Respectful Insolence

Note: Orac is away somewhere warm recharging his Tarial cells for further science and skepticism. In the meantime, he is rerunning some of his favorite posts. Given that the blog seems to have been infiltrated with Burzynski trolls again and Eric Merola threatens to make a sequel to the execrable movie he made about Burzynski a couple of years ago, now seems a perfect time to rerun a post of Orac’s from about a year ago. In fact, now might be a perfect time to rerun these posts. Indeed, maybe I’ll even rerun the whole trio, as Orac has been thinking he needs to do a major update and reanalysis, and where better to start than with the original analysis? (This is the second part, by the way.) Besides, at the very least, it’ll annoy Burzynski fans and start showing up in Google searches again.

Last week, I applied a little not-so-Respectful Insolence to a movie about a physician and “researcher” named Stanislaw Burzynski, MD, PhD, founder of the Burzynski Clinic and Burzynski Research Institute in Houston. I refer you to my original smackdown for details, but in brief Dr. Burzynski claimed in the 1970s to have made a major breakthrough in cancer therapy through his discovery of anticancer substances in the urine that he dubbed “antineoplastons,” which turned out to be mainly modified amino acids and peptides. Since the late 1970s, when he founded his clinic, Dr. Burzynski has been using antineoplastons to treat cancer. Over the last 25 years or so, he has opened a large number of phase I and phase II clinical trials with little or nothing to show for it in terms of convincing evidence of efficacy. Worse, as has been noted in a number of places, high doses of antineoplastons as sodium salts are required, doses so high that severe hypernatremia is a concern.

Although antineoplastons are the dubious cancer therapy upon which Dr. Burzynski built his fame, they aren’t the only thing he does. Despite the promotion of the Burzynski Clinic by natural medicine mavens as using “nontoxic” therapies that “aren’t chemotherapy,” Dr. Burzynski’s dirty little secrets, at least as far as the “alternative medicine” crowd goes, are that (1) despite all of the attempts of Dr. Burzynski and supporters to portray them otherwise antineoplastons are chemotherapy and (2) Dr. Burzynski uses a lot of conventional chemotherapy. In fact, from my perspective, it appears to me as though over the last few years Dr. Burzynski has pivoted. No longer are antineoplastons the center of attention at his clinic. Rather, these days, he appears to be selling something that he calls “personalized gene-targeted cancer therapy.” But what is “personalized gene-targeted cancer therapy,” according to Dr. Burzynski? Here is how it is described:

Our approach to cancer is a result of Dr. Burzynski’s extensive experience in cancer research in the field of genetics and genomics.

Personalized Treatments offered by the Burzynski Clinic are individual treatment plans, customized for each patient, based on:

  • Identification of oncogenes responsible for the growth of cancerous cells in individual patients
  • Selection of targeted pharmaceuticals that selectively kill cancer cells carrying the identified abnormal genes

The main goal of a Personalized Treatment is to match the right patient to the right treatment to achieve maximum effectiveness with minimum side effects.

Elsewhere, Dr. Burzynski claims:

In some cases conventional therapy is the most appropriate treatment for a patient. Our Clinic offers customized combination therapies consisting of conventional therapy and other approved targeted therapies to maximize effectiveness while minimizing the side effects that typically occur when using the traditional therapies alone.

And:

There are currently close to 30 targeted therapeutics approved by the FDA (as of January 2011). This number grows rapidly with the advancement of the research in genomics. All of the Food and Drug Administration (FDA)-approved gene-targeted medications are available for treatment at the Burzynski Clinic. The combination of targeted medications is customized for each patient and determined by the type of oncogenes involved in patient’s cancer (Personalized Treatment).

Dr. Burzynski is also not shy about being interviewed by promoters of alternative medicine, such as Mike Adams. For example, here are a typical radio interview (on Oprah Radio, of course!) and videos like this one:

And this one:

Note that the first few minutes of the second video are spent portraying Dr. Burzynski as the prototypical “brave maverick doctor,” a misunderstood genius, a pioneer being oppressed, suppressed, and persecuted by The Man. Dr. Burzynski also calls the FDA and NCI “criminal” and uses every “health freedom” argument in the book, while his antineoplastons are portrayed as a cancer cure that causes brain tumors to “vanish in many children.” Finally, around the 4:30 mark, we see Dr. Gregory Burzynski, Dr. Burzynski’s son, talking about genomic profiling of cancers and biomarkers in the blood and in circulating tumor cells. If this segment weren’t embedded in a bunch of paranoid conspiracy mongering about big pharma, the FDA, and the NCI, plus a claim that surgery will no longer be necessary for surgery, what’s left over doesn’t sound too different from what quite a few “conventional” cancer researchers say about “personalized medicine.” Well, that and what Dr. Burzynski says about tumor suppressors. He seems to think that all tumor suppressors prevent mutations, which is, of course, not true. Some of them do other things. Be that as it may, the claim made in the video is that, with a combination of antineoplastons and “personalized therapy,” Dr. Burzynski can cure many cancer patients with stage IV disease. But how credible is this claim? What, exactly, is he doing? It’s hard to figure out from his website, but looking elsewhere can provide hints. Let’s

“Personalized cancer treatment” in science-based medicine

At the risk of annoying some colleagues I know, I’m going to point out that I never really liked the term “personalized cancer therapy” or its many variants, for the simple reason that it always struck me as more of a marketing term than a scientifically meaningful description of what targeting therapy to the genetic makeup of a patient’s tumor will eventually entail. In fact, I think I now prefer another term, which has been used by Cancer Research U.K., namely “stratified medicine.” The reason is that what we as clinicians are doing when we “personalize” or “individualize” therapies isn’t really “personalizing” the therapy so much as using various measurements and biomarkers to place patients into groups of patients who respond to specific therapies. What the modern version of “personalized” therapy is really doing is producing more and more groups of patients, each of which, is smaller than the last, to be matched to more and more therapies. Whether the groups will eventually reach an N of 1, I don’t know, but that is the goal. Only then will we truly have “personalized medicine.”

My personal irritation at the proliferation of certain terms notwithstanding, I actually do believe that the stratification and matching of patients with therapies based on genomics, proteomics, and biomarkers is the future of cancer treatment, and, to some extent, the future is now. However, “personalized” medicine is in its infancy, as I have pointed out in previous posts on the topic, Progress mixed with hype in genomics and “personalized medicine” and Integrating patient experience into research and clinical medicine: Will this lead to true “personalized medicine”? True, we do have several targeted therapies that inhibit or target a single important molecule. For instance, in breast cancer, Herceptin (trastuzumab) targets the HER2 oncogene, which is amplified in some breast cancers. Another example, Gleevec (imatinib mesylate), inhibits the tyrosine kinase activity of the bcr-abl oncogene product as well as receptor tyrosine kinases encoded by the c-kit and platelet-derived growth factor receptor oncogenes and is very effective against tumors that make too much of one these oncogenes, such as gastrointestinal stromal tumor and Philadelphia-positive (Ph+) hematological malignancies such as chronic myelogenous leukemia and acute lymphoblastic leukemia. Now, there are numerous other examples, so many that they are listed on the NCI website.

In fact, the idea of targeted therapy in cancer is not new. For example, it’s long been known that the presence of the estrogen receptor (ER) in breast cancer implies that treatment with antiestrogen drugs like Tamoxifen is likely to result in a a response and that lack of ER in a tumor means that Tamoxifen won’t work. Similarly, we’ve used prostate-specific antigen (PSA) as a biomarker for prostate cancer and carcinoembryonic antigen (CEA) as a biomarker for colon cancer for decades. The difference between the way drugs were targeted to cancers a couple of decades ago and now is the explosion of genomics knowledge that has occurred over the last decade. As I’ve pointed out, we are now producing terrabytes and petabytes of genomic data about cancers, a flood of information that we have only relatively recently started seriously developing the tools needed to analyze this flood of data and disciplines (systems biology, bioinformatics, genomics, etc.) to organize and determine how best to translate it into therapies. We even use one such test in breast cancer, the Oncotype DX, assay, which has allowed oncologists to identify patients who can safely skip adjuvant chemotherapy.

What we are learning, as I have lightheartedly appropriated a quote from Douglas Adams’ masterwork to say before, is that cancer is complicated. You just won’t believe how vastly, hugely, mind-bogglingly complicated it is. I mean, you may think it’s complicated to understand basic cell biology, but that’s just peanuts to cancer. All you have to do is to look at the genetic derangements in typical prostate cancers to get a flavor for how daunting the task of developing personalized treatments of cancer will be, much less curing it. Think of it this way. The examples of genomic derangements in a few prostate cancers were incredible, and there are different sets of genomic derangements that vary by cancer type, of which there are hundreds. Add to that the fact that, as Dr. Burzynski himself emphasizes, cancers are heterogeneous, with different genetic derangements in different parts of the tumor, and you get a flavor of how difficult “personalizing” cancer therapy based on its genomic makeup and biomarkers will be. It will take an incredible amount of research, both basic and clinical, in order to learn the best ways to match the genomic makeup of patient tumors to the most effective targeted therapies.

Unfortunately, Burzynski’s approach to “personalized gene-targeted anticancer therapy” appears to fall prey to the assumption that he knows enough about the molecular pathways to be investigated to reliably use the results of various genomics assays to guide anticancer treatment. In essence, it’s as though Dr. Burzynski read a book called Personalized Cancer Therapy for Dummies and decided he is an expert in genomics-based tailoring of targeted therapies to individual cancer patients. I’ll try to show you what I mean.

What Burzysnki claims he can do with “personalized gene-targeted therapy”

In order to determine what it is that the Burzynski Clinic is doing that it calls “personalized gene-targeted cancer therapy,” I started searching around the web. I also had a brief e-mail correspondence with Renée Trimble, Director of Public Relations for the Burzynski Institute. She’s the one who, in the wake of Marc Stephens’ harassment of bloggers, sent out a press release apologizing for his behavior while at the same time basically saying that the Burzynski Clinic would keep using the legal system to try to silence bloggers who criticize it. However, she was polite with me, probably because of the positions I hold at an NCI-designated comprehensive cancer center. Mostly, her information was only marginally more helpful than what I could find on the Burzynski Clinic website and around the Internet, but she did confirm at least one fact that needed confirming. Then, there is also this video, produced by the Burzynski clinic itself:

What interested me about this video, ironically enough, is how bland and unremarkable a lot of it was. Clearly, the producer went to great lengths to make Burzynski’s lab look like any other molecular and cell biology lab–even like my lab. The other thing that interested me was how the video emphasizes the use of FDA-approved medications. Finally, there was a clue (to me, at least) about what it is that Burzynski is doing. At around the three minute mark, the announcer states:

We combine gene-targeting drugs and low dose chemo, if needed.

Then a very sharply-dressed man named Azad Rastegar appears and says:

The way we look at cancer here at the Burzynski Clinic is that it’s more than just the tumor site. Obviously, that’s very important and significant for figuring out how to address the cancer in the patient, but what we want to do is to identify the genes that are involved in that particular patient’s cancer. With that, then we can start creating more customized and personalized treatment plans that involve gene-targeted medications targeting, obviously, the genes involved in that patient’s cancer. This way we’re able to reduce side effects. We’re able to reduce any time-wasting on ineffective drugs and cater it, obviously, much more to the patients and their individual cancer needs.

