Science-Based Medicine ? Dr. Stanislaw Burzynski's cancer ...

The year 2012 was rung out and the year 2013 will be rung in by news that Eric Merola, propagandist for ?brave maverick doctor? Stanislaw Burzynski who claims to have developed a cancer treatment far superior to current conventional science- and evidence-based cancer treatments, is releasing releasing a sequel to his wildly successful documentary (in the ?alternative cancer? underground, that is) Burzynski The Movie: Cancer Is Serious Business. In fact, the sequel is coming out on DVD on March 5, and you can even preorder it now. I somehow doubt that Eric Merola will send me a screener DVD to review, but I did review the first movie because it easily falls into a genre that I like to refer to as medical propaganda movies, which are almost always made in support of dubious medical treatments. My mostly lame jokes about proposed titles aside (e.g., Burzynski II: Electric Boogaloo, Burzynski II: This Time It?s Peer-Reviewed, or even Burzynski II: Quack Harder), it?s very clear that in the wake of the Texas Medical Board?s decision to drop its case against Burzynski on a technicality, Burzynski and his very own Leni Riefenstahl named Eric Merola are planning on a huge publicity blitz, in which Burzynski will be portrayed as, yes, a ?brave maverick doctor? whom ?They? (as in the FDA, drug companies, and the Texas Medical Board, a.k.a ?The Man?) tried to keep down but failed because he has The Natural Cure For Cancer ?They? Don?t Want You Sheeple To Know About.

I come back to this again because Merola?s strategy for Burzynski II, as I pointed out, is going to involve ?conversion stories? of oncologists who didn?t believe in Burzynski?s magic antineoplastons but do now, attacks on skeptics who have been critical of his work (like me), and, of course, testimonials for success stories. I don?t know how I missed this before, but what exactly that will mean in practice is actually spelled out pretty well in an installment of a video blog by a Burzynski patient named Hannah Bradley. Bradley became famous for her battle against a malignant brain tumor, her decision to go to the Burzynski Clinic, and the prodigious fundraising efforts of her partner Pete Cohen through their Team Hannah website and vlog. In this vlog, recorded on September 7, 2012, Pete and Hannah are happy because in their previous vlog of July 27, 2012, they reported that, after having received Dr. Burzynski?s antineoplaston treatment Hannah has had a ?complete response,? and indeed the MRI scans shown in their movie, Hannah?s Anecdote, do appear to show just that (more on that later).

We then meet Eric Merola himself:

From the banter between Eric Merola, Pete Cohen, and Hannah Bradley, we learn that Hannah decided to go to the Burzynski Clinic after seeing the first Burzynski movie. We also learn that Hannah is going to feature very prominently in Merola?s sequel as a success story. Indeed, from this video, and the trailers on the Burzynski Movie website. It?s fairly clear how Burzynski II will be constructed, particularly if you look at the latest trailer, released just yesterday:

Taking the previous trailer and this one together, along with Merola?s appearance on Hannah and Pete?s vlog, I know that Burzynski II will likely consist of four elements:

• Testimonials (or anecdotes), including Hannah?s, of ?success stories? coupled with the aforementioned ?conversion stories? of oncologists who have become Burzynski believers. These will be contrasted with a rehash of conspiracy theories from the first movie about the ?cancer establishment? trying to suppress Burzynski because he is a threat to their profits. Never mind that, even if Burzynski?s antineoplastons were FDA-approved, they would be in the same class as the chemotherapies that are disdained in the trailer as being more for profit than anything else because they have to be given for a long time. One notes that Burzynski?s protocol requires at least 18 months of near-continuous infusion of high doses of his antineoplastons.
• Attacks on skeptics and critics of Burzynski. If you don?t believe me, just read question #12 in Merola?s FAQ), in which he states, ?You will notice the ?anti-Burzynski bloggers refuse to do that or adhere to reputable sources. You might say, they are preying on desperate cancer patients and families of cancer patients by carelessly misleading their readers about Burzynski and his invention.? One marvels at Merola?s amazing level of projection. However, every movie needs a villain, and it doesn?t take psychic abilities to guess whom Merola will portray as villains, particularly given the scene of Hannah crying at her treatment by ?skeptics? who think Burzynski is a charlatan. Yes, I?m guessing that I?m going to be part of the group that, according to the trailer, was ?formed to terrorize and misinform the patients,? along with Bob Blaskiewicz, Josephine Jones, Keir Liddle, and other bloggers critical of Burzynski. Merola also direly accuses and threatens, ?In the worst case scenarios, some bloggers intentionally publish fabricated information to their readers in an attempt to curb new patients from going to the Burzynski Clinic. These individuals are also responsible for ?gate keeping? the Wikipedia Page on The Burzynski Clinic. This issue, as well as the identities of those involved, will be covered in great length in the new 2013 ?Chapter 2? documentary.? I can hardly wait.
• An attempt to reframe Burzynski?s enormous bills for his antineoplaston therapy and criticism that he?s making clinical trial subjects pay to be in his clinical trials. The new claim is that Burzynski isn?t making patients pay for his antineoplastons (see question #13 in Merola?s FAQ), just for ?clinical management? (as if that weren?t incredibly transparent)
• Vindication. A prominent mention of a supposed randomized clinical trial out of Japan plays prominently, but one wonders why these investigators appeared in Burzynski?s movie before they had published their results.

