...
Off the top of my head, I can think of at least one chemotherapeutic drug that does: Cyclophosphamide. The drug is converted in the liver to 4-hydroxycyclophosphamide, its active metabolite.
While I certainly appreciate the desire of a dying person to improve their situation anyway possible, experimenting with DCA soudns like a bad idea. It's a drug with known side effects. We don't have any clue of what dose would even help and it has the very real possibility of negative interactions with current palliation.
As awful as the proposition is for folks with terminal cancer and no other curative options, it may be better the maximize the time one has left instead of wasting those last few months on a drug that could do more harm than good.
Phase 3B melanoma dx 2/06, currently NED. WLE and SNB (positive micromet): Cost $15,000. Two PET/CT scans: Cost $10,000. Other Onc, Radiologist and Hospital: Cost $1500.
Opted for obs and I'm taking self prescribed supplements with the advice of Naturapath: Cost $500 per year.
Could be taking DCA, if I chose to, I guess, at a cost of $700 per year.
Remind me who is getting rich of my disease, again?
Right on Chester:
Cost of the anti angiogenesis supplement to my chemo (not the chemo - just the supplment) for stage 4 colorectal cancer 50,000. Additional life expectancy increase as a result - 6 months.
Risks ? - Warnings on the box:
Treatment with xxxxxxx can result in the development of a potentially serious side effect called GI perforation. In clinical trials, these events occurred throughout the course of treatment and in some cases resulted in fatality.
Hemorrhage: Some people receiving xxxxxx with chemotherapy for lung cancer experienced hemoptysis (a severe bleeding problem at the site of the tumor). In some cases, this event resulted in fatality. People with recent hemoptysis should not receive xxxxxx
In clinical trials, additional serious side effects in patients receiving xxxxx with chemotherapy included strokes or heart problems (blood clots), hypertensive crisis (severe hypertension), reversible posterior leukoencephalopathy syndrome (nervous system and vision disturbances), neutropenia (a reduced white blood cell count that may increase the chance of infection) and infection, nephrotic syndrome (a sign of severe kidney malfunction), and congestive heart failure. The most common adverse events seen in patients receiving Avastin with chemotherapy across all studies were weakness, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, loss of appetite, mouth sores, constipation, upper respiratory infection, nosebleeds, difficulty breathing, skin irritation, and proteinuria (a possible sign of kidney malfunction).
Tell me again about the reversable neuropathy and the 600.00 a year cost of DCA.
I can only empathise with your situation.
That would be your insurance company and possibly the pharmaceutical companies getting rich. Also your naturopath. It certainly isn't medical researchers getting rich- I can assure you.
This cost problem and the 6 month 'benefit' has nothing to do with showing that DCA works. It's just showing you the cost of managed care in action coupled with the lack of good treatment for your condition. The rest of the world thinks managed care is nuts and uses the USA as a prime example of how to not manage health. However, none of that information helps decide if DCA is any good for cancer, completely useless, or worse toxic as hell.
Chris then lists the side-effects associated with a particular drug. It's worth noting that the side-effects are all listed as having been discovered in CLINICAL TRIALS. You need clinical trials to evaluate treatment effectiveness and what the side-effects are.
What are the side-effects of taking DCA in addition to having cancer of any type with or without additional therapeutics which have previously been shown to work in clinical trials? The answer: UMMMMMM.... It could interact with cancer/s in some way that's particularly harmful or it might interact with one of the cancer treatment drugs. How can you tell? A properly designed clinical trial.
In addition because DCA isn't properly regulated there may or may not actually be any DCA in the formula you are taking. (see also Coin's comment on dose finding)
I'm not saying definatively that DCA doesn't work. I don't know. ORAC doesn't know. Nobody knows. We're in an information vacuum until people start behaving responsibly with this potential treatment.
Please don't make me read a whole article about DCA without seeing my name until the very bottom. I was highly distressed thinking that you didn't love me anymore then right about when my emotions were so crushed I was thinking about ending it all I see the gratuitous mention of pseudoscientist DaveScot at the end. It brought a tear to my eye.
He's quite correct; if patients can start taking various experimental drugs outside the context of clinical trials, it could indeed mean the death of organized research as we know it.
Could you possibly be any more melodramatic? What a drama queen. Get a grip you anal retentive windbag. These people are doing something out of your control and it pisses you off. That's like SOOOOO obvious. If you don't like what they're doing don't read about it. It's their lives not yours you insufferable arrogant prick.
