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What Dr. Stanislaw Burzynski doesn’t want you to know about antineoplastons

Over the last couple of weeks, I’ve been spending a lot of time (and, characteristically, verbiage) analyzing the phenomenon known as Dr. Stanislaw Burzynski, his “cancer cure” known as antineoplastons, and his incompetent version of “personalized gene-targeted cancer therapy.” In this third and final part, I want to come back to antineoplastons, because it has been pointed out to me that there is an aspect of this story that has received little attention. One of my readers in particular has helped enormously. I wish I could credit this person by name to express my gratitude, but, for reasons I fully understand, I am not permitted to. However, this person’s input was essential, and I’ve even appropriated (with permission, of course) a bit of text here and there e-mail exchanges to “integrate” into this post. Putting this together with information in my previous posts, I think we can come to some conclusions about what it is that Dr. Burzynski is really doing.

Antineoplastons = sodium phenylbutyrate

In the first part of this series, I pointed out that back in the 1970s Dr. Burzynski claimed to have discovered cancer-fighting substances in human urine, which he dubbed “antineoplastons.” However, I was pretty vague about just what these substances were, other than to point out that they were modified amino acids and that since 1980 Dr. Burzynski has been synthesizing them in a chemistry lab rather than isolating them from urine, as he had done before. This vagueness came simply from my interest in moving straight to looking at Burzynski’s claims rather than what these substances were. In retrospect, that might have been a mistake. The reason is that understanding what two of Burzynski’s antineoplastons are is critical to understanding what he is doing with them and why he might occasionally appear to be observing an antitumor response.

So what are antineoplastons? According to Quackwatch:

By 1985, Burzynski said he was using eight antineoplastons to treat cancer patients. The first five, which were fractions from human urine, he called A-1 through A-5. From A-2 he made A-10, which was insoluble 3-N-phenylacetylamino piperidine 2,6-dione. He said A-10 was the anticancer peptide common to all his urine fractions. He then treated A-10 with alkali, which yielded a soluble product he named AS-2.5. Further treatment of AS-2.5 with alkali yielded a product he called AS-2.1. Burzynski is currently treating patients with what he calls “AS-2.1” and “A-10.”

In reality, AS-2.1 is phenylacetic acid (PA), a potentially toxic substance produced during normal metabolism. PA is detoxified in the liver to phenylacetyl glutamine (PAG), which is excreted in the urine. When urine is heated after adding acid, the PAG loses water and becomes 3-N-phenylacetylamino piperidine 2,6-dione (PAPD), which is insoluble. Normally there is no PAPD in human urine.

What Burzynski calls “A-10” is really PAPD treated with alkali to make it soluble. But doing this does not create a soluble form of A-10. It simply reinserts water into the molecule and regenerates the PAG (Burzynski’s AS-2.5). Further treatment of this with alkali breaks it down into a mixture of PA and PAG. Thus Burzynski’s “AS-2.1” is nothing but a mixture of the naturally occurring substances PA and PAG.

If you peruse ClinicalTrials.gov for Burzynski’s current clinical trials, you’ll find that pretty much all of them use antineoplastons AS-2.1 and A-10; i.e., phenylacetic acid (PA) and phenyl acetyl glutamine (PAG). But wait! you might say. Why does this matter? PA and PAG are not sodium phenylbutyrate! True enough. However, right there, in one of the e-mails from Renée Trimble, PR flack from the Burzynski Clinic. I had asked her in an e-mail how the Burzynski Clinic did its “personalized gene-targeted cancer therapy,” and she responded:

The combination contains drugs which have synergistic activity which permits reduction of doses. The combination proven ineffective by prior data, is not used. Antineoplastons and their prodrug, phenyl butyrate, are important ingredients of the combination because they cover the spectrum of approximately 100 genes. Two articles in peer reviewed journals have been published by our group recently and are attached.

I’ve discussed the fallacy of the “100 to 200 genes” before in parts I and II of this series. However, what caught my eye was the statement that phenylbutyrate is a prodrug for these antineoplastons. For those who are not familiar with basic pharmacology, a prodrug is a drug that is metabolized into something else, and it is that something else that is the actual active molecule that produces a therapeutic effect. In other words, a prodrug must undergo a chemical conversion in the body before it is active. It is also interesting to note that the complaint against Dr. Burzynski from the Texas Medical Board also mentions phenylbutyrate:

Respondent prescribed a combination of five immunotherapy agents – phenylbutyrate, erlotinib, dasatinib, vorinostat, and sorafenib-which are not approved by the Food and Drug Administration (“FDA”) for the treatment of breast cancer, and which do not meet the FDA’s regulations for the use of off-label drugs in breast cancer therapy.

One of the papers that Ms. Trimble sent to me also features sodium phenylbutyrate. It’s a paper testing phenylbutyrate on esthesioneuroblastoma and nonsmall cell lung cancer and explains its rationale thusly:

Sodium phenylbutyrate (PB) is an FDA-approved drug for urea cycle disorders, and it is also indicated for the treatment of primary and recurrent glioma and acute promyelocytic leukemia [5,6]. PB is partially metabolized in the human body into phenylacetate (PN) [7]. Both PB and PN have been extensively studied for their effect on neuroblastoma [8]. Integration of PB into ne- uroblastoma therapy has been highly recommended [9]. Previous studies reveal that PB has cytotoxic effect on human neuroblastoma, and that it can be combined with cisplatin in novel chemotherapy regimens [8]. PB is a histone deacetylase (HDAC) inhibitor. New publications recommend the use of such FDA-approved drugs for the treatment of neuroblastoma [10,11].

And there you have it. Burzynski’s antineoplastons are nothing more than the byproducts of the body’s metabolism of a known drug, sodium phenylbutyrate. Yes, it does target genes, but not in the way commonly meant when we refer to “targeted therapy,” which normally means targeting one or a handful of related genes. Rather, it targets lots of genes, making it, in essence, no more “specific” than chemotherapy.

Let’s explore the implications of this little-publicized bit of information that Burzynski doesn’t exactly advertise.

An orphan drug

Sodium phenylbutyrate, it turns out, is a drug that was originally marketed as a treatment for urea cycle disorders. It goes under the trade names Buphenyl (Ucyclyd Pharma, Hunt Valley, USA Ammonaps (Swedish Orphan International). As you might gather from the name of the Swedish company that makes it, it is an orphan drug. What that means is that it is a drug that was developed to treat a rare medical condition. Because so few people suffer from such conditions (they are, after all, rare), there is little profit to be made in selling such drugs, meaning that for a pharmaceutical company it doesn’t make economic sense to go through the many hundreds of millions of dollars that it requires to obtain FDA approval for such drugs for such indications. That doesn’t even take into account that it might be difficult to accrue enough patients to do a phase III clinical trial to demonstrate efficacy and safety. Both the U.S. and the European Union have laws to facilitate the development and marketing of orphan drugs.

It turns out that sodium phenylbutyrate potentially has several indications. There is, of course, the aforementioned treatment of urea cycle disorders, which are inborn errors of metabolism. However, that’s not the only indication, as can be deduced by searching PubMed and ClinicalTrials.gov for the search term “phenylbutyrate.” What you’ll find are over 1,300 articles on PubMed and 35 clinical trials on ClinicalTrials.gov. These clinical trials include trials testing phenylbutyrate in amyotropic lateral sclerosis (i.e., Lou Gehrig’s disease), spinal muscular atrophy type I, spinocerebellar ataxia type 3, and, of course urea cycle disorders.

Doing a search for “phenylbutyrate AND cancer” on PubMed and ClinicalTrials.gov is also informative. There are currently several trials listed on ClinicalTrials.gov, most of them completed. Trials of sodium phenylbutyrate that do not list Dr. Burzynski as an investigator including trials of lung cancer, prostate cancer, metastatic solid tumors unresponsive to chemotherapy. Most of these trials are either completed or terminated, and some of them even have published results. For example, here are the results from a phase I clinical trial in glioma, conducted by the New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium, which is funded by the National Cancer Institute (NCI), and published in Neuro-Oncology in 2005. Sadly, they are not promising, even for a phase I trial, which, as you might recall, is the preliminary “first in humans” sort of trial designed to test for safety and maximum tolerated dose, not efficacy, except as a secondary endpoint:

Of the 23 patients enrolled, 19 could be evaluated for tumor response. One CR and no PRs were noted, providing an overall response rate of 5% (95% confidence interval, 0-26%). Five patients (four GBM, one AA) demonstrated stable disease (SD) as the best response and a median time to progression of 5.4 months (range, 1.9-5.7 months). Thirteen patients (11 GBM, 2 AA) demonstrated progressive disease without a period of SD, and they all received fewer than four cycles of PB therapy. Fifteen patients were on enzyme-inducing anti-epileptic drugs. Of note, four of the six patients with CR or SD were on enzyme-inducing antiepileptic drugs. Nineteen of the 20 patients who could be evaluated for survival have died. The total number of person-years of follow-up was 18.2, and the surviving patient has been followed for more than five years. Median survival time was 5.4 months.

