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 and his “cancer cure” known as antineoplastons. In part I of this series, Stanislaw Burzynski: Bad medicine, a bad movie, and bad P.R., I used the legal threats against bloggers criticizing the credulous promotion by the British press of fundraising campaigns to send children with terminal cancer to the Burzynski Clinic and the promotion of the medical propaganda movie Burzynski The Movie: Cancer Is Serious Business to review the movie’s claims and look into Burzynski’s claims for antineoplastons. Not surprisingly, I found the evidence for extravagant claims for their anticancer effects unconvincing. In part II, Dr. Stanislaw Burzynski’s “personalized gene-targeted cancer therapy”: Can he do what he claims for cancer?, I looked into Dr. Burzynski’s recent efforts to “diversify his portfolio, in which he has apparently decided to ride the new wave of genomic medicine to claim he can do “personalized, gene-targeted cancer therapy.” I concluded that he does appear to do that, only very badly, in essence “making it up as he goes along.”

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 reader in particular has helped enormously in my education about this aspect of the Burzynski saga. I wish I could credit this person by name, but, for reasons I fully understand, I can’t. However, this person’s input was essential, and I’ve even appropriated (with permission, of course) a little bit of text here and there from our 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.

Burzynski and an orphan drug

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,” claiming that patients with cancer had lower levels of these substances in their blood and urine. 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 up until then. 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.

If you wander over to the Burzynski Clinic website, you’ll note that he’s kind enough to have provided the actual chemical structures of what he calls the active ingredient of antineoplastons. These include phenylacetate sodium (PN), phenylacetylglutaminate sodium (PG), phenylisoacetylglutaminate sodium (isoPG), and 3-phenylacetyl-2, 6-piperidinodione (A10). 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 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 that “something else” produces a a therapeutic effect, either by itself or in combination with unaltered drug and/or other metabolites. In other words, a prodrug undergoes a chemical conversion in the body into something active. Often, the prodrug has no activity, and all of its pharmacological activity is due to the metabolite. 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. What Burzynski calls antineoplastons are nothing more than the byproducts of the body’s metabolism of the orphan drug sodium phenylbutyrate. In fact, according to the paper cited, the “conversion of phenylbutyrate to phenylacetate was extensive (80 ± 12.6%), but serum concentrations of phenylacetate were low owing to rapid, subsequent conversion to phenylacetylglutamine.” In other words, phenylbutyrate is nearly completely converted to PA, which is then rapidly converted to PAG. According to this study, within about four hours of an IV dose, phenylbutyrate levels in the blood approach zero, even in a patient receiving 2,000 mg/m2. This sort of conversion of a prodrug to a drug is not at all uncommon. For example, one common chemotherapy drug used in breast cancer and a lot of other malignancies, cyclophosphamide, works through its metabolite 4-hydroxycyclophosphamide, or 4-HC. As for phenylbutyrate being a “targeted” therapy, yes, it does target genes, but not in the way commonly meant when we refer to “targeted therapy,” which normally refers to targeting either one gene product or a handful of related gene products (i.e., similar tyrosine kinases). Instead, phenylbutyrate targets lots of genes, making it in essence no more “specific” than many kinds of chemotherapy.

Let’s explore the implications of this little-publicized bit of information about antineoplastons. It’s something that Dr. Burzynski doesn’t exactly go out of his way to publicize.

The orphan drug that works wonders

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 for the search term “phenylbutyrate.” What you’ll find are over 1,300 articles on PubMed and 35 clinical trials on 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 is also informative. There are currently several trials listed on, 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 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. Of interest, note that Dr. Burzynski combined Vorinostat with phenylbutyrate (and several other drugs) in one of the patients in the Texas Medical Board complaint. Why he would combine two HDAC inhibitors, I don’t know. Normally in cancer therapy, we try to target different mechanisms when combining drugs.

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. 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 ol’ Dr. Gorski 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. Even I fell into that way of thinking for a long time. However, whether or not I think Dr. Burzynski is a quack is a question I’ll leave for the very end of this post. In the meantime, 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 in that pharmacokinetic studies indicate that phenylbutyrate does not generate clinically useful concentrations of PA in the blood. The PA is immediately metabolized to PAG, which is apparently not active. 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, and he extravagantly overpromises, while making a claim that is probably not true, namely that phenylbutyrate is a good source of antineoplastons. 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 are Dr. Burzynski and his promoters so keen to portray his therapy is “nontoxic” and, above all, “not chemotherapy,” even to the point of implying that it is a natural product rather than the product of big pharma, even though we have just seen that most of the drugs he uses are, in fact made by the big, bad pharmaceutical companies?