It all sounds so reasonable, and, indeed, this is exactly the sort of thing that lots of cancer centers are trying to do. But how this sort of approach is implemented makes all the difference in the world, and the question I had was whether Dr. Burzynski is taking anything resembling the right sort of approach to this problem. From the description above, it sounded very much to me as though Dr. Burzynski is combining various targeted agents with metronomic chemotherapy. I know a thing or two about metronomic chemotherapy, because I was involved in a project whose end result was to be the testing of metronomic chemotherapy against cancer and because the concept is a spinoff of the work of one of my scientific heros, the late Judah Folkman. Basically, metronomic chemotherapy is an approach to chemotherapy that uses repetitive, low doses of chemotherapy drugs (or even continuous infusions of low dose chemotherapy) designed to minimize toxicity and target the tumor blood vessels rather than targeting the tumor cells themselves. The concept behind this strategy is that blood vessels are lined by genetically stable endothelial cells, they do not evolve resistance, and chemotherapy can be antiangiogenic. The drawback to metronomic chemotherapy is that long periods of therapy may be required and the cumulative doses of chemotherapy may end up being actually higher than more standard therapies. On the other hand, this latter aspect may not be a drawback because metronomic chemotherapy may allow a greater cumulative dose, with a concurrent greater cumulative effect. Unfortunately, thus far clinical trials in humans of such approaches can only be characterized as fairly disappointing.

Whether this is what Dr. Burzynski is doing or not with the chemotherapy part of his approach, I don’t know for sure, but it sure sounds like it. For example, in Knockout: Interviews With Doctors Who Are Curing Cancer and How to Prevent Getting It in the First Place by Suzanne Somers, Dr. Burzynski is interviewed and, ironically, reveals a great deal (to me, at least) about what he is doing. For example:

For the majority of Dr. Burzynski’s patients he does not use any chemotherapy, but for some patinets the chemotherapy is used in lower dosages, which are below the threshold of significant side effects. Dr. Burzynski takes advantage of the synergistic effect of such combinations…

Except that he doesn’t demonstrate that these combinations are synergistic in preclinical studies or clinical trials before prescribing them off-label.

Later in the interview, Somers (SS) asks Dr. Burzynski (SB) about breast cancer, and Dr. Burzynski replies:

SS: What about breast cancer?

SB: At the moment we use a different approach. We study which genes in individual patients are abnormal, trying to determine the genetic signature of cancer in these patients. With our methods, we can have answers for the patient in about three days based on blood tests. Once we identify the most important oncogenes involved in cancer for that individual, we select a group of four to six medications from those twenty-four which are now approved by the FDA and use them to hit those genes which are causing the cancer to progress. This is like “boutique treatment” because for every patient we design a treatment plan. When we do this we have a very good chance to have positive results in most patients.

SS: How many respond?

SB: About 85 per cent for whom we have the proper gene signature; about 15 percent do not respond. In our responders many of them have tumors which disappear completely and in others the tumors remain small. The problem is finding the genetic signature because for many of these different genetic signatures we don’t have blood tests…yet.

Note that at the time this book was published, Dr. Burzynski was claiming that he could identify who would benefit from specific targeted therapies simply from blood tests. If he could do this for real, Burzynski could easily publish in high impact journals like Clinical Cancer Research, the Journal of Clinical Oncology, or another high impact clinical cancer journal. Heck, a result like that could probably make it into general medical journals, such as the New England Journal of Medicine or The Lancet, which have an even higher impact factor. If he were able to demonstrate that his method of testing tumors and picking targeted therapy could result in a complete response rate anywhere near 85% for breast cancer, even more so. If, as he claims later in the chapter, Dr. Burzynski has patients with pancreatic cancer and advanced liver cancer whose tumors have disappeared within two months after he began treatment, the same would be true. If, as Burzynski claims, he achieves a 50% complete response rate in advanced brain tumors, again, the same would be true. He doesn’t submit his results to these journals. Why not? No doubt it’s The Man keeping him down.

So what tests does Dr. Burzynski use to determine the cocktail of targeted therapies to use in any given patient, anyway?

I learned from multiple patient blogs (and it was confirmed by Ms. Trimble) that Dr. Burzyski uses a test from a company called Caris Life Sciences. The test appears to be the Caris Target Now™ Molecular Profiling test, and this is how it’s described on the company website:

Caris Life Sciences’™ molecular profiling test, Caris Target Now™, examines the genetic and molecular changes unique to a patient’s tumor so that treatment options may be matched to the tumor’s molecular profile.

Caris Target Now helps patients and their treating physicians create a cancer treatment plan based on the tumor tested. By comparing the tumor’s information with data from published clinical studies by thousands of the world’s leading cancer researchers, Caris can help determine which treatments are likely to be most effective and, just as important, which treatments are likely to be ineffective.

The Caris Target Now test is performed after a cancer diagnosis has been established and the patient has exhausted standard of care therapies or if questions in therapeutic management exist. Using tumor samples obtained from a biopsy, the tumor is examined to identify biomarkers that may have an influence on therapy. Using this information, Caris Target Now provides valuable information on the drugs that will be more likely to produce a positive response. Caris Target Now can be used with any solid cancer such as lung cancer, breast cancer, and prostate cancer.

It’s also noted:

Caris Target Now™ was developed and its performance characteristics were determined by Caris Life Sciences, a medical laboratory CLIA-certified in compliance with the U.S. Clinical Laboratory Amendment Act of 1988 and all relevant U.S. state regulations. It has not been approved by the United States Food and Drug Administration.

All of which sounds suspiciously like a Quack Miranda Warning. At least, it’s a little too close for comfort in my book. From my perspective, this test looks perfectly fine as a test to be used for research and clinical trials, but clearly using it to treat patients with off-label cancer drugs is something that I’d be very, very concerned about.

But how does it work? It’s described thusly:

Caris Target Now begins with an immunohistochemistry (IHC) analysis. An IHC test measures the level of important proteins in cancer cells providing clues about which therapies are likely to have clinical benefit and then what additional tests should be run.

If there is access to a frozen sample of patient tissue available, Caris Life Sciences™ may also run a gene expression analysis by microarray. The microarray test looks for genes in the tumor that are associated with specific treatment options.

As deemed appropriate based on each patient, Caris will run additional tests. Fluorescent In-Situ Hybridization (FISH) is used to examine gene copy number variation in the tumor. Polymerase Chain Reaction (PCR) or DNA sequencing is used to determine gene mutations in the DNA tumor.

Immunohistochemistry is standard for many cancers. For example, in breast cancer, pretty much every pathology lab does immunohistochemistry (using antibodies to detect specific proteins) for at least two proteins, the estrogen receptor and the HER2 oncogene. Sometimes, depending upon the lab and the clinical situation, pathologists will stain for proliferation markers, like Ki-67, or other receptors such as epidermal growth factor receptor. Not uncommonly, pathologists stain for E-cadherin in order to differentiate between two common types of breast cancer, infiltrating ductal carcinoma versus lobular carcinoma. similarly, breast cancers are often subjected to FISH in order to determine whether the HER2 oncogene is amplified. In other words, none of this is anything particularly remarkable from a clinical standpoint.

What Caris appears to do that’s different from normal clinical evaluation of a tumor sample is, if fresh frozen tissue is available, the performance of cDNA microarray analysis of the messenger RNA isolated from the tumor tissue. cDNA microarrays are a technology that allows scientists to analyze the level of messenger RNA from every known gene in the genome simultaneously. In actuality, technology has moved on from cDNA microarrays, which these days are so 2005, but they’re still good tools and still used to examine differences of thousands of genes simultaneously, either between tissues or in response to drugs or other interventions. Also, newer technology, such as next generation sequencing (NGS) and RNA-Seq. RNA-Seq, for instance, provides the same information that a cDNA microarray does, plus everything else in the transcriptome, such as microRNAs and long non-coding RNAs. microRNAs, in particular, are being appreciated as very important regulators of gene activity because a single microRNA can often regulate hundreds of genes. RNA-Seq is also unbiased in that cDNA microarrays can only measure genes we know, whereas RNA-Seq can be used for discovery of previously unknown RNAs.

However, these techniques are expensive and not yet as common and practical as cDNA microarrays. That Caris isn’t using the latest technology for the test doesn’t mean it might not be potentially worthwhile; after all, a cDNA microarray will detect the levels of all known oncogenes. Caris also apparently does some mutational analysis and fluorescence in situ hybridization (FISH), a test designed to measure gene copy number and thus detect amplified genes. The result is a report like this example report that Caris Life Sciences has posted on one of its websites. The problem, of course, is what a clinician should do with the results. That’s why I say that such a test should probably, except in rare circumstances, only be used for research purposes. Besides, much of what I see isn’t that helpful anyway. For example, if you look at the report, the first agents listed are anthracyclines, such as doxorubicin, because topoisomerase-2A is elevated and taxanes, such as paclitaxel, because TLE3 is elevated. These are basically “Well, duh!” suggestions, because doxorubicin and paclitaxel are normally standard-of-care chemotherapeutic agents for triple negative breast cancer anyway! Particularly useless is the mention that “Lack of HER2 amplification has been associated with lack of benefit from HER2-targeted antibody.” No kidding, given that trastuzumab was designed to treat HER2-positive breast cancer and that clinical samples are routinely checked for HER2 amplification as part of the standard-of-care!

As for the other recommendations, the gene associations listed, many of them are based on associations with response to specific therapies in other tumor types, such as irinotecan in ovarian cancer and cisplatin in gastric cancer, small cell lung cancer, for example. The relevance of many of these recommendations to breast cancer is questionable, to say the least. To apply them to individual patients outside the context of a clinical trial is hard to justify except in rare cases, but that’s exactly what Dr. Burzynski appears to be doing for large numbers of his patientss, picking off-label chemotherapeutic agents based on the results of this test and selling it as “personalized gene-targeted therapy” without letting patients know that (1) the evidence base behind these recommendations is often not relevant to the specific tumors being treated because it’s from different cancers; (2) the studies used to support these recommendations have a lot of uncertainty; and (3) most of these recommendations haven’t been validated in clinical trials.

Even worse, the very concept of “gene-targeted cancer therapy” hasn’t been convincingly shown to improve cancer outcomes, at least not yet. Believe it or not, I actually am in the camp who believes that eventually such a strategy will ultimately be proven useful and revolutionize cancer therapy, but that time is not yet. Gene-targeted cancer therapy is currently in its infancy and, except in rare situations outside of the existing currently validated biomarkers (such as HER2, ER, c-kit, and other genes for which targeted therapies exist) for the response of specific cancers, is not to be undertaken outside of the context of a clinical trial. In essence, Burzynski appears to be using such information on a “make it up as you go along” sort of fashion. Indeed, an e-mail from Renee Trimble confirmed this suspicion of mine when I pointed out to her that gene-targeted cancer therapy is in its infancy and that in the vast majority of cases we don’t know what to do with this information. I also wanted to know what the Burzynski Clinic was doing that is different from what the major cancer centers are doing. Her answer was, to put it mildly, unsatisfying, as I will discuss in the next section.

Compare and contrast, ideal versus results

Before discussing how the Burzynski Clinic does personalized cancer therapy, I think it’s worth looking at how real scientists do it right now. In essence, real scientists use information of the sort provided by Caris Life Sciences or by their own genomic testing to stratify patients and identify them for clinical trials. An excellent example of this is a study hot off the presses in the November issue of Science Translational Medicine by a group from my very own alma mater, the University of Michigan entitled Personalized Oncology Through Integrative High-Throughput Sequencing: A Pilot Study. In essence, the investigators (Roychowdhury et al) began a pilot study to study the practical difficulties involved in using high-throughput sequencing in clinical oncology, which they identified in the introduction:

Translating high-throughput sequencing for biomarker-driven clinical trials for personalized oncology presents unique logistical challenges, including (i) the identification of patients who could benefit, (ii) the development of an informed consent process that includes a way to deal with incidental findings, (iii) the implementation of efficient and integrative computational pipelines for data analysis, (iv) the selection of the results that should be disclosed to patients, and (v) the completion of the sequencing analysis in a cost-effective and clinically relevant time frame (Table 1). We implemented an exploratory study that we call the Michigan Oncology Sequencing Project (MI-ONCOSEQ) to address these challenges.

