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Revealed by the FDA: The results of the most recent inspection of the Burzynski Clinic

After posting the talks that Bob Blaskiewicz and I gave at TAM this year, I realized that it’s been a while since I’ve written about the topic of those talks, namely Stanislaw Burzynski, the Houston cancer doctor who inexplicably has been permitted to continue to administer an unproven cancer treatment to children with deadly brain cancers for nearly 37 years now. Beginning in 1977, when he left Baylor College of Medicine and opened up the Burzynski Clinic, Burzynski has administered a cancer therapy that he calls antineoplastons to patients. After nearly four decades and several dozen phase II clinical trials started, he has never published a completed phase II trial. The only evidence he’s published consists mainly of cell culture studies, case reports, and couple of preliminary reports of his phase II clinical trials. Of course, Burzynski’s lawyer, Richard Jaffe, even dismissively admitted that these clinical trials are designed solely to allow Burzynski to keep giving antineoplastons.

So Burzynski operated from the late 1990s until summer 2012, charging exorbitant “case management” fees to enroll patients in his clinical trials, working with a credulous filmmaker who wanted to make a movie about him—twice—and flouting regulations designed to protect human subjects involved in clinical trials. Meanwhile, he branched out to “personalized gene-targeted cancer therapy,” which he promoted through Suzanne Somers; to AminoCare, which is basically antineoplastons sold as an antiaging nostrum (or, as Burzynski puts it, a “genetic solution to aging“); and to selling an orphan drug as a “prodrug” for antineoplastons.

So what happened in the summer of 2012? Apparently, there was a treatment-related death of a child, which led the FDA to issue a partial clinical hold on the Burzynski Clinic that prevented him from enrolling any new children on his clinical trials, although he could keep treating existing patients and enroll new adult patients. That partial clinical hold was extended to adults in January 2013, at which time the FDA arrived at the Burzynski Clinic to investigate. It was an event that was included at the tail end of Eric Merola’s second propaganda film about Stanislaw Burzynski and represented as, in essence, jackbooted fascists trying to keep the cure for cancer from The People. None of this stops credulous reporters from writing misleading articles with titles like Young mother with brain cancer given just a year to live BEATS the disease and gets married after having controversial treatment in the US, which is a story about Laura Hymas, a woman whose good fortune is most likely not due to Burzynski. Not long before that, there was another credulous article featuring another Burzynski patient, Hannah Bradley, as one of four patients treated for cancer with alternative therapies who are allegedly doing well. Again, Hannah Bradley’s good fortune is highly unlikely to be due to Burzynski’s nostrums.

All of this is why those of us who follow Burzynski have been waiting with the proverbial bated breath to find out what the FDA concluded. Just before the government shutdown the first shoe dropped, when the FDA released a warning letter to the Burzynski Research Institute (BRI). Then last week, the second shoe dropped, when the FDA released the original forms describing its findings regarding the inspection. The findings are, to put it mildly, damning in the extreme. In fact, now, more than ever, I wonder how on earth Burzynski has been allowed to continue to run clinical trials—or even practice—for so long. The findings include massive deficiencies in the Burzynski institutional review board (IRB), the committee responsible for making sure that regulations designed to protect human subjects in research are adhered to.

Stanislaw Burzynski versus human subjects protections: Human subjects protections lose

Before looking at the new FDA findings, let’s recap what is known about Burzynski’s IRB. First, we know that the IRB is headed by Carlton F. Hazlewood, PhD, who just so happens to be on the board of directors of the Burzynski Research Institute. As I noted before, given that the Burzynski Clinic has been trying for decades to commercialize antineoplastons, this is a profound conflict of interest. I also ask you to think of it this way again: What would Burzynski’s defenders say if they found out that a sitting member of the board of directors of Merck, for example, was serving on the IRB that oversees Merck’s clinical trials? Having Hazlewood serve on the BRI IRB is the same thing. True, it’s not quite as bad as having the principal investigator of a study chair the IRB overseeing his studies, as Mark Geier has done, but it’s pretty bad. Again, one wonders how Burzynski supporters would react if pharmaceutical companies or even research institutes trying to commercialize a discovery made by their investigators allowed high ranking leadership sit on their IRBs.

Last year, a certain “friend” of mine had discussed the problems with Burzynski’s IRB before, and these notes simply amplify and add detail to the problems that were already known. These notes suggest how Burzynski uses his IRB to get around some of the restrictions that were placed on him using antineoplastons. As you might recall, the Common Rule demands that all clinical trials by investigators whose institutions receive federal funding or that are being done in order to win FDA approval for a drug or device must be overseen by an IRB, whose purpose is to protect the human subjects who take place in the trials. This is an absolutely essential purpose of the IRB, its key reason for existence. It is not there to evaluate the science, except to the extent that badly designed clinical trials based on bad science endanger human subjects. Its purpose is to make sure that the risks and benefits of clinical trials are reasonably balanced, make sure that patients entering clinical trials receive adequate informed consent, and to keep an eye on the trial as it is being carried out, evaluating adverse event reports and, if necessary, shutting the trial down if there are too many or if one group starts doing too poorly relative to the other.

These are duties and functions that the Burzynski Clinic’s IRB utterly failed to carry out over the years. Before I take a look at the FDA warning letter and its accompanying notes, let’s go on a stroll down memory lane and recap some of the violations that the FDA has found in the past, gleaned from a a letter to the Burzynski Clinic Institutional Review Board from 2001; a report of a site visit to the Burzynski Clinic by the FDA Southwest Regional/District Office, Dallas District; and a warning letter from the FDA’s Human Subjects Protection Team, Division of Scientific Investigations, Office of Compliance, dated 2009:

  • Enrollment of subjects into antineoplaston study protocols prior to the protocol-specified interval following prior chemotherapy and/or radiation therapy.
  • Failure to report all serious adverse events (SAEs) and adverse events (AEs) to the agency and/or IRB.
  • Failure to follow proper informed consent procedures.
  • Failure to maintain adequate drug accountability records.
  • Discrepancies between case report forms and source documents.
  • Failure to keep a copy of the study protocol and informed consent form.
  • Failure to receive and/or require progress reports from the principal investigator for the study.
  • Failure to receive and/or require a final report from the principal investigator for the study prior to removal from the IRB’s active list of studies.
  • Failure to assure that FDA approval was obtained by the principal investigator for the study prior to the treatment of a patient under a special exception.
  • Approval of special exceptions via expedited review.
  • The IRB approved research without determining that the following criteria were met: That risks to subjects were minimized and that risks to subjects were reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be expected to result.
  • The IRB failed to prepare, maintain, and follow written procedures for conducting its initial and continuing review of research.
  • The IRB failed to ensure that informed consent would be sought from each prospective subject or the subject’s legally authorized representative.
  • The IRB failed to ensure that no member participated in the initial or continuing review of a project in which the member had a conflicting interest.
  • The IRB failed to conduct continuing reviews.

