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Stanislaw Burzynski: Bad medicine, a bad movie, and bad P.R.

And the Lord spake, saying, “First shalt thou take out the Holy Pin. Then shalt thou count to three, no more, no less. Three shall be the number thou shalt count, and the number of the counting shall be three. Four shalt thou not count, neither count thou two, excepting that thou then proceed to three. Five is right out. Once the number three, being the third number, be reached, then lobbest thou thy Holy Hand Grenade of Antioch towards thy foe, who, being naughty in my sight, shall snuff it.

Cleric from Monty Python and the Holy Grail

I’ve always wondered about the power of the number three. When it comes to quackery propaganda movies, certainly three seems to be the magic number. For example, The Greater Good, an anti-vaccine propaganda film, features three anecdotes, three children allegedly suffering from vaccine injury, and it interspersed its interviews with experts, both real (such as Dr. Paul Offit) and phony (such as Barbara Loe Fisher) with vignettes from these children’s stories interspersed between them in a highly biased manner. I have to wonder whether these cliches are taught in film school, given that they seem to be so common. Such were the thoughts running through my brain as I watched the latest medical propaganda film by writer/producer Eric Merola that’s floating around the blogosphere and the film circuit, Burzynski The Movie: Cancer Is Serious Business. In this movie, there are three testimonials, and, if anything, they are far more manipulative than even the testimonials featured in The Greater Good, because each of them are of the type that portrays doctors as sending a patient home to die; that is, until a “brave maverick doctor,” one Stanislaw R. Burzynski, MD, PhD, comes to the rescue with his unconventional and unproven therapy. The only difference is that this film counts testimonials up to the number three in the beginning as “proof” that Burzynski can cure cancer before lobbing the Holy Hand Grenade of Burzynski towards its foes in the hopes that, being naughty in the filmmaker’s sight, the FDA and Texas Medical Board will snuff it. Or, as a caption says right at very the beginning of the movie:

This is the story of a medical doctor and PhD biochemist who has discovered the genetic mechanism that can cure most human cancers. The opening 30 minutes of this film is designed to thoroughly establish this fact — so the viewer can fully appreciate the events that follow it.

It turns out that the grenade is a dud.

The evidence presented to “thoroughly establish” that Burzynski “can cure most human cancers” consists not of clinical trials, not of animal studies, not of basic science. Rather, it consists of three testimonials that take up the first 30 minutes of the movie, along with testimony before a Congressional subcommittee by Sgt. Ric Schiff, who opines that because he is a policeman he can spot fraud and he doesn’t see any fraud in Dr. Burzynski. He tells the story of his daughter who, according to him, developed a highly malignant brain tumor that had “spread throughout her spine and brain” that Burzynski is said to have successfully treated.

The remaining tedious hour-plus of the movie consists of one big, JFK-style conspiracy theory. Because of Burzynski’s “miracle cure” for most cancer in the form of what he calls “antineoplastons,” the movie argues, the FDA, big pharma, and the rest of the “cancer establishment” want to put Burzynski out of business. The movie claims they want this not to protect the public but rather to protect industry profits and FDA power. The rest of the movie shows lots of archival footage with an ominous, biased voiceover, of the FDA, the NCI, the Texas Medical Board, and various other entities investigating, or, as the movie implies, persecuting this “brave maverick doctor” because he’s found a cure for most kinds of cancer.

But has he?

I’ve been meaning to do a post about Burzynski ever since the beginning of this blog but have tended to back away because summarizing the Burzynski situation would be more work than the average post. I’ve also been meaning to do a review of this movie for quite some time now, given that it was first released over the summer and was made available for free online for a period of time in June. Since then, it’s been percolating through the cancer quackery underground and showing up at various film festivals. In a way, I have Burzynski’s apparent shill himself, a man named Marc Stephens, to thank for reminding me to get to this topic, particularly given that I’ve been meaning to write about Burzynski since the very beginning of this blog. How Marc Stephens operates will inform you a bit about Burzynski; so I will briefly describe what happened last week.