The last time I discussed Merola?s forthcoming movie, I mentioned that he had contacted me in December and asked me to appear as a Burzynski critic. After consultation with skeptics with more media savvy than I, not to mention the PR department at the Barbara Ann Karmanos Cancer Institute (whom I thought it wise to give fair warning that one of their faculty might be featured as evil incarnate in a new documentary and to give the background on what it?s all about, in case there were press inquiries), I politely declined. However, from the video above, it is very clear how I and other skeptics will be attacked. While going on and on about how he thinks most of us have ?good motives? and how we want to be the white knight riding in to save patients from quackery (a desire he somehow manages to convey with clear dismissiveness and contempt), Merola turns immediately around to claim that we don?t know what we?re talking about and we don?t read the literature. This, of course, is complete nonsense, as I?ve read many of Burzynski?s papers (such as they are), delved into ClinicalTrials.gov to look at his clinical trials, examined the plausibility of his claims from a scientific standpoint, and examined the literature from others, both on antineoplastons and related topics. I?ve dissected Burzynski?s claims for antineoplastons based on science, assessed his ?personalized, gene-targeted cancer therapy? claims and found them wanting, and pointed out how what he is peddling isn?t really anything new at all (more on that later), all based on my knowledge, skills, and understanding of cancer as a breast cancer surgeon and researcher. No doubt that?s why Merola needs to discredit me. Other bloggers who have been critical of Burzynski might or might not have my scientific background, but they?ve delved just as deeply into his claims and the evidence for them, and, as I have, they?ve found them highly overinflated and largely not based in science. They?ve also taken on aspects of the Burzynski phenomenon, such what I consider to be his questionable ethics and finding out what happened to a lot of patients who trusted Burzynski, far better than I have. Merola?s dismissal of Burzynski?s critics is, quite frankly, insulting to them and to me.

Merola also makes the unfounded claim that many of the bloggers critical of Burzynski are in the pay of big pharma or work for blogs that are in the pay of big pharma. I know exactly where he got that one from, at least with respect to me; so I?ll deal with it briefly right here and right now. I don?t know what sort of attacks on the UK bloggers who produce the bulk of the skeptical blog posts about Burzynski are coming in Burzynski II, but when it comes to me no doubt Merola is referring to this bit of yellow journalism in 2010 from an antivaccine propagandist named Jake Crosby, entitled David Gorski?s Financial Pharma Ties: What He Didn?t Tell You. The long version of why Crosby?s hit piece is without merit consists of two posts I wrote at the time, here and here. The short version follows. Crosby?s entire chain of logic can be summarized in a brief, blisteringly dumb thesis: My university (Wayne State University) has received grants from Sanofi-Aventis. I also work on the repurposing of a drug originally used to treat amyotropic lateral sclerosis that has anticancer properties that apparently Sanofi-Aventis markets. Even though I haven?t received a penny from Sanofi-Aventis to work on that drug, Crosby inferred that because my university apparently got a significant grant from Sanofi-Aventis my working on that particular drug must indicate a quid pro quo. (Never mind that I didn?t even know my university had gotten any funding from Sanofi-Aventis). Add a bit of conspiracy-mongering about how Sanofi-Aventis vaccines are apparently responsible for the ?autism epidemic? and how I?m very much involved in countering the misinformation of the antivaccine movement, throw in a dash of Crosby?s paranoia, and the conspiracy theory writes itself. In any case, in the interests of complete transparency, I did get a Bayer Healthcare Grants4Targets grant of ?30,000 for one year, but that ended in 2012. That might sound like a lot, but it wasn?t even enough to pay the full salary and benefits of my postdoc for a year. Finally, I fully expect that my not-so-secret other blog will also come under fire for accepting pharmaceutical company advertisements and that that will also come into play in Merola?s movie. We won?t have long to wait, unfortunately.