There are other trials as well, a few of which I will briefly mention:

  1. The Novel Deacetylase Inhibitor AR-42 Demonstrates Pre-Clinical Activity in B-Cell Malignancies In Vitro and In Vivo. (Preclinical study.) This study used a modified version of sodium phenylbutyrate (AR-42, also known as OSU-HDAC42) in preclinical models of B-cell malignancies including cell culture and SCID mice to show that AR-42 showed promise in this class of malignancies.
  2. A phase I dose-finding study of 5-azacytidine in combination with sodium phenylbutyrate in patients with refractory solid tumors.. (Phase I trial.) Conclusion: “”The combination of 5-AC and phenylbutyrate across three dose schedules was generally well tolerated and safe, yet lacked any real evidence for clinical benefit.”
  3. Combination of cytotoxic-differentiation therapy with 5-fluorouracil and phenylbutyrate in patients with advanced colorectal cancer. (Phase I trial) Conclusion: “Weekly infusions of FUra followed by PB were fairly well tolerated with disease stabilization in 3/4 (75%) of patients. This is the first report to demonstrate the feasibility of combining a cytotoxic agent with a HDACi as a cancer treatment.”
  4. Phase I dose escalation clinical trial of phenylbutyrate sodium administered twice daily to patients with advanced solid tumors. (Phase I trial.) Conclusion: “Administration of PBA in a twice-daily infusion schedule is safe. The maximum tolerated dose is 300 mg/kg/day. Study designs with more convenient treatment schedules and specific molecular correlates may help to further delineate the mechanism of action of this compound. Future studies evaluating PBA’s ability to induce histone acetylation and cell differentiation alone or in combination with other anti-neoplastics are recommended.”
  5. Complete response of a recurrent, multicentric malignant glioma in a patient treated with phenylbutyrate. (Case report.) After treatment of an anaplastic astrocytoma of the frontal lobe with radiation therapy and Procarbazine-CCNU-Vincristine, the tumor recurred as multiple lesions in this patient, who was started on sodium phenylbutyrate. This patient’s tumors regressed over nine months until they disappeared. Her complete response lasted over 20 months, which continued after discontinuation of sodium phenylbutyrate. The authors concluded: “This is the first report, to our knowledge, of a complete and durable response of a malignant glioma to phenylbutyrate. These clinical findings are consistent with the antiglioma effects of phenylbutyrate noted by Engelhard et al. [4], who described antiproliferative effects, inhibition of urokinase and c-myc expression, as well as impairment of cell migration and invasiveness, and induction of differentiation.”

If you look over the PubMed references, it turns out that researchers first examined phenylacetate as a potential treatment for cancer as far back as 1959, and there are some clinical trials still listed on ClinicalTrials.gov testing phenylacetate against various cancers, although there is understandably some overlap with the trials testing sodium phenylbutyrate, most likely because somewhere in the trial it’s mentioned that phenylacetate is a metabolite of phenylbutyrate. This trial, however, only used phenylacetate in children with recurrent or progressive brain tumors. It’s been completed, but unfortunately no results have yet been reported.

But why should sodium phenylbutyrate be suspected to be a potential anticancer drug? It turns out that it inhibits an enzyme known as histone deacetylase. Histones, the molecular biology geeks out there will know, are proteins around which DNA is wrapped in such a way that a “scaffolding” is formed. The whole complex of DNA and its associated proteins is called chromatin. When DNA is wrapped around its histones, it is usually transcriptionally inactive or silent; i.e., it’s not transcribed into RNA and translated into protein. Histone acetylases and deacetylases modify histones to make them either more or less “sticky,” respectively, to DNA. In other words, chromatin that is more acetylated is generally more active in making its gene products and chromatin that is less acetylated is less active or even silent. Indeed, histone acetylation and deacetylation are major epigenetic mechanisms of controlling gene activity. It turns out that histone deacetylase (HDAC) inhibitors (HDIs) can have anticancer effects by inducing the accumulation of hyperacetylated chromatin, thus shutting down certain genes, and inhibiting the acetylation of other proteins that regulate gene expression. Some of the mechanisms proposed include inhibition of a protein known as p21WAF1/CIP1, which regulates p53, among others. No doubt this is the sort of rationale that leads Dr. Burzynski to tout his claim that his antineoplastons shut down “100 to 200 genes.” Currently, besides sodium phenylbutyrate, two other HDAC inhibitors are FDA-approved: Vorinostat and Romidepsin, both for cutaneous T-cell lymphoma. Several others are in the pipeline, from phase I to phase III clinical trials.

One interesting take on phenylbutyrate as a cancer treatment can be found at, of all places, the website of an insurance company. Basically, Aetna has a policy regarding antineoplastons and phenylbutyrate which is worth considering. Basically, Aetna states that it considers antineoplastons and associated medical services to be “experimental and investigational because there is insufficient evidence published in the peer-reviewed medical literature validating the effectiveness of antineoplaston therapy for any indication.” However, in contrast, Aetna considers sodium phenylbutyrate to be:

  • “…medically necessary for the treatment of acute promyelocytic leukemia and malignant glioma.”
  • “…experimental and investigational for the treatment of breast cancer, prostate cancer or cancers other than acute promyelocytic leukemia and malignant glioma.”
  • “…experimental and investigational for the treatment of amyotrophic lateral sclerosis, beta-thalassemia, insulin resistance and beta-cell dysfunction, maple syrup urine disease, sickle cell anemia, spinal muscular atrophy, and for all other indications.”

Insurance companies tend to be pretty conservative in deciding what therapies to cover; so the fact that Aetna will cover sodium phenylbutyrate for some indications, including at least one cancer, puts a rather fascinating spin on the issue that will become important later in this discussion.

A blind squirrel

At this point, the reader might be tempted to ask whether Orac has gone off the deep end and become a Burzynski apologist. He might be wondering whether I’m invoking a couple of old and corny sayings about how even a blind squirrel finds an acorn every once in a while or how a stopped clock is correct twice a day. Such a reader has only to go back to part II in my series to disabuse himself of that notion, given how I pointed out that it’s not the concept of “personalized gene-targeted therapy” to which I object. It’s how Burzynski does it and how he corrupts the very concept through his “everything but the kitchen sink” approach to throwing “targeted” therapies at cancer patients willy-nilly without a systematic rationale for picking them or, it seems, any concern for potential adverse reactions due to combining drugs that have not been tested adequately in combination.

My point is that the Burzynski saga is more complicated than the simple narrative that a lot of skeptics, even skeptics I admire greatly, have imposed on it, which appears to be that Burzynski is a quack; antineoplastons are “toxic byproducts” and don’t work; and that’s that. Quack Dr. Burzynski might be, but unfortunately his possible quackery has intersected and contaminated real science. So let’s put sodium phenylbutyrate and antineoplastons in context. While it is true that, thus far, there is little evidence that sodium phenylbutyrate is effective in most cancers (some brain tumors like gliomas might be an exception), it’s also not correct from a scientific and skeptical standpoint to dismiss it, and thus antineoplastons, out of hand. There is enough evidence out there (the complete response in a glioma patient, for instance) to suggest that there might–just might–be something to this approach. However, is it a magic bullet?

Of course not!

And that’s where Dr. Burzynski goes astray. Not only is he “doing it wrong” but he’s “selling it wrong” as well, charging huge sums of money for his special cocktail of targeted therapies and sodium phenylbutyrate under the guise of clinical trials and forcing patients to bear the cost, while enticing them to bear that cost by making extravagant promises and wrapping his selling of antineoplastons up as part of “personalized gene-targeted therapy.” He’s also prescribing huge doses of antineoplastons (up to 25 g/kg/d for A10 and 80 mg/kg/d for AS-2.1, as we have seen). both of these are so far above the maximal tolerated dose of 300 mg/kg/d determined in the phase I trial I cited above as to be terrifying. True, in all fairness, antineoplastons A-10 and AS-2.1 are not sodium phenylbutyrate, making comparisons of MTDs perilous, but they are metabolites of this drug and their molecular weights are not so different that using nearly 100-fold more than the MTD seems advisable or safe. It’s also true that Dr. Burzynski often claims that very high doses are needed to be effective. Indeed, a key part of the collapse of his NCI trial in the 1990s was due to Dr. Burzynski’s unhappiness with the dosing schedule and his belief that it should be higher, while the NCI was concerned about the risk of serious side effects. Even if he were correct, which he might have been, a drug that requires doses so high that it causes hypernatremia due to the sodium in its salt is rarely a particularly useful drug. Even worse, switching to phenylbutyrate as drug that “generates neoplastons in the blood,” as Burzynski has called it, isn’t a particularly good strategy. The phase I trial I mentioned above that studied the pharmacokinetics of phenylbutyrate indicates that it’s not a good source of phenylacetate, as the authors concluded:

In summary, phenylbutyrate exhibits saturable, nonlinear pharmacokinetics after intravenous administration and achieves peak concentrations in the range of in vitro tumor activity. Concentrations of the active, intermediate metabolite (phenylacetate) were low in this study and did not achieve levels at which saturation occurs. The conversion of phenylbutyrate to phenylacetate was high (80%), but the rapid, subsequent conversation to phenylacetylglutamine resulted in serum levels of phenylacetate that were much lower than those seen when the drug is given intravenously. We conclude that phenylbutyrate should not be considered a clinically useful prodrug of phenylacetate and that phenylbutyrate and phenylacetate should be pursued as independent antineoplastic agents.