The latest round of findings from the FDA’s most recent investigation eight months ago reads like an acid flashback of investigations past. According to the FDA warning letter based on this FDA Form 483, covering the inspection dates from January 22 to February 7, 2013, here’s what the FDA dinged Burzynski for this time. The CliffsNotes version is this:

  1. The IRB failed to follow FDA regulations regarding expedited review procedures [21 CFR 56.110(b)].
  2. The IRB approved research without determining that the following criteria were met: risks to subjects were minimized [21 CFR 56.111(a)(1)]; risks to subjects were reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be expected to result [21 CFR 56.111(a)(2)].
  3. The IRB failed to determine at the time of initial review that studies involving children are in compliance with 21 CFR part 50, subpart D, Additional Safeguards for Children in Clinical Investigations [21 CFR 56.109(h)]. This is a repeat violation from our 2010 inspection.
  4. The IRB failed to prepare, maintain, and follow written procedures and maintain adequate documentation governing the functions and operations of the IRB [21 CFR 56.108(a), 21 CFR 56.108(b), and 21 CFR 56.115(a)(6)].

More detailed observations can be found in the Form 483. Basically, the Burzynski Clinic and BRI ran roughshod over human subjects protection. Most of the violations are fairly simple, even for lay people, to understand. For example, not making sure that patients enrolled on clinical trials meet the inclusion criteria, not reporting adverse events in a timely fashion, and not removing patients with adverse events from the study quickly are all fairly self-evident violations and not difficult to explain. It’s fairly easy to understand why failing to remove a patient who suffers an adverse event that the protocol says should be a reason to remove the patient from the protocol is a violation. One violation, however, is not as easy to understand for those not involved in clinical trials and therefore deserves a bit more discussion. I’m referring to Burzynski’s apparent abuse of the expedited approval process through his IRB. This seems to be the “theme” that ties together much of what is reported in this warning letter to the BRI; so I feel the need to explain a bit, in order to put it all into some context.

Quite reasonably, the Office for Human Research Protections (OHRP), the office in the Department of Health and Human Services that oversees IRBs, does not require the same sort of approval process for every sort of human subjects research. Not every study that involves human subjects research is a randomized clinical trial. For instance, in the case of human subjects research that involves pre-existing samples that have been de-identified can be exempted from full IRB review and oversight because, well, there are no human subjects to be endangered, even through linking of their identities to a specimen demonstrating a disease. Lots of research gets done this way, for example analyzing or staining pre-existing samples looking for a biomarker or a change in expression of a protein. I’ve done projects like this. This is commonly known as Exemption 4, and there are several other exempt categories.

However, Burzynski doesn’t abuse the exemption process, which, let’s face it, would be very hard to abuse for the most part. What he appears to have abused is the expedited approval process. The expedited review process generally involves approving things like minor revisions to research protocols and informed consent forms. “Expedited” generally means just that: Expedited. A full IRB review is not done, and a streamlined, faster process is used. Expedited approval can also be used for protocols that fall under categories that the Department of Health and Human Services (HHS) deems to be “minimal risk,” described thusly on the University of Kentucky website:

Expedited procedures can only be used to review a study if the only involvement of human subjects fits one or more of the categories specified in the federal regulations and if all of the procedures present no greater than “minimal risk.”

The IRB reviewer confirms that all of the research activities fit in one or more of the expedited categories. If the research includes activities that do not fit in the categories, the study is not eligible for expedited review even if the research involves “minimal risk.”

The Department of Health and Human Services defines minimal risk to mean “the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests” [45 CFR 46.102(2)(i)].

Investigators are asked to provide a risk assessment, but it is the IRB reviewer’s responsibility to determine whether the research meets the federal definition.

The IRB reviewer must consider two questions:

  • Is the probability of the harm or discomfort anticipated in the proposed research greater than that encountered ordinarily in daily life or during the performance of routine physical or psychological examinations or tests?
  • Is the magnitude of the harm or discomfort greater than that encountered ordinarily in the daily life or during the performance of routine physical or psychological examinations or tests?

If the answer is “yes” to either of these questions, then the research does not meet the definition of minimal risk.

A list of the types of research that can be approved through expedited review can be found on the OHRP website. These include things like blood draws, prospective collection of biological specimens by noninvasive means (one could collect urine specimens, for instance, under a protocol approved through the expedited review process), and research involving data that has already been collected. Here’s a hint: Approving “single patient protocols” for an investigational drug that is not FDA-approved does not fall into any of the categories for which expedited review is appropriate, particularly when so many of the patients involved are children and particularly when the drug being tested can cause severe hypernatremia. Basically, from my reading, Burzynski seems to be using the expedited review process to treat patients with antineoplastons who do not qualify for any of his numerous phase II trials, and until last year he was getting away with it. Again, one of the great mysteries is: How?

But that’s not all. The second Form 483 answers a question that many of us interested in Burzynski have wondered about for a very long time.

One mystery solved: What happened to all those complete responses?