The challenges, and the response of investigators, are well described in Table I:

i-e6d0a04ab294b158503abafe741dfbcc-Table1-thumb-400x781-71097.jpg

Before undertaking this study in actual humans, in order to verify that their sequencing strategy would work, Roychowdry et al first grew in mice xenografts made from tissue taken from the tumors of two patients with metastatic prostate cancer. They performed their genomic analysis and found that one carried a common gene fusion found in prostate cancer and another previously undescribed gene fusion. They also found the androgen receptor gene was amplified and two tumor suppressors were inactivated. For purposes of the study, they set up a special tumor board to evaluate their findings and decide what clinical trials would be best for a patient. The authors then tried their strategy on two actual patients, one with colorectal cancer and one with melanoma. The tumor board suggested a combination of inhibitors that would be suitable for each patient on clinical trial. Unfortunately, at the time there were no appropriate clinical trials. This is the sort of preliminary work that needs to be done before genomic analysis of individual patient tumors, as will the implementation of clinical trials that patients can be assigned to based on their genomic information.

Another example was reported this spring, when M.D. Anderson Cancer Center presented initial data at ASCO for over 1,000 patients in a phase I trial in which patients’ tumors were analyzed for genetic abnormalities and, when a drug existed to target that genetic abnormality, received that drug. Unfortunately, I didn’t go to ASCO this year; so I didn’t see the presentation, but the results are summarized on the M.D. Anderson Cancerwise blog:

For the 175 patients with one aberration, the medical response rate was 27% with matched targeted therapy. The response rate was 5% in 116 patients when treated with non-matched therapy.

Patients who received matched targeted therapy had median survival of 13.4 months, compared to nine months for unmatched targeted therapy. Median survival without cancer progression was 5.2 months for those receiving matched therapy, compared to 2.2 months for patients who received unmatched therapy.

True, this is not a home run by any means, but it suggests that “personalized” cancer therapy can improve outcomes.

Now let’s take a look at how the Burzynski Clinic does it, at least as far as I can figure out from my various sources and from Ms. Trimble. In response to my query about personalized gene-targeted therapy offered by the Burzynski Clinic, Ms. Trimble stated that a gene expression analysis is performed, as well as mutational analysis, FISH, immunohistochemistry for selected genes and that a blood test is also performed to measure the “concentration of proteins which are products of most important oncogenes.” How on earth they do this latter test, I really don’t know, because most oncogenes are not secreted proteins and most cancers don’t have good serum biomarkers. Next, according to Ms. Trimble, the “medications which are shown to be best candidates for treatment, as well as those which are poor candidates, are identified from FDAs’ approved gene targeted medications and chemotherapy drugs list.” In addition, drugs are supposedly selected based on the patient’s clinical information, standard of care, FDA indication, data from phase II and III clinical trials. On the surface, up to this point it all sounded reasonable and not unlike what is being done at quite a few big cancer centers, hence my question (which was never answered to my satisfaction) of what Burzynski is doing that is different from (and presumably believed by Burzynski to be superior to) what everyone else is doing.

Then there was a hint. In addition, Burzynski then formulates a preliminary treatment plan that “will consist of medications which should cover approximately between 100 to 200 genes,” after sometimes doing a SNP analysis to “eliminate drugs which are not metabolized properly.” The result, or so it is claimed, is a set of drugs that have “synergistic activity which permits reduction of doses.” But why 100 to 200 genes? The very idea of targeted therapy is to hit the bare minimum of targets necessary to eradicate or control the tumor. Burzynski is going against the very concept of targeted therapy by making sure his therapy hits “100 genes,” a claim that resonates from what he said in the movie about him I reviewed last week. According to Ms. Trimble, “Antineoplastons and their prodrug, phenyl butyrate, are important ingredients of the combination because they cover the spectrum of approximately 100 genes.”

To support this claim, Ms. Trimble also sent me two papers from the Burzynski Clinic, both of which appeared in a journal I had never heard of before, the Journal of Cancer Therapy, which is clearly not indexed on PubMed because these papers never showed up when I searched PubMed for Burzynski. One described Burzynski’s approach for triple negative breast cancer (TNBC), the other for esthesioneuroblastoma and nonsmall cell lung cancer. What I found odd about both of these papers is that neither of them really examined whole genome expression profiling, although the paper about triple negative breast cancer did mention measuring the expression of “important” oncogenes. Meanwhile, the paper on esthesioneuroblastoma and nonsmall cell lung cancer primarily used sodium phenylbutyrate rather than any sort of gene targeting. I note that, while the esthesioneuroblastoma case is mildly interesting, it is a case report. I also note that the TNBC paper is a case report and small series in which a cocktail of targeted therapies plus chemotherapy appear to have produced somewhat durable responses. Unfortunately, in the absence of a control group or a clear prospective rationale for choosing these therapies, it’s hard for me to get too excited, particularly given that we don’t know the denominator; in other words, we don’t know how many patients with TNBC Burzynski has treated with this regimen who didn’t respond. We also don’t know the survival rates for these patients, only response rates.

It turns out that perhaps the best description of what “personalized” treatment means in Dr. Burzynski’s hands comes from the Texas Medical Board’s complaint against him, which can be found in over at the Ministry of Truth or at Casewatch. This complaint is based on the cases of two patients. First, here’s Patient A, who is described in the complaint thusly:

1. Patient A:

a. In approximately May of 2008, Patient A presented to Respondent with breast cancer that had metastasized to her brain, lung, and liver.

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

c. In combination with the five immunotherapy agents, Patient A was prescribed capecitabine, a chemotherapy agent. The concurrent prescription of five immunotherapy agents in combination with a chemotherapy agent resulted in Patient A suffering unwarranted side effects.

d. Respondent owned the clinic pharmacy from which the multiple drugs were ordered. Respondent failed to affirmatively disclose to Patient A his ownership interest in the pharmacy.

This is what’s known as “throwing everything but the kitchen sink” at the tumor without any thought of interactions, as most of these agents have no proven role in the treatment of breast cancer. For example, erlotinib (brand name: Tarceva) is used to treat pancreatic cancer and non-small cell lung cancer. It works by inhibiting the tyrosine kinase of the epidermal growth factor receptor (EGFR) and is not FDA-approved for breast cancer. However, it’s not unreasonable to think that it could work in breast cancer, as EGFR is believed to be important in some breast cancers, which is why this is an area of active research. Dasatinib (trade name: Sprycel) is also a kinase inhibitor. It inhibits the Src family tyrosine kinase. Vorinostat is a histone deacetylase inhibitor approved for use against cutaneous T-cell lymphoma. Finally, Sorafenib is another tyrosine kinase inhibitor that inhibits the tyrosine kinases of different receptors, as well as raf kinases. The big problem with this sort of approach is that the more drugs you add, no matter how “targeted” they are, the more chance for interactions that increase toxicity, and throwing all these kinase inhibitors together in a cocktail with chemotherapy is a recipe for disaster, particularly because such cocktails haven’t been tested in proper phase I clinical trials to evaluate toxicity. They’re also all incredibly expensive as well, and Dr. Burzynski sells them through his own pharmacy.

Patient B appears to be the patient with esthesioneuroblastoma whose case report I described above. This is the relevant passage from the complaint:

Follow-up magnetic resonance imaging (“MRI”) scans were conducted in approximately August and December of 2003, and March of 2004, which showed progressive disease. Patient B was continued on phenylbutyrate during this 11 -month time period, and was not sufficiently informed about the drug’s lack of efficacy on her disease.

Which sounds rather unlike the glowing case report above, now, doesn’t it?

This is how Dr. Burzysnki does “personalized, gene-targeted therapy.”

The cost

It’s very telling to look at the literature that Dr. Burzynski sends to prospective patients, one example of which is reproduced by Xeno. For example, rather than summarizing sound papers describing well-designed clinical trials, Dr. Burzynski only lists “response rates.” Looking at the table included in the literature, I noticed immediately that Dr. Burzynski says nothing about survival rates, only what he calls “objective response rates,” which are not defined in a meaningful way. The pamphlet defines them as as anything from an “improvement” (defined as “decrease in size of the tumors, not confirmed yet by the second follow-up radiological measurement”) to “complete disappearance of all signs of cancer,” which is utter bollocks. There are standardized ways of measuring tumor response agreed upon by radiologists and oncologists, such as the RECIST criteria. Burzynski lumps all responses together in an oncologically meaningless way. Also remember, Burzynski often uses standard-of-care chemotherapy along with his antineoplastons; so we would expect some responses. The chart above, however, is virtually meaningless, if only for the simple reason that initial tumor response often doesn’t correlate to overall survival, and overall survival is what we care about. As Xeno also notes, the out-of-pocket costs are staggering. Contrast this to the clinical trials I mentioned above, where patients do not pay for the genomic profiling or chemotherapy.

As bad, Dr. Burzynski massively oversells what he is doing to desperate patients, and, if what he tells patients is the same as what he told Suzanne Somers in her book, appears to be misrepresenting what he does:

SS: When you talk about gene-targeted therapy, is that chemotherapy?

SB: No, this is not chemotherapy. Most of my patients have already had chemotherapy and it has not been effective for them. The beauty of antineoplastons is that they are natural compounds. They exist in our blood and form a protective system against cancer. You don’t expect to have toxic side effects from chemicals which are normal in your blood. And they cover a broad spectrum of genes, which means from the very beginning we have a much better chance to help this patient.

Cytotoxic chemotherapy “covers” an even broader spectrum of genes; so by Dr. Burzynski’s criteria, cytotoxic chemotherapy ought to be the best therapy of all! In any case, as we have seen, Dr. Burzynski does give chemotherapy. Lots of chemotherapy. He combines that chemotherapy with a gmish of “targeted therapies” based on a commercially available but not FDA-approved gene expression profile test and calls it “personalized gene-targeted therapy.” Unfortunately, in my not-so-humble opinion, he doesn’t have a scientifically supportable rationale for combining his targeted therapies. Instead, skirting the line between science and pseudoscience, Dr. Burzynski gives every appearance of recklessly throwing together untested combinations of targeted agents willy-nilly to see if any of them stick but without having a systematic plan to determine when or if he has successfully matched therapy to genetic abnormality.

One has only to compare what Dr. Burzynski does to what the group the University of Michigan, among other large research institutions, are doing to see that. The result is that his outcomes are basically uninterpretable, making them useless for determining whether his approach works. At the same time, the cost is personal in terms of giving patients false hope and unneeded side effects for little or no benefit and financial in terms of bills that run from tens to hundreds of thousands of dollars charged to patients who are so desperate that they will pay them for even a glimmer of hope.

Comments

  1. #1 c0nc0rdance
    December 13, 2012

    I’m going to work on a YouTube video bringing all this together. The key points, as I see them are:
    1. Burzynski has never yet completed a useful drug trial out of 60+ attempts, but instead exploits Phase I and II clinical trials to use untested mixes of chemo, urine compounds and immune therapy.
    2. Burzynski’s experimental treatment regimen, unlike every drug trial I’ve ever heard of, charges the patients for time, material, and tests. The fees seem excessive to me, but the key point is that even if he is a brave and maverick doctor, he ain’t a charitable one.
    3. Burzynski’s cure rate, when you strip away the marketing, is not any better than conventional therapies.
    4. When he claims “gene-targeted therapies” or “personalized medicine” he’s using the same tumor marker tests as any other cancer center to prescribe the same targeted immunotherapies and drugs as any other cancer center. His only unique addition is by no means gene-targeted and quite probably less effective than front-line therapy.

    Conclusion: If Burzynski really does have something uniquely effective, he needs to set aside this short-term loop-hole (and patient) exploitation and actually complete a clinical study, conduct rigorous basic science, publish his results in a high-impact journal, and stop profiting from the tragic hope of suffering families. If he really had a light, and he hid it in a bushel (and charged admission to see); what a horrible, horrible profiteer.

    I’m honestly prepared to be wowed by some solid science from the Burzynski Clinic, but given their business model, I won’t hold my breath.

    C.

