Respectful Insolence

It’s been a long time, been a long time,
Been a long lonely, lonely, lonely, lonely, lonely time.

- Led Zeppelin

Not nearly long enough.
- Orac

Some rats never die, it would appear.

You may recall last year, when I spend a considerable amount of verbiage writing about a promising cancer drug called dichloroacetate (DCA). There were many reasons. One reason was that the drug was being represented as a “cure” for cancer that big pharma wouldn’t fund because it was outside of its patent. There was also plenty of fascinating cancer biology there to discuss, given the mechanism by which this drug works. But what made this story compelling and disturbing was the entry of a do-it-yourself entrepreneur named Jim Tassano, the owner of a pest control company in Sonora, California, decided to have the chemical manufactured himself in order to sell it to cancer patients. Actually, he claimed he was selling it to pets only, but it was incredibly obvious from delving into the discussion forums at Tassano’s website that the real purpose was to sell the drug to human cancer patients. There, false hope and magical thinking about cancer, along with massive misconceptions about cancer biology, were the order of the day.

Ultimately, Tassano’s disingenuous “we’re not selling this to people” (wink, wink, nudge, nudge) caught up with him, and the FDA shut him down about a year ago. The reaction was predictable in that Tassano’s supporters claimed that he was being shut down because he was “making a cancer cure available to the people.” Never mind that, as I put it, DCA was promising as a new chemotherapy drug to add to our armamentarium, but it was by no means a “miracle cure” of any kind. In the meantime, DCA finally reached clinical trials in cancer patients in October. Indeed, when last I left this topic several months ago, I thought that the saga of Jim Tassano and his attempt to do an end run around the clinical trial process and make some money on the basis of claims not justifiable on the basis of science was over.

I was wrong. He’s back, and, even though I had planned an entirely different topic for today (anyone see the vitamin C study last week?), but this one takes precedence because of its history here. Besides, I’m annoyed:

A controversial website marketing a promising yet untested treatment for cancer is once again running after U.S. officials shut it down last year.

“We ship internationally, everywhere in the world, except the United States and its territories,” reads the site’s home page, www.buyDCA.com.

The U.S. Food and Drug Administration ordered the California-based operation closed last summer after its owners began selling the drug, dichloroacetate, or DCA, as a cancer treatment.

The marketing efforts followed developments here in Edmonton by University of Alberta researcher Evangelos Michelakis that showed DCA — a common and cheap drug — shrinks tumours in rats.

That’s right, Jim Tassano’s BuyDCA.com is back, and it’s a bigger scam than ever. Apparently Mr. Tassano has hired some lawyers to scrub his website of any claims that might get the attention of the FDA. Here’s what the front page says:

DCA is available for purchase, worldwide.

However, at this time, we cannot ship into the United States or its territories.

The World’s Purest and Lowest Priced DCA

The leader in DCA, BuyDCA.com makes the purest and lowest priced DCA available.

BuyDCA.com’s Sodium Dichloroacetate (DCA) is 99+% pure and is made with our patent-pending synthesis process. There are no organic solvents used in making BuyDCA.com’s dichloroacetate salts.

Notice how there is now no mention of why one would want to purchase DCA, although there are lots of mentions of being able to ship it internationally to anywhere other than the United States. This makes me wonder: Where is Jim Tassano? Is he still in California? It seems likely, because he appears to be positioning himself as selling DCA for export and thinks he won’t get in trouble as long as he doesn’t sell to anyone within the U.S. He’s not fooling anybody, though. All it takes is a visit to his other site, TheDCASite.com and its discussion forums to realize that Tassano’s selling DCA for the same reason he always sold DCA: To separate desperate cancer patients from their cash.

Showing up prominently on TheDCASite.com is an announcement that the site had been hacked and that data had been lost, which perhaps explains why many of the links to discussion comments in my old posts about DCA appear no longer to work. It still doesn’t matter, though. The forums may be sparse, a mixture of very old posts from last spring and new posts with little in between, it’s fairly easy to see that the same sorts of discussions are going on. Worse, however, is an “observational” report linked to from TheDCASite done by Medicor, which, as you might recall, is a practice run by a husband and wife, one of whom is a physician and the other of whom is a family practice doctor. Last year, they decided to get on the DCA train and start dispensing it outside the auspices of a clinical trial. The result of their “experrience” is this “report,” which is a travesty and has nothing to do with clinical trials. In the report, Medicor claims a 60% response rate for DCA, but does not define a a clinical response. But first, the report starts out, of course, with a disclaimer:

This is our second DCA data analysis update. This data is not from a clinical trial. It is based on a review of patients we have treated so far with DCA. Since our primary purpose is patient care and not data collection, this data may not meet the rigorous criteria employed in clinical trials. It may not be generalizable and should be interpreted with caution. We are sharing this data to help further patient care and knowledge.