Predictable and tiresome attacks aside, Pete and Hannah?s video made me curious about the specific success stories that Merola will focus on as ?proof? that Burzynski is on to something; so I decided I should look into their stories. Merola mentioned how he had been looking for patients before they even went to the Burzynski Clinic and even pointed out Amelia Saunders as one. Last year, Burzynski apologists frequently pointed to Amelia as a success story but, very sadly, her family saw her tumor begin to progress again in December, ultimately resulting in her death about a month and a half ago. In the process, Burzynski did what he all too often does and misinterpreted her MRI, in which cystic structures commonly seen in Amelia?s form of cancer as it progresses were seen, as evidence that her tumor was regressing. They were not. So let?s take a look at two cases frequently pointed out to me as Burzynski success stories: Laura Hymas (whose website is Hope for Laura) and the aforementioned Hannah Bradley (whose website is Team Hannah). On the surface to those not familiar with cancer they do look like success stories. If one digs deeper, the true story is a lot murkier. More importantly, as I will show, even if they really are success stories?which is not at all clear?they do not constitute convincing evidence of the general efficacy of Burzynski?s antineoplastons, nor do they justify what I consider to be Burzynski?s highly unethical behavior.

Go Team Hannah!

I will start with Hannah Bradley?s story because I?ve watched the entire 40 minute video Hannah?s Anecdote (whose title is even more appropriate than perhaps Pete Cohen imagined when he made it). The documentary ends triumphantly several months after the events portrayed during the bulk of the film with Hannah apparently having had a complete response to Burzynski?s antineoplaston therapy:

Let me just first say something before I begin my usual analysis. I love these two. I really do. They are the cutest couple, and their love for each other oozes from the video and envelopes the viewer, sucking him in like The Blob, but in a good way. The same is true of every video of them I?ve watched on their video blog. Yes, it?s true that Pete can be a bit annoying with his seeming desire to videotape everything, but I want Pete and Hannah to be able to live a long and full life together, growing old in each other?s company. I really do. In fact, I?d love to hang with these two and maybe buy them a pint or two at their local pub (except that it?s pointed out multiple times that Hannah can no longer drink alcohol). Sadly, this is unlikely ever to pass even if Hannah does completely beat her disease and is still around the next time I make it to London (which is likely to be at least a year or two), because I fear that if they see this (which is likely) they will misinterpret my analysis as trying to destroy their hope. Certainly the families of other cancer patients who have gone the ?alternative? route have attacked me in that way, but what are skeptics supposed to do? Not undertake a dispassionate analysis for fear of what patients will say?

After talking about how he needed to raise ?200,000 in order to take Hannah Bradley to the Burzynski Clinic for what he characterizes as ?life-saving? treatment, a campaign that produced media coverage in the form of articles with titles like ?I?ll try anything to beat brain cancer?, Pete Cohen describes Hannah?s diagnosis, and elsewhere we find out that Hannah underwent awake brain surgery as the surgeons tried to remove all the tumor:

I first met Hannah in April 2010 and we fell in love and since then our relationship has gone from strength to strength. Hannah is 28, has a great personality and has a fantastic sense of humour. Our world took a dramatic turn in February 2011 when, out of the blue, Hannah had a major seizure in the middle of the night. She lost consciousness and was rushed to hospital.

Hannah does not remember much about the two months that followed as she had constant headaches and a number of seizures. She was diagnosed with a very serious brain tumour called Anaplastic Astrocytoma. Hannah decided to have surgery and the 1st of April 2011 and underwent a six and a half hour operation. She was awake for nearly three hours of this operation.

The operation was a success and they managed to remove nearly all of the tumour. We had to wait for the results of the biopsy for a few weeks and we remained positive. However, the news was not good and our world was rocked once more as the results showed a Grade III tumour. Hannah?s bravery and resolve once again rose up as shortly after this she started a six week course of radiotherapy. This went well for the first few weeks but was followed by Hannah?s hair falling out and bouts of tiredness and lethargy.

On top of all of this, Hannah has been dealing with losing her driving licence as she has had a number of seizures and now has epilepsy.

Six weeks after the radiotherapy finished, Hannah had another MRI to see what was going on with the tumour, Once again more bad news, as there were still remnants of this aggressive tumour.

Hannah?s treatment options are very limited and her life expectancy is for this type of tumour is normally around 18 months and this is why I started a mission to find people who had the same condition and are still alive today. I managed to track down a number of these people to speak to them.

