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Burzynski Clinic by SBM

March 24, 2013

The excellent Science based Medicine http://www.sciencebasedmedicine.org whom are bunch of Medics who write on a wide range of topics have evaluated the Bursynski story to try to make sense of the myth surrounding this Doctors methods. Here are some interesting snippets from the evaluation.

ANP‘s

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.

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.

One of the papers that Ms. Trimble sent (Bursynski PR Person) 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].

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.

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.

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.

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.

The US 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.”

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.

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 very soon.
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