One week ago, a skeptical blogger whose work I admire, Andy Lewis, wrote a post about two charity concerts that a British performer named Peter Kay was doing to raise money to pay for the medical care of a four-year-old girl named Billie Bainbridge, who, tragically, has an inoperable and very rare brain tumor known as Diffuse Intrinsic Pontine Glioma (DIPG). Now, given that the UK government funds the NHS, which guarantees health care for its citizens, you might wonder why such spectacular sums of money (in this case, £200,000) would be needed for this child. It turns out that the money raised is to be used to take Billie to the Burzynski Clinic in Texas. This reminded me very much of a campaign I remember seeing two years ago for a woman with medullary thyroid cancer named René Louis, who, although she had health insurance, wanted to pursue Burzynski’s methods, which her insurance quite correctly wouldn’t pay for. In fact, it turns out that this is not an uncommon scenario for Burzynski patients, with patients like Louis or families like the Bainbridge or the Hofsess family, having been convinced that Burzynski is their only hope, going to the media and managing to get human interest stories written about their campaigns to raise money. Some, like René Louis or the Hofsess family, go so far as to set up charitable organizations to continue to raise money for others seeking Burzynski’s treatment. Unfortunately, the “human interest” interest in these stories rarely mixes with a skeptical or science-based viewpoint, even though the more appropriate spin on such stories is to portray them as consumer issues. If only the spin on such stories was more like that of the story of Wayne Merritt!

Given that Burzynski is known for having promoted a scientifically unproven cancer treatment called “antineoplastons,” Andy was, quite understandably, alarmed and expressed his alarm in a blog post a few days ago entitled The False Hope of the Burzynski Clinic, in which he nicely summarized the history and evidence about antineoplastons. He pointed out that there is little or no convincing clinical evidence that antineoplastons have activity against cancer, much less that they offer hope to a desperate patient like Billie. As a result, legal thuggery commenced a couple of days later, courtesy of the aforementioned Burzynski fan Marc Stephens, whose name can’t be found on the Burzynski Clinic or Burzynski Research Institute‘s websites but can be found in Marketing and Sponsorship for the Burzynski Patient Group, a patient group that does not appear to be actually affiliated with the clinic. It turns out that this appears to be common practice for this Marc Stephens, as Peter Bowditch can attest. Indeed, recently, Mr. Stephens even decided to issue legal threats against a teenager named Rhys Morgan.

It was this confluence of events that led me to think that now is time to look at Burzynski’s claims from the perspective of a cancer surgeon and researcher; i.e., myself. Looking at the evidence presented in Burzynski The Movie seemed a perfect way to begin.

For those who have the time and inclination to do so before my discussion, the whole movie is still available on Mike Adams’ quack website and on YouTube:

NOTE: Apparently, The Documentary Channel has asserted some sort of copyright claim and forced YouTube to take down the video for this movie. The movie is, however, still available at that other wretched hive of scum and quackery (besides the Huffington Post), namely the video outlet for Mike Adams, NaturalNews.tv.

Burzynski and “antineoplastons”

Before I return to the content of the movie, it’s essential that I provide a bit of a background on Dr. Burzynski, his claims, and the evidence behind them. An excellent summary can be found in Quackwatch (of course), as well as at the NCI website, the American Cancer Society, and others. The short version of the story behind antineoplastons is that there is no good clinical evidence to suggest that they have any significant activity against cancer. A somewhat longer version follows, so that readers here have the background to understand my review of Burzynski The Movie.

Dr. Burzynski first gained fame for his cancer therapy back in 1988, when Sally Jesse Raphael featured four “miracle” patients of Burzynski’s, who, according to her, had had incurable cancer and failed conventional therapies but were rendered cancer-free, thanks to Dr. Burzynski. Unfortunately, four years later in 1992, Inside Edition followed up these four patients and found that two of the four had died and a third had recurred, while the fourth had had bladder cancer with a good prognosis. In that report, the widow of one of Raphael’s guests reported that her husband and five others had sought treatment from Burzynski and that all had died. In addition:

In 1995, a federal grand jury indicted Burzynski for mail fraud and marketing an unapproved drug. The indictment charged that he had billed insurance companies using procedure codes for chemotherapy, even though his treatment was not chemotherapy. He was tried in 1997 but not convicted.

Of course, antineoplaston therapy is chemotherapy, despite Burzynski’s attempts to portray it otherwise, but more on that near the end of this post. In the meantime, testimonials and no firm clinical trial data to support Burzynski’s methods have been par for the course ever since, for over three decades now. It all began in the late 1960s, when Burzynski proposed that a system separate from that of the immune system helped to keep developing cancer cells in check by “reprogramming misdirected cells.” He dubbed these compounds “antineoplastons” and believed them to be naturally occurring peptides and amino acid derivatives that inhibit the growth of malignant cells but do not harm normal cells. In early reports, he found that healthy people had more antineoplastons in their blood and urine than people with cancer (results portrayed in cartoon form in the movie). From this observation, Burzynski postulated that antineoplastons could be used to treat cancer. Not long after that, he left academia in the late 1979s, formed his own institute (the Burzynski Research Institute) and clinic (the Burzynski Clinic), and began doing research into antineoplastons. In 1980, Burzynski characterized the structures of antineoplastons and, instead of isolating them from urine, started synthesizing them chemically, whereas previously he had been isolating them from urine collected from underground tanks in public parks. These days, preparations now used in clinical studies to treat cancer are antineoplastons A10, AS2-5, AS2-1, A2, A3, and A5.