No, they’re sharing this “data” for marketing purposes and nothing else. Otherwise, they would have tried to publish their clinical observations as a case series in a peer-reviewed journal, rather than posting it in the form of a dubious and sloppy report on their website. In any case, their “experience” includes a hodge-podge of many different cancer types, with no one tumor making up more than 22% of the total, and that was lung cancer. Here’s how Medicore describe its “data”:

Based on this criterion, out of the total of 180 patients treated, we have been able to evaluate 90 patients (50%) as of March 20, 2008. The other 90 patients were not evaluated for the following reasons:

  • 52 patients (58%) died within 4 weeks of starting DCA due to unrelated reasons (we do not deny patients access to safe treatment based on the stage of illness, and some of our patients are very advanced stage).
  • 22 patients (24%) have recently started DCA treatment (< 4 weeks) - their data will be available soon.
  • 16 patients (18%) stopped DCA after < 4 weeks for various reasons. Three patients started other treatments, 2 had other medical reasons (like admission to hospital), 2 had side effects (confusion), 1 had non-medical reasons, and 8 were lost to follow up.

The death rate within four weeks strongly suggests to me that the selection criteria at this clinic were not particularly rigorous. Moreover, it’s truly disingenuous to say that these patients died of “unrelated” reasons. No, they did not die for “unrelated” reasons. True, DCA almost certainly didn’t kill them, but the reason they died was also almost certainly not “unrelated” to their cancers. Indeed, they almost certainly died of their cancers or of complications from the progression of their cancers. Trying to paint the cause of their demise as “unrelated” is akin to implying that these patients all walked out of the Medicor clinic and met their demise by getting hit by the proverbial bus. This description also causes another concern. That 52/180 (28.9%) of all patients died within four weeks of starting implies very advanced diease. Such advanced disease in the patients on the study leads to the concern that these patients, in being given DCA, were not being given sufficient access to palliative therapies appropriate for patients that close to death, instead being sold false hope. It makes me wonder if they were being provided with adequate pain relief and other therapies designed to minimize the unpleasantness and pain of dying of cancer and to make their last weeks on earth as tolerable as possible.

Let’s look at the numbers, though. Medicor cites a tumor response rate of 11%. If true, that would be within the range of tumor responses typically observed in the context of a phase I trial of a new chemotherapeutic agent with some activity. Here’s the problem: The writers didn’t prospectively define exactly what they mean by “tumor shrinkage.” In the world of oncology clinical trials, there is a very specific definition of the term “partial response” or “tumor shrinkage.” It does not mean a small decrease in tumor size, as in the tumor shrinking by a few percent in diameter, as that could be within the range of error of measurement on some imaging tests. Rather, it means a decrease in the diameter of the tumor of at least 30-50%. Anything less is generally defined as “stable disease.” Without a rigorous, prospective definition for what constitutes a partial response, citing an 11% response rate is utterly meaningless. I don’t know what they are talking about.

The Medicor writers also report a reduction of tumor markers in 5.5%, which is pretty unimpressive, actually, in the context of a claim of an 11% response rate (whether real or not). Worse, they don’t report whether the reduction in tumor markers allegedly observed actually correlated with clinical tumor response in individual patients, which would not be hard to do. In other words, if 11% of patients had tumor shrinkage, why did only 5.5% have reduction in tumor markers? We’d expect the number to be as large as the response rate or, more likely, higher. Overall, this figure strikes me as fishy. So does their citing of 40% of patients having disease stabilization. The reason is that you can’t really reliably judge disease to be stable in only four weeks. Lots of tumors, even advanced tumors, don’t grow fast enough to demonstrate easily detectable changes in volume in merely four weeks. (This is particularly true of breast cancer, for example, which can appear “stable” for several months at a time.) Generally, stable disease is defined over a course of at least two to three months. Indeed, it has been argued that even that definition uses a time period that may be too short.