  2. #2 Narad
    December 13, 2012

    I’d add…

    5. If you hear the words “cystic formation,” you know you’ve been had.

  3. #3 Didymus Judas Thomas
    Given that this blog seems to be run by someone Biased...
    December 17, 2012

    Should I trust this Doctor’s credentials over Orac’s?

    Dr. Nicholas Patronas, is currently the Senior Clinician, Chief. Section of Neuroradiology,, Radiology and Imaging Sciences, National Institutes of Health, NIH Clinical Center
    http://www.cc.nih.gov/drd/staff/nicholas_patronas.html

    Court Testimony Of Nicholas Petronas, MD

    (Board-Certified Radiologist Professor of Radiology at Georgetown University, and Founder of the Neuroradiology section of the National Cancer Institute)

    Discussing the effectiveness of antineoplaston treatment vs. chemotherapy and radiation treatment in brain cancer.

    May 24, 1993

    Administrative Hearing Docket .503-92-509

    License No. D-9377

    In The Matter Of The Complaint Against Stanislaw R. Burzynski, M.D.

    Before The Texas State Board Of Medical Examiners

    Before Earl A. Corbitt, Administrative Law Judge

    Volume I of II

    May 24, 1993

    Pg. 113

    Direct Examination

    Q: Dr. Petronas, what is your profession?

    A: I’m a radiologist, a medical doctor specializing in radiology.

    Q: Would you tell us briefly your educational background?

    A: Well, after the medical school we have a year internship, four years residency in radiology, and in addition I had an entire year of training in neuroradiology. So my subspecialty is neuroradiology. It is the evaluation of the regions of the central nervous system.

    Pg. 114

    Q: And would you relate your work experience, please?

    A: when I finished my training I was at the University of Chicago for seven years as a staff radiologist at the University Hospital. And then I moved to the National Institutes of Health where I worked from ’81 to ’85 as a staff radiologist at the clinical center, which is the hospital of the National Institutes of Health. Then I moved to Georgetown University where I became full professor of radiology. And the National Institutes of Health contracted Georgetown radiological services, and I was sent from Georgetown back to NIH to cover the section.of Neuroradiology.

    Q: And so you work at the National Institutes of Health hospital; is that where you work?

    A: yeah, at the hospital initially as a federal employee from ’81 to ’85, and then on contract from Georgetown University. So I am one of the 17 radiologists who provide radiological services to the National Institutes of Health.

    Q: What is the function or purpose of the hospital of the National Institutes of Health?

    A: As you know, there are a lot of research protocols that

    Pg. 115

    are going on, and people who are admitted to this facility are being admitted to try experimental treatment. As they are admitted to the hospital, the hospital requires an X-ray Department and radiologists to man the department. And so we evaluate the various lesions that are being admitted under these approved protocols, and we assess the effectiveness of the treatment given there, using imaging modalities such as MRI or CT scans and regular radiology.

    Q: And that would be for the various health departments or what’s called institutes?

    A: Exactly, the various institutes, yes.

    Q: Like the National Cancer Institute, that’s one of them?

    A: That’s the biggest of all, yeah.

    Q: What– Basically then, you do the, in layman’s terms, you do all the imaging work and interpretation for the National Cancer Institute testing of drugs?

    A: Exactly.

    Q: Because– and what happens is, they give the drugs to the people and you have to get– they have to have a scan before to see what they had–

    A: Exactly.

    Q: –then when they go into treatment they have to get scans to see what, if any, effect–

    A: To see whether they are effective or not, yes.

    Pg. 116

    A: That’s my job, to assess the effectiveness of the drugs that are given there and to provide the diagnosis at the initial stage, upon admission.

    Q: Dr. Petronas, did there come a time when you became aware of Dr. Burzynski?

    A: Yes, it was when Michael Hawkins from NCI asked me to join a group of other physicians and scientist and come to Houston on a site visit to Dr. Burzynski’s Institute in order to assess the best case scenario that he had to present us of his patients who were treated with antineoplastons. So that was the first time when I was aware that there was an anticancer agent. And I was called as an expert in assessing the images to evaluate, together with the rest, the other five members of that team, to evaluate the effectiveness of his treatment.

    Q: And did you have occasion to actually go down to Houston, Texas?

    A: Yes, we spent about seven hours at the Burzynski Institute and we reviewed the material that was given to us.

    Q: What material did you review?

    A: Initially there was a presentation of the cases by Dr. Burzynski; each different case was studied seperately. We were given the history, the pathology, the previous treatment and the timing of these treatments, and we have someone who recorded these data.

    Pg. 117

    Then the histological slides were presented to one of our neuropathologist, one neuropathologist who was also a guest consultant in the team. We reviewed the slides and confirmed the histological of the grade of the tumor that Dr. Burzynski was indicating in his presentation. Then there were assessments of the images, either CT scans or CAT scans, or MRI scans. They were serial studies in any given patient. So we were able to see how the tumor started and how it ended up under treatment.

    Q: How many patients did you concern yourself with at that time?

    A : we reviewed the material of seven cases. We did not have more time to review more. These were the–

    Q: So that basically took up the whole day?

    A : The whole day. yes; one hour per case.

    Q: And what happened after you reviewed the cases?

    A: Well, we took our notes and we discussed the findings, and there was a report that was issued indicating what we found.

    Pg. 118

    Q: We have marked for identification Exhibit 27. Will you see if you can identify that for us?

    A: Yeah, I have seen this. Yeah.

    Q: And is this– What exactly is this?

    A: it was a letter to Dr. Burzynski from Dorothy Macfarlane, one of the people who was part of the team. And the memorandum shows or summarizes are findings for each individual patient. And this is exactly document that we came up with.

    Q: What was the basic conclusion of the– that you indicated?

    A: The basic conclusion was that in five of the patients with brain rumors that were fairly large, the tumor resolved, disappeared.

    Q: Was that just happenstance? I mean, was that just by some miracle of–

    A: Well, since the treatment given was started after the previous conventional treatments which had failed previously, we took the position that this probably represents the result of this new treatment. And so there was only minimal residual tissue at the tumor bed, which looked like a sca, and had no fissures to support that there was a tumor in the majority of the cases. Two of seven patients did not do very well. One of them deceased. The tumor dissolved at least

    Pg. 119

    microscopically; we could see it with the naked eye, but it recurred later, a year later. And the other, there was
    very, very minimal decrease in the size of the tumor. But the tumor was very big, the last one, the seventh, last two cases did not survive, although there was definite improvement in one of the two last cases.

    Q: I guess that would be called an objective response in that these patients–

    A: exactly, because we were six people and we all looked at images and we saw the chronological order. We checked the names of the patients on the films, and the files were obtained at different institutions from the entire country, basically where the patients were located. And we had no reason to believe that these were not the results of the treatments.

    Q: Doctor, based on what you have testified to before about your background and credentials, it’s fair to say, isn’t it, that you have seen a lot of brain cancer patients?

    A: yes, in fact, we see a lot of these cases.

    Q: And that’s part of what you do at the hospital, is to evaluate treatments on brain cancer patients?

    A: Well, different cancers, but since I am the neuroradiologist I see all brain rumors. And I see a large volume of then.

    Q: Now, with regard to at least the five patients, I think

    Pg. 120

    you testified that five of the patients had their rumors resolved, they all–

    A: Disappointed.

    Q: –disappeared. Can you give us some kind of context of that? How often does that happen with any– with no treatment, just by spontaneous remission, or by whatever it is that you–

    A: I’m not aware that spontaneous remission occurs; I don’t think it does. And the available treatment only rarely produce results like that. The only medication– the only treatment, which I think is the last resort, is radiation therapy. Chemotherapy has very little to offer unless there is an experimental protocol somewhere. However, conventional chemotherapy is– provides very little, nothing, basically. Radiation, there are some reports indicating that radiation treatment in children particularly could lead to resolution of the rumors, although I don’t know whether it is a permanent one or temporary. So when this happens it is very rare. And I have seen only isolated here and there where that has happened with radiation .

    Q: With one case here or there–

    A: Yeah.

    Q: –an isolated report, you are talking about on a case by

    Pg. 121

    case basis?

    A: Yeah. Well, radiation should give these results, if it works at all, the first two months after completion of the treatment. In these cases, all the patients had already failed radiation because they were treated months, several months after radiation was
    given and had failed.

    Q: What happens with these patients? Lets say they failed radiation; what happens then to the patient with brain cancer?

    A: Well, it depends on the grade of the tumor. If the tumor is low grade, astrocytoma, and we are talking about primary gliomas, if it is low grade, survival for years is possible. If it is an intermediate grade, the anaplastic, the mean survival is two years, and if it is the high grade glioma the mean survival is about 12 months. That’s it; they die in 12 months, they disappear.

    Q: Now– So are you saying basically for someone that’s failed radiation– It sounds like you are saying that if someone has already failed radiation, at least, that there’s not too much else–

    A: nothing to offer, exactly.

    Q: –and that these people are going to eventually die of their disease, barring any unforeseen event or cure?

    A: Exactly.

    Q: and there is nothing that any– that you could do at NCI?

    Pg. 122

    A: Nothing we can do, no; not at the present time.

    Q: All right. What about these five patients that are all basically doing– how come they lived?

    A: Well, it’s amazing, the fact that they are living and some of them are doing well. They are not– they are not handicapped from the side effects of any treatment, and worse than the tumor itself. So these particular individuals not only survived, but they didn’t have major side effects. So I think it is impressive and unbelievable.

    Q: How many times have you ever seen this, in your experience, that someone comes with a drug like this, to have this kind of effect? How often does that happen?

    A: I don’t– I have not seen it at any time with the medication that is given systematically. We have done– we have an experimental protocol at the NIH where we inject a chemotherapeutic agent through the carotid artery, the artery that goes to the brain, and we have three survivals with this technique, by providing massive amounts of chemotherapeutic drugs to the brain that harbors the tumor. And we destroy the tumor, but we destroy a large part of the brain as well, and the patients became severely handicapped , and a life that’s not worth living.

    Pg. 123

    And so I have three cases with this particular experimental protocol which resulted in killing the tumor, but a large part of the healthy brain as well. So overall the protocol was abandoned and is not any more in effect because of the serious side effects that we witnessed.

    Q: Now, let me ask your opinion or advice. Based on what you have seen from these patients– I mean, I think the opinion actually, or the letter actually concludes that the site team concluded that there was antitumor effect from the antineoplastons. What would happen, let’s say for some reason Dr. Burzynski’s brain tumor patients can’t get the medicine any more and have to go off treatment. What’s going to happen to them, in your opinion?

    A: I think these patients will die.

    Pg. 124

    Q: One of the patients you reviewed was F.M.; is that correct? What happened in his case?

    A: The tumor was very large and very involved the hypothalamus, a very sensitive part of the brain cannot be operated, and had both cystic components and fleshy components, mass like. And the lesion disappeared . This patient did not have previous treatment, if I recall, other than– previous chemotherapy or radiation, and the tumor disappeared under our eyes. It was a low grade astrocytoma, wich is comparable with long survival. However, even those low grade astrocytomas, when we see them, they don’t go away even though they may permit the person to live for many years. In this particular patients case the tumor disappeared, and there was a small, tiny remnant left, small percentage of the original size. And there has been several years since then and the patient is well, I’m told.

    Q: So at least for the patient you would not recommend that

    Pg. 125

    he go off the treatment, would you?

    A: No.

  4. #4 MI Dawn
    December 17, 2012

    Well, well, well. A radiologist talking about chemotherapy. Somehow, I suspect he’s a little out of his realm of experience. Hint to DJT: it’s always much more reliable for someone to talk about their field of experience – i.e. radiology – than for them to wander off and discuss chemotherapy.

    And did you happen to notice this testimony is from 1993???? Almost 20 years ago, when the NIH thought there might be something in Burzynski’s protocol. But here we are, 20 years later, and the still hasn’t proven it works.

    Next time, try using a copy/pasta that is a *wee* bit more current, OK?