In reviewing Burzynski’s history, one thing that stands out to me as a cancer researcher who has been involved in drug development is data from the preclinical studies summarized by the NCI. To cut to the chase, the concentrations required in in vitro and in animal studies to show any effect at all are quite high:

Japanese scientists have tested antineoplastons A10 and AS2-1 in vitro for cell growth inhibition and progression in several human hepatocellular cell lines.[2,3] Tests were performed in a dose-dependent manner at concentrations varying from 0.5 to 8 µg/mL for A10 and AS2-1, and growth inhibition was generally observed at 6 to 8 µg/mL. This dose level is considered excessively high and generally reflects a lack of activity. Growth inhibition of one of the cell lines (KIM-1) was observed at low concentration for a mixture of cisplatin (CDDP) and A10, but this result was probably caused by the cisplatin, which was effective at concentrations of 0.5 to 2.0 μg/mL when tested alone.[4] AS2-1 was reported to induce apoptosis in three of the cell lines at concentrations of 2 and 4 μg/mL.

These are not results that would get me excited about these compounds, because levels that high would be very difficult to achieve in humans. This will become very relevant later. These observations are also why it it is not in the least bit surprising that the NCI ultimately came to this conclusion about antineoplastons:

Antineoplaston therapy has been studied as a complementary and alternative therapy for cancer. Case reports, phase I toxicity studies, and some phase II clinical studies examining the effectiveness of antineoplaston therapy have been published. For the most part, these publications have been authored by the developer of the therapy, Dr. Burzynski, in conjunction with his associates at the Burzynski Clinic. Although these studies often report remissions, other investigators have not been successful in duplicating these results. (Refer to the Human/Clinical Studies section of this summary for more information.) The evidence for use of antineoplaston therapy as a treatment for cancer is inconclusive. Controlled clinical trials are necessary to assess the value of this therapy.

“Inconclusive” is putting it mildly, but because Burzynski reports remissions, the ever-cautious NCI had little choice but to word its conclusion that way. In any case, the fact remains that Burzynski’s antineoplastons are not approved by the FDA for the treatment of cancer because there is no compelling evidence that they work. Not that that stopped Burzynski, who kept providing antineoplastons to desperate cancer patients. Ultimately, in 1998, the State of Texas secured a consent agreement with Burzynski stipulating that he:

  1. cannot distribute unapproved drugs in Texas;
  2. is allowed to distribute “antineoplastons” only to patients enrolled in FDA approved clinical trials, unless the FDA approves his drugs for sale;
  3. cannot advertise “antineoplastons” for the treatment of cancer; and
  4. on his website and in promotional material his ads must have a disclaimer that the safety and effectiveness of “antineoplastons” have not been demonstrated.

Obviously, big pharma got to Texas.

Dr. Burzynski is a rather difficult woo-meister to tackle for a variety of reasons. First, he apparently really is a legitimate MD/PhD (although Saul Green has questioned whether Burzynski’s PhD is legitimate), proving beyond a doubt that having an MD/PhD double-threat degree does not necessarily inoculate one from falling prey to pseudoscience. He’s also an example of a brave maverick doctor (specifically the “iconoclast” type) who has convinced himself that he’s discovered The One True Treatment for cancer. Like many brave maverick doctors, be they Mark and David Geier, Andrew Wakefield, or Robert O. Young, Burzynski appears to believe that he is a crusading researcher rather than a quack. He also has many of the trappings of a reputable scientist, including publications in good journals (although none recently). In all this, he resembles Andrew Wakefield before he was booted from Thoughtful House.

Burzynski also resembles Andy Wakefield in that other scientists have had a great deal of difficulty replicating his results. The substances that Burzynski claimed to have isolated from urine (his “antineoplastons”) have never been shown to do much against cancer by anyone other than Burzynski. As the article at Quackwatch points out, the NCI could not replicate Burzynski’s early results. Neither could drug company Sigma-Tau Pharmaceuticals. Neither could the Japanese National Cancer Institute. So what we have here is a therapy that, contrary to what some skeptics say, is not without a modicum of biological plausibility. After all, it’s not entirely implausible to think that the body might make substances that arrest the growth of cancer that can be isolated from the urine, and no less a figure than Dr. Judah Folkman himself demonstrated that the body produces endogenous anticancer substances. Indeed, I’ve studied some of these myself, including angiostatin and endostatin, both of which Judah Folkman first isolated from mouse urine.