In his movie, Pete points out that these people all led back to Burzynski. Of course, as I?ve said before, dead patients don?t produce testimonials for alternative cancer cures. More importantly, Burzynski has a network of true believers, such as the Burzynski Patient Group and a filmmaker like Eric Merola, all of whom actively promote the Burzynski Clinic online. Add to that Suzanne Somers, who included Burzynski as one of her ?doctors who are curing cancer? in her book Knockout: Interviews with Doctors Who Are Curing Cancer and How To Avoid Getting It in the First Place. Indeed, Chapter 7 is all about Burzynski, whom Somers describes as having invented ?the most important and successful non-FDA-approved alternative cancer drug therapy ever in this country.?

In any case, that was the end of July 2011. By November 2011, Pete had raised ?35,000, which was enough to go to Houston, and that?s where his documentary begins, as he and Hannah are preparing to fly to Houston in December 2011 to have a consultation at the Burzynski Clinic. These are interspersed with footage from earlier in which the couple document their quest, talk about how they were warned by their oncologists and other doctors not to waste their money and effort, and talk about their hopes. Not long after they appear at the Burzynski Clinic, they meet with doctors there who tell them that Hannah?s most recent MRI scan showed progression of her tumor (around 8:30 in the movie). Now, I?m not a radiologist, much less a neuroradiologist, but I wondered at all the enhancement on the superficial area of the brain, just under where her neurosurgeon must have raised the bone flap to remove what he could of the tumor. One wonders if much of the remaining enhancement could be still post-surgical and post-radiation change. Certainly, the tumor is cystic-appearing, and after surgery such cysts would likely shrink and be reabsorbed even if the tumor were to keep growing.

Be that as it may, there were a number of things I found very interesting in this video. First, one notes that patients don?t see the great Dr. Burzynski right away. Underlings see them first and commence treatment, assuring the patient that Dr. Burzynski is aware of what they are planning. Second, I?m not particularly impressed with the sterile technique used for putting her Hickman catheter in, nor am I particularly impressed with the sterile technique used to access it by the nurses, who appear to be rather inconsistent about wearing gloves and a mask when accessing the line.

As important as sterile technique is when inserting and accessing long-term indwelling catheters, these complaints are quibbles compared to what this video shows about antineoplaston therapy. First, I notice that nowhere was there anything mentioned about enrolling Hannah on a clinical trial. Remember, part of the consent agreement with the Texas Attorney General back in the late 1990s stated that Burzynski can distribute ?antineoplastons? only to patients enrolled in FDA approved clinical trials, unless or until FDA approves his drugs for sale. Given what a thorough videographer Pete Cohen obviously is, I find this omission very curious. Certainly, given how much detail he?s used in this video and in his vlogs I?d expect that if the subject of clinical trials was mentioned he would have included it.

The other thing that struck me was just how much Burzynski is full of it when he advertises antineoplastons as not being chemotherapy and, more importantly, as being nontoxic. At least a third of the video consisted of the difficulties that Hannah had with her treatment, including high fevers, a trip to the emergency room, and multiple times when the antineoplaston treatment was stopped. She routinely developed fevers to 102? F, and in one scene her fever reached 103.9? F. She felt miserable, nauseated and weak. I?ve seen chemotherapy patients suffer less. I was also very puzzled at how the Burzynski Clinic could allow a cancer patient to linger with a fever of 102? F and sometimes higher, accompanied by shaking chills, to go back to a temporary lodging without admitting her to the hospital. It?s not clear what sort of workup was done to evaluate her either, what her white blood cell count was, or what her other labs were. Did they draw blood cultures? Did they get urinalyses and cultures? Did they do chest X-rays to rule out pneumonia? It?s all very unclear, other than that she apparently was given some antibiotics at some point. Did she have the flu, given her flu-like symptoms, or was this due to her antineoplaston therapy? The reaction of the clinic staff (i.e., rather blas?, even though at one point Hannah clearly demonstrates a change in mental status, appearing ?drunk? and complaining of double-vision) made me wonder if this sort of problem was a common occurrence. At another point, Pete and Hannah come to believe that the fevers might have been due to the tumor breaking down, which strikes me as implausible. Later, she develops an extensive rash. It?s difficult to tell for sure what it is at the resolution of the video, but it looks like erythema multiforme, which is generally an allergic rash. What?s the most likely cause of such a rash? Guess. Erythema multiforme is usually a drug reaction.

