Antineoplastons

Cancer Science

Cancer is complicated. Few subjects lead to as much anxiety, anguish and desperation. Some cancers are completely curable; others are fatal. Some patients have highly uncertain prognoses, leading sufferers and their families to feel uncertain and anxious. Patients facing a high likelihood of suffering and/or death often become desperate. Any hope for a cure is better than no hope at all.

We have learned a lot about cancers, and our knowledge continues to progress through proper adherence to the scientific process. No other method is reliable.

Oncologists will tell you that cancer is not any one particular disease, but rather a group of diseases that range from manageable to deadly. The National Cancer Institute offers this definition: “A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems”. In 2010, the World Health Organization listed cancer as the second leading cause of death in the U.S. 

In 1990 in the U.S., cancer deaths reached approximately 275 per 100,000 men and 175 per 100,000 women. The science of cancer treatment is a broad topic as it is really dealing with a large host of diseases. Science has made much progress in recent years, resulting in a steady decline in cancer death rates since 1990. According to the NCI, “From 2000 through 2009, cancer death rates decreased by 1.8 percent per year among men and by 1.4 percent per year among women.” We seem to be making incremental progress, but the problem remains huge.


Science is a process of systematically evaluating ideas. The science of cancer involves researching the many individual disorders termed “cancer” (including epidemiology, physiology, histology, genetics, molecular biology, etc) and also potential treatment research. The science of treatment for any disease requires up-to-date knowledge of the disorder, a reasonable hypothesis about the treatment and the disorder, and proper investigation of the treatment’s effects and side-effects. It is an incremental science. Advances have been made slowly and incrementally, resulting in observable declines in morbidity and mortality.






Cancer Pseudoscience



Over the years, many alternative, non-scientific schools of thought have been proposed and defended regarding cancer and its treatment. A recurrent characteristic of pseudoscience in medicine involves some form of the claim for the “one cure for all disease”. This essentially (and wrongly) boils complex groups of diseases down into a common pathway with a common cause. The proponents claim knowledge of this common cause and then the cure for the whole gambit of diseases by treating this common cause. The common cause may take the form of unobservable, vitalistic forces (eg chi, innate intelligence). Many take the form of more sciency-sounding ideas such as parasites, acidity, “toxins”, and others. Many of the clinics that offer such therapies operate in Mexico to avoid regulation by the F.D.A.

The field of cancer is ripe with pseudoscience. Dr. Stephen Barrett described some apparent characteristics of cancer pseudosciences in his article, “Questionable Cancer Therapies”. He states:


Cancer cures attributed to questionable methods usually fall into one or more of five categories:

  1. The patient never had cancer.

  2. A cancer was cured or put into remission by proven therapy, but questionable therapy was also used and erroneously credited for the beneficial result.

  3. The cancer is progressing but is erroneously represented as slowed or cured.

  4. The patient has died as a result of the cancer (or is lost to follow-up) but is represented as cured.

  5. The patient had a spontaneous remission (very rare) or slow-growing cancer that is publicized as a cure.”


For instance, the late Hulda Clark, PhD, N.D. wrote in her book (The Cure for All Cancers), “All cancers are alike. They are all caused by a parasite. A single parasite! It is the human intestinal fluke. And if you kill this parasite, the cancer stops immediately. The tissue becomes normal again. In order to get cancer, you must have this parasite. ” Of course, she offered various treatments to kill the liver flukes and rid the body of toxins (at fairly high costs to patients). Hulda Clark died in 2009 of multiple myeloma, a form of bone marrow cancer.

Others cancer pseudosciences include various detoxification methods such as The Gerson Method, Metabolic Therapy, psychic surgery, Immuno-augmentative Therapy, and Hyperoxygenation Therapy.

The American Cancer Society provides a brief overview of more such practices (see Questionable Cancer Practices in Mexico).

Both of the above lists also include a therapy called “Antineoplastons”.





What are Antineoplastons?

In the late 1960’s and early 1970’s, a physician and researcher from Poland named Stanislaw Burzynski studied biologically active peptides (molecules made of short chains of amino acids linked by peptide bonds). He published a series of papers from 1973 to 1976 describing the isolation of peptides from human urine. During this time, he claimed to find that people suffering from cancer had lower levels of certain peptides in their blood and urine than people without cancer. He made an interesting speculation that these particular peptides act to inhibit the transformation of normal cells into cancer cells, a process known as malignant ‘neoplasia’ (new formation) . He then speculated that people suffering from cancer are deficient in these peptides. He called this group of peptides “antineoplastons”.