  5. #5 MI Dawn
    December 17, 2012

    Gah! I hate typos…”and HE still hasn’t proven it works”

    Oh, and yes, DJT: the host and most of the commenters on this blog ARE biased. We are biased in the direction of Science-Based Medicine, which has been tested and shown to reliably work. If Stan would give us some of his results, to allow replication, and his protocols were shown to work, we’d accept his methods too. But right now, all we get is hand-waving.

  6. #6 LW
    December 17, 2012

    We learn from The Dividing Line Between the Role of the FDA and the Practice of Medicine: A Historical Review and Current Analysis that between 1977 and 1997, Burzynski “treated” some three thousand patients, or about 150 per year. Thus we can estimate that between 1977 and 1993, he “treated” 2,400 patients. Out of those 2,400, those described are presumably his seven best cases. And one died and another did not respond. So the results Burzynski presented appear to indicate that five out of 2,400 — a little over 0.2% — went into remission. That’s ever so impressive.

    The radiologist said he was not aware that these tumors ever underwent spontaneous remission. But would he know if the rate were as low as, say 0.2%?

  7. #7 JGC
    December 17, 2012

    DJT, you’re posting a lot of irrelevant cut and pastes from SEC filings, court testimony, etc.

    None of theses cut and pastes support a claim that antineoplastons are effective at treating advanced cancers.

    To support such a claim what youl need to provide aren’t SEC filings, or court testimony, lists of patent applications–what is needed are published results from 60+ clinical trials Burzynski’s supposedly conducted over the past couple fo decades.

    Direct question: are you unable to provide published results from these trials?

  8. #8 Didymus Judas Thomas
    The Realm of where I question your MOTIVATION & GOOD FAITH
    December 17, 2012

    LW,

    I really enjoy your “New Math for Dummies!!”

    Please cite your credentials so I may compare them to:

    Dr. Nicholas J. Patronas,
    http://www.cc.nih.gov/drd/staff/nicholas_patronas.html

    Senior Clinician, Chief. Section of Neuroradiology,, Radiology and Imaging Sciences, National Institutes of Health, NIH Clinical Center.

    Academic Degrees
    MD, Salonica University, Greece
    Residency, University of Illinois
    Fellowship, Northwestern University

    Well, after the medical school we have a year internship, four years residency in radiology, and in addition I had an entire year of training in neuroradiology. So my subspecialty is neuroradiology. It is the evaluation of the regions of the central nervous system.

    When I finished my training I was at the University of Chicago for seven years as a staff radiologist at the University Hospital. And then I moved to the National Institutes of Health where I worked from ’81 to ’85 as a staff radiologist at the clinical center, which is the hospital of the National Institutes of Health. Then I moved to Georgetown University where I became full professor of radiology. And the National Institutes of Health contracted Georgetown radiological services, and I was sent from Georgetown back to NIH to cover the section.of Neuroradiology.

    I delight in your “Cherry Picking.”

    _____”And one died and another did not respond.”

    The basic conclusion was that in five of the patients with BRAIN TUMORS THAT WERE FAIRLY LARGE, THE TUMOR RESOLVED, DISAPPEARED.

    Q: Was that just happenstance? I mean, was that just by some miracle of–

    A: Well, since the treatment given was started after the previous conventional treatments which had FAILED previously, we took the position that this probably represents the result of this new treatment. And so there was only minimal residual tissue at the tumor bed, which looked like a sca, and had no fissures to support that there was a tumor in the majority of the cases. Two of seven patients did not do very well. One of them deceased. THE TUMOR DISSOLVED at least microscopically; we could see it with the naked eye, but it recurred later, a year later. And the other, there was very, very minimal decrease in the size of the tumor. But THE TUMOR WAS VERY BIG, the last one, the seventh, last two cases did not survive, although THERE WAS DEFINITE IMPROVEMENT in one of the two last cases.

    Q: Doctor, based on what you have testified to before about your background and credentials, it’s fair to say, isn’t it, that you have seen a lot of brain cancer patients?

    A: YES, IN FACT, WE SEE ALOT OF THESE CASES.

    Q: And that’s part of what you do at the hospital, is to evaluate treatments on brain cancer patients?

    A: Well, different cancers, but since I am the neuroradiologist I see all brain rumors. AND I SEE A LARGE VOLUME OF THEM.

    Q: Now, with regard to at least the five patients, I think
    you testified that five of the patients had their TUMORS RESOLVED, they all–

    A: DISAPPEARED.

    Q: –DISAPPEARED. Can you give us some kind of context of that? How often does that happen with any– with no treatment, just by spontaneous remission, or by whatever it is that you–

    A: I’m not aware that spontaneous remission occurs; I don’t think it does. And the available treatment only rarely produce results like that. The only medication– the only treatment, which I think is the last resort, is radiation therapy. Chemotherapy has very little to offer unless there is an experimental protocol somewhere. However, conventional chemotherapy is– provides very little, nothing, basically. Radiation, there are some reports indicating that radiation treatment in children particularly could lead to resolution of the rumors, although I don’t know whether it is a permanent one or temporary. So when this happens it is very rare. And I have seen only isolated here and there where that has happened with radiation .

    A: Yeah. Well, radiation should give these results, if it works at all, the first two months after completion of the treatment. In these cases, all the patients had already FAILED radiation because they were treated months, several months after radiation was
    given and had FAILED.

    Q: What happens with these patients? Lets say they FAILED radiation; what happens then to the patient with brain cancer?

    A: Well, it depends on the grade of the tumor. If the tumor is low grade, astrocytoma, and we are talking about primary gliomas, if it is low grade, survival for years is possible. If it is an intermediate grade, the anaplastic, the mean survival is two years, and if it is the high grade glioma the mean survival is about 12 months. That’s it; THEY DIE in 12 months, they disappear.

    Q: Now– So are you saying basically for someone that’s FAILED radiation– It sounds like you are saying that if someone has already FAILED radiation, at least, that there’s not too much else–

    A: NOTHING TO OFFER. EXACTLY.

    Q: –and that these people are going to eventually DIE of their disease, barring any unforeseen event or cure?

    A: EXACTLY.

    We have done– we have an experimental protocol at the NIH where we inject a chemotherapeutic agent through the carotid artery, the artery that goes to the brain, and we have three survivals with this technique, by providing massive amounts of chemotherapeutic drugs to the brain that harbors the tumor. And we destroy the tumor, but we destroy a large part of the brain as well, and the patients became severely handicapped , and a life that’s not worth living.

    _____”1977 and 1993, he “treated” 2,400 patients. Out of those 2,400, those described are presumably his seven best cases. And one died and another did not respond. So the results Burzynski presented appear to indicate that five out of 2,400 — a little over 0.2% — went into remission. That’s ever so impressive”

    What a disingenuous statement.

    You have no idea what the resolution of the “2,400” was.

    5 out of 7 were AMAZING and IMPRESSIVE and then you try with your “New Math” to imply that this means that because 2 did not survive after radiation FAILED and the prognosis was that they would have DIED anyway, you want us to believe your false numbers.

    If you had 7 patients you could call that: 70%.
    5 successful patients would then be: 50%
    Change 70% to: 100% (by adding 30%)
    Change 50% to: 80% (by adding 30%)
    80% minus 100% = 20%
    So 20 deaths out of 100 = 80% survival rate.
    That would be a base-line calculation.
    If you factor in that the survival rate may NOT have been as high as 80% because these were his Best Case Scenarios, we still come nowhere near your 0.2%.

  9. #9 Mephistopheles O'Brien
    December 17, 2012

    You have no idea what the resolution of the “2,400″ was.

    Do you know what the results were for the estimated 2,400 patients treated by Dr. Burzinsky? How do you know?

  10. #10 LW
    December 17, 2012

    Oh my. Oh my.

    If you had 7 patients you could call that: 70%.
    5 successful patients would then be: 50%
    Change 70% to: 100% (by adding 30%)
    Change 50% to: 80% (by adding 30%)
    80% minus 100% = 20%
    So 20 deaths out of 100 = 80% survival rate.

    Is that how they do math in your grade school? No wonder you think simple division requires a doctorate. Oh my.

  11. #11 Didymus Judas Thomas
    In the Realm of questioning your GOOD FAITH and MOTIVATION
    December 17, 2012

    JGC

    Ignorance is no excuse for NOT knowing the Law, and neither is ignorance an excuse for not knowing ;

    1986 – All…were submitted for PHASE I CLINICAL STUDIES…

    http:// assets0. pubget. com/paper/3527634/Antineoplastons__history_of_the_research__I_
    .
    .
    1987 – Initial CLINICAL STUDY…with 5 years’ follow-up.

    This paper describes PHASE I CLINICAL STUDIES…

    http:// assets0. pubget. com/paper/3569010/Initial_clinical_study_with_antineoplaston_A2_injections_in_cancer_patients_with_five_years__follow_up
    .
    .
    1987 – PHASE I CLINICAL STUDIES…

    …was submitted for PHASE II CLINICAL STUDIES…

    http:// assets0. pubget. com/paper/3569012/Phase_I_clinical_studies_of_antineoplaston_A3_injections
    .
    .
    1987 – PHASE I CLINICAL STUDIES…

    CLINICAL TRIALS described in this paper…

    http:// assets0. pubget. com/paper/3569014/Phase_I_clinical_studies_of_antineoplaston_A5_injections
    .
    .
    1990 – The present study describes the results of treatment… in PHASE II CLINICAL TRIALS…

    http:// assets0. pubget. com/paper/2152694/Treatment_of_hormonally_refractory_cancer_of_the_prostate_with_antineoplaston_AS2_1
    .
    .
    2003 – PHASE II study…

    A PHASE II study…

    http:// assets0. pubget. com/paper/12718563/Phase_II_study_of_antineoplaston_A10_and_AS2_1_in_patients_with_recurrent_diffuse_intrinsic_brain_stem_glioma__a_preliminary_report
    .
    .
    2004 – PHASE II study…

    http:// assets0. pubget. com/paper/15563234/Phase_II_study_of_antineoplaston_A10_and_AS2_1_in_children_with_recurrent_and_progressive_multicentric_glioma___a_preliminary_report
    .
    .
    2004 – These TRIALS…

    http:// assets0. pubget. com/paper/15312271/Long_term_survival_and_complete_response_of_a_patient_with_recurrent_diffuse_intrinsic_brain_stem_glioblastoma_multiforme
    .
    .
    2005 – …were treated in PHASE II studies…

    http:// assets0. pubget. com/paper/15911929/Long_term_survival_of_high_risk_pediatric_patients_with_primitive_neuroectodermal_tumors_treated_with_antineoplastons_A10_and_AS2_1
    .
    .
    2006 – CLINICAL TRIALS…

    http:// assets0. pubget. com/paper/16774296/Treatments_for_astrocytic_tumors_in_children__current_and_emerging_strategies
    .
    .
    2006 – in 4 PHASE 2 trials

    http:// assets0. pubget. com/paper/16484713/Targeted_therapy_with_antineoplastons_A10_and_AS2_1_of_high_grade__recurrent__and_progressive_brainstem_glioma

  12. #12 MarkL
    December 17, 2012

    If you had 7 patients you could call that: 70%.
    5 successful patients would then be: 50%
    Change 70% to: 100% (by adding 30%)
    Change 50% to: 80% (by adding 30%)
    80% minus 100% = 20%
    So 20 deaths out of 100 = 80% survival rate.

    OMG! We have been wasting time replying to a halfwit. With mathematical skills like this, I would be surprised if he is able to dress himself in the mornings.

    Safe to say that, after this display of imbecility, we can ignore any future moronic screed from diddums and he can go back to his cartoons, cookies and milk before bedtime

  13. #13 Narad
    December 17, 2012

    Ignorance is no excuse for NOT knowing the Law, and neither is ignorance an excuse for not knowing

    Are you under the impression that moving to another thread allows you simply repeat the same failed efforts?

  14. #14 Shay
    December 17, 2012

    If you had 7 patients you could call that: 70%

    Don’t give up your day job, Sir Diddimus.