There are two central mysteries about Stanislaw Burzynski that I would really, really like to see answered, and, hopefully, I will see them answered soon. The first is, of course: How has he gotten away with it for so many years? The second is: What are his real results? I’m not referring to the results Burzynski and his sycophants claim, but the real results? People like Paul Goldberg and others have been reporting for years that Burzynski’s results don’t seem to match his claims, with cancer experts who have seen some of his actual data reporting that Burzynski’s data “can never be useful to show true merit or lack of merit of his drug” because of an absence of rigorously reported results and independent verification” and “what we have here are bad trials that could never get past peer review of any clinical trials cooperative group.” Indeed, even back in the 1990s, serious adverse reactions were reported, mostly due to the hypernatremia. Now, thanks to these additional two FDA reports (here and here), we finally see a glimmering of light through the shroud of secrecy overlying the Burzynski Clinic.

Much of what is contained in these additional reports overlaps what I discussed before, but there is one kind of violation that does not. It’s a truly egregious violation that I find very difficult to comprehend, given how much it goes against every tenet of clinical research and clinical trials that I’ve been taught and learned over the years. It appears on this Form 483, where it’s discussed under “Observation 1,” and this other Form 483, where it’s discussed under “Observation 1″ and “Observation 2.” The brief versions are stated either as “Failure to monitor the progress of an investigation under your IND”; “an investigation was not conducted in accordance with the signed statement of investigator and investigational plan”; or “failure to prepare or maintain adequate case histories with respect to observations and data pertinent to the investigation.” What does this mean? Basically, it means that the BRI misclassified tumor responses to therapy and adverse reactions. Worse, records that would allow the validation of responses to therapy are missing.

Before I get more specific, let me just briefly review what I mean by tumor response. Whenever a drug is given to treat a tumor, the response is the degree of tumor shrinkage that occurs in response to the treatment. In general, there are four categories of results defined and reported in clinical trials of new chemotherapeutic agent:

  • Complete response (CR): The tumors shrink away to the point that they are no longer detectable by physical examination, imaging studies (MRI, CT scan, etc.), or tumor markers. Obviously, this is the best possible result. This is further divided into a pathological complete response, which means that there are no detectable tumor cells in the resected tumor specimen. Obviously, when this happens, it is a very good thing and a very good prognostic sign. Sadly, it is not seen that often in clinical trials.
  • Partial response (PR): This is usually defined to mean that the tumors shrink by more than 50% (or, in the case where tumor volume cannot be measured easily, tumor markers fall by more than 50%) in response to therapy but remain detectable. More recent definitions have at times loosened this criterion to include tumors that shrink by 30% or more. Whatever the specific criteria used, a certain degree of tumor shrinkage, or evidence of tumor regression, defined before the clinical trial, must be observed.
  • Stable disease (SD): The tumors either shrink by less than the criteria for a PR or remain the same size. In some trials, this definition may be broadened to include tumors that increase in size slightly during therapy by less than, depending on the trial, 0-25%, although I’ve personally always been suspicious of calling any detectable growth above random variation in imaging measurements “stable.”
  • Progressive disease (PD): Tumors increase in size on therapy and/or new metastatic tumors appear. This is obviously strong evidence that in that patient the therapy did not work.

How tumor response is measured varies according to the tumor. Most commonly RECIST criteria are used. For brain tumors, there are criteria other than RECIST that are often used, such as the Macdonald criteria or its update, the RANO criteria. Other methods are being developed, as well. Obviously, there are pros and cons associated with each method. However, when you write a clinical trial, you have to pick one, stick with it, and use it appropriately to classify clinical trial subjects as either having CR, PR, SD, or PD. If these FDA reports are to be believed, Burzynski failed to do that. Worse, he either destroyed, or allowed to be destroyed, the original primary records used to make these determinations.

For example, the FDA notes that:

a. …For 18 of 27 (67%) of subjects, the investigator did not comply with the protocol requirements for assessing the efficacy endpoint of tumor response and recorded inaccurate assessments for tumor response in study records. For example:

  • Study [REDACTED]: Subjects 005297 and 007197 were inaccurately classified as Complete Response (CR). Subjects 004721 and 008765 were inaccurately classified as Partial Response (PR). Subjects 005974, 011373, 012184, 012206, and 12252 were inaccurately classified as Stable Disease (SD).
  • Study [REDACTED]: Subjects 06389, 11819, and 13660 were inaccurately classified as CR. Subjects 21428 and 23399 were inaccurately classified as PR.
  • Study [REDACTED]: Subject 009990 was inaccurately classified as CR. Subject 004881 was inaccurately classified as PR.
  • Study [REDACTED]: Subject 006239 was inaccurately classified as PR. Subject 004240 was inaccurately classified as SD.

b. You did not have a QA monitor properly monitor CRFs [case report forms] and subject records. The investigator destroyed critical subject case history records (target tumor measurement worksheets) or misplaced case history records (original subject CRFs) for all subjects.

Elsewhere, the FDA investigators note:

Your MRI tumor measurements initially recorded at baseline and on-treatment MRI studies for all study subjects were destroyed and are not available for FDA inspectional review.

The other Form 483 goes into a little more detail. Unfortunately, much of what I’d really, really like to know is redacted, specifically how each of these patients didn’t meet one or more of the criteria for the given response level to which Burzynski assigned them. Be that as it may, there’s plenty of damning information in these reports. For example, there are more examples of Burzynski’s failure to report adverse events (i.e., complications or bad things that happened to subjects being treated according to his protocols) in a timely fashion as required by the OHRP and the FDA. For example:

You failed to monitor as required by Section 16 of your Monitoring Plan. The investigator did not report adverse events (AEs) experienced by study subjects, including 18 cases of hypernatremia.

Now let’s look at what I mean when I said that Burzynski misclassified AEs. AEs are graded according to a system known as the Common Terminology Criteria for Adverse Events (CTCAE). The CTCAE is nothing more than a list of AEs and SAEs (serious adverse events) commonly encountered in oncology. Each AE term is defined in the CTCAE and accompanied by a grading scale for severity. The AE terms are also organized by System Organ Classes defined by the Medical Dictionary for Regulatory Activities. The CTCAE is a long list, which can be downloaded as a Microsoft Excel spreadsheet, and it’s been updated several times. The most recent update is v.4.0, released in May 2009. Most of the AEs discussed by the FDA were from before that, so that CTCAE v.3.0 was being used to classify them. AE grades generally range from grade 1 (minor), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life-threatening), to grade 5 (death).