The Office of Technology Assessment: Unconventional Cancer Treatments (1990) states:


“In the late 1960s, Stanislaw R. Burzynski, MD, proposed that a naturally occurring and continuously functioning biochemical system in the body, distinct from the immune system, could "correct" cancer cells by means of "special chemicals that reprogram misdirected cells." He called these chemicals "Antineoplastons," and defined them as naturally occurring peptides and amino acid derivatives that inhibit the growth of malignant cells while leaving normal cells unaffected.”


Dr. Burzynski further speculated that cancers could be treated and cured by isolating these antineoplastons from urine and infusing them into patients with cancer. He claimed to have isolated several different fractions of antineoplastons and apparently classified them according to anti-tumor effect.


Dr. Burzynski described antineoplastons in a 1986 paper :


Antineoplastons are naturally-occurring peptides and amino acid derivatives which control neoplastic growth. The theory of antineoplastons was conceived through the application of the cybernetic theory of autonomous systems to studies of peptides in human blood. The original research began in 1967, when it was noticed that there were significant differences in the peptide content in the serum of cancer patients as compared with the control group. Since similar peptide fractions were isolated from urine, a research programme was established for the identification of antineoplastic peptides from urine.


Dr. Burzynski isolated his antineoplastons from urine. Because of the vast quantities of urine required to isolate these peptides, they were then synthesized in a chemistry lab.


Medicinal use of urine and urine extracts has been known for centuries in ancient Egypt, Greece, Rome, India and North and Central America. In modern times, the first study of growth-inhibiting substances in urine was conducted in 1937. The research on urinary peptides has a long history and was initiated by a Polish researcher, S. Bondzynski, in 1897.”


This implies that the use of substances extracted from urine is supported by appealing to ancient practices and historical precedent.


Antineoplastons were found to be completely different from peptides and amino acid derivatives isolated from urine by other authors. Research on antineoplastons led to the isolation of different peptide fractions from urine, named Antineoplaston A1, A2, A3, A4 and A5, which possessed high anticancer activity and low toxicity.”


His research appeared to be unique because no other researchers have isolated these peptides. Prior to any organized phase II or III human trials, Dr. Burzynski claimed that the peptides were highly effective against cancer with few side-effects.


The first active component was identified as 3-phenylacetylamino-2,6-piperidinedione and was named Antineoplaston A10. Two synthetic derivatives of Antineoplaston A10 were named Antineoplaston AS2-1 and AS2-5. All antineoplaston formulations were submitted for Phase I clinical studies in advanced cancer patients. The treatment was free from significant side-effects and resulted in objective response in a number of advanced cancer cases.


Cancer.gov describes Antineoplastons further:


Antineoplaston A was further purified and yielded antineoplastons A1, A2, A3, A4, and A5. These mixtures of 7 to 13 peptides were patented in 1985. In vitro tissue culture studies and in vivo toxicity studies in animal models were performed for antineoplastons A1 through A5. According to the developer, each individual fraction had a higher level of antitumor activity and lower toxicity level than antineoplaston A. Phase I trials of this antineoplaston group in patients with various advanced cancers showed A2 as contributing to the highest tumor response rate, so it was selected for further study. The active compound in A2 was found to be 3-phenylacetylamino-2,6-piperinedione, which was named antineoplaston A10.[7] From antineoplaston A10, three other compounds have been derived:

AS2-5, which is phenylacetylglutamine (PAG).

AS2-1, which is a 4:1 mixture of phenylacetic acid (PA) and PAG.

A5, which is PA and an aromatic fatty acid.

Other antineoplastons (A3, A4, A10-1, AS5) were added to this group after further studies.
There have been no independent analyses of which amino acids comprise the antineoplastons used in any of the reported studies
.
” (emphasis added).






Antineoplastons: Evidence

As we noted above, cancer research takes many approaches towards this complex group of issues. The medical and scientific community should welcome new ideas. But as with all ideas in science, we cannot claim to know what works and what doesn’t without proper testing. Our biases blind us to empiric knowledge. The scientific method must be applied to weed out the hypotheses that work from those that don’t. Without the proper rigors of science, no treatment can be claimed as knowledge.