In other words, Dr. Burzynski’s rationale for using phenylbutyrate, namely that it’s a prodrug for antineoplastons, while technically true, is deceptive. The reason is that pharmacokinetic studies suggest that phenylbutyrate does not generate clinically useful concentrations of phenylacetate in the blood. Also, as we have seen, the NCI’s concerns were not without foundation, particularly its concern about the risk of severe hypernatremia, which several of Dr. Burzynski’s patients have experienced. Also in all fairness, in the publications of two trials of sodium phenylbutyrate that Ms. Trimble sent me, Dr. Burzynski used 200 mg/kg/d or 6 g/d, which in a typical 70 kg adult is around 85 mg/kg/d, both of which are below the maximum tolerated dose determined in the study I mentioned above. Also, given that they are below the MTD, they are also almost certainly at a dose that fails to generate significant concentrations of “antineoplastons” in the blood. Worse, Dr. Burzynski is also adding sodium phenylbutyrate to a whole bunch of other drugs whose interactions with it have not been studied.

As much as I hate to admit it, there is a modicum of science here. It’s just that, in Dr. Burzysnki’s hands, unfortunately it’s incredibly sloppy science, Trials are not designed so that they can ever answer the question of whether the real drug, namely sodium phenylbutyrate, is effective, either alone in combination, against cancer, and, if it is, against which cancers. Rather, they appear custom-designed so that Dr. Burzynski can keep administering antineoplastons (which, remember, are nothing more than the metabolic breakdown products of sodium phenylbutyrate) to patients. It’s also incredibly unethical science in that Dr. Burzynski is requiring patients to pay huge amounts of money out-of-pocket for unvalidated combinations of targeted therapies thrown together with (these days, at least) sodium phenylbutyrate and sold as “personalized gene-targeted cancer therapy.” As for his clinical trials, he has been warned by the FDA about lax Institutional Review Board procedures that fail to protect human subjects, fail to guarantee adequate informed consent, do not adequately monitor studies with ongoing reviews, and fail to report conflicts of interest of IRB members. In other words, not only does Dr. Burzynski do “personalized targeted therapy” badly; he does clinical trials badly as well.

So what exactly is Burzynski up to? Why, if sodium phenylbutyrate is available from not one, but two pharmaceutical companies as an orphan drug and the NCI and many other researchers are investigating it (and were investigating phenylacetate before that), would Dr. Burzynski have such an interest in portraying himself as a “brave maverick doctor“? Why does he still have such an intense interest in attracting people to his clinic using the “antineoplaston” brand name, now coupled with his new brand, “personalized gene-targeted cancer therapy”? Why does he sell so much chemotherapy–yes, chemotherapy, as I have shown–along with cocktails of expensive targeted therapies which, although less toxic than cytotoxic chemotherapy, still carry risks, not to mention cost a lot of money? Why do his supporters (and, let’s be honest, Dr. Burzynski himself) portray his therapy as “nontoxic” and “not chemotherapy,” even implying that it is not a product of big pharma, even though we have just seen that it is?

Looking at the claims of the Texas Medical Board against Dr. Burzynski, which include overprescribing without benefit and running his own pharmacy, and the costs of treatment at the Burzynski Clinic, which are freely discussed on patient blogs such as Supatra’s Fairy Fund and Cancer is a Bad ASS Bitch But We Are Badder (not to mention the claims of Wayne Merritt that Dr. Burzysnski is massively overcharging) that I discussed last week, I start to get the impression that what we are dealing with is not a misunderstood scientist or a “brave maverick doctor, but something more slippery, someone who skirts the fuzzy line between bad science and outright quackery for profit.

This starts to become very important when you consider what price people will pay for hope. As far as I can see and based on what I’ve found out, Dr. Burzynski’s antineoplastons appear to be nothing more than a different way of administering sodium phenylbutyrate. The difference is that they are administered at very high doses, and added to (in what appears to be most patients at the Burzynski Clinic these days) a luxury cocktail of chemotherapy and eye-wateringly expensive targeted cancer therapies prescribed off-label using a “Targeted Cancer Therapy for Dummies”-level interpretation of a genomic assessment of the patient’s tumor the company Caris, which is still also at an experimental stage.

Here’s where it gets even more interesting.

As I mentioned above, the insurance company Aetna has a policy outlining under what conditions and for what diseases it will cover sodium phenylbutyrate therapy. In that policy, it also states:

Since sodium phenylbutyrate has been approved by the FDA for treatment of other indications, physicians can prescribe it for patients without any danger of legal sanctions or need for compassionate use exemptions. However, there is no adequate evidence in the peer-reviewed published medical literature demonstrating that the use of sodium phenylbutyrate improves the clinical outcomes of patients with cancers of the prostate, breast, or cancers other than acute promyelocytic leukemia and malignant glioma. Current evidence is limited to in vitro and in vivo studies and Phase I studies. Prospective Phase III clinical outcome studies are necessary to determine the clinical effectiveness of sodium phenylbutyrate for cancer.

Note this phrase: “…physicians can prescribe it for patients without any danger of legal sanctions or need for compassionate use exemptions.”

Here’s what the Memorial Sloan Kettering Cancer Center has to say about it, with full links to many of the studies and a handy rundown of toxicology data (including the fact that each 500 mg tablet of sodium phenylbutyrate contains approximately 62 mg sodium – which is why, at the doses Burzynski must be using, is a massive risk of side effects including hypernaetraemia and death). Note this important phrase: “Patients are prescribed phenylbutyrate off-label to treat cancer.”

So the main thing that Burzynski stands to gain from continuing the way he is continuing is uninformed patients who have (or, like some patients who manage to raise a lot of money through medical fund raisers, can get) lots of money. These are patients who are already prone to be attracted to woo and who have come to think from reading various websites and other sources of information that antineoplastons are somehow something magical and amazing. Of course, they don’t realize it’s nothing more than phenylbutyrate and, more importantly, that, if they have one of the cancers for which there is evidence of efficacy, they could ask their oncologist to prescribe the drug off-label, although their insurance may not pay for it. They also don’t appear to be informed that there is a significant body of published evidence about the safety and efficacy of phenylbutyrate and that the way Dr. Burzynski uses its metabolites A-10 and AS-2.1 often far exceeds what one might estimate to be the MTD.

What Burzynski is really doing

It appears that during his urine and blood purification process so many decades ago, Burzynski stumbled on known compounds, PA and PAG, and has been using them to treat all sorts of cancers at extremely high doses based on weak evidence of clinical efficacy (probably brain tumours are the only real indication where it might be useful). Despite the persistent lack of evidence that these compounds have significant anticancer activity in humans, he continues to use and promote them at his clinic, charging patients through the nose to join his clinical trials rather than joining in a wider research effort test the drug in the right way. Indeed, the Burzynski website is still putting out this line: “Antineoplastons (ANP) are peptides and amino acid derivatives, discovered by Dr. S. Burzynski, M.D., Ph.D. in 1967.” As the literature shows, however, what is probably one active metabolite (phenylacetate) was already being researched in the 1950s, and the other probable active metabolite, phenylacetylglutamine, was investigated in the urine of cancer patients in 1958. Burzynski didn’t “discover” these two chemicals. All he did was to purify them from urine, then throw them them at patients in extremely high doses. This he did for decades until, sometime in the last several years, he apparently discovered that these chemicals are metabolites of sodium phenylbutyrate; so he switched to that. Then, like the “brave maverick doctor” that he thinks himself to be, he decided that the way to sell his antineoplastons and phenylbutyrate was to “rebrand” them as part of his “personalized gene-targeted cancer therapy.”

What cancer patients considering going to the Burzynski Clinic need to know is that antineoplastons (or to give them their correct name, phenylbutyrate) appear to be no better than many experimental therapies at a very early stage of development. There is phase I data that has produced toxicity data and an MTD. However, there is no convincing evidence of efficacy, except maybe in certain brain tumors. Indeed, it is quite possible, based on the case report and phase I trial testing phenylbutyrate in patients with glioma, that Dr. Burzynski’s therapy does, almost quite by accident, produce the occasional complete response. The problem is that we have no idea if this is any better or worse than anyone else’s results because Dr. Burzynski doesn’t do the necessary phase III trials to find out, even though he has well over 60 phase I/II trials listed at PubMed over the last 15 or 20 years.

Be that as it may, Dr. Burzynski’s antineoplastons are not “natural, non-toxic compounds that cure cancer.” They are drugs, plain and simple. Worse, they are drugs of unknown efficacy. Nor is Dr. Burzynski doing anything unique or in any way superior to what cancer researchers elsewhere do, his claims otherwise notwithstanding. In fact, what Dr. Burzynski does and how he does it are a pale shadow, a parody, of what real cancer research centers do. He does “personalized therapy” so badly that it’s a joke, and he uses an orphan drug off-label in combination with other off-label chemotherapy drugs and targeted therapy while selling his combination as some sort of radical breakthrough in cancer therapy. Meanwhile, the alt-med underground promotes Dr. Burzynski as “the man who cures the most intractable cancers” naturally. He’s not. He’s being represented to desperate patients with incurable cancers as their “last hope,” worth any price to reach. After all, what price would you pay for your last chance at survival or that of a loved one? Of your child? To what lengths would you go to get to the man who, you are told, is the only man in the world who can save your life?