Hypernatremia as I have discussed many times before, is a sodium concentration in the blood that is too high. If the hypernatremia is bad enough, it can be life-threatening. These reports document at least two subjects whose hypernatremia was graded a 2 when it should have been graded a 4. Of course, these two subjects pale in comparison to the number of patients whose hypernatremia either wasn’t reported or wasn’t reported for a long time. For example:

You failed to protect the rights, safety, and welfare of subjects under your care.

Forty-eight (48) subjects experienced 102 investigational overdoses between January 1, 2005 and February 22, 2013, according to the Weekly List of Hospitalizations/SAE [REDACTED] Overdose [redacted]/Catheter Infection report. Overdose incidents have been reported to you on a weekly basis during your Monday, Wednesday, and Friday staff meetings. There is no documentation to show that you have implemented corrective actions during this time period to ensure the safety and welfare of subjects.

This last sentence bears repeating: “There is no documentation to show that you have implemented corrective actions during this time period to ensure the safety and welfare of subjects.” So what we have here is a report finding that not only did Burzynski fail to report in a timely fashion a lot of SAEs, but that he tended to downplay the severity of the ones that he did report. Some AEs weren’t reported until as much as seven years later. Subjects also weren’t removed in a timely fashion for toxicity. For instance, one protocol stated that subjects would be removed after a third episode of Grade 3 or 4 toxicity or any single Grade 4 toxic effect that is “truly life-threatening or is not easily and rapidly reversible.” Of course, one wonders how the IRB could have approved such wording, as there is no distinction between “truly” life threatening and “life threatening” in the definition of Grade 4 toxicity. One patient had seven instances of Grade 3 or 4 toxicity but was not terminated from the trial until over a month after the seventh.

Other violations, although not as egregious, were nonetheless still quite bad. For instance, the informed consent didn’t include a statement of any additional costs to the subject that might result from the research. Several examples of patients who signed the informed consent days to weeks before they signed the billing agreement were presented. In addition, the Burzynski Clinic didn’t keep adequate records of its stocks of antineoplastons and could not account for how much was used by subjects. The number of bags of antineoplastons unaccounted for are truly staggering. One subject had 159 bags unaccounted for. Others ranged from one to 23 bags unaccounted for. Record keeping this sloppy would shut down nearly any clinical trial in and of itself.

The most serious violations of regulations designed to protect human subjects are clearly: (1) the BRI IRB’s misuse of the expedited approval process as an excuse to treat any patient Burzynski wanted to treat; (2) failure to keep original records to document baseline tumor measurements and tumor response; and (3) failure to report AEs and SAEs properly. However, there are a whole bunch of other lesser, but still serious, violations, so many that I find it hard to fathom.

The central mystery of the Stanislaw Burzynski saga

As a translational researcher who frequently works with clinical investigators, I just can’t figure out how Burzynski keeps getting away with it. Either the FDA is more impotent than I had thought, or Burzynski has some serious pull with some powerful people. If my university received even one report like one of the previous FDA reports about Burzynski, it would be quite possible that all federal research funding to the university for biomedical research would be suspended until the university fixed the problems to the satisfaction of the OHRP and FDA. Yet the FDA has found Burzynski to be deficient in numerous areas of human subjects protection multiple times over the last decade. These latest FDA Form 483 reports tell us nothing new, really, other than that Burzynski’s claims of complete responses are very likely nonsense.

If there’s one thing I’ve learned over the years about Brave Maverick Doctors, it’s that they often come to believe that the rules don’t apply to them. They crave the respectability of science, of course, but they are too impatient or too arrogant to play by the rules of science. Unfortunately, that often includes the rules designed to protect human subjects in clinical trials. We’ve seen it before with Mark and David Geier, who formed their own IRB stacked with their cronies. We’ve now seen it with Stanislaw Burzynski, who formed his own IRB. In the world of these Brave Maverick Doctors, the IRB apparently exists not to protect human subjects, but is instead viewed as a formality to funnel patients into whatever they want to do to treat them.

I’ve said it before, and I’ll say it again, though: The central mystery behind Burzynski is how he’s gotten away with what he’s gotten away with for nearly 37 years. It is the single question about Burzynski whose answer I want to know more than the answer to any other question about him before I shuffle off this mortal coil. Why does the FDA keep investigating him, finding serious violations, and giving him, in essence, a slap on the wrist? Since 2000, he’s been investigated multiple times, and he’s received FDA warnings for his violation of human subjects regulations. True, this is the first time since the 1990s that the FDA has taken substantive action against him, issuing a partial clinical hold that appears unlikely to be lifted any time soon, if ever. Still, I’m worried. If Burzynski comes up with a response that satisfies the FDA, he could conceivably have his same old bogus trials resurrected yet again. Why doesn’t the FDA shut down any clinical trials done by the BRI and Burzynski Clinic permanently? Why doesn’t it at least shut down the BRI IRB, which would have the effect of shutting down the Burzynski Clinic because no reputable IRB would ever approve the clinical trials that Burzynski proposes? To get its scientifically dubious clinical trials approved, Burzynski needs an IRB run by an old crony of his from Baylor (Carleton Hazelwood) who just so happens to be the chairman of the board of the BRI, a massive conflict of interest. Any other IRB with so many repeated violations and such a massively obvious conflict of interest would be shut down. Any other research institute with so many violations of FDA regulations would not be allowed to do clinical trials of any kind.