Before we look at the evidence for Antineoplastons, we should first review the 4 phases of clinical trials that proposed treatments should go through before they can be considered “settled science”. ClinicalTrials.gov defines them thusly:


Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

  • Phase I: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

  • Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.

  • Phase III: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

  • Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

In the mid-1970’s, Dr. Burzynski was a licensed physician in private practice in Texas. He had been affiliated with the Baylor College of Medicine prior to this, but left Baylor over various disagreements regarding his research. Details of his experience at Baylor are chronicled in Dr. David Gorski’s review in Skeptical Inquirer (Stanislaw Burnzynski: Four Decades of an Unproven Cancer Cure).


Dr. Burzynski began administering his antineoplastons to patients in his private practice. He published papers on the peptides including their chemical nature and toxicology. Cancer.gov states: “In vitro studies using a variety of human cell lines have been used to assess the effectiveness of antineoplastons as antineoplastic agents.He published preclinical studies.” 


The early publications were:


-- Biological active peptides in human urine: III. Inhibitors of the growth of human leukemia, osteosarcoma, and HeLa cells.

- Antineoplaston A in cancer therapy. (I).

- Polypeptides that inhibit human breast cancer cell division.

- Preclinical studies on antineoplaston AS2-1 and antineoplaston AS2-5.

- Toxicology studies on antineoplaston AS2-5 injections in cancer patients.

- Toxicology studies on antineoplaston AS2-1 injections in cancer patients.

- Preclinical studies on antineoplaston A10 injections.

-Toxicology studies on antineoplaston A10 injections in cancer patients.

- Chronic animal toxicity studies on antineoplaston A2.

- Initial clinical study with antineoplaston A2 injections in cancer patients with five years' follow-up.

- In vitro cancer growth inhibition and animal toxicity studies of antineoplaston A3.

- Phase I clinical studies of antineoplaston A3 injections.

- Tissue culture and animal toxicity studies of antineoplaston A5.

- Phase I clinical studies of antineoplaston A5 injections.

- Pharmacokinetic study of radioactive antineoplaston A10 following oral administration in rats.

- Chemoprevention by antineoplaston A10 of benzo(a)pyrene-induced pulmonary neoplasia.


There has been some publications of Phase I data on antineoplastons outside of Dr. Burzynski’s group, mainly from Japanese anesthesiologist, Dr. Hidaeki Tsuda of the Kurume University Hospital in Japan. His publications are as follows:


-Demethylation effect of the antineoplaston AS2-1 on genes in colon cancer cells

-Antineoplaston induces G(1) arrest by PKCalpha and MAPK pathway in SKBR-3 breast cancer cells.

-Effects of antineoplaston AS2-1 against post-operative lung metastasis in orthotopically implanted colon cancer in nude rat.

-Long-term survival following treatment with antineoplastons for colon cancer with unresectable multiple liver metastases: report of a case.


This collection lends some support to Dr. Burzynski’s hypothesis by providing some laboratory data (animal and in vitro data) and anecdotal cases. Phase I trials are meant to be preliminary. Phase I is the beginning of research, not the end (unless the idea does not survive this initial stage). Phase I studies can help establish plausibility and determine if a subject is worth pursuing into higher phases of research. Phase 1 data is never definitive for any research topic.



What about Phase II studies?


In 2003, Dr. Burzynski reported preliminary data on 12 patients enrolled in a Phase II study. The abstract reads:


Phase II study of antineoplaston A10 and AS2-1 in patients with recurrent diffuse intrinsic brain stem glioma: a preliminary report.

Of ten evaluable patients, complete response was determined in two cases (20%), partial response in three (30%), stable disease in three (30%) and progressive disease in two (20%). Survival at 2 years was 33.3%. Currently, of all 12 patients, two (17%) were alive and tumour free for over 5 years since initial diagnosis; one was alive for more than 5 years, and another for more than 4 years from the start of treatment. Only mild and moderate toxicities were observed, which included three cases of skin allergy, two cases of anaemia, fever and hypernatraemia, and single cases of agranulocytosis, hypoglycaemia, numbness, tiredness, myalgia and vomiting.

CONCLUSION:

The results of this study compared favourably with the responses of patients treated with radiation therapy and chemotherapy. The study continues with accrual of additional patients.”