However, the fact that the body does produce endogenous inhibitors of tumor growth and progression does not mean that antineoplastons function as endogenous inhibitors of cancer progression, and scientific evidence that they do function that way has been elusive at best, other than from Burzynski’s research institute and groups affiliated with him. If there’s one thing that should raise a red flag for pseudoscience, it’s when only one scientist can produce the reported results and no one else can. Replication is utterly key to the acceptance of science, and if other groups could replicate Burzynski’s work I might scratch my head and say, “You know, Dr. B may be on to something there.” But no one else has yet, and I’m left scratching my head and wondering how so many people can believe in Burzynski’s results given the paucity of science and evidence. And it’s not for lack of opportunity, either. Back in the 1990s, the NCI practically bent over backwards to give Burzynski every chance to prove that his antineoplastons have anticancer activity in humans.

Another red flag is that, like other brave maverick iconoclasts frustrated with the “arrogance,” “blindness,” and “inflexibility” of his academic colleagues, Dr. Burzynski founded his own clinic, which offers a “variety of alternative cancer treatments for patients diagnosed with over 50 different types of malignancies, including colon, pulmonary, breast, prostate, head and neck, ovarian, pancreatic, esophageal, hepatic, renal, bladder, brain, malignant melanoma, lymphoma, and many others,” and research institute, whose website describes it as “a biopharmaceutical company committed to developing treatment for cancer based on genomic and epigenomic principles.” (Apparently it’s not just about the antineoplastons anymore.) Since then, it’s been a life on the fringes of science for Dr. Burzynski, and of late he appears not to be even trying anymore, as he hasn’t published in anything resembling a reputable journal for a long time. A PubMed search reveals no publications in the peer-reviewed literature since 2006, and the closest I find to a recent publication in a reputable journal is this report in 2004 of a single arm uncontrolled trial in children. Since 2004, Burzynski has only published three papers, two of which were published in Integrative Cancer Therapy (not a a good journal), one of which was a review article in Paedatric Drugs. His science, which was always weak to begin with, is getting even weaker still.

Instead, Burzynski relies on testimonials for evidence, all the while charging patients (like Billie Bainbridge) huge amounts of money to take part in his clinical trials, a practice that, while not illegal — although it should be — is highly unethical and quite properly viewed with suspicion by legitimate cancer clinical trialists like myself. It is in presenting these testimonials that Burzynski The Movie is its most manipulative.

Three testimonials

If you thought The Greater Good was bad in its emotionally manipulative use of testimonials, you ain’t seen nothing yet. Burzynski The Movie takes such manipulativeness to a new level, and, unlike The Greater Good, Burzynski The Movie doesn’t even try to present an alternative viewpoint, even if just to knock it down. The primary “expert” it relies upon is Julian Whitaker, who happens to have gained fame as Suzanne Somers’ doctor and claims he can cure diabetes. It shows, given that he is hugely impressed by unimpressive evidence; that is, as long as it supports Burzynski he likes it. Indeed, very early in the movie Whitaker is inordinately impressed with a case series from Burzynski, which he characterizes as the “most important discovery in cancer treatment—ever.” It’s not. It’s a series of “best cases” chosen by Burzynski himself. If you look at the cases, you’ll see that most of them are, at best, only suggestive of anticancer activity due to antineoplaston therapy. More importantly, we don’t know the denominator; i.e., how many patients with similar tumors were treated and didn’t respond. Remember, this is a best case series, and, although some of the cases look as though there might have been a antitumor response, I’d hardly call this the “most important discovery in cancer treatment—ever,” and that’s even if the data were exactly as reported.

Burzynski The Movie starts out with three testimonials. Actually, it’s four if you count the testimony of Sgt. Ric Schiff at the very beginning of the movie, but only three of them are listed on the website, complete with “interactive transcripts” and medical records. His story, while harrowing, doesn’t inform us if antineoplastons work, for the simple reason that it is a story where his daughter received conventional therapy in addition to the antineoplastons. That’s why this testimonial strikes me as being of the type of testimonial where the conventional therapy worked better than expected but the parents attribute their daughter’s cancer disappearance to antineoplastons. Ultimately, sadly his daughter died, and Sgt. Schiff goes on and on about how the radiation and chemotherapy had “destroyed her brain.” Given that, unlike the case of the three main testimonials, no medical records are presented, there’s no reason for this testimonial to be there other than for emotional manipulation, no matter how sorry I as a viewer feel for a loving father who lost his daughter as a child.

More useful are the three testimonials that follow. These include Jodi Fenton, Jessica Ressel, and Kelsey Hill. It turns out that jli has done an capable analysis of the three testimonials in this movie. As a cancer surgeon and researcher, however, I feel have something to add of my own, particularly in terms of clinical cancer treatment; so let’s dig in.