Yet the BRI persists. No matter how many times the FDA investigates it, no matter how many warning letters the FDA sends it, the BRI continues. In the 1990s, a powerful Congressman, Rep. Joe Barton, put serious pressure on the FDA through public hearings, the public dressing down of then-FDA director David Kessler, and who knows what behind-the-scenes pressure tactics to let Burzynski open clinical trials of antineoplastons. As Burzynski’s own lawyer put it, those trials were “all an artifice, a vehicle we and the FDA created to legally give the patients Burzynski’s treatment.” Since the FDA folded in response to Barton’s pressure in the 1990s, I haven’t heard news of Barton applying pressure to the FDA again over its investigations of Burzynski. True, the Republicans were in the minority during four years of the period since then, but even after they won the House back in 2010 I haven’t heard of any political pressure being brought to bear on the FDA. So I wonder: Is the FDA still so cowed from its previous experience that it can’t just pull the plug and shut Burzynski down completely?

It boggles the mind.

Posted in: Cancer, Clinical Trials, Medical Ethics, Politics and Regulation

Leave a Comment (47) ↓

47 thoughts on “Revealed by the FDA: The results of the most recent inspection of the Burzynski Clinic

  1. Dan Hackam, MD PhD says:

    Off topic but we tend to see most cancers as a sporadic, a “sh$t happens” phenomenon driven by the accumulation of random genetic mutations in tumor suppressor genes and the like. I no longer believe this to be true. I think a large proportion of many malignancies are due directly to diet. I am now reading the book “Whole: Rethinking the Science of Nutrition” by the nutrition scientist (Cornell) Colin Campbell. It is a fascinating book. Why did I never learn in medical school that casein (milk protein) boosts tumor formation in rats by 100% (a 20% casein diet vs a 5% casein diet), and that this effect has been replicated by independent researchers on multiple continents going back to the late 1960′s? There are apparently correlates in human epidemiology to support this (case-control studies).

    My feeling is that a whole foods plant-based diet could prevent many malignancies and thus abuse by the likes of Burzynski et al. People wouldn’t need to resort to desperate and unfounded measures like antineoplastons for their stage 3 and 4 disease if they didn’t get that condition in the first place. There will likely always be hereditary forms of malignancy – and these may not respond well to disease prevention (although even this is contestable) – yet diet appears to be key to preventing many of these Western civilization diseases (I would urge your readers to visit nutritionfacts.org for further information). Certainly bad diets explain the three-fold growth in diabetes and obesity in the last 40 years, since our genes have not changed in that timespan.

    Unfortunately, as Campbell points out, all of this is outside the current therapeutic paradigm and thus will never be accepted by medicine. Don’t hold your breath waiting for a large randomized trial on prevention of cancer through healthy diet; HSPH and others have not lost their attraction to testing isolated micronutrient supplements which do nothing to prevent disease. That is where your NIH clinical trial dollars are going. This situation reminds me of the early days of Marshall’s hypothesis that peptic ulcer disease was caused by bacteria – I think he was laughed at by his senior colleagues.

    1. nancy brownlee says:

      @Dan Hackam
      ” Don’t hold your breath waiting for a large randomized trial on prevention of cancer through healthy diet; ”

      How, exactly, would you do that?

    2. James says:

      My feeling is that a whole foods plant-based diet could prevent many malignancies and thus abuse by the likes of Burzynski et al

      I disagree most plant based diet does not provide enough nutrient to patients especially b12.

      However I do believe intermediate fasting can beneficial when used in conjunction with chemo.

      http://www.cancer.gov/ncicancerbulletin/071012/page5

    3. Calli Arcale says:

      Well, obviously less people getting cancer would mean less people for Burzynski to prey upon, but I’m not sure that’s really the sensible approach to stopping him. What makes you think he wouldn’t simply find a different common ailment to abuse? Even ignoring whether or not the diet you suggest would indeed reduce malignancies, it’s naive in the extreme to think the *main* problem here is that people get cancer. The main problem here is that charlatans prey upon people.

      But that might be difficult to notice when your main concern appears to be finding a way to paint medicine in a bad light. (Seriously? You claim medicine doesn’t recommend lifestyle changes? Well, maybe you personally don’t. But every doctor I’ve ever seen has pushed prevention, and doctors are so famous for lecturing patients on their lifestyle that there are whole jokebooks on the subject.)

      And remember, it was science-based medicine that Marshall used to prove his thesis correct. We should never accept things merely because they are paradigm shifting. We should accept things based on the state of evidence for and against them. Marshall was right. A lot of other people suggested a lot of other explanations, which were wrong; of course he had to prove why his suggestion was better.

      1. James says:

        Some doctors do not always push lifestyle changes to their patients.
        I have a high risk of diabetes so when my blood sugar was dangerously close to being considered diabetic (139 to be exact).
        The advice the doctor I was seeing at the time was zero.
        Not even a pamphlet.
        Which shocked me so when I asked him about seeing a nutritionist his comment was simply “I guess that a good idea”.

        Your mileage may vary.

        1. Calli Arcale says:

          Indeed, there are bad doctors, lazy doctors, enabling doctors, and more. But my issue was with generalizing that to “doctors don’t push prevention”. Most definitely do; I’ve yet to meet a non-prevention-oriented one personally. Perhaps I have just been lucky.

    4. James says:

      Dr. Hackam,

      I apologize I quickly read your post.
      You were more focused diet as preventative than therapeutic.

      However your point on milk is flawed because milk is not casein.

      For instance are some studies showing the benefit of full fat milk over low fat milk.

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656401/
      http://www.ncbi.nlm.nih.gov/pubmed/16210722
      http://adc.bmj.com/content/98/5/335

      Of course this is not valid for subsets of the population who has issue with dairy.

      James

    5. mousethatroared says:

      This article is addressing pediatric cancer treatments by Burzynski’s. Are you suggesting that milk – including breast milk, which contains casien – is the cause of pediatric cancers? Are you suggesting that replacing breast feeding in infants and dairy consumption by children with a vegtable based diet will prevent childhood cancers? You are basing this on the fact that you read a book…and a study in rats?

      You are advocating this a “healthy diet”? without addressing any of the risks associated with eliminating casien from an infant/child’s diet?

      That sounds far fetched.

    6. WilliamLawrenceUtridge says:

      all of this is outside the current therapeutic paradigm and thus will never be accepted by medicine

      …except for all the evidence, support for and mainstream recommendations that pay attention to the importance of a high-plant diet rich in fruits and vegetables.