Unfortunately, it’s not even clear to me that Dr. Burzynski’s cured a single cancer. In fact, Skeptical Humanities has been tallying publicly available cases of patients who went to Burzynski and did not survive. It’s a depressing read, and these are stories we don’t see, even from much of the mainstream press. In the process, the harm he is doing is incalculable as he tarnishes the reputation of a perfectly fine experimental anticancer drug (phenylbutyrate) and the very concept of “personalized cancer therapy” with the stench of quackery. Certainly, it doesn’t help that of late he’s branched out into dubious anti-aging remedies, forming a new division of his clinic called AminoCare.

Unfortunately, what we have here is a case of crank magnetism, and the people who pay the price are the desperate patients enticed to spend tens of thousands of dollars for a combination of chemotherapy, thrown-together targeted therapies, and an orphan drug sold as something unique and brilliant.

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

282 replies on “What Dr. Stanislaw Burzynski doesn’t want you to know about antineoplastons”

Thanks Orac – extremely useful. Effectively Burzynski’s operation is exposed as even more despicable. BTW the FDA has failed to meet its agreed deadline to answer my letter. I will give them one more day and then tweet.

This phrase makes me feel sick to my stomach:
>Note this phrase: “…physicians can prescribe it for patients without any danger of legal sanctions or need for compassionate use exemptions.”

Burzynski has fooled the world into thinking he has a unique “cure” when he is really just rebranding a known experimental drug. Who knows how many people have been misled and possibly defrauded?

It’s vital that as much fuss is made about this as possible – he is a liar, who is exploiting vulnerable patients. The Texas Medical Board hearing is in April, and they should throw the book at him, as should the FDA.

Burzynski disgusts me.

Sounds a lot like an alchemist from the middle ages: treating urine with acids or alkali, he stumbles on a way to make gold.

I’m not at my best today, I’m cuddling up to Big Pharma until the bobo goes away, but did I correctly understand that Burzynski didn’t even invent/discover these ‘antineoplastons’, he just invented the name and took out patents to limit others’ use of it?

The man is beyond despicable.

Great post! Amazing. Taking an HDAC inhibitor and rebranding it as a magical cure for cancer, then charging patients vast sums for his “miracle cure” — it just makes me feel all warm and fuzzy to know there are such wonderful people out there. I hope they shut him down.

How hard would it be to just disprove the FDA test results? With cancers with 99% fatality rates with chemo treatments, there are FDA tests showing Byrzynski’s drug had better results and didn’t give the side effects that come from poisoning humans with radiation. Why not go after those studies instead? Because you can’t argue against success?
http://www.ncbi.nlm.nih.gov/pubmed/16484713?dopt=Abstract

I wrote when this story first broke that even if you accept that there might be something to antineoplastins, and even if you are of the mindset that when all else fails it is acceptable to try to shoot the moon with a completely unproven therapy… the Burzynski Clinic is still behaving unethically by charging people exorbitant sums of money to be enrolled in trials of an experimental drug, doubly so since the trials do not seemed designed in such a way that they are going to actually answer any questions about the drug’s efficacy.

This comprehensive and enlightening post dovetails nicely with that idea. Do his treatments maybe sort kinda work? Possibly. Even if we ignore that he appears to be doing a very lousy job of it all, what he is doing is still unethical to the extreme.

Uhh, Jay? Did you happen to note which journal you were citing above? I guess it’s a step up from J. Med Hypotheses, but still…

I’ve said this before, but apparently sodium phenylbutyrate acts on urea cycle disorders by binding glutamine. There’s a long history of failures on that target – cancer cells in a dish are dependent on glutamine, because that’s what you feed them, but the drugs just don’t work when that cancer is attached to a body.

As I understand it, previous drugs in that category have flamed out in Phase I due to toxicity. This one does seem to be better tolerated, even if that’s because you have to give enough of it to make hypernatremia (!) your dose-limiting toxicity.

But there are much, much saner ways to go after HDAC, if that’s indeed the mechanism. And I’m seriously skeptical that it is; there’s too much else wrong with that molecule.

With cancers with 99% fatality rates with chemo treatments, there are FDA tests showing Byrzynski’s drug had better results and didn’t give the side effects that come from poisoning humans with radiation.

Hate to tell you this, but in the real world, we don’t consider a treatment to be well-supported by the evidence until they do well in tests that aren’t run by the original investigators. It’s misleading in the extreme to call them “FDA tests” when they’re tests conducted by Burzynski, of Burzynski’s treatment modality.

Dr B is hailed by alt med as a brave maverick persecuted by the powers-that-be: I expect that that message should be ramped up as the medical board hearing approaches. It is heaven-sent copy for folks like Adams: proof positive yes, we have yet another feisty under-dog- a brave maverick one- that BigPharma-Gov wants to dispatch because he *cures* people by *natural* means. Oh Lord! Let the bait-and-switch games begin.

However, the under-dog who fights the power appears to be making *mucho dinaro* but never you mind that. Web woo-meisters have an ulterior motive in supporting Dr B ( or Gonzalez or AJW): since they are in trouble with the “Orthodoxy” they are automatically worthy because “the enemy of my enemy is my friend” so they adroitly over-look the fact that Burzinski uses chemotherapy of the sort they routinely castigate dismissively as being “poisonous”.

The alternative methodology to the (alleged) SB focus on “cut, burn, poison” appears to be “exaggerate, over-look salient details, and initiate research ideas via free association.

-btw- speaking of research by free association: today @ AoA, Olmstead shows how wrong Freud really was: go back to the drawing board- it was the *mercury*, Siggy!

Very interesting and useful analysis, Orac. I’m starting to wonder if he may be deliberately doing the trials badly; after all, if his therapy were to become accepted by the mainstream at all, your analysis suggests to me that his patents wouldn’t hold up. By being marginalised he can continue to charge huge fees to the desperate.

Supreme Court Takes a Look at Medical Patents

The world, it appears, is determined to turn me into a full-fledged
libertarian. What with SOPA, PIPA, the NDAA, software patent trolling,
police violence, and now patents on how doctors provide treatment to
their patients, it’s becoming more and more clear how pernicious the
law can be when it’s designed for powerful special interests, national
security hawks, and big corporations.

There may indeed be a place for patents, but the way they’ve been used
to stifle competition and innovation in software shows how limited
their utility really is – at least for the majority of people. A small
handful of patent-entrepreneurs make loads of money. They just don’t
produce anything in order to make that money. It’s a sort of legal
banditry. Loophole highwaymen waiting to waylay the unfortunate
software engineer or doctor.

http://www.forbes.com/sites/erikkain/2011/12/08/supreme-court-takes-a-look-at-medical-patents/

Lab at Hershey Medical Center identifies a virus that could kill cancer
Published: Sunday, November 27, 2011, 12:00 AM

Even once a drug or therapy passes through the FDA approval process,
there’s one final step before it makes it to the general public —
production and distribution.

“You’ve got to get funding to bring it to the market, which involves
getting [pharmaceutical industry] support,” Ayres said.

And, she asked, what is the industry going to spend development costs on?

“Something they can make money on,” she said. “These are the realities.”

Bottom line: Even with unlimited funding, it could be another two to
four years before Meyers injects AAV2 into the first patients.

Until then, he’ll continue to receive the emails from desperate
people, begging him for a cure.

“It’s a very emotional topic. Everyone has somebody they know who has
one type of cancer or another,” Meyers said. “And cancer’s not like
one day you’re alive and the next day you’re dead. It’s a long,
debilitating, chronic problem.

Remember Muzyczka at the University of Florida?

He’s among the many researchers looking at AAV2 for its use as a
transportation device for genes.

Because the virus is so simple, it’s relatively easy for scientists to
remove its small amount of genes and replace them with human ones.

The idea is to introduce the carrier virus into the body of a person
who might be suffering from a genetic disorder due to a problem in
their own body’s DNA structure.

AAV2 virus, carrying the human genes, enters the patient’s cells and
inserts its DNA fragment into our genes, repairing or replacing the
broken sequence.

Because the virus is small, simple and doesn’t easily replicate, it
reduces the chances of something going wrong.

Not only could it kill cancer cells, but it could be the vehicle to
treat other genetic conditions, such as Alzheimer’s disease,
Parkinson’s disease and cystic fibrosis.

“No one’s at the point where the Food and Drug Administration has
approved it,” Muzyczka said. “But it is getting to the point where
people think it’s going to work.”

http://www.pennlive.com/midstate/index.ssf/2011/11/lab_at_hershey_medical_center.html

So, if you call it sodium phenylbutyrate, it costs $12 a gram (250 grams powder for $3000; 500 250mg pills for $1500); how much if you call it “antineoplastons”?

Prometheus

Everyone needs to be making as much noise as possible about this story – the alt-meddies will come out in support of Burzynski against the Texas Medical Board, and there is a risk he won’t be struck off. What we have here is good evidence that the Burzynski clinic has deliberately mislead vulnerable patients, and potentially defrauded them.

This is a scandal that should be covered by every newspaper in the land – not only does he need to be struck off, but he needs to be totally discredited for this kind of behaviour too.

@Jay (#7)

Okay. Leaving aside, for a moment, that the study you linked to was performed by Burzynski and colleagues and was published in a low-tier journal, let’s look at the value of the study itself.