Near the end of the video, we see a series of MRIs. Hannah and Pete are told that the first MRI, done about a month after the antineoplaston therapy started, shows that the tumor has decreased in enhancement and size, with a decrease of about 10%. I don?t know who this person is at the Houston Medical Imaging facility just up the road from the Burzynski Clinic is, but from what I could see it isn?t clear at all that the tumor decreased in size by 10%. In fact, it?s rather hard to tell if a tumor has decreased in size at all. With a tumor that size detecting a 10% decrease in size is almost within the margin of error of the test. Even Burzynski didn?t try to sell this as a true decrease; he called it stable disease, which is what it was:

However, later in the video, there are more convincing MRIs. Indeed, the MRI dated July 29, 2012 looks quite good, with little or no enhancement left. The question, of course, is: Does this mean that Burzynski?s antineoplaston treatment worked for Hannah? Sadly, the answer is: Not necessarily. It might have. It might not have. Why do I say this? First, she didn?t have much residual disease after surgery and radiotherapy, and in fact it?s hard to tell how much is tumor and how much is postop and radiation effect. Second, the median survival for a grade III astrocytoma is around 2 to 3 years, and with different types of radiation therapy five year survival is around 15% or even higher. This is not so rare that Hannah?s survival is so unlikely that it has to have been Burzynski?s treatment that saved her. More likely, she is a fortunate outlier.

I?m also very worried about Hannah. Her last couple of vlogs are the reason. For instance, in her vlog of December 2, 2012, in marked contrast to past vlogs, Pete is noticeably evasive when discussing her latest scan, and both Pete and Hannah appear uncomfortable, in marked contrast to previous vlogs:

Even more worrisome was a cryptic Facebook post from November 1, 2012:

It?s been a long time coming but here is our new Team Hannah Blog. I am sorry we don?t have the best of news but I am ok. http://www.teamhannah.com/2012/11/01/team-hannah-blog-011112/

The vlog entry referenced no longer exists. Then there was Hannah and Pete?s Christmas message:

In this vlog, Hannah and Pete are even more evasive than before, using vague terms about having had a ?little blip? and saying that the latest scan showed that the treatment was working, almost as though they were trying to convince themselves that this was so. Particularly noticeable is the lack of new scans being shown on the Team Hannah Facebook page. The last scan shown was from August 27, 2012. Up until that point, Peter was religiously posting Hannah?s new scans and (quite understandably) exulting over the lack of visible tumor mass. All of this is why I really, really fear something bad has happened. I hope I?m wrong. Assuming that I am wrong, however, a single case tells us very little. Will the second case that I know that Merola will exploit tell us more? Let?s find out.

Is there Hope for Laura?

The other Burzynski success story that Burzynski supporters dare us to take on is that of Laura Hymas, whose website Hope for Laura. Her story is described on her website thusly:

Laura was diagnosed with an Oligodendroglioma, which is a rare brain cancer and in the UK there is no cure. The tumour goes deep into the brain and is in a location that is inoperable so our doctors applied a ?watch and wait? approach which is standard for this type of cancer where you have a scan every three months to see if anything changes rather than applying treatment. However we recently had worse news in April 2011 Lauras MRI scan revealed growth and changes, she had a biopsy and we learnt that the tumour had progressed into a Glioblastoma Multiforme which is the most agressive type of brain cancer with a much poorer prognosis.

Many aspects of Laura?s story are similar to Hannah?s story, but one thing is different in that she started out with a less aggressive tumor, which was managed by ?watchful waiting? for a time, and ultimately the tumor underwent malignant degeneration to become a glioblastoma. More details can be found at her page on the Burzynski Patient Group website. Laura started having more seizures; she was unable to care for her son; she felt as though her ?life was slipping away,? and so it appeared to be. Then, like Hannah, she decided to go to Houston to the Burzynski Clinic, and like Hannah and Pete Laura and her fiance started raising money, such that they raised ?100,000 in just a few weeks from donations. What happened next is described here:

I have now been on antineoplaston therapy since the 8th August 2011. The side effects I have suffered are tiredness, a skin rash which subsided after a few days when I began treatment and a severe thirst! The medicine is rich in sodium and I have to infuse 2 litres of it daily (a dose which lasts 90 minutes every 4 hours 24/7) so I drink approx 5 litres of water daily. This is a very full on treatment; it isn?t making me feel ill but while the pump is running it does affect my day to day decisions like for example going shopping or Ben is driving us to see family far away I need water to drink and a toilet close by! I am carrying around an infusion pump all day connected to my Hickman line in my chest. It?s like having another baby!

To be honest though, for me it?s really worth it. I won?t be connected to the medicine pump forever! I have an MRI scan at a private hospital every 6 weeks. When we came home in August it took me until the middle of October to slowly increase my antineoplaston dose up to ?maintenance dose? ? this is the dose that Dr Burzynski deems is most effective for my body weight.