As a medical professional, the first thing I noticed about these medical reports is that they have the definite air of having been cherry-picked. For example, in none of them is there a good clinical history, a description of operative findings, or other essential information that helps with determining prognosis. They all consist of a series of radiology and pathology reports, and in one of them a key pathology report is missing. In the movie, little snippets of these reports, key parts of the text highlighted in yellow, are rapidly flashed onscreen, after which they disappear, all of which is designed to draw the viewer’s attention to what the filmmaker wants, as jli points out in the case of Jodi Fenton, who was diagnosed with an anaplastic astrocytoma (click to embiggen):

While jli is correct to concentrate on the sentence that was not highlighted, mainly that a mass like this could be lymphoma or an abscess, in the end as a clinician I can say that this uncertainty doesn’t really matter, because it’s trumped by the pathology report that shows this mass to be an “anaplastic astrocytoma which contains many gemistocytic forms.” So what the radiologist thought it was is less important after tissue for pathology was obtained. More important to me are two observations. First, it is reported that there is no mass effect, compression of the ventricles, or midline shift, all of which imply that this mass was probably fairly slow growing. Second, a growth curve based on serial MRI tests is presented that is most curious. Most of the pre-biopsy imaging suggests that the tumor is around 2 cm in diameter. However, the following table begins on 6/1/2000, which is two weeks after Fenton underwent a stereotactic biopsy of her lesion:

Notice something? The tumor’s maximum diameter is now 0.5 cm, which is less than one-quarter what was reported. Given that tumor volume is proportional to the cube of the radius, that means that the tumor volume two weeks after her biopsy was roughly 64-fold (or more) smaller than it was before the biopsy. What’s interesting is that then the residual tumor disappears within a month. It’s highly unusual for any chemotherapy (and, make no mistake, antineoplastons are chemotherapy) to shrink a tumor that fast.

This brings up an intriguing possibility, mainly that the bulk of the tumor was removed by the biopsy process. I’m not a neurosurgeon, but I’ve seen the same sort of thing happen occasionally in small breast cancers that undergo a core needle biopsy, especially using a large biopsy needle; so it’s not inconceivable to me that the same thing might happen in brain tumors. Whether such a thing is possible or not, it should also be noted that anaplastic astrocytomas can have a highly variable prognosis and growth rate, which means that Fenton’s prognosis might not have been as bad as portrayed in the movie.

So what happened here? It’s clear that this case was presented first because the film’s producers thought this was their strongest case, mainly because the patient hadn’t undergone any therapy before being treated with antineoplastons. So one of three things happened:

  1. The biopsy removed the cancer, and what was left behind was an inflammatory reaction.
  2. The biopsy removed much of the cancer, and antineoplastons worked on the rest
  3. Fenton is an outlier whose tumor regressed on its own

Again, if Burzynski had real evidence that his therapy worked (i.e., clinical trial evidence), then he wouldn’t be resorting to anecdotes like this one, which doesn’t show conclusively that it was the antineoplastons that eliminated the tumor.

The second case was Jessica Ressel, who was diagnosed with a diffuse brainstem glioma in 1996. One thing that I noticed right away in perusing the records included with the film is that there is no pathology report. I found this rather curious, given that the pathology report was included in the other two cases presented. I also found the actual MRI view included in the report to be odd as well. See what I mean:

Do you see what bothers me? I’ll give you a hint: there shouldn’t be any yellow in this MRI scan. The authors obviously marked the area of abnormality with the same yellow marker that was used elsewhere. Trying to look under the yellow mark to see the most important parts of the scan, I don’t see anything “diffuse” about that glioma; it looks pretty well encapsulated. Unlike the definition of a diffuse brainstem glioma, it doesn’t take up anywhere near 50% of the brainstem diameter, although the yellow marking does conspire to make it look larger.

More importantly, looking at the tumor size tables, I see another problem, mainly that the size of the enhancing lesion is all over the place, jumping up and down for several months. In fact, it takes the tumor over a year to disappear, and it doesn’t even start to shrink consistently until nearly nine months after antineoplaston treatment started. This sort of behavior is strongly suggestive to me that the treatment probably had little to do with the disappearance of the mass, as drugs that are active against a tumor generally result in measurable shrinkage a lot faster than that and the tumor actually increased in size for a while during antineoplaston therapy. Moreover, the changes in tumor size don’t appear to correlate very well to the changes in dosage. After all, if the tumor shrank significantly on the MRI of September 21 and Burzynski attributes that to doubling the dose of antineoplastons, then how does he explain the tumor size increasing significantly again on the November 11 scan? In any case, the behavior of this tumor makes me wonder about the diagnosis, which makes me wonder why the pathology report isn’t included, as it was for the other two testimonials. Could it be that there was no biopsy of this tumor? If that’s the case, then there are many reasons to doubt that this was ever a brainstem glioma in the first place, first, because its behavior was not consistent with one and, second, because brainstem tumors are heterogeneous and even highly suspicious lesions on MRI can be benign 13% of the time.