  2. windriven says:

    Dr. Hackam,
    You seem to have made a rather long leap from modest data to:

    “My feeling is that a whole foods plant-based diet could prevent many malignancies and thus abuse by the likes of Burzynski et al.”

    Is your ‘feeling’ based on what you have read to date in this single book? If there is more, can you provide some citations from the professional literature that might help us to follow the trajectory that brought you to this rather startling and broad-reaching conclusion?

  3. Dan Hackam says:

    Windriven, (is that “Wind driven” or “Wind riven”?)

    Great points and questions all. A mea culpa for not citing evidence – line-by-line, chapter-and-verse – from PubMed or EMBASE. As with many others, I rely on some syntheses by others of this field as well as reading original high-quality human work. I don’t have a database of citations that I can just cut-and-paste however.

    In essence it comes down to the following streams of evidence, which by themselves and in isolation, are frail and limited, but when combined do suggest converging lines of data:
    - in vitro data (e.g. take blood from vegans and add it to petri dishes of cancer cell lines, and compare the effect on cell killing versus taking blood from omnivores)
    -in vivo animal data (grafting tumors into live rodents and comparing rates of cancer growth on plant-based vs animal protein-based diets)
    -human epidemiology studies – case-control based
    -human epidemiology studies – cohort-based
    -clinical trials with surrogate outcomes like telomere length (a la Ornish) and PSA relapse, e.g. in prostate cancer patients
    -clinical trials with hard outcomes like the Lyon Heart Trial showing a very large reduction in cancer — Archives of Internal Medicine in the late 1990′s or early 2000′s

    When any of these are looked at in isolation alone, they look piss-poor. When you put the entire picture together as a gestalt, it becomes quite compelling. Mechanisms at bottom-most levels support effects at those levels which are then correlated with epidemiological data (such as the Nurses Health Study, the Physicians Health Study, the Adventist Health Study, etc) and finally on to surrogate-outcome-based clinical trials and hard outcomes based clinical trials. I would urge you to consider the entirety of the picture rather than just dissecting or disdaining one level as Level 5 evidence (which it is, but this misses a key point). Or you could read “Whole” by T. Colin Campbell. Although his style is abrasive and a bit self-serving, what he discusses is rather remarkable.

    Anyway, the original post wasn’t about cancer prevention but rather cancer charlatanism and thus I apologize for bringing up my rant, which I will not pursue further as it will only distract from Dr. Gorski’s purpose in bringing the case against Stanislaw Burzinski up to date for us.

    1. windriven says:

      @Dan Hickman

      “(is that “Wind driven” or “Wind riven”?) Or win driven. The ambiguity is intentional. Also the name of my quondam sailboat.

      I understand that the commentary about nutrition and cancer was tangential to Dr. Gorski’s point. I was really trying to figure out if you are a serious scientist or a one-true-cause-of-all-disease wackaloon.

      I’m going to order up Campbell’s book – though I will approach it with profound skepticism. There has been so much jabber about various diets and the positive and negative health impacts associated with them that it is difficult to take any of them seriously anymore. But evidence is evidence and high quality evidence is always worthy of attention. It will be interesting to see if the book takes me in the same direction it took you.

      1. James says:

        Windriven, (is that “Wind driven” or “Wind riven”?)

        I always thought it was an anagram.

        vin rewind
        wivern din

        Learn something new everyday

        1. windriven says:

          vin rewind :-)

          That would certainly be appropriate!

      2. Dan H. says:

        Believe what you want to believe. And I will do the same. Though I do not wholeheartedly subscribe to Campbell’s views, I think there is much in there of value. Perhaps a little less polemic would be appreciated – and make his arguments that much more persuasive. But he writes for the general reader, not for scientific colleagues who have (already long ago) written him off.

        Maybe only 1 in 1000 mavericks are to be believed, and 999 should be discarded, so the trick is to find the 1 in 1000 who are telling the truth – a needle in a haystack. That’s very difficult to do without training in critical appraisal of the literature (though you would never know that from reading garbage posted on the internet).

        1. windriven says:

          “Believe what you want to believe. And I will do the same.”

          For me it isn’t a question of belief. It is a question of evidence. If the evidence is compelling, has been replicated and is largely unambiguous, I would cautiously sign on. I would likely modify my diet. And I’d thank you for the tip. But this is an extraordinary claim and it requires extraordinary evidence.

          1. Dan says:

            Windriven,
            I’m already convinced by all the data I have seen; several books read; papers read and analyzed in detail; authors contacted for further discussion; etc. Ultimately we come at the data with our own a priori biases and no one (human at least) is immune to this phenomenon. You might also want to add “Eating Animals”, by Jonathan Safran-Foer, to your reading list. Very eye-opening and among the best of its ilk.

  4. Angora Rabbit says:

    Can only post quick response as am writing from family event in Oregon (waves at Dr. Crislip).

    Re: human subjects, speaking as a member of our campus HRPP oversight committee, the list of violations by Burzynski is horrifying to the extreme. If even ONE of these happened on our campus. all human subjects research could be shut down. How on earth does this…criminal is the only word for it…get away with all these violations?? And without a single ethical qualm on his or his IRB’s part. Horrifying doesn’t begin to cover it.

    Re: Dan Hackham, those of us who are nutritional professionals have looked at this question for years. Please note that epidem work, like Colin’s, is only circumstantial. While we absolutely endorse moderate diets rich in fibers, plants, moderate proteins, and low in processed foods, Colin and colleagues take it to extremes and go well beyond the data. Case-controlled studies do not support his extreme claims. Mention his name to colleagues at Cornell and there’s a lot of wincing. It’s sad, because there is a core of truth but he has ventured well beyond it. Not Science-Based. But he can be a very convincing story teller. When I started teaching nutrition 20-some years ago, I spent two lectures on nutrition and cancer. Over the years, the data have collapsed such that I now spend just one day, mostly on cancer basics, and in future years I’ll probably drop it all together because the data just don’t support a major link.