I had no idea you were still even paying attention. As much as you try to dismiss me, you keep coming back, still as idiotic as ever, looking for just a little drop of Respectful Insolence (in your case, however, not-so-respectful) sent your way in the form of a mention of your 'nym.
Dr. Michelakis put it in somewhat stronger terms than I would have before I read the article; then when I read his words I realized that he's probably right. Oh, and do come back later today; there's one more article that I'm sure you'll really like...
"It's their lives not yours...."
True enough. But if they're folks you care about, then you may not want them to spend the last months of their lives unable to "walk...touch or feel," in Dr. Michelakis' words. If there was greater assurance that DCA would be effective for particular cancers, or even a better idea of what the treatment protocol should be in order to maximize effectiveness and minimize risk, such concerns might be outweighed. But I haven't read anything that makes me (as an inexpert layperson) feel we're at that point yet.
then you may not want them to spend the last months of their lives unable to "walk...touch or feel," in Dr. Michelakis' words
If there were any data at all indicating this is a possible side effect of DCA at chemotherapeutic dosages used for decades in treating lactic acidosis, which are the same as were used in Michelakis' rat study and substantially more than anyone is trying in self-medicating experiments, then I'd say this warning should be shouted from the highest hilltop. But the fact of the matter is that patients were on DCA for YEARS without any substantial adverse effects, no adverse effects anywhere near what most cancer chemical, radiation, and even surgerical therapies engender for just a single treatment. There is simply no empirical data to substantiate these chicken-little claims of horrible side effects and decades of use with humans to substantiate claims that side effects are small to nothing even after years of use. Some patients who were resistant to DCA's effect at lowering lactic acid were even given short term doses of 1500mg/kg of DCA, which is 30 times the amount that any self-medicators on the DCA site have reported using, and it didn't kill them. Compare that with the known effects of conventional cancer treatments.
I'm all for doing this through clinical trials but Mikelakis' has known about this for two years (his US patent application on the DCA treament method was applied for in 2005) and no phase one trial has even started yet. Even now, several months after the public disclosure, no clinical trial has begun. 1500 people die of cancer every single day that passes by. How many more have to die because this drug doesn't hold enough financial interest for the usual suspects to begin clinical trials should people expect to be a reasonable number? Maybe this isn't a cure but the few initial results from just a few weeks of treatment are showing enormous biological response in cancer markers. Moreover, there are a few physicians self-medicating and reporting the results. One was disturbed because his PSA-DT decreased to an unprecedented 20 days when he expected it to increase. After doing some research into how PSA gets into the bloodstream it seems likely that this is the result of a cancer integrated into prostate barrier cells that normally keep PSA out of the blood stream dying and opening up the PSA floodgate. As well, a cancer cell undergoing apoptosis will split into many smaller membrane enclosed pieces for consumption by other body cells. That splitting up will increase the membrane surface area that PSA leaks through and be reasonably expected to get more PSA into the serum. If only this were no expenses spared clinical test we could be using weekly PET/CT scans and something like M30-Apoptosense to get rid of the ambiguity. Too bad no one wants to pay for the trials since no one stands to make any money from this drug. Another self-medicating physician with sarcoma who got blood tests and PET/CT scan after 24 days reported that his alkaline-phosphate level which was highly elevated before DCA had dropped to normal and his primary tumor had shrunk and showed a decrease in PET activity. His metastatic tumors continued to grow but they grew 10 times slower than the prior month and due to a lag of one week between getting a PET/CT scan and starting DCA the metastases might have actually been completely arrested shortly after beginning DCA treatment. It would really be great if there were more resources than single patients on their own could afford but this is the best we have to work with and again I reiterate that the medical establishment has had two years to begin clinical trials and still none have begun. That's simply outrageous. If this drug were patentable trials would have begun two years ago. Clinical trials may NEVER begin under these circumstances.
Now as to the purity of Tassano's product at buydca.com I advised him a month ago to get an independent analysis done on his product and publish the results. He did. The spectrogram results are posted on his website and his product is purer than anything else available. Moreover, he gave the name and credentials of the chemist who developed his novel NaDCA synthesis. The chemist has a long history of developing synthesis methods for FDA-approved chemotherapeutics and is a university professor of chemistry. Everything is being done right as well as can be done under the difficult circumstance of having a drug that has no profit potential to pay for traditional development protocols. Tassano isn't going to get rich off this. He's charging a very modest amount for his product, far less than any other source of similar purity, and says he owes this to the novel synthesis process developed by the cancer drug chemistry professor.