No, testimonial number two is not very convincing either.

The last patient is Kelsy Hill. Basically, at age 6 months, Hill was diagnosed with a baseball-sized tumor in her abdomen, which, according to the parents was in her kidneys, as well as in her liver and lungs. She was operated on, and a mass was removed, as described on this pathology report. What was initially curious to me about this particular testimonial is the question of why a surgeon would have operated if the baby already had liver and lung metastases at the time of diagnosis. The only reason to operate in the presence of lung metastases that I could think of would be if the surgeon thought he was going after a neuroblastoma, which is not an unreasonable assumption, particularly if the adrenal cortical carcinoma was nonfunctioning. Neuroblastoma is a childhood tumor that presents as a rapidly growing abdominal mass, but even when there are metastases it is often still potentially curable. It’s also the most common cancer in infancy. Consequently, an infant presenting with a large abdominal mass and metastases is often considered to have neuroblastoma until proven otherwise, although the presence of lung metastases is more consistent with an adrenal cortical carcinoma. Finally, there is the issue of whether the child had an adrenal cortical carcinoma or adenoma. The former is malignant; the latter is benign, and it’s not always easy to differentiate the two. The parts of the pathology report with special stains that can help differentiate between the two are missing.

More puzzling is, again, the behavior of the multiple liver and lung masses noted in the supplemental data. First, the raw data presented don’t match the parents’ description in that there are no liver masses noted until 2/22/2006, which is nearly six months after the initial surgery. It’s also inconsistent with the narration of the movie:

Upon the removal of Kelsey’s left kidney and left adrenal gland, her diagnosis was confirmed at the University of Texas Medical Branch, and again at M.D. Anderson cancer center. Where, a month later, M.D. Anderson also confirmed that Kelsey’s cancer had spread to her lungs. After desperately researching Kelsey’s situation, her family decided to decline all chemotherapy treatments offered my M.D. Anderson, and instead, enroll Kelsey into one of Dr. Burzynski’s clinical trials. By this time, Kelsey’s cancer had also spread into her liver.

Again, Kelsy’s surgery was in September 2005; no evidence of liver metastases appears to have been noted until February 2006. When did she start the antineoplaston therapy? Was it shortly after surgery? If that’s the case, then her liver lesions developed and her lung lesions grew while she was on the antineoplaston therapy. Or did she not start antineoplastons until the appearance of liver lesions in February? If that’s the case, then why did her doctors leave her untreated for five months while her lung masses increased in size? No, what seems most likely is that antineoplaston treatment began soon after surgery, Kelsy’s tumors grew for several months after that, and new liver lesions appeared while she was on therapy. Of course, it’s not even clear if these lesions were metastases because there’s no evidence that Burzynski or Kelsy’s other doctors ever biopsied any of them. Again, there are no pathology reports of core needle biopsies of the suspected metastases.

In brief, Merola’s pledge that the the opening 30 minutes of the movie would “thoroughly establish” that Burzynski has discovered the genetic mechanism that can cure most cancers was not kept. These three testimonials do not constitute convincing evidence that antineoplastons can cure cancer. Given that they are almost certainly the absolute best cases that Burzynski could come up with, I’m once again forced to wonder what the denominator was. Meanwhile, interspersed throughout these testimonials are comparisons of Burzynski’s results to results of standard therapy that are deceptive in the extreme, given that small, unrandomized groups subject to selection bias are not comparable to larger clinical trials of standard-of-care treatments. Merola also can’t resist using all sorts of scary graphics when discussing the chemotherapy drugs used as standard of care, referring to doxorubicin as the “red death” and taking care to point out that mitotane was derived from an insecticide. One thing’s for sure, Eric Merola isn’t subtle. He hits you over the head with his pro-Burzynski anti-pharma message over and over and over again.

Help, help! I’m being persecuted!