Then six weeks later on the 29th November 2011 scan my tumour started shrinking, by 36%. On the 10th January 2012 I had another scan ? 56% tumour decrease!

I just had a scan on the 21st February and it was even better news ? 77% tumour decrease!

As of August 2012 there is now no trace of my Tumor at all. I always get a second opinion from a UK radiologist who confirms there is just a cavity left which should resolve over time.

So is Laura?s case proof that there?s something to Burzynski?s treatments? Is the fact that Burzynski has apparently discharged Laura as a patient slam-dunk evidence that Burzynski has cured her of her incurable tumor? Sadly, no.

For one thing, late complete responses to radiation are not as rare as Burzynski supporters imply, as described in this Medscape article on glioblastoma:

The responsiveness of glioblastoma multiformes to radiotherapy varies. In many instances, radiotherapy can induce a phase of remission, often marked with stability or regression of neurologic deficits as well as diminution in the size of the contrast-enhancing mass. Unfortunately, any period of response is short-lived because the tumor typically recurs within 1 year, resulting in further clinical deterioration and the appearance of an expansile region of contrast enhancement

Moreover, complete remissions in glioblastoma do occur. They?re uncommon, but they do occur. There are case reports in the literature, such as this one, and a recent series describes the outcomes of long-term glioblastoma survivors as rare, but increasingly common. The bottom line is that we don?t know why Laura is still alive. It?s possible that it was the antineoplastons; it?s possible that it was the radiation therapy alone.

Moreover, discharging a patient after her treatment for cancer is complete is something real oncologists almost never do right away. They usually follow their patients, often for five years, sometimes even longer. At this point, Laura is less than six months out from the first MRI scan showing no residual tumor, and she only just finished her antineoplaston therapy. Next, keeping an open mind I will admit that Laura?s case is more suggestive of an antitumor effect due to antineoplaston therapy than Hannah?s case is. What I find curious is the delayed effect. Laura started her therapy on August 8, 2011 but it was not until nearly four months later that the tumor showed evidence of shrinking. That?s a long time for an active therapy to start to work, particularly for a tumor that is as aggressive as a glioblastoma. It?s possible, but in general, even if antineoplastons really saved Laura, a treatment that takes three or four months to kick in is generally not that enthusiastically embraced by oncologists. Basically, Laura Hymas? case seems a bit more consistent with an antitumor effect due to antineoplastons than Hannah Bradley?s case, but it is only a single case.

So what might be going on here?

Antineoplastons versus sodium phenylbutyrate

Back in late 2011, when I first took a serious interest in Stanislaw Burzynski and what he?s been doing, I wrote a three-part series in which I (1) analyzed Burzynski The Movie, its claims, and whether there was any evidence that antineoplastons do anything for cancer; (2) discussed why Burzynski?s claims that his ?personalized gene-target cancer therapy? are overblown and nonsensical; and (3) how there might be a way to understand how antineoplastons might actually be real drugs, with the problem, of course, being that, when it comes to demonstrating efficacy, Burzynski is doing it wrong?very wrong indeed. They say that even a blind squirrel occasionally finds an acorn. Is it possible that antineoplastons are the acorn that Burzynski found?

I pointed out originally that antineoplastons A-2.1 and A-10 are nothing more than simple chemicals based on amino acids. Saul Green explained years ago:

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.

One notes that whenever a bag of antineoplastons is shown in any of these videos, it shows antineoplaston A-10 at a whopping 30% concentration (300 g/L). In any case, here?s a recent review article on a drug called sodium phenylbutyrate (PB):

Sodium phenylbutyrate (figure 1), a HDACI, is an aromatic fatty acid that is converted/oxidized in vivo into phenylacetate (PAA) by ?-oxidation.[11] In humans the so formed PAA is eliminated by conjugation with glutamine to form phenacetylglutamine, which is excreted in the urine. This metabolic pathway is the mechanism by which phenylbutyrate acts as an ammonia scavenger in patients with urea cycle disorders (UCDs) and hyperammonemia.

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). It turns out that PB is a prodrug for PA and PAG, which means that the drug is converted into an active metabolite to work. 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 this report, 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.