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.” Music to Dr. Burzynski’s ears, no doubt, except that off-label use doesn’t mean you can use a drug for whatever you want, particularly when, as the Memorial Sloan Kettering Cancer Center points out, each 500 mg tablet of sodium phenylbutyrate contains approximately 62 mg sodium. That’s why at the doses Burzynski must be using, even the lower ones that he uses, there is considerable risk of side effects including hypernatraemia and death.

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 and their doctor might not consider it advisable. Of course, I’d sooner rely on the judgment of almost any oncologist over that of Dr. Burzynski, given that Dr. Burzynski appears to want to give antineoplastons to every cancer patient. 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 based on studies of their prodrug.

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.”

So, after all this, including my previous two posts on Dr. Burzynski’s therapies, what can we conclude? At least three things:

  • Although this probably wasn’t true 10 or 20 years ago (mainly because it wasn’t so widely known that PA and PAG are metabolites of sodium phenylbutyrate), these days “antineoplastons” are just another name for phenylbutyrate, an orphan drug that any physician can prescribe off-label. Dr. Burzynski markets antineoplastons in the alt-med underground through movies like Burzynski The Movie and interviews with Suzanne Somers as “not chemotherapy,” even though phenylbutyrate is an HDAC inhibitor, which is a class of chemotherapy drug under active research by many university laboratories and pharmaceutical companies. Either through gross incompetence or deception (take your pick), he is, in my opinion, misleading patients when he claims that phenylbutyrate is a good source of antineoplastons; it’s not.
  • Dr. Burzynski uses chemotherapy, and lots of it, in combinations that have not yet been demonstrated to benefit cancer patients, all based on reports from Caris. This he brands “personalized, gene-targeted therapy,” even though, as I’ve said before, it’s very much at the level of “Targeted Therapy for Dummies,” in which he combines a bastardized version of metronomic chemotherapy with expensive cocktails of targeted agents. There is no evidence that his results are any better than those obtained elsewhere, despite his claims otherwise.
  • Allegedly (according to Wayne and Lisa Merritt and the Texas Medical Board), Dr. Burzynski provides these drugs at inflated prices from his own pharmacy and without fully informing his patients about the treatment they’re getting. The determination by the Texas Medical Board of whether this allegation is true or not awaits the results of legal proceedings against Dr. Burzynski that are scheduled to begin early next year.

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. One of his products is even called AminoCare A10, which is billed as being made of “blend of amino acids, an amino acid derivative and vitamin B2.” (Any guess as to what Dr. Burzynski’s “proprietary” amino acid derivative is, given the name A10?)

Which brings me back to the question of whether Dr. Burzynski is a quack. My answer may surprise you: Although he might be one, in the end I don’t really care that much if he is or not. Certainly (and not surprisingly), Dr. Burzynski is emphatic that he is not. However, to me the line between being a quack or “merely” a bad doctor and scientist is a blurry one. Quack Dr. Burzynski might be, but to me more important than whether or not he is a quack is how he behaves. Even if the science Burzynski were doing were pristine, how he is selling himself and his products to his patients as the one man who has what can cure cancer speaks volumes about his ethics, and what’s in those volumes is not good. The Burzynski Clinic’s motto might be, “First, do no harm.” However, Dr. Burzynski’s actions, coupled with the lack of evidence supporting his methods, make that slogan ring hollow these days. One can only hope that the Texas Medical Board finally puts a stop to his activities.

The complete Burzynski series:

  1. Stanislaw Burzynski: Bad medicine, a bad movie, and bad P.R.
  2. Dr. Stanislaw Burzynski’s “personalized gene-targeted cancer therapy”: Can he do what he claims for cancer?
  3. Dr. Stanislaw Burzynski, antineoplastons, and the selling of an orphan drug as a cancer cure


Posted by David Gorski

Dr. Gorski's full information can be found here, along with information for patients. David H. Gorski, MD, PhD, FACS is a surgical oncologist at the Barbara Ann Karmanos Cancer Institute specializing in breast cancer surgery, where he also serves as the American College of Surgeons Committee on Cancer Liaison Physician as well as an Associate Professor of Surgery and member of the faculty of the Graduate Program in Cancer Biology at Wayne State University. If you are a potential patient and found this page through a Google search, please check out Dr. Gorski's biographical information, disclaimers regarding his writings, and notice to patients here.