First off, it’s appears to be a meta-analysis, as evidence by this line from the abstract:

The objective of this report is to summarize the outcome of patients with HBSG treated with antineoplastons in 4 phase 2 trials.

Unfortunately, I don’t have access to the full paper, so I can’t see what these four trials were, how they were designed, etc. My suspicion, though, is that they were all studies by Burzynski, et al.

Second, with 4 trials, the total population was 18 subjects. That’s far too small to come to any meaningful conclusions on the value of antineoplastons. There will be a lot of statistical noise. The end result is that any positive outcomes would merely suggest that a larger, more rigorously designed trial might be a possibility.

Third, all but 6 of the subjects had radiation or chemotherapy. From the abstract, it’s unclear whether the conventional therapy ended before participation in the trials, during participation or continued all the way through. As such, some of the positive results may have been due to conventional therapy, rather than the antineoplastons. The way to figure that out is with controls.

That brings us to the fourth problem: no control groups. It appears that not one of the 4 trials included in this analysis used a control group, so we cannot tell what results were due to antineoplastons, which were due to radiation or chemo nor which may simply have been due to natural progression of the disease. The lack of controls just adds to the noise in the final analysis.

In the end, Burzynski cannot make the conclusion that he does. The data simply are not robust enough to say that antineoplastons had any definitive effect on the progress of the subjects’ disease.

@Jay and @ToddW
You’re both slightly missing the point that there’s 230 published papers about phenylbutyrate with full methodology, tox data, preclinical data etc and antineoplastons ARE phenylbutyrate (at least as currently used by the clinic).

The point is that Burzynski has seriously misled, and highly likely defrauded, extremely vulnerable people by making out that antineoplastons are some kind of special unique drug. They’re not.

Patients in the US can be prescrigbed phenylbutyrate by their physician for some types of cancer ALREADY. No need to go on one of Burzynski’s extortionate (and uninterpretable) “trials” for $$$$$. This is an absolute scandal.

I’m not sure where Aetna’s getting their statement that phenylbutyrate is effective in APL and GBM. It seems like it’s only been tested in phase I’s and in vitro and not found particularly effective there. Has anyone seen any evidence that would sway an insurance company?

Random thoughts in no particular order:

The Texas Medical Board’s description of what B was dosing is deeply disturbing. “Respondent prescribed a combination of five immunotherapy agents – phenylbutyrate, erlotinib, dasatinib, vorinostat, and sorafenib-which are not approved by the Food and Drug Administration (“FDA”) for the treatment of breast cancer, and which do not meet the FDA’s regulations for the use of off-label drugs in breast cancer therapy.”

Any lay person with a passing knowledge of Dr. Google would have to question FIVE agents given at one time. OMG doesn’t begin to cover it for me. Where is the FDA in monitoring this guy? Where are some sanctions against his misuse of these agents? Last I read, his clinic was the only place his antineoplastons were legally allowed to be used “in clinical trials”, by FDA decree. That means all of his patients are participating in a clinical trial or he’d be behind bars. Have to wonder if they sign off on something that indicates their awareness that it’s a clinical trial.

While many clinical trials are listed for HDAC/HDIs, phenylbutyrate is just one of many inhibitors being explored.

(Thank you to Prometheus for posting $$$ and saving me the next logical step in searching.)

Question: Who are the people that spend time trolling the internet to promote Dr. B? Are they his followers or his own paid employees? There has been a sudden rash of pushing his methods in the last 9+ months. All the standard altie “chemotherapy doesn’t cure” talking points are included. Anyone know the reason for the spike in activity?

Thanks for this article and I must go back and peruse Parts I & II.

OK, I’m a little slow this month. I was looking at the list of Dr. Burzynski’s “therapies” from the Texas Medical Board complaint and I finally noticed the “pattern”:

Erlotinib, dasatinib and sorafenib are all tyrosine kinase inhibitors. They all have different specificities and work best on different cancers, but they all share an effect on tyrosine kinases. Vorinostat and phenylbutyrate are both histone deacetylase inhibitors.

What Dr. Burzynski is doing is akin to the “shotgun” antibiotic therapy once widely used in primary care (especially emergency room / urgent care settings). By “nailing” three families of tyrosine kinases and using two histone deacetylase inhibitors, he hopes to get sufficient “spread” that he’ll hit just about any cancer in the room.

The ironic part of this is that Dr. Burzynski claims to be doing “personalised cancer care” when, in fact, he is using a “one size fits all” therapy. Not surprising, since just about every time I read about some practitioner who touts their “personalised” approach, it turns out that they have a favorite “tool” and use it on everyone who comes through the door.

“To a man with only a hammer, every problem looks like a nail.”

Prometheus

@K

I know. I was simply responding to Jay’s specific citation that he thinks supports Burzynski’s work. Of course, the preponderance of studies and other evidence showing how Burzynski is, at best, misguided and, at worst, fraudulent/dishonest, is enough to give anyone pause.

5 grand juries and ZERO indictments. If Dr. B was “seriously misleading” and “defrauding” the public, why has he never been successfully indicted? As well, why do we have Dr. Oz and Oprah citing his story as a remarkable “David vs. Goliath” battle? Have you all watched the Burzynski film in its entirety to understand the mountain of evidence that supports his claim for antineoplastines?

Lastly, please explain why antineoplastines are in Phase III Clinical trials by the FDA if indeed they do not work??

You do realize all of what you’re “uncovering” is on his website and explained to his patients, right?

Bottom line – His team conducts FDA clinical trials with intravenous Antineoplastons. He also has a completely separate private practice where he’s using a targeted cancer approach (which involves sodium phenylbutyrate among other drugs).

Ummm… and your point?

I’ve spoken to at least a dozen of his patients and all of which knew they were NOT on FDA clinical trials with IV Antineoplaston because they didn’t meet the criteria to enroll in them (not to mention the other little clue that they weren’t getting it like how they didn’t have a catheter placed in them).

They KNEW they were getting “sodium phenylbutyrate” which converts into one of the forms of Antineoplaston (which you described) and it was in combination with other targeted meds (SOME off-label, which is acceptable oncological practice – In fact, the National Cancer Institute (NCI) has stated, “Frequently the standard of care for a particular type or stage of cancer involves the off-label use of one or more drugs. Off-label use of drugs is widespread in cancer treatment”). And if needed they would receive low-dose chemo. EVERY patient signed consent forms knowing what was happening, plus side effect, etc. So what exactly is it you unraveled?

Funny enough you make slight (emphasize SLIGHT) hints that this works for some. Of course you minimalize it (SHOCKER).

Listening to your rhetoric and your “OMGZ LOOKIE I FOUNDZ DA TROOF TANKS TO MUH INVESTIGATIONAL SKILZZ!!” is seriously laughable when none of this was hidden in the first place.

You sound like that Kevin Trudeau guy with his “WHAT THEY DON’T WANT YOU TO NOEZ!” books. Ironically you’re just as much of a “conspiracy theorist” as you claim others are who believe FDA is “hiding the cure”. It’s pathetic.

Rich (#16):

“Lab at Hershey Medical Center identifies a virus that could kill cancer. Published: Sunday, November 27, 2011, 12:00 AM”

AAV2 (Adeno-associated virus 2) has been the darling of gene therapy research for over a decade because it inserts its DNA into a very specific place in the human genome (on chromosome 19) and doesn’t disrupt any other genes in the process. That means that the issues of copy number control and genetic disruption are taken care of.

However, it is not a panacea for all ills, as gene therapy is often portrayed. As our host has so often explained, “cancer” is many diseases with many causes. Gene therapy in humans hasn’t been a spectacularly successful as was once hoped, largely because genetics – especially human genetics – is very complex.

While I am excited by Dr. Meyers’ work, I think it is far too early to say that he has a “treatment for cancer” that is being held up for lack of funding. What he has is an idea that might treat certain types of cancer, if it can work in an intact human. Once he gets that idea a bit closer to reality, he’ll have to hire someone to answer all the offers of funding from pharmaceutical companies

Prometheus

In this third and final part

Oh sure. And I’ve got a bridge for sale — cheap. Sorry, but Burzynski is a target-rich environment. Even if the TMB strips him of his license and the FDA shuts down his lab, he’ll be baaaaaaaaaack, just like the other disgraced woo-meisters.

Thanks, BTW, for a great set of posts taking down this unethical fraud.

This starts to become very important when you consider what price people will pay for hope.

I’d change that to “… pay for baseless hope.” I’ll pay a ton for real hope, but not a penny for something like this.

Prometheus — Precisely what he’s doing. Guess I didn’t get that point across, but you bingo’d with your last post. It’s akin to giving Cipro for a specific infection, that a lesser approach would address. The big guns.

FYI — I was in recent contact with a couple who had an anti-B website detailing their personal experience with his treatment. Apparently they were getting the same threatening emails from some so-called attorney. Maybe they posted a comment in Part I, but I didn’t see one. Their website is now down.

@tim. Then why, when people are asking for proof that antineoplastons work, doesn’t he come out and point to the 230+ papers on phneylbutyrate and cancer? Why does he make people buy it only from him? Why isn’t the actual identity of the drug mentioned anywhere in his previous papers or abstracts or trials protocols? And why would the Merola movie and his altimed supporters be so vociferous about antineoplastons as a “non-toxic non-chemo” treatment when they are in fact chemo and available off label? At the very least burzynski is guilty of a serious sin of omission by not being straight about the drugs he’s giving people.