  15. #15 Mephistopheles O'Brien
    December 17, 2012

    Shay,

    I fear LW is right (as usual) – it is quite likely Diddimus is too young to be employed legally in most first world countries.

  16. #16 Militant Agnostic
    December 17, 2012

    Apparently Squidimus considers “New Math” to be any math developed after that advent of agriculture or possibly even any math developed the invention of the spear.

  17. #17 Didymus Judas Thomas
    In the Realm of I question YOUR GOOD FAITH AND MOTIVATION
    December 17, 2012

    MI Dawn,

    If you had actually read the above you would know that there were 6 individuals as part of the team.

    Ignorance is NOT an excuse for NOT knowing the Law, and neither is it an excuse for not knowing:

    2004

    Managing social conflict in complementary and alternative medicine research: the case of antineoplastons.

    Authors

    Mitchell R Hammer and Wayne B Jonas

    Integr Cancer Ther 3(1):59-65 (2004), PMID .15035877

    Journal

    Integr Cancer Ther. 2004 Mar;3(1):59-65.

    Affiliation

    International Peace and Conflict Resolution Program, School of International Service, American University, Washington, DC, USA.

    Abstract

    From December 1991 to December 1995, the National Cancer Institute (NCI) initiated phase II clinical trials of A10 and AS2-1 (antineoplastons) infusions in patients with diagnosed primary malignant brain tumors.

    Four years and more than a million dollars later, these studies were stopped before it was possible to determine the effectiveness of antineoplastons.

    In an effort to determine why this study failed to be completed.

    The intent was to understand the social dynamics surrounding this failed study and to develop a method for managing and possibly preventing such failures in the future.

    This article summarizes the findings from this case study.

    PMID .15035877 [PubMed – indexed for MEDLINE]
    HighWire Press

    http://assets0.pubget.com/paper/15035877/Managing_social_conflict_in_complementary_and_alternative_medicine_research__the_case_of_antineoplastons

  18. #18 LW
    December 17, 2012

    ‘m going to try to explain this in terms that DJT may possibly be able to grasp. 

    Let’s play “Let’s Pretend”. We’ll pretend that I have a great big pile of candies, 2,400 of them in fact, but don’t worry about the big number. Now I tell you to pull out your seven most favoritest candies. Your very most favoritest candies are cherry. So you start looking through aaaallll the candies, and they all seem to be icky licorice. But you go through all of them, and you find just five cherry candies. But I said you should get seven, so you look through aaaallll the candies again, and there just aren’t any more cherry, so you take two licorice candies. Now you have seven even though you don’t really like the last two.

    Now, let’s think about Burzynski. He was supposed to make people well, or at least to make them not die. He was supposed to present his seven best cases. So he looked through aaaallll his 2,400 or so cases and he found five patients that recovered for his “best case scenario”.

    Why did he stop at five?  Why didn’t he present seven patients that recovered?  Surely a patient that died is not so good a case as a patient that recovered.  I deduce that he did not present seven patients that recovered because he didn’t have seven patients that recovered.  In twenty years.

    Do you have a better explanation for why he didn’t present seven patients that survived? 

  19. #19 Didymus Judas Thomas
    In the Realm of J don't need a Doctorate to Smell what the CROCK is COOKING
    December 17, 2012

    LW,

    If I need to break Math down to a simplistic level so you can understand it, that’s what I’ll do.

    I see you had “NO COMMENT” about the final conclusion but resorted to your usual blatherskite.

    Try again!!!

  20. #20 MarkL
    December 17, 2012

    @ Diddums.

    If I need to break Math down to a simplistic level so you can understand it, that’s what I’ll do.

    You might want to re-check your math whilst referring to a 5th grade math primer………………….

  21. #21 Didymus Judas Thomas
    Has anyone seen those 2 Tu-Quackers MarkL & Narad ???
    December 17, 2012

    Ya know, the 2 faceless beings who combat “FACTS” with no “FACTUAL” cites, and want to ask questions but not answer them?

  22. #22 LW
    December 17, 2012

    Oh, DJT. Oh my. You have absolutely no idea what a fool you’ve made of yourself. I shouldn’t even mock you anymore. In a battle of wits you are totally unarmed. It’s a good thing you use a pseudonym, because when you grow up and look for a job, you sure won’t wa t prospective employers to see this.

  23. #23 Mephistopheles O'Brien
    December 17, 2012

    Didymus Judas Thomas,

    LW skewered you well and truly. You clearly do not know how to do math. Try again.

    Let’s take 3 possible cases:

    1. Burzynski picked the 7 best possible cases. In that case the math works out exactly like LW states.

    2. Burzynski picked an absolutely representative sample of his results. in that case, his survival rate is 5/7 – or 71.4% This would be very respectable, but in no way matches your calculations.

    3. Burzynski picked 7 cases at random. In that case, we have absolutely no basis on which to determine what his overall survival rate is. These 7 could have been better than his average; they could have been worse than his average.

    Don’t embarrass yourself any more than you have to. Please.

  24. #24 JGC
    Watching DJT double-down on meaningless copy-pasta
    December 17, 2012

    The URL’s you’ve provided aren’t resolvable–is it too much to ask that you provide links that actually work?

    From the titles however it’s evident that you’re again offerring non-peer-reviewed abstracts from conference poster seessions (e.g. “Phase II study of antineoplaston A10 and AS2 1 in children with recurrent and progressive multicentric glioma “), review articles e.g., “Treatments for astrocytic tumors in children: current and emerging strategies”), editorials, etc., rather than what you’ve been specifically asked for (published reports of completed Phase II clinical trials demonstrating efficacy of antineoplastons in treating advanced stage cancers).

    I prety much have to conclude therefore that your answer to my questionis “No, I am not in fact able to provide citations of published reports for any of the 60+ clinical trials Burzynski’s conducted over the past 2 decades.”

  25. #25 Didymus Judas Thomas
    Looking to see if LW has any COBOLS
    December 17, 2012

    LW,

    Let’s say I have a “Cherry Picked” question, and I know who would most likely know the answer, but I don’t have the COBOLS to contact them directly & ask. I’d rather blatherskite on a blog & throw out hypothesis and “guesses” instead. What should I do? Grow a Pair or continue on in the same vein?

    We can play “Guessing” Games all day long, but “Guessing” Games are nothing but Speculation and Assumptions.

    I could ASSUME that Patient X was going to DIE anyway because their Cancer had progressed to that stage & radiation had FAILED, but still show investigators that the Cancer was being reduced before they DIED.

    Please cite where SRB says he can cure ALL forms of Cancer.

  26. #26 Mephistopheles O'Brien
    December 17, 2012

    @Didymus Judas Thomas – please cite where SRB published in a peer reviewed article the results of studies that show that antineoplaston therapy (either in conjunction with conventional therapy or in the absence thereof) is more effective than conventional therapy. That will settle the question nicely.

    Note: the citations you’ve brought up before simply aren’t sufficient, as discussed by others in this blog.

  27. #27 Mephistopheles O'Brien
    December 17, 2012

    @Didymus Judas Thomas – please cite where LW has claimed that SRB made any such claim. Thanks.

  28. #28 LW
    December 17, 2012

    I’m not responding to DJT because I don’t believe in cruelty to children.

  29. #29 Didymus Judas Thomas
    Helping JGC learn how to use an electronic device.
    December 17, 2012

    JGC,

    I am not interested in Orac’s Spam BOT Tu-Quack Blocking, so I add spaces after the periods and/or http:// so the post doesn’t get stuck in the “Review” stage.

    Simply remove the spaces.

  30. #30 Didymus Judas Thomas
    LW the breeze of Hot Rising Air
    December 17, 2012

    LW,

    This:

    _____”It’s a good thing you use a pseudonym, because when you grow up and look for a job, you sure won’t wa t prospective employers to see this.”

    From someone going by “LW.”

    Seriously!!

    Is THAT the best you’ve got???

  31. #31 MarkL
    December 17, 2012

    Diddums,

    You keep pushing the same publications over and over again, despite being told by everyone that they are not hat you say they are.

    THEY ARE NOT THE RESULTS OF CLINICAL TRIALS.

    All you are doing is proving what we already know. That Burzynski has started scores of clinical trials in order to continue bilking cancer patients and their friends and families out of hundreds of thousands of dollars.

    Show us the RESULTS of these trials, and your argument might begin to gain some traction.

    Oh, and please note for future reference that mastery of the Strawman logical fallacy in no-way makes up for your lack of understanding of even basic mathematical skills.

    Seriously, my 6 year old niece has a better grasp of basic math than you do.

  32. #32 Mephistopheles O'Brien
    December 17, 2012

    @Didymus Judas Thomas,

    I say this as a friend. Well, as a person who doesn’t actively mean you harm.

    LW is not wasting an A game on you. Based on what you’ve said so far, you don’t rate.

    The comment you quoted is more on the lines of good advice.

    And yes, I do go by a pseudonym. This is not so I can gratuitously insult people. What’s your reason?

  33. #33 Didymus Judas Thomas
    Metaphysical O'Brien needs assistance reading between the lines
    December 17, 2012

    MB,

    ___”Why did he stop at five? Why didn’t he present seven patients that recovered? Surely a patient that died is not so good a case as a patient that recovered. I deduce that he did not present seven patients that recovered because he didn’t have seven patients that recovered. In twenty years.”

    He asks why not 7? Thus he posits a theory that SRB could be claiming to cure all Cancers.

  34. #34 Mephistopheles O'Brien
    December 17, 2012

    @Didymus Judas Thomas-

    Au contraire – as LW clearly stated, these were presumed to be SRB’s seven best results. If SRB treated exactly 7 patients over 20 years, then the best would also be a representative sample. If, as LW suggests, these are the best out of 2,400 patients in that time, then the results are abysmal regardless of SRB’s claims.

  35. #35 JGC
    December 17, 2012

    Treatments for astrocytic tumors in children current and emerging strategies.

    Sure thing–just let me know which of the many URL’s directs me to the published report for a completed Phase II clinical trial demonstrating that antineoplastons safely adn effectively treat advanced stage cancers. There’s no sense, after all, in reomving the undersores to arrive at an abstract from a conference talk or poster session, an editorial opinion or a general review article.

    So, which one(s) do you suggest I examine?

  36. #36 JGC
    December 17, 2012

    He asks why not 7? Thus he posits a theory that SRB could be claiming to cure all Cancers

    he’s simply asking why he’s picked onl;y 5 of the thousands of patients he’s treated. Are you suggesting that Burzzynski has been treating (and charging hadnsomely for the privilege) thousands of patients for cancers he never believed he could cure?

  37. #37 MarkL
    ..........in stitches at DJT's attempts to ignore his own imbecility.
    December 17, 2012

    @Diddums

    He asks why not 7? Thus he posits a theory that SRB could be claiming to cure all Cancers.

    You still believe that the Strawman will replace mathematics in Science as the best way to carry an argument?

  38. #38 LW
    December 17, 2012

    @Mephistopheles O’Brien: that was indeed meant as advice. I have no objections to pseudonyms unless they’re used to do harm, and I *especially* do not object to pseudonyms for children and young adults. Indeed I think they *should* have pseudonyms. It is all too easy to say something stupid on the Internet — and the Internet never forgets.

    I’ve seen Twitter feeds from young people whose contents would absolutely convince me that I never wanted to work with them. But they will grow up and perhaps learn better, and a prospective employer should judge them by what they have become, not what they were. But if an employer googles them and finds hostility and bad language, that may create an impression that is hard to overcome.

    I think of the children of today trying to get jobs in a tough labor market, with their Twitter feeds and their facebook pages and their blogs following them through life … and yes, I am sincerely glad that DJT uses a pseudonym and won’t be tagged with this silliness for life.

  39. #39 Didymus Judas Thomas
    All the whiners about Clinical Trial publication
    December 17, 2012

    Does this mean any of you have actually reviewed one of these or are you just all “ASSUMING” that because it doesn’t have the Title you think it should have, that that automatically excludes it from being an actual Clinical Trial Publication.