In 2004, another set or prelimary Phase II data was published. Its abstract reads:

Phase II study of antineoplaston A10 and AS2-1 in children with recurrent and progressive multicentric glioma : a preliminary report.

OBJECTIVE: To evaluate the response rates, survival and toxicity of treatment with antineoplaston A10 and AS2-1 (ANP) in the first 12 children enrolled in our studies diagnosed with incurable recurrent and progressive multicentric glioma.

PATIENTS AND METHODS:

The patients' median age was 9 years. Six patients were diagnosed with pilocytic astrocytoma, four with low-grade astrocytoma and one with astrocytoma grade 2. In one case of visual pathway glioma, a biopsy was not performed due to a dangerous location. Patients received ANP intravenously initially and subsequently orally. The average duration of intravenous ANP therapy was 16 months and the average dosage of A10 was 7.95 g/kg/day and of AS2-1 was 0.33 g/kg/day. The average duration of oral ANP was 19 months and the average dosage of A10 and AS2-1 was 0.28 g/kg/day. Responses were assessed by MRI according to the National Cancer Institute's criteria and confirmed by PET scans in some cases.

RESULTS:

Complete response was accomplished in 33%, partial response in 25%, and stable disease in 33% of patients, and there was no progressive disease. One patient was non-evaluable due to only 4 weeks of ANP and lack of follow-up scans. One patient who had stable disease discontinued ANP against medical advice and died 4.5 years later. Ten patients are alive and well from 2 to >14 years post-diagnosis. Only one case of serious toxicity of reversible tinnitus, of one day's duration, was described. The study continues with accrual of additional patients. (emphasis added)

CONCLUSION:

The results of the present study are favourable in comparison with radiation therapy and chemotherapy. We believe that confirmation of these results through further studies may introduce a new promising treatment for incurable paediatric brain tumours.”


These two Phase II studies have not been completed.


In 2014, Dr. Burzynski published a single-arm Phase II study describing 17 patients with brainstem gliomas (The response and survival of children with recurrent diffuse intrinsic pontine glioma based on phase II study of antineoplastons A10 and AS2-1 in patients with brainstem glioma.).

His conclusion states: “The results suggest that ANP shows efficacy and acceptable tolerability profile” There were a total of 40 patients enrolled, but only 17 were reported. We are not told in this nonrandomized study about the other 23 patients, and (as has been pointed out) therefore it is considered incomplete.

Since 1999, Dr. Burzynski’s clinic has set up 72 protocols for enrolling patients into clinical trials and has 61 clinical trials registered at ClinicalTrials.gov. As of this writing, Dr. Burzynski has not published any completed Phase II trials. There have been no published randomized controlled trials of antineoplaston therapy on cancer patients. No Phase III studies have been published.






Antineoplastons: Evidence Against


Four years prior to Dr. Burzynski's uncompleted phase II studies, a multicenter Phase II trial was published by researchers from the Mayo Clinic (Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma). Dr. Burzynski was not involved in this study. It was designed to assess safety and pharmacodynamics. There were only 9 patients enrolled.

At the time of study publication, all patients had died. The median survival time was 5.2 months and the mean survival time was 7.2 months. All patients except one died of tumor progression. The remaining patient died of sepsis related to complications from chemotherapy, which was administered after antineoplaston treatment was discontinued.

None of the six assessable patients showed evidence on computed tomography (CT) scan or magnetic resonance imaging (MRI) of tumor regression associated with antineoplaston treatment; however, all nine patients showed evidence of tumor progression. Antineoplaston treatment was administered for 6 to 66 days, after which treatment was discontinued. Toxicity caused three patients to discontinue treatment and subsequent scans of these patients showed tumor progression. The mean time to treatment failure (progression or unacceptable toxicity) was 29 days.” (emphasis added)



It seems odd that the only Phase II level study completed and published (by a source independent of the Burzynski Clinic) was uniformly negative, yet no completed trials have been published by Dr. Burzynski (as of this writing).


Dr. Gorski writes:

“To date, although Burzynski has published occasional case studies and partial results of two phase 2 trials, he has not published the complete results of any of his phase 2 trials. Of the sixty-one clinical trials registered on ClinicalTrials.gov with Burzynski as the principal investigator, only one has been completed, but it has not been published. Of the remaining sixty trials, the statuses of fifty are unknown; seven were withdrawn; two have been terminated; and one has not yet been opened to accrual (ClinicalTrials.gov 2013), and the phase 3 trial has never accrued a single patient.”