@tim. Then why, when people are asking for proof that antineoplastons work, doesn’t he come out and point to the 230+ papers on phneylbutyrate and cancer? Why does he make people buy it only from him? Why isn’t the actual identity of the drug mentioned anywhere in his previous papers or abstracts or trials protocols? And why would the Merola movie and his altimed supporters be so vociferous about antineoplastons as a “non-toxic non-chemo” treatment when they are in fact chemo and available off label? At the very least burzynski is guilty of a serious sin of omission by not being straight about the drugs he’s giving people- antineoplastons are phenylbutyrate. And if you canrt see why that’s ethically dubious, you need to look at your own morals.

The problem with AAV is that it is highly immunogenic. So you can use AAV2 for gene delivery exactly once. But there are over 100 AAV identified…it is a promising approach and not one being taken by a number of researchers, including NIH funded researchers.

djc200:

5 grand juries and ZERO indictments. If Dr. B was “seriously misleading” and “defrauding” the public, why has he never been successfully indicted?

I wasn’t aware our criminal justice system was a) particularly well tuned to preventing medical fraud and b) 100% effective. As far as the individual court cases, I have not looked at them and cannot comment.

As well, why do we have Dr. Oz and Oprah citing his story as a remarkable “David vs. Goliath” battle?

Dr Oz is only slightly more respectable than Oprah as a source of medical advice. That they frame his story as a “David and Goliath” battle speaks more to the need to find dramatic tension for a story than it does to the merits of his work.

Have you all watched the Burzynski film in its entirety to understand the mountain of evidence that supports his claim for antineoplastines?

Why should I watch a promotional film intended for a lay audience to find scientific evidence? I know he claims to have a mountain of evidence. I’d like to actually *see* this mountain of evidence, not hear more claims of its existence. It seems odd that he’s been studying this for so long and produced so few scientific publications on the subject.

Lastly, please explain why antineoplastines are in Phase III Clinical trials by the FDA if indeed they do not work??

Same reason anything goes into trials — to find *out* if it works and whether there are serious side effects. Now perhaps you can explain something to me — why has he been studying them (essentially unchanged, as far as I can tell) for decades without producing any publishable results? If they do indeed work, and he has indeed been studying them and not just giving them to patients under the guise of a clinical trial, surely by now he’d have evidence.

@TIM
His patients had better know they are doing clinical trials, specifically conducted by his clinic alone. They aren’t in conjunction with the FDA in the least. That’s merely the provision that the FDA gave him to keep utilizing that which didn’t cut the mustard in NCI coordinated trials.

From the NCI:
Have any clinical trials (research studies with people) of antineoplastons been conducted?

To date, no phase III randomized, controlled trials of antineoplastons as a treatment for cancer have been conducted.

Many cancer patients have been treated with antineoplastons at Dr. Burzynski’s clinic and studied there. A few trials and case studies have been done outside of the clinic. Some of the cancers studied include breast, bladder, cervical, prostate, liver, and lung cancers, leukemia, lymphoma, and brain tumors.

Published information includes results from phase I clinical trials, phase II clinical trials, and case reports.
==============
From NCI again:
Are antineoplastons approved by the U.S. Food and Drug Administration (FDA) for use as a cancer treatment in the United States?

Antineoplastons are not approved by the FDA for the prevention or treatment of any disease. In the United States, antineoplaston therapy can be obtained only in clinical trials at Dr. Burzynski’s clinic.

Lastly, please explain why antineoplastines are in Phase III Clinical trials by the FDA if indeed they do not work??

The FDA doesn’t run clinical trials. Clinical trials, if they exist and are active, are run by researchers in academia, at the NIH, or in industry (which includes Burzynski, admit it or not.) So, there are no antineoplaston trials “by the FDA”. Are there any existent trials at all? If one goes to clinicaltrials.gov and put in Burzynski’s name, you’ll get 61 results. Sounds very productive…except that not a single one of them is listed as open and recruiting patients. They’re all withdrawn, unknown status, (occasionally) completed, or, in one case, not yet recruiting. So, can not confirm a single trial that is open and recruiting.

@ tim

Listening to your rhetoric and your “OMGZ LOOKIE I FOUNDZ DA TROOF TANKS TO MUH INVESTIGATIONAL SKILZZ!!” is seriously laughable when none of this was hidden in the first place.

So, rather than blathering in LOL-speak, why don’t you show how easy it is to find this information? Where are the links that show what “antineoplastons” really are?

If you can’t, then all you have is a feeble attempt to attack the messenger, because you can’t attack the message.

@ Calli (responding to djc200)

Lastly, please explain why antineoplastines are in Phase III Clinical trials by the FDA if indeed they do not work??

Same reason anything goes into trials — to find *out* if it works and whether there are serious side effects. Now perhaps you can explain something to me — why has he been studying them (essentially unchanged, as far as I can tell) for decades without producing any publishable results? If they do indeed work, and he has indeed been studying them and not just giving them to patients under the guise of a clinical trial, surely by now he’d have evidence.

My take is that the FDA is tired of Burzynski gaming the system and approved this as a put-up-or-shut-up test. Far better to have him fail at a Phase III trial than otherwise; it’s hard to claim martyrdom if you’ve been given the chance to prove yourself, on your own terms.

They KNEW they were getting “sodium phenylbutyrate” which converts into one of the forms of Antineoplaston (which you described) and it was in combination with other targeted meds (SOME off-label, which is acceptable oncological practice – In fact, the National Cancer Institute (NCI) has stated, “Frequently the standard of care for a particular type or stage of cancer involves the off-label use of one or more drugs. Off-label use of drugs is widespread in cancer treatment”). And if needed they would receive low-dose chemo. EVERY patient signed consent forms knowing what was happening, plus side effect, etc. So what exactly is it you unraveled?

Burzynski certainly doesn’t exactly publicize that this is what he is doing. One wonders why. BTW, I’d love to see one of those consent forms. I really would. As for the rest, if Burzynski is so proud of what he is doing, then he ought not to mind that I synthesized all this information and put it in one convenient place for the curious. After all, according to you, I’m not telling anyone anything Burzynski himself doesn’t tell them himself. Well, with the possible exception of how sodium phenylbutyrate is a crappy source of antineoplastons, how it’s real chemotherapy, and how it doesn’t seem to work that well, if at all, against most cancers.

BTW, one notes that your IP address resolves to Houston. I normally don’t point these things out about commenters, but when someone shows up spewing the Burzynski line out of nowhere I’ll make an exception. You don’t happen to work for Burzynski, do you?

Just an observation from an outsider: as I read through these comments I couldn’t stop thinking how much they remind me of the Climategate e-mails. The establishment has always coalesced to vehemently reject those who threaten their beliefs (and research grants). That’s just human nature.

Perhaps I missed them, but I didn’t see any comments expressing disgust with the Gestapo-like behavior of the Texas Medical Board and/or the FDA in this matter. Can I then infer that you all support their behavior? Or is it that you are too timid to express any negativity towards these powerful organizations? Just wondering…

Lastly, please explain why antineoplastines are in Phase III Clinical trials by the FDA if indeed they do not work??

First off, the FDA is not conducting the phase III trials. Secondly, if the investigator is not pursuing FDA approval of a New Drug Application (NDA), then they do not need to get FDA approval for any phase of the trial.

It’s important to remember that FDA approval of a drug is primarily a commercial one. An approved NDA allows a manufacturer to advertise and commercially promote their drug.

Perhaps I missed them, but I didn’t see any comments expressing disgust with the Gestapo-like behavior of the Texas Medical Board and/or the FDA in this matter. Can I then infer that you all support their behavior? Or is it that you are too timid to express any negativity towards these powerful organizations?

If anything, the Texas Medical Board and FDA have been maddeningly ineffective in shutting Burzynski down. In my opinion, of course. Here’s hoping the TMB succeeds this time. Again, in my opinion.

@Orac

If anything, the Texas Medical Board and FDA have been maddeningly ineffective in shutting Burzynski down.

Then again, at least for the FDA, their power is not exactly sweeping. They are rather constrained in what they can do and for what violations. I would like to see them take a closer look at his practice of charging subjects to participate in studies. As I wrote over at my blog, while he may be following the regulations, it does sound awfully fishy. I’d love to see the FDA authorization for charging subjects and just which charges he’s allowed to bill.

And I second your consent form comment. I, too, would like to see what subjects are receiving.

Lastly, please explain why antineoplastines [sic] are in Phase III Clinical trials by the FDA if indeed they do not work??

Trial, singular.

Calli Arcale

I wasn’t aware our criminal justice system was a) particularly well tuned to preventing medical fraud and b) 100% effective.

It doesn’t seem to be particularly well tuned to preventing financial fraud either as the dearth of investment bankers doing perp walks in the aftermath of the financial crisis shows.

As well, why do we have Dr. Oz and Oprah citing his story as a remarkable “David vs. Goliath” battle?

Because it increases ratings. Dr Oz and Oprah are in the business of providing a gullible audience for advertisers sell market overpriced crap to. That is their job. Oprah is the queen of bullshit.

@Encino: Further clarification: Gestapo-like behavior is something like seeing how well Burzynki can practice medicine without his head.