The rest of the movie can be dispensed with rather quickly, as it’s basically one big conspiracy theory, in which the NCI, the Texas Medical Board, the FDA, and, of course, big pharma (as represented by PhRMA all persecute poor, poor Dr. Burzynski because, if you believe the Eric Merola, (1) Burzynski has cured cancer and is a threat to big pharma and its chemotherapy monopoly; (2) Burzynski is a threat to the fees big pharma pays to the FDA to oversee clinical trials; (3) the NCI can’t abide the competition. This whole section of the movie is introduced thusly by a narrator with an exceedingly creepy, robotic voice, complete with ominous-sounding background music:

The pharmaceutical industry is arguably the most profitable industry on our planet, with its profits being triple that of all of the Fortune 500 companies. Rising profits result in rising stock prices, the only way this industry can sustain this profitable momentum is by continuing to introduce new patented drugs. And since the pharmaceutical industry relies on the FDA as it’s gatekeeper to introduce these new drugs, it’s in their best interest to insure the FDA remains as compliant as possible. And since the FDA is also an office of the United States government, it’s in the government’s best interest to preserve one of it’s most powerful industries. The former editor-in-chief of the New England Journal of Medicine, Dr. Marcia Angell, has been very outspoken with the idea that it’s time to take the Food and Drug Administration back from the drug companies.

Repeat variations of this sort of passage over and over and over again interspersed with archival footage of various legal proceedings against Burzynski and excerpts of interviews with Drs. Whitaker and Burzynski, both of whom whine incessantly about how Burzynski is being persecuted, and you’ll get an idea of what the last hour of this poorly produced documentary is like. It was painful to sit through. Particularly disgusting was the liberal use of numerous testimonials of crying parents and patients telling various bodies of lawmakers or the Texas Medical Board that they or their children will die if Dr. Burzynski is convicted or has his license revoked. The paranoid conspiracy aura that surrounds Burzynski The Movie is palpable and becomes quite oppressive by the end of the movie. Pharma, the NCI, the FDA, the Texas Medical Board, and every medical authority are all against Burzynski, the lone heroic doctor battling against all odds to bring his cure for cancer to all. Yes, it’s just that nauseatingly blatant. At every point, antineoplastons are presented as nontoxic, effective, and downright miraculous when they are none of these.

How can Burzynski keep doing clinical trials?

Out of curiosity, I did a quick search of ClinicalTrials.gov for clinical trials by Burzynski or containing the word “antineoplaston.” I found 61 clinical trials, of which only ten are listed as still recruiting subjects, with one listed as not yet open. Over thirty are of unknown status, and only one is completed. This is an an apparently unrandomized, open-label phase II trial trial testing antineoplastons A10 and AS2-1 therapy in melanoma. In fact, none of the currently open antineoplaston trials are phase III trials, which are the type of trial that can potentially give a definitive answer about a therapy, because phase III trials are randomized, controlled trials. The only phase III trial listed is A Randomized Phase 3 Study of Combination Antineoplaston Therapy [Antineoplastons A10 (Atengenal) and AS2-1 (Astugenal)] vs. Temozolomide in Subjects With Recurrent and / or Progressive Optic Pathway Glioma After Carboplatin or Cisplatin Therapy. It’s a small trial (only 70 subjects) and appears at first glance to be underpowered to detect anything but very large differences in outcomes. I realize that many of Burzynski’s trials date back before the database used in ClinicalTrials.gov was active, but come on! Sixty-one clinical trials since the 1990s, with the end result being only one phase III trial, and that phase III trial hasn’t even started yet? And most of the phase II trials of “unknown” status and only one of them listed as “completed” (with that one apparently not having been published)? That’s a failure in my book. No drug company or researcher would keep doing trials of a drug (and, yes, antineoplastons are drugs when used this way) with such an abysmal track record. A drug company would give it up as unpromising, and a university researcher would soon find he could no longer secure funding for more trials.

All of this leads to the question of how Burzynski could have run so many clinical trials and have so little to show for it? There are at least 61 clinical trials registered at ClinicalTrials.gov; yet finding the results of any of them is very difficult. Among the open trials, most of them are several years old, some 16 years or more, but have not accrued their targets, even though they are all phase II trials with accrual targets of fewer than 50 subjects each. When a trial takes that long to accrue, the vast majority of the time its results will be meaningless.

Burzynski: A “brave maverick doctor” whose “antineoplaston” therapy remains unproven

Despite all the claims that they are somehow “natural,” antineoplastons are chemotherapy, as much as Drs. Whitaker and Burzynski try to portray them as “targeted.” In fact, they’re no longer even isolated from urine but synthesized and purified in Burzynski’s laboratory, something that would normally be anathema to the “natural remedies” crowd. Indeed, early in the movie, there’s a hilarious part where Burzynski, outraged at the criticism he received for using something extracted from urine, points out that hormone replacement therapy in the form of Premarin is isolated from horse urine. So obviously Burzynski’s antineoplastons are just like Premarin, and doctors don’t heap such contempt on that drug! The difference, of course, is that no one doubts that the estrogens and progesterone actually work; it’s just that the question of an elevated risk of breast cancer has led to Premarin’s having fallen out of favor.