    1. David Gorski says:

      A lot of it is probably because the Burzynski Research Institute is a private corporation that does not receive government funding. The Common Rule only has real teeth against institutions that receive federal funding, like universities; companies that want FDA approval for their drugs, because clinical trials that don’t follow the human subjects protection regulations under the Common Rule don’t count in an application for FDA approval; and for trials in states that have adopted laws or regulations that demand that institutions within their borders must follow the Common Rule. (I doubt Texas has such a law.) An institute like the BRI falls under neither of those categories. (Burzynski’s clinical trials are shams, designed only so that he could keep using antineoplastons.) Also, interstate commerce is key, and because the BRI is very careful about interstate commerce it’s been difficult for the FDA to claim jurisdiction.

      Even so, given the magnitude and number of violations, it boggles my mind that Burzynski is still operating and that he was enrolling patients on clinical trials until as recently as January.

    2. windriven says:

      Thanks for an interesting and informative counterbalance to Dr. Hackam’s comment. It will inform my approach to Campbell’s book.

    3. Dan H. says:

      Angora, I’m not sure which stream of literature you have been reading but there does seem to be a connection between diet and malignancy (high-quality, prospective cohort studies, case-control studies, and even the Lyon randomized trial all have shown this).

      But Campbell makes the general point that if you take a society where virtually everyone eats a diet centered around meat, dairy, fish and eggs, it is almost impossible to study the relationship between carnivorous dietary habits and any health outcome. He makes a similar point about cholesterol. Virtually no one has ultra low cholesterol in Western society (compared with rural China), and thus the people who do are likely to be sick at baseline, rather than consuming a healthy diet. Your “moderate diets rich in fibers, plants, moderate proteins, and low in processed foods” sounds exactly like a whole foods, plant based diet to me. But I am singing from the choir!

      Maybe his overall thesis and message is too extreme and eyebrow-raising and thus he has gone beyond the scope of the evidence and this has antagonized his colleagues. But I won’t throw out the baby with the bathwater.

      1. James says:

        Dr Hackham,

        Context is everything

        The Maasai tribe are very healthy
        They eat a mostly high fat diet.
        http://sciencenordic.com/maasai-keep-healthy-despite-high-fat-diet

        The discernment of variation is the most important skill a scientist should have in their toolbox.

        Sleep patterns, diet, exercise, stress management strategies should also be taken in account to understand difference between groups of people.

        James

    4. MadisonMD says:

      Dan H:
      If population of rural China represents the paragon of good health, then what is life expectancy compared to the US? What is the age-adjusted cancer death rates in rural China versus US? If eating animal-based foods is the cause of all cancer, than can you show us the cancer death rates of vegans versus vegetarians versus carnivores?
      You keep citing the last book you read. It would be more helpful to cite the primary evidence.

      Maybe his overall thesis and message is too extreme and eyebrow-raising and thus he has gone beyond the scope of the evidence and this has antagonized his colleagues. But I won’t throw out the baby with the bathwater.

      I love an extreme message when supported by evidence. Its the sine que non of top-notch science. If you enjoy extreme ideas beyond the scope of evidence, perhaps you would like to try a bit of Burzynski’s anti-aging cream.

      1. Dan says:

        For a synopsis of the data on disease rates, I’d refer you to the following URL, which is written by an RD with long experience in vegetarian health – he actively tracks this literature, which has accumulated over several decades.

        http://veganhealth.org/articles/dxrates

        It is very telling that you think that eating mostly plants to promote health constitutes an “extreme message” (in your words). Nothing else tells me more about your preformed biases than those two words. Labeling an argument as ‘extreme’ does not necessarily negate that argument’s validity. The prevailing, majority view of astronomy would have considered heliocentrism to be an “extreme message”, circa 1500 or so. Are we so much further along in our nutritional practices and knowledge to believe that we are eating an optimal diet in 2013? Something is rotten in the state of Denmark….

        1. WilliamLawrenceUtridge says:

          I believe the first person to bring up the “extremity” of the message was you.

          But I think what we may be seeing here is the tendency for the internet to bring out the worst in people. I think we’re all probably a lot closer than the arguments might suggest. The recommended healthy diet is high in fiber, fruits and vegetables, and is not followed by a significant number of first-world citizens.

        2. MadisonMD says:

          Yes, Dan I think you were the one that labeled the message extreme, not I. As I said, I do enjoy an extreme message when supported by evidence. Thank you for providing the link to vegetarian versus non-vegetarian cancer rates. I read through to this page and discovered:
          (a) No difference in cancer-specific mortality (all types) between vegetarians and meat eaters.
          (b) Colorectal cancer: In sum no difference in risk (one study shows lower risk in meat eaters and another study lower in vegetarians, others no difference).
          (c) Prostate cancer: 4 studies showed no difference. 1 study showed 35+/-30% lower incidence among vegetarians.
          (d) Breast cancer: 6 studies showed no difference. 1 studied showed 62% +/- 60% HIGHER incidence among vegetarians.
          (e) Lung cancer. No difference (I’m surprised b/c I thought vegetarians would be less likely to do unhealthy things like smoke).

          In sum, these data do not support the hypothesis that you can prevent or greatly reduce cancer risk by becoming a vegetarian. Whether you or I regards such an assertion as ‘extreme’ or not is irrelevant.

          I will agree with you that diet does play some role in cancer risk, largely related to obesity, as nicely summarized by the page you cite:

          “Since the 1981 Doll and Peto review on diet and cancer mortality (12), about one third of cancers have generally been thought to be related to dietary factors. More recent evidence suggests that this number may be too high, but a revised quantitative estimate is beyond the scope of this review. Among the diet-related factors, overweight/obesity convincingly increases the risks of several common cancers. After tobacco, overweight/obesity appears to be the most important avoidable cause of cancer in populations with Western patterns of cancer incidence. Among non-smoking individuals in these populations, avoidance of overweight is the most important strategy for cancer prevention.”

  5. Scote says:

    Is there any way we can stop using Burzynski’s framing? Calling his unproven chemotherapy drugs “antineoplastons” makes them seem legit, as if they actually do what is implied in the name “antineoplastons” and as though that is a settled issue.