    Please explain how FDA approved Phase II Clinical Trials without what you allege not having been published. & how FDA approved Phase III Clinical Trials under the same criteria.

    Is it possible that if those publications do not contain what you allege they do not contain, that possibly you have not read all the FDA regulations to see if there is an “Exception” that the FDA allows for certain reasons?

    None of you disproved my math. If you have 7 individuals & 2 die, you still don’t get 0.2%, but none of you alleged “Wizards of Math” had the cajones to call LW out on it, just like none of you had the Gonads to contact Merola like I did when I was “Fact-Checking” Orac’s Movie blog.

    The “FACTS” are that I have cited issues with both sides of the discussion whilst people like Tu-Shay adds nothing to the discussion – no cites, no research, just blah, blah, blah!

    In fact, above I just disproved the NIH claim about their alleged valid clinical trials.

    And I’m still just getting warmed up. ;-)

  40. #40 Narad
    December 17, 2012

    In other news, BZYR is down to a nickel with a bid-ask spread of 18 cents.

  41. #41 Narad
    December 17, 2012

    Does this mean any of you have actually reviewed one of these

    Yes.

    None of you disproved my math.

    Wrong.

  42. #42 AdamG
    December 17, 2012

    If you have 7 individuals & 2 die, you still don’t get 0.2%,

    Oh, honey.

  43. #43 Mephistopheles O'Brien
    December 17, 2012

    None of you disproved my math.

    Er, dude, I did. Repeatedly from multiple angles. The fact remains that given a particular set of assumptions, LW’s math is correct. In no set of assumptions is your math correct. Deal with it.

  44. #44 LW
    December 17, 2012

    None of you disproved my math.

    Wrong.

    I think most people either were overcome by laughter, or recoiled in horror.

  45. #45 MarkL
    December 17, 2012

    @Diddums

    I am getting sick of your bluster and bullsh*t.

    If you have 7 individuals & 2 die, you still don’t get 0.2%, but none of you alleged “Wizards of Math” had the cajones to call LW out on it……

    No – we didn’t call LW on his math, because THIS ISNT WHAT HE CLAIMED you feckless moron.

    You obviously have a reading age of below double figures too. You are about as much use as a one legged man in an arse kicking contest.

    Seriously, give it up, you are just making a complete and utter fool of yourself.

  46. #46 Krebiozen
    December 17, 2012

    I think it may be worth pointing out that Dr. Patronas is quoted as saying:

    Michael Hawkins from NCI asked me to join a group of other physicians and scientist and come to Houston on a site visit to Dr. Burzynski’s Institute in order to assess the best case scenario that he had to present us of his patients who were treated with antineoplastons.

    So there 7 patients are undoubtedly a best case series, the very best examples that Dr. Burzynski could find in his records of the thousands of patients he had treated at that time.

    By the way, I have written to Dr. Patronas, asking his current opinion of Burzynski’s work. I will report any reply here.

  47. #47 Krebiozen
    December 17, 2012

    Sorry, typo: “these 7 patients”.

  48. #48 LW
    December 17, 2012

    @Mephistopheles O’Brien: “The fact remains that given a particular set of assumptions, LW’s math is correct.”

    The particular set of assumptions and conclusions is:

    1) By 1993 Burzynski had treated approximately 2400 patients.

    2) Burzynski needed to produce seven “best case scenario” patients.

    3) a patient that survives is a better “best case scenario” that a patient who died of the disease.

    4) Therefore Burzynski would produce seven patients who survived if he could.

    5) Burzynski produced only five patients who survived, and two who did not.

    6) Therefore Burzynski could not produce more than five patients who survived.

    7) Therefore no more than five patients out of approximately 2400 actually survived.

    8) 5/2400 is approximately 0.00208, rounded to 0.2%.

    Now you can argue that there were more survivors but Burzynski had no records for them, but that is a condemnation of Burzynski in itself.

    You can also argue that there were more survivors but they refused to consent to release of their records, but why would they do that? We’re supposed to believe that they believed they owed their lives to him. Why wouldn’t they consent to release of their records to save his license so he could save more patients like them?

    So, as I finished before, what other reason is there for Burzynski not to produce seven patients who survived, out of thousands treated?

  49. #49 herr doktor bimler
    December 17, 2012

    In his one-sided rearguard battle against LW’s mathematical conspiracy, DJW seems to be channeling Captain Redbeard Rum:

    “I was under the impression that it was common maritime practice for a ship to have a crew.”
    “Opinion is divided on the subject: All the other captains say it is, I say it isn’t.”

  50. #50 LW
    December 17, 2012

    @herr doktor bimler

    Ack! DJT, not DJW! DJW is my sister.

  51. #51 Shay
    December 17, 2012

    Herr Doktor: perhaps he’s channeling The Princess Bride.

    “We’ll never survive.”

    “You’re just saying that because no one ever has.”

  52. #52 Krebiozen
    December 17, 2012

    From Dr. Patronas:

    Well, radiation should give these results, if it works at all, the first two months after completion of the treatment. In these cases, all the patients had already FAILED radiation because they were treated months, several months after radiation was given and had FAILED.

    From Late response to radiochemotherapy in pediatric glioblastoma: report on two patients treated according to HIT-GBM protocols.

    The authors report on 2 patients with incompletely resected glioblastoma multiforme in which response was lacking 3 weeks after radiochemotherapy but became evident 12 weeks later.

    So it is entirely possible that the response noted by Dr. Patronas and his team was a late response to conventional treatment, and not a response to Dr. Burzynski’s treatment at all.

  53. #53 herr doktor bimler
    December 17, 2012

    Going on past form, DJT will now remind you of the qualifications now held by Dr Patronas as evidence of his infallibility 19 years ago.

  54. #54 flip
    In the Realm of I question YOUR ENGLISH AND MATH SKILLS
    December 17, 2012

    And here I was thinking you were satirising Squidymus from the other thread, re: his terrible math.

    This requires a serious facepalm. Or a Poe’s law. Or a retreat from Diddums from the internet and back to kindergarten.

    *INTERCOM VOICE* Would the parent please pick up their child from aisle 5? His google droppings are getting everywhere. Parent to aisle 5 please, aisle 5 kid needs a parent. *INTERCOM VOICE*

    Please explain how FDA approved Phase II Clinical Trials without what you allege not having been published. & how FDA approved Phase III Clinical Trials under the same criteria.

    Holy crap, does he think the results come *before* the clinical trials? Or am I parsing that wrong?

    Is it possible that if those publications do not contain what you allege they do not contain, that possibly you have not read all the FDA regulations to see if there is an “Exception” that the FDA allows for certain reasons?

    Care to point us in the direction of this “exception” in the regulations, proof Burzyinski got such an exemption, and a reason why he was allowed such an exemption?

    None of you disproved my math. If you have 7 individuals & 2 die, you still don’t get 0.2%, but none of you alleged “Wizards of Math” had the cajones to call LW out on it, just like none of you had the Gonads to contact Merola like I did when I was “Fact-Checking” Orac’s Movie blog.

    Or Squidymus, you don’t have to “fact check” an equation that primary school children would see through. Even if it wasn’t needed, several people provided explanations of why you were wrong.

    And I’m still just getting warmed up

    Oh goody. Where’s the popcorn? Anyone got some butter?

  55. #55 LW
    December 17, 2012

    @flip: “And here I was thinking you were satirising Squidymus from the other thread, re: his terrible math.”

    I’m not that imaginative.

  56. #56 novalox
    December 17, 2012

    Man, djt is good for some laughs, at his/her/its utter ignorance of kindergarten math and elementary school science.

    @flip, pass the popcorn, I’m going to have some nice laughs when djt comes back and keeps proving his own idiocy.

  57. #57 Politicalguineapig
    December 17, 2012

    Popcorn or cookies, tough choice.

  58. #58 c0nc0rdance
    December 17, 2012

    @Didymus
    I’m interested in your info because it is a compelling testimonial. It suggests that some patients may respond to antineoplastons plus conventional therapy, which is apparently what they get at the Burzynski Clinic. I frankly expect that; given the plural nature of cancer and the chaotic nature of human physiology, I would expect any given therapy that targets a single causative pathway would be highly effective in ~5% of refractory cancer cases.

    Suppose I grant that some surprising results, miraculous even, can be got by Dr. B’s methods. Now comes the tougher question:
    Why the hell is he just sitting there, hoarding it?

    If you heard that Pfizer had some miracle cure for 5% of cancers, but they only sold it “cash-up-front” at their private clinic in Miami at a premium price… wouldn’t you be out front, picketing? Why hasn’t Burzynski done what every other cancer researcher does when they hit on some amazing discovery: sell it to a drug company for broader distribution and rigorous testing?

    Why the lack of clinical testing, or scientific rigor?

    The most damning statistic for me is that 62 studies have been attempted, and only 1 has been marked completed, and it was a Phase II in end-stage melanoma (CDR0000066552). If I compare that to a small pharma-tech in the same state, Reata, a company of ~100 people … they have 23 studies and 11 are completed. The big boys in Research Triangle Park have 100 to 200 studies, but 60-70% typically are marked as completed…

    My conclusion from all of this is not that antineoplastons CANNOT work…. clearly they could. So could DCA, sylvestrin, cannabinoids, shaman magic and pixie dust. There may yet be something useful to be gleaned from this set of compounds. What I am suspicious of is the marketing machine of the Burzynski Clinic and their exploitation of both the federal guidelines around clinical trial management and their exploitation of the desperate hope of a family with an afflicted loved one. I’m not opposed to the possibility of a breakthrough in cancer treatment being made, but these people are making no progress on that front. It stinks of salesmanship, not science.

    Something is rotten in the Independent Republic of Texas.

  59. #59 c0nc0rdance
    December 17, 2012

    @Didymus
    Something that I should add to my previous comment:
    Why does Burzynski charge for clinical trials? He owns the patent (US Patent 7,427,619) on antineoplastons, actually several of them. Again, if you had the choice between being the exclusive source for a cancer cure, or licensing it to a major pharma for world-wide distribution… what kind of monster would you have to be to limit it to cash-up-front patients in the numbers Burzynski has seen in the last 30 years? What about the millions who died without having the means to seek his miraculous cure?

    Best case scenario for me: He’s either a
    1. fraud/marketing machine or
    2. a megalomaniac, hoarding something that should be released to the world for his own small profit.

    Is there some third alternative I’m not considering? If it really works, what the heck is he up to with his business model? Hell, I’ll make the introductions to some friends at Baylor or MD Anderson just across the city (both world-class research institutions that have completed thousands of clinical trials) if he needs some help getting his miracle cure properly and rigorously tested.

  60. #60 flip
    December 18, 2012

    Sharing the popcorn… and grabbing a cookie for myself.

  61. #61 MarkL
    December 18, 2012

    I fear you are wasting your time C0nc0rdance.

    A) You have failed to take into account Diddum’s inability to comprehend anything but the very shortest of sentences.

    B) Even if he understand’s the gist of your questions, his inability to do even basic maths means you lost him as soon as you used something as complex as a percentage.

    C) I have my doubts as to whether even a blatant bullsh*tter like Diddums would dare reappear after making such an arsehat of himself.

    D) LW owns him – have you asked permission to speak to him?

  62. #62 MarkL
    December 18, 2012

    oops………… apologies for extraneous apostrophe in B) above

  63. #63 LW
    December 18, 2012

    Oh, I disclaim all ownership. Y’all feel free to try to communicate with DJT.

    I think c0nc0rdance set out the possibilities quite well: either Burzynski does have what he claims, in which case he’s a monster (also shortsightedly greedy) for keeping it to himself for thirty years while people die all over the world for lack of it; or else he doesn’t have it, in which case he’s a monster preying on the hopes and fears of dying people, torturing them too since his treatment is apparently quite unpleasant. Either way he’s a monster. 