Contrary to the exagerated claims by Orac, Abel, and Michelakis' this isn't the death knell of legitimate drug development. It's a fluke that this particular drug can be made available outside the clinical test process. And still there are millions of people who would gladly sign up for any clinical trials of DCA if only one were there to sign up for. There are many benefits of a clinical trial that people can't get through self-medicating so even though in this case the drug IS easily and inexpensively obtained by purchasing it from buydca.com there still won't be any lack at all for clinical trial volunteers. If a clinical trial ever gets started, a BIG if, then you'll find I'm absolutely correct that this self-medicating phenomenon is no impediment to the usual process. It's simply a response to lack of action in the usual process that's made possible because of the simplicity of DCA manufacture and no one owning a patent on the drug that can limit its availability.
Another self-medicating physician with sarcoma who got blood tests and PET/CT scan after 24 days reported that his alkaline-phosphate level which was highly elevated before DCA had dropped to normal and his primary tumor had shrunk and showed a decrease in PET activity. His metastatic tumors continued to grow but they grew 10 times slower than the prior month and due to a lag of one week between getting a PET/CT scan and starting DCA the metastases might have actually been completely arrested shortly after beginning DCA treatment.
I've already addressed this fallacious interpretation that this patient's observation says much, if anything, about whether DCA is working in a post that is scheduled to autopost later today.
Why the observation you describe is probably meaningless with regards to deciding if DCA is doing anything in this patient comes straight out of Tumor Biology 101, and, not surprisingly, you flunk.
Off to the O.R. for my afternoon cases...
I don't see any such link on the BuyDCA website. Can you actually post it here so it can easily be critiqued?
In the world of economics we have something called "cost-benefit analysis." As an extremely well-educated and intelligent individual, I'm sure you are familiar with it.
Are you claiming that, for all (or even most) individuals with cancer, the risk-return calculations make it a bad bet for them to try DCA - or any other drug with a postulated anticancer mechanism, which may or not be effective for their particular disease, but which has manageable side effects - under their doctor's supervision?
It doesn't strike me that you are.
So you must be claiming that there is some societal gain from preventing individuals from making their own decisions on this matter. For example, if cancer was a communicable disease to which DCA therapy could induce resistance, the societal cost of leaving individuals to make their own choices would be obvious.
One potential argument of this sort is that if DCA (or, again, any untested drug) is available freely, no one will sign up for a study that tests its efficacy, which will thus never be known. At least not to the scientific standards you prefer.
Perhaps. But if this is an actual practical problem, surely you could just impose a lottery which forced not all potential patients, but only the number you need for the study, to submit to a blind program in which only half got the drug. This would be a Pareto optimization - improving outcomes for some but not all. Moreover, the patients in the lottery could be financially compensated by those who escaped it.
All this, I'm sure you believe, is "unethical." Again, perhaps. If you follow a strict set of ethical rules laid down 2500 years ago and interpreted by the sages, and believe that everything allowed in these rules is good and everything else is bad, no one can convince you otherwise. But this seems more like the MO of a priest, not a scientist. If ethics are not subject to simple logical concepts - like risk analysis and Pareto optimization - how can one pretend to impose them on others?
The problem is that there is another explanation for your perspective and that of the medical industry as a whole, which as I'm sure you'll agree is quite uncharitable.
This perspective is that the effective result of medical regulation is not to optimize risk-adjusted outcomes for patients, but to optimize the prestige of the medical profession.
When prestige can be gained by optimizing risk-adjusted outcomes, as of course it often (in fact, usually) can, there is no conflict of interest. But it is impossible to suggest that cases do not exist in which these very different interests conflict.
In our society, when they do conflict, whose interest wins? My impression is that it tends to be the interest of the profession.
Certainly, if you applied the rule that 100 patients should die for lack of a drug that would save them, rather than 1 patient die as a result of taking a drug that kills them, or waste his or her own savings on a drug that is worthless and ineffective, you would end up with a system very similar to the one we have now.
It is also interesting to note how different the regulatory system is for surgery than for drugs. Is there some ethical justification for this? Or is it just a result of history?
For more unethical thinking along these lines, check out fdareview.org.
Perhaps. But if this is an actual practical problem, surely you could just impose a lottery which forced not all potential patients, but only the number you need for the study, to submit to a blind program in which only half got the drug. This would be a Pareto optimization - improving outcomes for some but not all. Moreover, the patients in the lottery could be financially compensated by those who escaped it.
All this, I'm sure you believe, is "unethical."