    1. WilliamLawrenceUtridge says:

      That’s why I try to call them “piss extracts” whenever I post a comment.

  6. Carl says:

    “Why does the FDA keep investigating him, finding
    serious violations, and giving him, in essence, a
    slap on the wrist?”

    I don’t know, but it’s not just Buttzynski. I’ve been reading Quackwatch for probably 10 years, and it is common to see some outrageous BS end with “…a $1,500 fine and an agreement to stop violating the rules.”

    1. James says:

      Not necessarily in this order
      * Incompetence
      * Good lawyers
      * Loopholes
      * Friends in high places
      * Friends in low places
      * Corruption
      * They got lucky

      My top 2 guesses are Incompetence & Good lawyers.

      1. Bob Blaskiewicz (@rjblaskiewicz) says:

        I would also say opacity has contributed to his longevity. That’s something we can actually do something about.

        1. pmoran says:

          Cancer quacks have proved difficult or impossible to eliminate, and we must live with that, at least until we have much better treatments of cancer.

          Part of the reason is that the public is reluctant to give any body the power to TOTALLY control what others can do in private and at their own risk.

          They certainly will never deliver that up to the medical profession, even if indirectly via legal or administrative proxy. To the lay mind the issues will be seen to be too cloudy and the conflict of interest too obvious.

          So, the harder we try to impose our will via those means the stiffer will become the resistance. I think bodies such as the FDA probably do about the best they can with limited resources and a politically restricted mandate.

          1. Harriet Hall says:

            So what would you do? Not try to protect these vulnerable patients from this kind of egregious exploitation simply because doing so might stiffen resistance to regulation? False dilemma: trying to eliminate the worst quacks doesn’t mean giving any regulatory body the power to TOTALLY control practice.

          2. Carl says:

            pmoran,

            I disagree with the description of quack-stomping as total control. I don’t think it would be so fascist if the feds required that a doctor reveal his current research for a drug before selling it and/or conducting further “trials” with humans as test subjects.

            I also disagree that it is a hopeless battle. There is plenty of room for improvement. One of the selling points (offered up by some of his victims and believers) has been his stated approval for a phase 3 trial. That means something to people. Yes, the real nuts will go for it either way. But not all of his victims are just idiots. They were desperate people turning to what was officially classified by the FDA as legal research. You can’t seriously think that no significant portion of them would have thought twice if the FDA’s official statement were, “it’s illegal because he has no evidence for it despite having done several trials already” vs. “approved to do human research on this drug.”

  7. Julia B says:

    As a clinical study monitor with an interest in the ethics of medical research, I am just horrified by the issues with this entire case. The whole point of the development of guidelines for medical research was to avoid situations that place people at undue risk. It was based on atrocities such as the inhumane research done by Nazis during the Second World War, the thalidomide treatment and the Tuskagee syphilis experiment. The multiple deficiencies found by the FDA regarding informed consent of subjects and issues with competing interests from the IRB (which should be safeguarding the rights of subjects) in this case is just terrifying. I fear that this is another example to be added to the list of questionable ethics regarding experimentation in humans. Just awful.

  8. Lawrence says:

    As horrible as this situation is, I believe the FDA is hamstrung by Dr. B’s location in Texas (and the air-cover the TMB has provided, by not stepping in themselves) and that the vast majority of patients that Dr. B has swindled over the years are basically terminal anyway…..which, by itself, is even more horrible that the attitude would be “these people are going to die anyway, why not let them have a go at Dr. B” that seems to be the unofficial position of the FDA – through their lack of serious action against him.

    Perhaps we’ll see something different this time around, with the very damaging information that has come to light around the lack of safety and reporting mechanisms…..I’m not holding my breath, but we can certainly hope.

    1. Carl says:

      The TMB took Doc Bullzhitski to court, and the court told them they couldn’t convict Bullzhitski, who at this point is merely operating the “clinic”, for the bad treatment choices made by the licensed doctors working in his clinic.

      Legally, that kind of makes sense if the TMB is not going to change their default position that those doctors are OK to hire. It seems like there is plenty of history to argue for a continuous disregard or something like that.

      But I don’t know why the TMB did not take the court’s hint/offer and immediately file charges against the licensed staff whose names are on the paperwork. Those bastards aren’t mindless slaves, they knew dam well what they were getting into when they went to work for the head vampire.

  9. pmoran says:

    Yes I see that my comment can be read as going too far.

    Regulators do, however, have one arm tied because we are unable to provide them with the material they would need to pursue cancer quacks much more aggressively.

    Applying broad strokes to the matter, it is difficult to prove absolutely that the treatments never help anyone in any way. Nor is it usually possible to gather a compelling body of patients who have been seriously misled or harmed by any individual “quack”. Typically there will be far more patients and supporters springing to their defence.

    That is before we even get into the “push” factors that sustain cancer quackery, mainly the fact that a lot of people still end up dying of their cancer despite the most gruelling of medical regimes. Can we entirely stop the “pull” while there is this kind of “push”?

    From within, medicine is a modern scientific miracle. It can look somewhat threadbare to those with more confined outside perspectives. Not being alive to this is one way in which well-meaning medical sceptics can inadvertently erode further the very high level of trust in medical/sceptical opinion that would be needed before cancer quackery can be more aggressively and successfully attacked.

  10. Scote says:

    That doesn’t really work for me either. While superficially satisfying to say, it is really more of an adhominem (ad toxicum ??? I don’t know any Latin… :-( ) to harp on the drug’s origins. It doesn’t really matter where a drug was first discovered. It only matters whether it is proven to work or not, and whether the risk benefit ratio is worth it. And it is now synthesized, so it isn’t even accurate to call it that anymore.

    I just think it is important to not let Burzynski control the conversation by making us use his framing, like those congressional bills that are named in Orwellian fashion to make them impossible to oppose, perhaps “The Saving Kids from Dangerous Drugs Act”, which would be something like a bill to push Homeopathy or some such. I also object when science-based medicine advocates let homeopaths and the long dead Samuel Hahnemann frame the conversation by calling science-based doctors “allopathic” physicians.

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