One part of the movie that truly insults the intelligence of anyone with a modicum of knowledge about drug therapy occurs near the beginning of the movie. It’s a part that, as a cancer surgeon who is interested in targeted therapies for breast cancer, I found particularly idiotic. First, there is a screen with this caption:

Antineoplastons target the specific genes that allow cancer to grow and flourish.

No evidence is presented to demonstrate this, of course, but there are nifty (and very science-y) images of DNA double helices flying towards the viewer, along with the chemical structures of various targeted drugs. A little later we see:

There are currently over 25 FDA-approved gene-targeted cancer drugs on the market today.

Many of them can only target single genes.

All of which is true but irrelevant if Burzynski is trying to sell antineoplastons as targeted therapy. Now here’s the kicker:

You know what you call a drug that works on “close to 100 genes”? I don’t know either, but you don’t call it a “targeted” therapy unless all those genes are genes affected by the single target being inhibited. In other words, Burzynski is trying to have it both ways. He’s administering chemotherapy to patients on clinical trials and charging them for the privilege, but he’s trying to represent his treatment as being somehow “targeted.” Worse, despite Burzynski’s representation of his therapy as being “nontoxic,” in contrast to chemotherapy, some of his antineoplaston preparations are quite toxic. The reason is two-fold: (1) high doses of antineoplastons are required; and (2) some antineoplaston preparations are very sodium-rich. Dr. Burzynski’s therapy requires the adminstration of so much antineoplaston as sodium salts that several of his patients developed hypernatremia, in one case as high as 180 mEq/L. (A normal serum sodium level ranges between 135 and 145 mEq/L.) Personally, I’ve never seen a sodium level that high in a living patient. When sodium levels get into the 155 mEq/L and up range, clinicians start to get very worried and usually start aggressive treatment to bring the sodium levels down. Worse, these are patients with brain cancer. One danger is that, in correcting the hypernatremia, sometimes cerebral edema (brain swelling) will result. In a patient with a brain tumor, cerebral edema could be even more dangerous than in a patient without such a tumor. Despite reviewers being alarmed at the hypernatremia some of Burzynski’s patients developed, astoundingly he still claimed that he had no “significant toxicity.”

Repeat after me: Antineoplastons are chemotherapy. Worse, they’re chemotherapy that almost certainly doesn’t work against cancer. At best, looking at the evidence, I conclude that they might have very minimal anticancer activity, and even that’s doubtful.

Writer/producer Eric Merola uses Burzynski The Movie as a forum to pound on what he perceives as the shortcomings of the current regulatory system overseeing drugs. If anything, he’s right that our drug regulatory system has severe shortcomings, but not because it’s trying to shut Burzynski down. To me, the huge flaw in our drug regulatory system is that, after over 30 years, it has failed to determine once and for all whether or not antineoplastons have any anticancer activity, despite allowing Dr. Burzynski to treat thousands of patients with them. Although every indication thus far is that antineoplastons do not, in fact, have any appreciable antitumor activity (certainly Burzynski has utterly failed to show convincingly that any of them do), there is just enough uncertainty to allow Burzynski to portray himself to believers in alt-med as a poor, persecuted, brave maverick doctor. More disturbing from an ethics standpoint, somehow, Burzynski is still able to enroll patients on clinical trials, despite having failed to show compelling preclinical evidence of efficacy; worse, he charges them huge sums of money for the “privilege” of being on one of his clinical trials, something I and many others view as highly unethical, to the point of wondering how any Institutional Review Board could possibly approve such studies, particularly given that the FDA has warned Burzynski about how his IRB fails to protect human research subjects. Unfortunately, the Texas Medical Board failed to shut him down in the 1990s. One can only hope that it’s more successful in its next attempt, for which hearings are to commence early next year.

Dr. Burzynski is not a miracle worker. He is not a doctor who sees something that mainstream science has not and who therefore has a cure for many cancers that mainstream medicine scoffs at. He is not a bold visionary. Rather, he appears to be a man pursuing pseudoscience. The reason that mainstream scientific medicine has not accepted the existence of antineoplastons or their efficacy against cancer is not because it is “out to get” Dr. Burzynski or is trying to protect the hegemony of the FDA or the profits of big pharma. Rather, it’s because there is no credible scientific or clinical evidence to support this therapy. Perhaps that’s why Burzynski and his followers rely on testimonials and legal threats against critics far more than they rely on clinical trials and scientific studies.

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 in: Basic Science, Cancer, Clinical Trials, Medical Ethics, Politics and Regulation, Science and the Media

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