Remember my post about the use and abuse of the term ?epigenetics? by various questionable practitioners, in which epigenetic effects and changes are invoked not unlike magic (or like another favorite buzzword ?quantum?) to ?explain? why various woo works? In that post, I explained a bit about epigenetics and why it?s a hot area in cancer research, as well as why histone deacetylase (HDAC) inhibitors are a promising new avenue for cancer therapy. I also puzzled about why HDAC inhibitors are considered ?targeted,? given that they have the potential to affect huge swaths of chromatin and the expression of the genes in the DNA therein, but that?s just me. I guess I can?t fault Burzynski too much for ?talking the talk,? even though it?s quite clear that when it comes to targeted therapy he doesn?t know what he is talking about, as has been amply documented. Indeed, Burzynski is so arrogant that he recently gave an interview in which he claimed to have been a pioneer-perhaps even the originator?of the concept of gene-targeted cancer therapy back in the 1990s. It?s utter rot, of course, but Burzynski really did make that claim.

Perusing the article, I find there is a fair amount of preclinical evidence that PB has antitumor effects in certain tumor types, specifically colon carcinoma, Burkitt lymphoma, primary acute myeloid leukemia, retinoblastoma, prostate cancer, U138 MG, T98G, U373 MG and A-172 glioma cells, medulloblastoma, and hepatocellular carcinoma. Ironically, however, its ability to pass the blood-brain barrier is a problem, which makes it odd that Burzynski keeps using it for brain tumors. In these preclinical models, PB shows evidence of being an HDAC inhibitor, chemical chaperone, and pro-differentiation agent. The clinical evidence is much less impressive, however. Indeed, I reviewed the clinical evidence for PB as an anticancer therapy the last time I discussed this, and all I found was a bunch of phase I studies showing safety but no real efficacy. Of course, phase I studies aren?t designed to show efficacy, but often investigators can get a hint of whether a drug is likely to have activity from phase I results. There was also a case report from 2002 showing a durable remission for four years in a malignant glioma treated with PB.

Given the impending release of Burzynski II, I decided to update my search, to see if there was anything more recent about PB and cancer. Of the references I found on PubMed, there were no new clinical trials published over the last 14 months since my last review. There were a few preclinical studies using cell culture and mouse models, but nothing new in human subjects. The state of our knowledge regarding PB and cancer can thus be correctly said to be more or less unchanged since late 2011. If Dr. Hideaki Tsuda, the Japanese anesthesiologist at Kurume University Hospital is correct when he states in the second trailer for the Burzynski sequel that he has done a randomized controlled clinical trial demonstrating the efficacy of antineoplastons in metastatic colorectal cancer, that would be the first convincing clinical evidence that antineoplastons (excuse me, PB) have significant efficacy in any cancer.

Of course, Tsuda hasn?t published the results of his clinical trial, which makes me wonder why he?s appearing in Burzynski II touting the results of his study when it hasn?t been published yet. The last study I see from his group is a study from 2005 examining breast cancer cell lines, although there is a case study from 2003 looking at colon cancer that shows mildly promising results. As Elton John would sing, I?ve seen that movie too. Burzynski?s been claiming he?ll publish the results of his clinical trials for decades now. Tsuda has been collaborating with Burzynski for over 25 years. Am I going to hold my breath waiting for him to publish the results of this randomized clinical trial he?s touting in the trailer? Not really. It?s time for Burzynski and Tsuda to put up or shut up.

The bottom line

So we come full circle, back to the question of whether the cases of Hannah Bradley and Laura Hymas are convincing evidence that Burzynski?s antineoplaston treatment works. Contrary to what Burzynski defenders claim, I started out agnostic regarding the question of whether antineoplastons have any value in cancer therapy. What I objected to was how Burzynski has continued to use them in patients and, in my opinion, abused the clinical trial process as a means of continuing to use them. Burzynski?s motivations and ethics aside, considering these cases and their (so far) good outcomes from from a purely scientific and medical standpoint, we have three possibilities:

1. Spontaneous remission
2. Treatment effect due to conventional therapy
3. Treatment effect due to antineoplastons

Note that the second and third possibilities are not mutually exclusive.

Given that spontaneous remission is rare in malignant brain tumors, possibility #1 is highly unlikely, albeit not completely impossible. In Hannah?s case, I tend to conclude that most likely possibility #2 is primarily at work here, although it?s not possible to exclude a contribution from possibility #3. The reason I conclude this is that the shrinkage of the enhancing part of her tumor is not outside the range of range of effects that can be observed due to her radiation therapy in mid-2011 in that the enhancing mass of her tumor continued to decrease in size. Given the biology of her tumor, a year and a half is too short a time to conclude that Hannah is a success story. Even if she is still in complete remission, six months is too short a time to know if this remission is durable. Unfortunately, as I described above, it also appears from Pete and Hannah?s more recent reports that her tumor might have recurred. How else can I explain their rather evasive comments in their last two vlogs, coupled with their cryptic Facebook comment, a vlog that is apparently no longer on her website, and the fact that they have not shown any of Hannah?s more recent scans, which is in marked contrast to what they did when her tumor was shrinking? I sincerely hope I?m mistaken. I don?t want either Hannah or Laura to recur and sincerely hope that they are, indeed, disease free and remain so for decades to come. But just because either of them might be disturbed by my frank discussion is no reason for me not to discuss their cases, particularly given that they have both apparently agreed to assist Eric Merola in producing his latest propaganda-fest.