Finally, Medicor reports that 31% of patients had “significant symptomatic improvement,” whatever that means. Although Medicore tries to argue that this observation could not possibly be due to the placebo effect, in actuality what they report is very much consistent with a likely placebo effect. Without a control group, it is simply impossible to judge whether there was relief of symptoms greater than a placebo would produce, and I note that a typical frequency of placebo effect for symptomatic relief of subjective symptoms is often around 30% in well-designed placebo-controlled clinical trials. Indeed, one would expect from the very nature of how DCA was given and all the hype around it leading patients to expect miraculous cures, that there would be a very powerful potential placebo effect. Add to that the likelihood that confirmation bias and regression to the mean confounded Medicor’s results, and its observation is no evidence at all for an objective antitumor effect.

The bottom line, is that, although there may be a hint of some positive evidence of a response in this report, given the unrandomized, self-selected nature of the patient populatoin, coupled with the lack of objective criteria to define what does and does not constitute a response to therapy, the data remain nearly uninterpretable. Of course, that doesn’t stop Jim Tassano from “interpreting” the data:

My analysis:

In the biggest picture of all the 87 patients in the review, including those with extremely severe cancer, DCA helped 36 of them, or 41 percent.

Of the patients who were on could stay on DCA for a least one month, the overall response rate was 67 percent.

No, it was not, nor is it justified to conclude that DCA definitely helped 41% of the patients. It may well have helped a subset of these patients, but let me emphasize once again that the data are simply not well enough described to allow this sort of conclusion to be made, much less this conclusion, in which Tassano extrapolates Medicore’s observations far beyond what is justified:

DCA works and is as good or better than FDA-approved chemotherapies. And it is vastly cheaper and safer than the approved patented drugs.

Once again, no, no, no, no, no. You can’t conclude that on the basis of Medicor’s experience. In the absence of some seriously major and obvious responses, you just can’t say that DCA “works.”

I should point out here that my guess is that DCA probably does have a significant antitumor effect in some tumors, but testing it willy-nilly in self-selected patients and–far more despicable–making these same patients pay for an experimental cancer chemotherapy out of pocket is highly unethical and, just as horrible, unlikely to produce usable data. Even drug companies don’t do pull stunts like this.

But Jim Tassano and the doctors at Medicor apparently do.

I can sympathize with patients who are facing death, at least, as much as it is possible for someone not himself facing imminent death from cancer can. I’ve observed it first hand. I can imagine the desperation. I’ve also discussed the ethics of clinical trials of such drug trials extensively in the past, which is why I don’t feel obligated to rehash the issue in detail here. I understand the conflict between a patient’s desire for self-determination in the form of being allowed to try anything versus the need to do rigorous clinical trials of new drugs in order to verify that they are effective and safe. It is a conflict that will always be there. However, regardless of what side one falls on in the conflict between personal liberty versus the need to test cancer chemotherapy rigorously, I would hope that we could all agree that unethically preying upon the desperation of cancer patients to dose them haphazardly with an unproven drug is the worst way to approach this problem.

Ironically, these data from Medicor, such as they are, tell us that, if anything, DCA is not special when compared to many other chemotherapeutic drugs. It is clearly not the miracle cure that it was touted to be a year and a half ago when news of its ability to shrink tumors in rats first hit the media. At the time, shades of Kevin Trudeau, it was being touted as the “cancer cure” that “they” (i.e., pharmaceutical companies) don’t want you to know about. As uninterpretable as Medicor’s results are, they’re still disappointing, given the hype. If DCA were indeed the “miracle cure” it was touted to be, even Medicor’s slipshod experience should have turned up suggestive evidence, but it did not. There are no complete responses reported (tumor shrinkage to undetectable). There have not even, as far as I can tell, been any truly unambiguous tumor responses reported. There haven’t even been any definite symptomatic responses that are unambiguously not potentially due to the placebo effect. In light of these data, it no longer makes sense (as if it ever did) to expect any “miracle cures” from this drug in the clinical trials being carried out at the University of Alberta.

What I predict is that DCA will probably show decent activity against some cancers, but nothing out of the ordinary when compared to other cancer chemotherapeutic agents typically used. I’d love to be wrong but doubt that I am in light of the experience on the DCASite.com’s discussion forums and Medicor’s report, because if this drug had such amazingly powerful antitumor activity there probably would have been at least one or two patients who demonstrated it during the last year and a half. The bottom line is that the Medicore experience, if anything, has shot in the foot the argument that DCA is such a compelling new drug with such potential to cure a wide range of cancers, that it must be allowed to bypass the clinical trial process and be brought straight to the people. Sadly, DCA, if it does have useful anticancer activity in humans, probably has no more activity than any of a number of other commonly used chemotherapeutic agents. Don’t get me wrong. If that’s what UA’s clinical trial shows. it would certainly be a good thing. It’s always good to have a new drug, particularly an inexpensive one with few side effects, to use against cancer. But a cure DCA almost certainly is not.