Not just me, but pretty much every bioethicist I've met would almost certainly say that your proposed scheme is highly unethical. Two of the most important precepts of clinical trials ethic as laid down in the Belmont Report and the Common Rule are that there must be no coercion used on or undue inducement that might unduly influence the judgment of potential subjects to act against their own best interests; what you propose sounds like it has both elements. It's an appalling idea, whether you realize it or not.
It also wouldn't work on sheer practicality. How, exactly, are you going to "force" anyone into this lottery anyway if DCA is already widely available through people like Jim Tassano? They'll just go to other sources or buy it and take it anyway if they suspect they are in the placebo group. Again, your idea is not a very good idea at all.
Just some thoughts, and as I'm a layperson, I have no doubt they're probably quite foolish - but here goes nothin':
My impression of what we have right now with regard to DCA is (1) no clinical trial; and (2) a bunch of folks accumulating anecdotes, where the plural of "anecdote" is not "data." Just wondering whether there's sufficient information available on how to set up a clinical study so that the people who are currently self-medicating could in effect form a cooperative clinical study, with well-defined protocols (that might be mailed to individuals and published on the Web) and careful data collection. People who did not wish to take the risk of self-medicating with DCA could form control groups.... This would not prevent a "real" clinical study from taking place, but it might allow those who don't want to wait to provide more helpful information if they're so motivated.
I'd be interested to hear why these preliminary thoughts are incredibly stupid/thought-provoking/what-have-you.
Arguments ad authoritatem ("most bioethicists") are not generally considered worthy of a scientist. And ad authoritatem reasoning about ethics strikes me as especially imprudent.
Institutional ethical judgments are very much the product of history. They tend to change over time. Nine out of ten Jesuits agree that abortion is evil. If we've agreed to let the Jesuits decide, well, abortion is evil. But who are these Jesuits? How did they get their jobs? Exactly the same question could be asked of your "bioethicists."
Ethics in today's society is a political construct. To put it very baldly, it is simply a product of military history. We made bigger and better bombs than the Nazis and we outlasted the Communists. So we think A is ethical, B and C are not. If the fortunes of war had been different, all the "bioethicists" you could shake a stick at would have very different opinions.
Not that I'm unhappy that the Nazis and Communists lost. As a liberal Jew, quite the contrary. But when you turn over your ethical judgment to these coincidences of history, you open yourself to quite a number of mistakes.
You are already coercing an entire society. I suggest - not as a practical matter, but as a thought-experiment (because I see no evidence that finding a sufficient quantity of human guinea pigs has ever been difficult, especially if (horrors) you are willing to pay them) - that it is better to apply the same level of coercion to fewer rather than more.
And you refer me to a committee. Or two.
Or to a long-dead prophet. Primum non nocere! Cost-benefit analysis, circa 2500 years ago. Just because it's ancient and revered doesn't make it wrong. But it doesn't make it right, either.
I mean, geeze, if this was the right way to think, why even bother with this science stuff? I'm sure all these topics are comprehensively covered in the relevant papal encyclicals.
What you fail to realize is that history affords many, many, examples of well-intentioned and brilliant scientists who, in large numbers, committed what we now recognize as monstrous ethical errors. And did so not because they questioned the ethical conventions of the society they lived in, but because they followed them.
Unless you take responsibility for your own ethical views, and are seriously willing to consider the possibility that the politically constructed ethical conventions of the society you live and work in are in fact themselves unethical, you run the risk of falling into exactly this category.
In some ways this is like gambling. You might win the lottery and become a multi-millionare, or you might lose everything that you have bet. Is it "ethical" to encourage people to gamble, as in advertising? Presumably the answer is yes because it it done all the time. Or how about encouraging people to smoke via advertising? Presumably that is "ethical" too because it is allowed to continue.
The issue of a "lottery", is that before the results are in, it is not known if DCA prolongs life, or shortens it, for which patients under what conditions. Has everyone seen the meta-analysis of supplemental antioxidants in JAMA?
Supplemental antioxidants increase mortality. I have no doubt because the specific state of oxidative stress is a "setpoint" issue, and excess antioxidants are something that need to be metabolically destroyed (at some cost, likely the source of the increased mortality).
Without clinical trials, we could be in the same situation with DCA that we are with supplemental antioxidants. Billions were spent on them because everyone "knew" they were good for you. Well, they aren't "good" for you.
If "saving lives" were the goal, we wouldn't spend $100k for 6 months of bedridden "life" extension, we would spend that money on miserable/starving/dying children in Africa and get multiple lifetimes worth of "saving lives" for the same money.