  64. #64 Didymus Judas Thomas
    Up in the Clouds Looking for MI Dawn's Brain
    December 18, 2012

    MI Dawn,

    _____””and HE still hasn’t proven it works”
    Oh, and yes, DJT: the host and most of the commenters on this blog ARE biased. We are biased in the direction of Science-Based Medicine, which has been tested and shown to reliably work. If Stan would give us some of his results, to allow replication, and his protocols were shown to work, we’d accept his methods too. But right now, all we get is hand-waving.

    I really & truly hate to break this to you, but the FDA wouldn’t have granted Phase III Trials if they didn’t have what they required.

    So guess what?

    It’s like my Middle School History teacher used to say:

    “YOU … DON’T … GET … A … VOTE!!!”

  65. #65 Shay
    December 18, 2012

    What concordance said.

  66. #66 LW
    December 18, 2012

    “I really & truly hate to break this to you, but the FDA wouldn’t have granted Phase III Trials if they didn’t have what they required.”

    DJT has a quite touching faith in the infallibility of FDA bureaucrats.

  67. #67 Antaeus Feldspar
    December 18, 2012

    I really & truly hate to break this to you, but the FDA wouldn’t have granted Phase III Trials if they didn’t have what they required.

    Uh-hunh.

    So your syllogism is basically:

    1) Burzynski has been allowed to start one Phase III clinicial trial.
    2) No treatment has ever been allowed to move to Phase III clinical trials, not even through a failure of oversight, without all the needed Phase II clinical trials having been satisfactorily concluded.
    3) Therefore all Burzynski’s Phase II clinical trials must have been satisfactorily concluded.

    I really don’t see any reason to think premise 2 is correct, especially as it appears to imbue the FDA with an infallibility that I’m sure you would NEVER grant them having when it comes to Big Pharma. You can’t go spouting off all over the place about how the FDA let GSK and Merck and Pfizer get away with murder and then turn around, blink your eyes innocently, and say, “Why, despite the smoking gun in Burzynski’s hand and the dead body on the floor, it must not be murder because the FDA would never have let him get away with it!”

    So guess what?

    It’s like my Middle School History teacher used to say:

    “YOU … DON’T … GET … A … VOTE!!!”

    Even if your history teacher from last semester were the arbiter of everything in the world and had the authority to take away the “votes” of everyone in the world (another premise I see no reason to grant) you are not he. Your teacher, I am sure, knows enough of third-grade math not to think “seven patients = 70%.”

  68. #68 MarkL
    December 18, 2012

    DJT also has little or no Knowledge of the FDA’s Special Protocol Assessment for phase III and how that shreds his argument that Burzynski MUST have proven efficacy to progress to a Phase III trial.

    http://www.ministryoftruth.me.uk/2011/12/05/burzynski-just-one-more-thing/

  69. #69 LW
    December 18, 2012

    I thought of trying to explain the correct computation to DJT, but that would involve explaining most of third grade math so I gave up. I did think s/he might recognize the absurdity of his/her method of computation by example, but I doubt s/he could even grasp that. Still, here it is:

    Let’s pretend there were only three patients and two died. Now let’s compute the survival percentage the DJT way:

    If you had 3 patients you could call that: 30%.
    1 successful patient would then be: 10%
    Change 30% to: 100% (by adding 70%)
    Change 10% to: 80% (by adding 70%)
    80% minus 100% = 20% (actually that’s -20%, but in this context a detail like a missing sign is trivial)
    So 20 deaths out of 100 = 80% survival rate.

    There you go! 1 is 80% of 3 and 2 is 20% of 3 according to the DJT method.

    Perhaps, DJT, you will now see why everyone reacted with various combinations of hilarity, horror, and pity at your attempt at mathematics.

  70. #70 MarkL
    December 18, 2012

    Further to my previous comment on Burzynski’s phase III trial:

    BKsea commented just a few short weeks ago on the “yet another Patient…..” thread:

    ……………..Burzynski has only gotten approval from the FDA of a Special Protocol Assessment (SPA) for his phase 3 trial. My understanding is that this is just an approval of the trial design, not permission to enter into the trial. He will still need an Investigational New Drug (IND) approval, which requires evidence of efficacy from phase 2. Presumably, he has not started phase 3 because he has no evidence of efficacy and cannot get an IND approval from the FDA.

    Can’t get anything right can you Diddums?

  71. #71 W. Kevin Vicklund
    December 18, 2012

    Very interesting find, MarkL. It looks as though the much-vaunted Phase III trial was actually nothing more than an approval of the trial protocol, submitted before the actual New Drug Application for the Phase III trial. But getting the protocol approved is only a step in the process of getting approved for a Phase III trial – you also have to provide the results of Phase II trials, among other requirements. This may explain why the FDA has repeatedly denied any knowledge of a Phase III trial by Burzynski, yet one such trial is listed on ClinicalTrial.gov.

  72. #72 Krebiozen
    December 18, 2012

    MarkL,
    I have been wondering about that Phase 3 trial for some time, so thanks for posting that link, which explains that it doesn’t mean what Burzynski’s supporters claim at all.

  73. #73 flip
    December 18, 2012

    It occurs to me that Squidymus is actually providing “defence of truth” even if it’s not in the way he intends it: the more he posts, the more digging shows that Burzyinski is up to no good.

  74. #74 LW
    December 18, 2012

    It occurs to me that there are fundraisers to allow desperate dying people to be experimented upon by Burzynski. Sometimes after they die these fundraisers are continued to allow other desperate dying people to be experimented upon by Burzynski. But are there any such cases where the patient *didn’t* die? Where they gratefully continued the fundraiser to help others be saved as they were? If there are no such cases, it’s a pretty good hint the Burzynski’s success rate is low, is it not?

  75. #75 herr doktor bimler
    December 18, 2012

    There’s interesting stuff in MarkL’s link for a disinterested seeker after truth such as DJT. For someone who likes to present himself to the alt-med world as a fiercely maverick foe of Big Pharma, Burzynski writes a lot of those truth-spinning press releases for the business world, trying to convince Big Pharma to invest in his company.

    If it’s only their money he defrauds I won’t feel so bad.

  76. #76 Narad
    December 18, 2012

    For someone who likes to present himself to the alt-med world as a fiercely maverick foe of Big Pharma, Burzynski writes a lot of those truth-spinning press releases for the business world, trying to convince Big Pharma to invest in his company.

    BZYR has been the focus of at least one organized pump-and-dump effort (PDF), in 2011 November.

  77. #77 MarkL
    December 18, 2012

    @ Narad

    And I guess we can conclude that the Phase III trial (or rather the approval of a putative trial protocol) is merely another attempt to bolster the scientific credibility of the brave maverick’s business venture so that he might open another revenue stream (bilking investors out of their money) before the whole edifice comes crashing down around his ears, rather than an earnest attempt to prove efficacy.

  78. #78 Narad
    December 18, 2012

    I doubt that Burzynski had anything to do with it; his income stream is fine. One might idly wonder whether Merola is or was a shareholder, though. I started to harbor the suspicion that Squidymus, who appears to be unsophisticated on nearly every level, might have been suckered into buying this when it started barfing up SEC filings. To quote pumpsanddumps-dot-com, “forums such as investorshub[.]com, siliconinvestor[.]com or the Yahoo Finance Message Boards usually contain contributions from child-like posters who are there for no other reason than to try and convince themselves that they made a good investment.”

  79. #79 thenewme
    December 18, 2012

    @LW
    Larry and Margaret Manning founded the “Setting Them Free Foundation” after Margaret was allegedly successfully treated by Burzynski. It’s one of several deceitful and scammy fundraising sites for Burzynski patients, and includes active fundraising links for deceased patients. They even offer a fundraising “campaign guide.” Ack.

    Seems to me they’ve sold their souls to Burzynski, like Merola (whose niece was apparently a Dr. B patient who died). Maybe it’s all part of an effort to pay off their outstanding debt from Dr. B’s treatment.

  80. #80 MarkL
    December 18, 2012

    @Narad

    In the disclosures:

    DGMR has received compensation for non-investment banking services on the small-cap universe, and expects to receive additional compensation for non-investment banking services on the small-cap universe, paid by issuers of securities covered by DGMR. Non-investment banking services include investor relations, and advertising services

  81. #81 Narad
    December 18, 2012

    In the disclosures

    Oh, they’re paid touts; that’s not in question.

  82. #82 Narad
    December 18, 2012

    (Or, to be more clear, the question is who paid them to put this one out. I’m doubt they’re unwilling to slap a “letterhead” on “client”-supplied copy and cram it in the pipe.)

  83. #83 Narad
    December 18, 2012

    ^ “I doubt.” Must be more careful with revising on the fly.

  84. #84 flip
    December 18, 2012

    @Narad

    Re: the ‘pump and dump’ link, I love how under “RECENT ARTICLES AND PUBLICATIONS” – a vimeo link, 2 youtube links and 1 article on Mercola’s site. And that’s it! No other citations, no links to peer-reviewed papers… just those.

    Why in the world would an investor put money into a medical company when they only cite videos?

  85. #85 herr doktor bimler
    December 19, 2012

    Larry and Margaret Manning founded the “Setting Them Free Foundation” after Margaret was allegedly successfully treated by Burzynski. It’s one of several deceitful and scammy fundraising sites for Burzynski patients, and includes active fundraising links for deceased patients. They even offer a fundraising “campaign guide.”

    Burzynski employee Marc Stephens (in charge of search-engine gaming) had a well-documented role in setting up the purported “Burzynski Patients Group” website. One wonders on how many other “help Patient X” might his slimy fingerprints be found.

  86. #86 herr doktor bimler
    December 19, 2012

    Plz to put italics around first paragraph above.

  87. #87 Narad
    December 19, 2012

    Why in the world would an investor put money into a medical company when they only cite videos?

    The marks aren’t investors, they’re nickel-slots, lottery-ticket types being preyed upon by low-rent bottom-feeders.

  88. #88 Militant Agnostic
    December 19, 2012

    @Flip

    Why in the world would an investor put money into a medical company when they only cite videos?

    Why don’t you ask DJT?

  89. #89 flip
    December 19, 2012

    @Narad and Militant Agnostic

    Evidently I should have used a /rhetorical tag… because it was rhetorical.

    As for asking DJT, I would if I thought he might answer in less than a few sentences. Or in a way I could understand the reply.

  90. #90 Healthy
    December 29, 2012

    Well, it seems that Dr. Burzynski is more after the money than after the cure. The “personalized” approach, either by grouping or by real “personalization” certainly helps. The problem is when this “personilzed” excuse is used for un-scientific approaches.
    Anyway I disagree that “personalized” treatments is the key. I’d say it really helps but the problem in my opinion lies on finding more effective generic approaches to cancer. All tumorous cells can be descrived by a few common characteristics that discern them from healthy cells. Those characteristics should be treated, like radiotherapy does, but in a more elegant way.

    For funding, research and peer finding please refer to the non-profit Aging Portfolio.

  91. #91 Renate
    December 29, 2012

    There must be something wrong if I tend to associate a screenname like ‘Healthy’ with someone willing to promote some quack.

    @ Healthy,
    I can only agree with your post.

  92. #92 Narad
    December 29, 2012

    There must be something wrong if I tend to associate a screenname like ‘Healthy’ with someone willing to promote some quack.

    Well, it’s clearly promoting something.

  93. #93 flip
    December 29, 2012

    @Narad

    Indeed. ‘Healthy’ has posted the same sentence on four different blog posts, and as an unrelated tag to the end of more contextually-apt comments. It seems to be spamming.

  94. #94 Lawrence
    December 30, 2012

    @flip – I was going to say the same thing….

  95. #95 Sal
    January 28, 2013
  96. […] mentioned above, some conventional chemotherapy drugs are targeted therapies. Thirdly, as described here and here, Burzynski had been making overblown and misleading claims for his version of […]

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