In the meantime, as UA’s clinical trial grinds on, the resurrection of the zombie DCASite.com demonstrates that you can’t keep a talented scammer down. As I said before, this particular scammer is doing something that even drug companies do not do. He’s distributing an experimental anticancer agent, and he’s making the patients pay for it. I wonder what he’ll do after the results of the UA clinical trial are finally reported.

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)
  22. Finally, the FDA acts on TheDCASite.com
  23. Dichloroacetate to enter clinical trials in cancer patients

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)
  8. Dichloroacetate (DCA) Phase II Trial To Begin

Comments

  1. #1 Hesitant Iconoclast
    August 12, 2008

    It never fails to amaze me the lengths people will go to in order to trade on people’s desperation for a cure, just for money. It equally amazes me how such people presumably sleep soundly at night.

  2. #2 madder
    August 12, 2008

    Tassano’s claim is somewhere between hilarious and heartbreaking:

    Of the patients who were on could stay on DCA for a least one month, the overall response rate was 67 percent.

    given, of course, that many of the less-than-a-month DCA victims stopped taking it because they died in that time frame.

  3. #3 Natalie
    August 12, 2008

    Wouldn’t he need some sort of export license to ship to other countries?

  4. #4 Rev. BigDumbChimp, KoT
    August 12, 2008

    Oh goody. How long until Dave Scott starts up on this again?

  5. #5 Gerlach
    August 12, 2008

    Orac,
    Are you referring to the vitamin C paper in PNAS? If so, I look forward to your take on the study. It looks promising to me, but then again the subject is well outside my area of expertise. On another cancer-related note, have you thought of writing anything about RF cancer treatment (i.e. Kanzius machine)? When I first heard about it I thought it was borderline woo, but it actually sounds plausible.

  6. #6 Sarah
    August 12, 2008

    I can’t believe this sleazebag is back! I hope the FDA will be able to take action against him again.

  7. #7 wfjag
    August 12, 2008

    “Wouldn’t he need some sort of export license to ship to other countries?”

    Depends on where it’s actually shipped from, and where it’s actually shipped to (import licenses). This is a major problem in regulating foreign-source legitimate (or, represented as legitimate) drugs. Just because you believe you are ordering from a Pharmacy in Canada doesn’t mean that what you receive wasn’t brewed in a used bathtub and car radiator in Lower Lostlandistan, and then smuggled into Upper Bribistonia and mailed from there – possibly to Canada, for re-packaging and mailing to you.

  8. #8 phisrow
    August 13, 2008

    The human capacity to preassign moral characteristics and judge all subsequent behavior on that basis never ceases to amaze me. Big Pharma = Rapacious, Alties = Not Big Pharma, ergo Alties = Not Rapacious, thus Anything Alties Do = Not Rapacious. Yup. That makes perfect sense to me.

  9. #9 Dr. T
    August 13, 2008

    How could any reputable medical scientist believe that halogenating acetic acid would create a cancer-killing drug? All of the existing small-molecule cancer drugs work by being similar to intracellular chemicals and interfering with DNA replication, transcription, or protein synthesis. What the heck is dichloroacetate going to do? My guess is that it will just produce expensive urine.

  10. #10 Abel Pharmboy
    August 13, 2008

    Dr T, since Orac was already kind enough to link to my less abundant coverage of this molecule, I’d direct you to my link #1 above where I reviewed the mechanism of tumor xenograft growth delay by DCA. It does indeed target a crucial glycolytic enzyme (via inhibition of pyruvate dehydrogenase kinase 2) but at extremely high concentrations that make one wonder what else it hits.

    I agree with Orac’s hypothesis on DCA in his next-to-last paragraph but for slightly different reasons. Should DCA have some single-agent activity in the UA trial, it would be notable in that it would conceivably have a non-overlapping mechanism of action with other chemotherapy agents. This would provide the rationale for combining it with other active agents so long as anticancer activity is additive or synergistic without a similar increase in dose-limiting toxicities.

    But to be pawning it off now as a cheap cancer “cure” is irresponsible, misleading, and potentially dangerous. Whac-A-Mole is a perfect analogy for Mr Tassano.

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