The cost of a clinical trial for a new drug or treatment is an enormous barrier to entry. The only drugs or treatments that even get a shot at being tested are ones that are potentially lucrative enough to be a reasonable investment. If the drug can't be patented, or if the target population can't pay for it, our private system of drug development can't develop it.
But that is a financial/business constraint, not a scientific/ethical constraint.
Another constraint is our legal system. What happens if someone takes DCA and decides that it "injured" them and decide to sue? A "sympathetic" jury might award millions irrespective of the science behind it. Dow Corning went bankrupt with no real scientific evidence that silicones are harmful, either before or since the trial.
I think that is the likely outcome of this DCA stuff. Once the promoters of it make "enough" money to be considered a "deep pocket", they will be a target of a class action lawsuit. That will end the use of DCA for a generation. If DCA is actually a reasonable treatment, how many will die during that period? How many women have had to forgo silicone breast implants?
If you think a "clinical trial" is expensive, just wait until there is a "judicial trial". At least a clinical trial give us data that is useful.
And you think this system works well? You wouldn't change a thing about it?
I don't think the system works well. But I don't think it is something that can be fixed piecemeal. I don't know of a path that will take us to a state where things will work well.
It is a classic "tragedy of the commons". Since DCA can't be patented, no one can "own" the use of it for treating cancer, so no one can recoup the cost of a clinical trial to see if it actually works or not.
But that is not a "scientific" or "medical" issue.
I have no doubt that there are many good and effective treatments that cannot be used (by doctors) because they have not been put through the gauntlet of a "clinical trial".
Because physicians are considered "professionals", they are required to conform their professional conduct to the "standard of care" that is appropriate to their profession. If they don't, they open themselves up to enormous personal liability, irrespective of whether the non-standard treatment is harmful or helpful.
Thanks for your sensible and well-informed response. But I will direct you to my comments above about the conflict of interest between the prestige of the profession and the goals of the patients.
I can think of such a path: returning to the regulatory system this country had in 1907.
Of course, this would mean that (a) quacks would flourish, and (b) that there would be, as there was in 1907, no precisely defined line between quacks and physicians.
But as for (a), don't they already? Hello, "alternative medicine"?
And as for (b), there is no precisely defined line between food and feces. So here we have public health regulations that prevent swishy restaurants from serving up a pile of rat droppings on a shiny white plate, and we are all eternally grateful to the State for saving us from this terrible fate. Said State, however, has not seen fit to prohibit the more intrepid of its serfs from buying airline tickets to, say, Thailand, where any fool can cook a plate of food and serve it for a dollar. I wonder how we survive - or did, for that matter, in 1907.
My father has a glioblastoma and has, in the view of his oncologist, a few weeks to a few months to live. He cannot walk. He has no quality of life. He is not being treated. Is there any harm to a "Hail Mary" here by trying DCA? My father dying without trying DCA won't add to the body of knowledge out there about DCA. His death without trying DCA won't increase the likelihood of formal trials. While I do find it disgusting that The DCA Site does not explain who they are (I was wondering... My sister-in-law who found the site thought it was connected with the University of Alberta), and this brings all the information I have read on their site into disrepute, I cannot get away from the fact that trying something is better than trying nothing. I would appreciate your views - but I am not interested in views regarding the societal good which ignores the fact that there is no benefit to society from my father dying a few weeks after his 60th birthday...
Over a week has gone by and nobody has responded to my posting. I hope you're all just busy and haven't checked this blog site, rather than just not responding because you can't find an argument against my father trying DCA and don't have the courage to say so. Well, it looks like we're not going to try it. My mother is afraid that it may just work well enough to prolong a fight that would likely be futile anyway. While my mother doesn't want my father to die, she would readily admit that she is a quitter when the chips are down. I have to admit, it is easier to accept the inevitable and give up rather than to face a long, hard fight you'll probably loose anyway.
On the other hand, if my mother had some support from the medical profession - someone willing to discuss the plusses and minuses, someone willing to consult intelligently from a personal, rather than a detached clinical perspective, she may have had enough information to make a different decision. Congradulations all you courageous doctors and scientists finding it so easy to stay detached and cheer from the bleachers.
I'm sorry about your father. However, if you've read all the copious verbiage that I've written on the subject (it's in all the links at the end of the post) and I still haven't convinced you that self-experimentation with DCA is a bad idea and that even terminally ill patients always have something to lose, then nothing additional that I say is likely to convince you now.
I would like your thoughts about this:
I read that dichloroacetate may act as a tumor promotor:
What do you think? May DCA actually worsen cancer instead of treating it?? In particular liver cancer?