I am a recent former patient of Buryznski who was duped along with countless others.
I also got ripped off to the tune of $100K and counting.
I was told I was talking antineoplastons and went through the Caris bs too.I was given several non FDA approved drugs in combination and took chemo. Everyone there took chemo. I went in the first place to avoid chemo. Surprise. To say I am angry is putting in mildly. I am going to sue.
It is a travesty. I dont know how much of a quack he is but I do believe he is a petty crook.

Thanks much for this informative article…it has given me more ammo to go after this jerk now that I know more.

I am also going to pubish a small blog telling of my experiences with him at word press as soon as I can make some time. It’s called Burzynski Fraud.

Gray Falcon

@Encino: Further clarification: Gestapo-like behavior is something like seeing how well Burzynki can practice medicine without his head.

We have already seen how well Burzynki can practice medicine without any ethics.

@ Mike: Might I suggest to you that you also contact the Texas Medical Board, while pursuing him civilly, as well.

Dr. Burzynski wanted publicity for his cancer treatment…Oprah and Dr. Oz must be pleased that their cancer poster boy has achieved worldwide notoriety.

Rich @16: Could you use one of the typographical conventions like italics, or blockquotes, or quote marks to distinguish between your own words and those of the articles you are spamming?

djc200 @25:

Lastly, please explain why antineoplastines are in Phase III Clinical trials by the FDA if indeed they do not work??

Todd W. @ 42:
First off, the FDA is not conducting the phase III trials. Secondly, if the investigator is not pursuing FDA approval of a New Drug Application (NDA), then they do not need to get FDA approval for any phase of the trial.
Narad @ 46:
Trial, singular.

— Note also the key words in the Clinical-trials database:
Not yet recruiting
— SO antineoplasticine or whatever is not, in fact, in a Phase III clinical trial. There is merely the administrative paperwork for such a trial in the future.

Is the explanation sufficient?

If Dr. B was “seriously misleading” and “defrauding” the public, why has he never been successfully indicted?

Burzynski has in fact been convicted for fraud.

I think it’s kind of telling that Encino (@41) points to the so-called “climategate” emails as an example of deception in science, when some large number of independent investigations, including some inclined to be very hostile, have found that there was no wrongdoing, EXCEPT of course the theft of these emails so they could be quoted out of context by the great denial machine.

I do have to admit, though, that “Encino is like, so bitchin’; they have the Galleria ….. ”

[from Frank Zappa, “Valley Girl”.]

@Tim – oh, and by the way, if it’s so obvious that antineoplastons are phenylbutyrate, why doesn’t the burzynski clinic website say so? This page (“What are antineoplastons?” http://www.burzynskiclinic.com/what-are-antineoplastons.html) claims:

“Antineoplastons (ANP) are peptides and amino acid derivatives, discovered by Dr. S. Burzynski, M.D., Ph.D. in 1967.

Dr. Burzynski first identified naturally occurring peptides in the human body that control cancer growth. He observed that cancer patients typically had deficiency of certain peptides in their blood as compared to healthy individuals. According to Dr. Burzynski, Antineoplastons are components of a biochemical defense system that controls cancer without destroying normal cells.

Chemically, the Antineoplastons include peptides, amino acid derivatives and organic acids. They occur naturally in blood and urine and they are reproduced synthetically for medicinal use. The name of Antineoplastons comes from their functions in controlling neoplastic, or cancerous, cells (anti-neoplastic cells agents).”

I don’t see anything there about phenylbutyrate – I just see a load of biological nonsense – for a start, the metabolic products of phgenylbutyrate are NOT peptides.

It also says
“Antineoplaston Therapy is an experimental therapy offered at the Burzynski Clinic, currently available only within clinical trials. To find out more about the eligibility criteria for enrollment in clinical trials, please contact our Cancer Information Specialist.”

Again – no mention of the fact that antineoplaston therapy – ir phenylbutyrate – *IS* available outside the context of a clinical trial, and can be prescribed off-label.

At the very least, this is extremely misleading to people considering the treatment. And does nothing to correct the mistaken belief among the alt-med community that antineoplastons are a “non-toxic non-chemo” treatment, when in fact they ARE toxic, particularly in high doses, and they ARE chemo – and they’re much less specific than the more targeted drugs that Burzynski also uses.

I simply don’t buy it. Yes – it’s all hidden in plain sight, but why doesn’t the Burzynski Clinic make it clear in all their publications, website etc that antineoplaston treatment is in fact phenylbutyrate?

Here is the pubmed record for “phenylbutyrate + cancer” – more than 230 publications: http://www.ncbi.nlm.nih.gov/pubmed?term=phenylbutyrate%20cancer

If Burzyski is so open and transparent about the fact that antineoplaston treatment is phenylbutrate, why not point people towards these papers? Why continue to let the medical and scientific world labour under the delusion that antineoplastons are some kind of fringe treatment?

He has shown nothing with his “antineoplaston” treatment that hasn’t already been shown by other researchers running well-organised trials of pheylbutyrate and transparently publishing their data. So why continue to run “clinical trials of antineoplastons” and insist on his website that the only way people can get this therapy is through a trial?

The answer is money. Money for treatments (allegedly from his own pharmacy) and money for his shoddy “clinical trials”.

I think Dr. Burzynski should be sending Orac a “thank you note” for all the free publicity he has gotten about his cancer treatment center. “Stas” could at least offer Orac a position as an “independent contractor”…now that Marc Stephens has vacated that position.

Using Dr Oz or Oprah as an example of why your woo is valid should be treated as a version of Godwin’s Law.

Sorry, but if it appears on Dr Oz, that counts as a point against it.

@ Encino

the Gestapo-like behavior of the Texas Medical Board and/or the FDA in this matter

Oh, poor Burzynski. I didn’t know. So, a couple of goons in trench-coats came in a black car to kidnap him, and then they submitted him to all sorts of torture. Flailing his skin, splashing acid on his hands, burning his face with a blowtorch, ripping off his nails, half-drowning him in a tub, before hanging him with a piano string (because it’s elastic, it takes longer for it to strangle the victim).
Yes, this is Gestapo-like behavior.

Here is your Godwin reward, Encino. Please put it where the sun doesn’t shine. Sideway.

Tim @ 26:
[Burzynski’s] team conducts FDA clinical trials with intravenous Antineoplastons

Who to believe? Tim, or all the people who keep pointing out that the FDA does not run Burzynski’s purported trials, does not approve them, is not associated with them in any way? Decisions, decisions.

@ Encino

Just an observation from an outsider:

Your self-proclaimed “independence” is rendered highly suspect by the rest of your comment.

as I read through these comments I couldn’t stop thinking how much they remind me of the Climategate e-mails. The establishment has always coalesced to vehemently reject those who threaten their beliefs (and research grants). That’s just human nature.

It was pointed out above that the “Climategate” e-mails were nothing of the kind. Nor is what Orac has done here anything like you describe. Dr. Burzynski doesn’t threaten anyone’s beliefs here. He threatens his victim’s pocket books and lives, but not anyone’s beliefs. This blog isn’t about belief, it’s about fact.

As far as threatening research grants (a not-so-subtle dig at our host), if Burzynski’s hypothesis had any merit whatsoever, I’m certain that Orac would be thrilled. Rather than being any kind of a threat, it would open a lot of potential research avenues — more opportunities for grants, not fewer.

Perhaps I missed them, but I didn’t see any comments expressing disgust with the Gestapo-like behavior of the Texas Medical Board and/or the FDA in this matter.

Two thoughts on this one. First, as the child of a family that was directly affected by the Gestapo and Nazis, I’m offended beyond belief that you would liken the treatment Burzynski is getting here to what the Gestapo did. Second, rather than criticize the host and commenters here on what we didn’t do or say, why not address what was said? Can you refute any of the facts that Orac and the rest have provided? Or, is your only defense of Burzynski a (very) weak attack?

Can I then infer that you all support their behavior? Or is it that you are too timid to express any negativity towards these powerful organizations? Just wondering…

No need to infer at all. I fully support their actions in dealing with this fraud, con-artist and disgrace to the medical profession. He’s a danger to the lives and pocketbooks of his marks and deserves jail time for his actions. Frankly, if you put a copy of the Hippocratic Oath in the same room with Burzynski, I wouldn’t be at all surprised if one or the other spontaneously combusted.

Your offensive “just wondering” insinuation that we’re somehow afraid of the TMB and FDA is complete and total bullshit. It’s particularly stupid since Orac was critical of the TMB over their approach to another fraud, Dr. Arafiles. Talking about being afraid of owning your opinions — why try to cover it up with a “just wondering?” No guts, huh? You’re a fanboi for Burzynski. Own up to it.

Your faux-independence, nasty and insulting insinuations and total Godwinning put you on an even par with Burzynski in my opinion — somewhere below the dog crap someone left on my lawn. At least that might help the lawn grow.

5 grand juries and ZERO indictments. If Dr. B was “seriously misleading” and “defrauding” the public, why has he never been successfully indicted?

Maybe the reason HE HAS BEEN SUCCESSFULLY INDICTED is because he is seriously misleading and defrauding the public. Can you read this document here: ftp://www.ca5.uscourts.gov/pub/93/93-02071.CV0.wpd.pdf ? Do you realize what it is? It is the United States Court of Appeals, Fifth Circuit, affirming the summary judgments against Burzynski for fraud and ERISA violations entered by the United States District Court for the Southern District of Texas.