Laura Hymas is different in that she provides somewhat more suggestive evidence for a possible effect from antineoplastons. The reason, of course, is the longer period of time it has been since she finished her radiation therapy and since her still being in complete remission five and a half months after her first scan showing no residual tumor. However, her case is by no means the slam-dunk evidence that Burzynski supporters represent it as (or, for that matter, that Merola touts it as in his upcoming movie), given that it has been less than six months since confirmation of a complete response. Moreover, given that HDAC inhibitors do seem to have some efficacy against glioblastoma, it is not unreasonable to expect that PB might actually have had activity in Laura?s case. Making claims, as Burzynski does, however, that his antineoplaston therapy is more efficacious than conventional therapy is unwarranted based on a single patient. Conventional therapy can produce durable remissions and complete responses, too, and, although they are still rare, they are becoming more common. That?s why legitimate randomized clinical trials are needed to determine if PB/antineoplastons have antitumor effects in humans; which tumors are sensitive; if there are any biomarkers of sensitivity; and to separate the signal from the noise. Anecdotes like those of Hannah Bradley and Laura Hymas can be suggestive, but prove nothing.

It?s also why what Burzynski appears to be doing is an incredible disservice to cancer patients. If, in fact, he has a treatment that is so much more effective against ?untreatable? cancers than anything we currently have, then he should have been able to demonstrate it by now. His excuses, in fact, are pathetic. He trots out the old alternative cancer treatment excuse that big pharma, the FDA, and the ?cancer industry? are out to get him because they don?t want a cure for cancer. You can see in Merola?s second trailer that this hoary old chestnut of quacks is going to play a central role in Burzynski II. He claims he has no pharma funding and no resources to do proper clinical trials, despite registering over 60 clinical trials since the 1990s and publishing none of them. This is in marked contrast to startup companies with fewer resources than Burzynski managing to take a drug concept through clinical trials within a few years. For example, contrast Burzynski?s story to a story like that of PLX4032, which was taken through phase I and II trials rapidly and is now in phase III trials.

No, I don?t buy Burzynski?s excuses at all.

Finally, what I have against Burzynski is not that I think he?s almost certainly wrong about antineoplastons being a huge advance in cancer. Scientists and physicians are wrong all the time; it?s the nature of science. I?ve been wrong on numerous occasions in my research. What I have against Burzynski is that, from my perspective, he?s ?doing it wrong.? He?s abusing the clinical trial process. He?s having patients pay exorbitant sums of money to be on clinical trials and then not publishing the results. He?s hiring dubious PR flacks to deflect the criticism, getting well-known quack apologists (such as Suzanne Somers and Joe Mercola) to defend and promote him; attacking skeptics by characterizing them as ?skeptics attacking recovering cancer patients on Twitter?: and, rather than publishing his results, he?s promoting his ?results? in documentaries by a fawning sycophant whose primary business is to produce commercials and promotional videos for large corporations and demonstrating a large number of other worrisome warning signs of dubious medicine.

Burzynski is not doing what real scientists and clinical investigators do, and neither is Hideaki Tsuda. Publicizing their alleged research in a movie made by a Burzynski sycophant, toady, and lackey is just not the way science is supposed to be done. Barring the publication of truly convincing clinical trial evidence by more sources than just Burzynski (given that Burzynski has already shown his methodology for conducting clinical trials to be questionable at best and that his preclinical data supporting his methods are at best weak and usually appear in publications that are not peer-reviewed), if we take in totality the evidence for the anti-cancer efficacy of PB along with all the evidence from the past 35 years for the anti-cancer efficacy (more properly, the lack of efficacy) of antineoplastons, the inescapable conclusion is that PB/antineoplastons might?I repeat, might?have very modest efficacy against some tumors through the HDAC inhibitor activity of PB. Whether that activity seen in some preclinical models truly exists and translates into human use and, more importantly, whether it is worth the not inconsiderable toxicity of antineoplastons as prescribed by Burzynski, are questions that Burzynski has, in my opinion, already shown that he will almost certainly never answer.

That?s why I hope that this time the FDA really does shut him down.

Source: http://www.sciencebasedmedicine.org/index.php/stanislaw-burzynskis-cancer-success-stories/

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