Seriously, I don’t like treating people like brain-dead idiots, but when you present arguments based on false premises like “Burzynski has never been successfully indicted,” which you would have easily discovered to be false with the tiniest imaginable investment of time and effort into a Google search, it’s hard to figure out anything else you could be. Burzynski has not only been successfully indicted for fraud, he has been found guilty of fraud and that judgment of fraud has been affirmed by a court of appeals. You need to start doing your own fact-checking because whoever’s telling you B. was never “successfully indicted” is feeding you a line of bull.

@djc200

Lastly, please explain why antineoplastines are in Phase III Clinical trials by the FDA if indeed they do not work??

[facepalm]

Trials are carried out to find out whether treatments work, not because they work.

@mojo

Trials are carried out to find out whether treatments work, not because they work.

But since the phase III trial is not actually being carried out, antineoplastons must work*.

*Well, antineoplastons work quite well for Bullshizki, although perhaps not so much for his patients.

I’ve found something disturbing. You go to cancer Q&A forums and you get a lot of “Burzynski save my life” stories. I get the feeling they’re planted. Like disreputable restaurant owners who rate their restaurants with 5-stars and write wonderful reviews.

Having eaten at the 4.5 star ‘Bistro 315’ in Nashville (since closed due to lack of customers), I don’t much trust any review that doesn’t come with a cachet of respectability and accountability.

@the clown Encino

Just an observation from an outsider: as I read through these comments I couldn’t stop thinking how much they remind me of the Climategate e-mails. The establishment has always coalesced to vehemently reject those who threaten their beliefs (and research grants). That’s just human nature.

Actually what they were pissed about was how the emails were butchered to indicate something that was not. Selectively editing and misquoting academicians is fraudulent in its conduct, yet those who did so were not pilloried, but (in fact) those who were victimized by the lies were…

That’s what that was about. Not so much the cyber-crime, but the phony scandal that ensued.

Perhaps I missed them, but I didn’t see any comments expressing disgust with the Gestapo-like behavior of the Texas Medical Board and/or the FDA in this matter. Can I then infer that you all support their behavior? Or is it that you are too timid to express any negativity toward these powerful organizations? Just wondering…

lol. Nazi analogies. What a tool.

Bottom line, he should have lost his license, not just gotten a bit of pointless trouble, for his fraud and bad-practice medicine.

@Antaeus, I’m sorry, I meant to say zero CONVICTIONS after 5 grand jury trials. You’re hilarious – like everyone else, trying to jump on any small typo in an attempt to debase my argument.
Please, just ask yourself for a moment why he’s not in jail right now if he has really criminally defrauded the public on the level that he has. Why does he have so much popular support among people he has treated and hundreds of thousands more who have followed his struggle? Why have 5 grand juries acquitted him of all charges brought against him?
I can’t believe how ardent you all are in castigating this scientist, simply by just reading what you want to believe. There’s no way any of you can claim to know for sure whether or not his treatment works. Do any of you actually have antineoplastons in your possession and a group of people who you can conduct a clinical trial on? Fact is, most, if not all, of you can only claim to have read something on some “science blog” that refutes his research.
And what is this nonsense about passing judgment without hearing both sides? At least I have gone and read/seen both sides of the argument myself (and not having took someone else’s word for it). What I do know is that our own government agencies, in this case the FDA (in collusion with the NCI), regularly engage in Washington politics, corporate pay-offs, and many other corrupt and criminal activities (e.g. the Vioxx scandal – http://www.naturalnews.com/011401.html).
FACT: Cancer is big business.
FACT: Current cancer treatments are often times more dangerous than the tumor itself.
FACT: Wall St. could not care less – just sell more drugs and increase profit margins.
http://jnci.oxfordjournals.org/content/94/18/1352.full
“It has become readily apparent that Wall Street, the pharmaceutical and biotechnology industries, and cancer researchers themselves (and now cancer organizations)—if not the federal government—are awkwardly bumping heads. Cancer has become extremely big business. ”
WAKE UP – our own government does not have the American public’s well-being in mind. It’s corruption from crony capitalism at its worst – taking payouts to protect those in power. It’s going on at all levels of our government and when it comes to healthcare and Big Pharma, they would rather know how much it would cost to shut you up (or jail you as a fraud) rather than promote more research into promising treatments. Also, in this case, since the FDA and NCI would be infringing on Dr. Burzynski’s patent on antineoplastons by producing/selling his cure for the public, they’d rather drag him through court trial after court trial to ensure no ONE person would reap the profits from a cure for cancer with no side effects.
All this chatter is pure speculation at this point. Leave it to the judge and jurors in 2012 to find out whether Dr. Burzynski is a charlatan or not. Until then, if you keep sticking your head in the sand to protect yourself from the truth, you’ll never amount to more than a troll who involves him/herself in circular arguments on a “science blog” that never was very scientific to begin with.

You go to cancer Q&A forums and you get a lot of “Burzynski save my life” stories. I get the feeling they’re planted. Like disreputable restaurant owners who rate their restaurants with 5-stars and write wonderful reviews.

That’s how this whole Burzynski imbroglio started. Marc Stephens was running one of the sock-puppet “patient support” websites that Burzynski sets up to pimp success stories, and was promoted to Burzynski’s main operation, where his incompetence was given full rein.

djc200:
@Antaeus, I’m sorry, I meant to say zero CONVICTIONS after 5 grand jury trials. You’re hilarious – like everyone else, trying to jump on any small typo in an attempt to debase my argument.

Did you read far enough into Antaeus’ comment to encounter the words “[Burzynski] has been found guilty of fraud and that judgment of fraud has been affirmed by a court of appeals”?

Your argument is quite sufficiently debased already.

@djc200:

Do you have a point, other than to spew thousands of words in an attempt to obscure the obvious facts that Burzynski is at best disingenous when it comes to his treatments, and is at worst an outright fraud?

@djc200: “I can’t believe how ardent you all are in castigating this scientist, simply by just reading what you want to believe. There’s no way any of you can claim to know for sure whether or not his treatment works. . . .Fact is, most, if not all, of you can only claim to have read something on some “science blog” that refutes his research.”

I don’t think you understand much about this audience. As opposed to those who follow CAM on the internet, most of whom have little actual real science background, you are speaking to people who are actually highly educated and entrenched in serious science. People who live it daily. They understand the innuendos and subtleties of research in a way that most people never could. They aren’t just “reading some science blog”; they immediately recognize the fallacies and pitfalls when bad science presents itself. They are not Orac’s “cheerleaders”, they are his peers.

Many people such as yourself accuse these people of following blindly, or believing only what they want to believe, and you don’t realize how ridiculous you sound. It’s projection of the highest degree. There are no hangers-on here, as opposed to the alt med world. Any one of them would jump all over a scientific misstep, whether it came from alties or from themselves. Problem for you is, the great majority of the time the scientific misstep comes from alties.

@ djc: You really need to read up on your hero Burzynski, who is a charlatan of the first order.

Obviously, you haven’t read…or don’t understand written English contained in the links provided to you by other posters…because you keep blathering the same nonsense.

“FACT: Current cancer treatments are often times more dangerous than the tumor itself.” Really? Have you any citations from real peer reviewed journals about “spontaneous remission” of cancerous tumors?

‘FACT: Wall St. could not care less – just sell more drugs and increase profit margins.
http://jnci.oxfordjournals.org/content/94/18/1352.full” This article that you linked to has nothing to do with “Wall Street” selling drugs, which “Wall Street” does not do. Your linked article discusses embargo on information that is presented at medical conferences, so that stock analysts don’t trade on “inside” information. Many of us have some early information about the success of drugs because we are overseeing trials of medicines and treatments. Why would we jeopardize our professional licenses and careers for the purposes of financial gain or to manipulate stock prices?

“All this chatter is pure speculation at this point. Leave it to the judge and jurors in 2012 to find out whether Dr. Burzynski is a charlatan or not.” You really haven’t looked at the Texas Medical Board’s website. There will be no judge and jury…it is an administrative hearing that Burzynski faces, presided over by his peers.

I think you need to take some reading comprehension courses and a few science courses, so that you can understand what is being debated here…you are out of your league.

Orac, once again I so admire HOW you wrote this. That there are parts where there are things that could be helpful, but he abuses them, uses them improperly, sells false hope, etc. The man is either totally in love with himself and suffering from a delusion that he can do no wrong, or he’s a charlatan of the worst kind. I hope for the former only because I think if he’s the latter I would hope Texas would consider death penalty possibilities. If he knowingly allows the death of another human being or recklessly endangers that person by his standard of care, that should be some type of homicide, and if that is being done while knowingly defrauding them, doesn’t it fall into the murder one category or is that only on television?

Maybe families of patients who end up dead from treatment should start taking things to criminal court. He might be a bit worried about fraud cases, but would know that in the alternative world that actually is a badge of martyrdom and makes him MORE authentic and believable, rather than less.

A few murder charges, though, well, that would be a different story.

[off-topic, but relevant in a tangential way?]

Loose question: should patient consent forms be disclosed publicly for all trials?

(e.g. put up alongside the rest of the trial information on-line for anyone to read.)

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