Over the past few decades, he treated thousands of patients and he (or others acting on his behalf) publicized anecdotal reports of supposed success.

But what have other investigators found?



Cancer.org states: (emphasis added)


“In 1982, consultants to the Ontario (Canada) Ministry of Health visited Burzynski's clinic and reviewed records of twelve patients selected by Burzynski from among the thousands he had treated. According to the OTA report, the Canadian doctors "found no examples of objective response to Antineoplastons."


In 1985, the Canadian Bureau of Prescription Drugs examined the records of Canadian doctors who had treated patients at Dr. Burzynski's clinic in Houston. 

Of 36 patients, 32 had died without showing signs of improvement. 

Of the remaining 4, 1 patient died after slight improvement, while 1 patient died after stabilizing for a year. 

The 2 remaining patients had widespread cancer.


During the 1980s, the United States Congressional Office of Technology Assessment (OTA) reviewed medical journal articles describing cases of cancer patients whom Dr. Burzynski had treated with antineoplaston therapy. Its report, published in 1990, concludes that, "Despite a substantial number of preliminary clinical studies published by Burzynski and his associates describing outcomes among the patients he treated with Antineoplastons and an attempt at a 'best case' review, there is still a lack of valid information to judge whether this treatment is likely to be beneficial to cancer patients." The OTA report criticized Burzynski's research process and noted that his definitions of advanced cancer and of complete and partial cancer remission were not used in accordance with generally accepted definitions. One example they pointed to was a patient said to have had a complete remission after treatment with antineoplastons. The report concluded that this claim was inappropriate because the cancer had been removed by surgery before the antineoplaston treatment was started.


In 1991, the National Cancer Institute (NCI) reviewed several “best cases” (involving patients with brain tumors) chosen by Burzynski. According to a 1992 article in the Journal of the National Cancer Institute, “two NCI extramural investigators independently reviewed the case histories of some patients treated with antineoplastons. At the investigators' recommendation, the NCI examined the case histories, pathology slides, and imaging studies from seven patients with primary brain tumors ….[T]he site visit team and, subsequently, the [NCI] Division of Cancer Treatment's Decision Network Committee believed that evidence of possible antitumor effect was demonstrated.” NCI concluded that these results warranted further investigation through clinical trials at other medical centers. But because of disagreement between NCI researchers and Burzynski, the clinical trials were terminated in 1995. By 1999, the researchers concluded that only 6 of the 9 patients treated in that study could be evaluated according to the study's initial requirements. None of the 6 showed evidence of tumor shrinkage. The researchers noted, however, that the small number of patients participating limited their ability to say with confidence that antineoplaston treatment had no benefit.


Many of the clinical trials at the Burzynski clinic have included certain standard cancer treatments such as radiation and chemotherapy treatments along with antineoplastons. However, according to the FDA’s website, a 2013 clinic observation reported that some of the patients who were classified as being in either complete or partial remission didn’t meet all the requirements to be classified as in remission. This would cast doubt on some of the reported successes in treatment.



The Phase I publications listed in the above section are preliminary. We cannot count them as anything more. The Burzynski Clinic has 72 research protocols and  61 registered clinical trials that are supposedly ongoing. Why haven’t any of the 72 registered research protocols resulted in a single completed Phase II or III study?


To understand this question, we should look at some of the history behind the 72 registered research protocols.




History of the Burzynski Clinic

http://www.usatoday.com/story/news/nation/2013/11/15/stanislaw-burzynski-cancer-controversy/2994561/
Much of the information that follows comes from the diligent work of other skeptics, namely Dr. David Gorski, Dr. Saul Green,  Robert Blaskiewicz, Josephine Jones and Liz Szabo.

Saul Green writes:

Burzynski received an M.D. from a medical academy in Poland in 1967 and a D.Msc. in 1968. He did not finish a residency or train in oncology, and his bibliography does not mention clinical cancer research, urine, or antineoplastons during this period.”


“Burzynski came to the United States in 1970 and worked in the department of anesthesiology at Baylor University, Houston, for three years, isolating peptides from rat brains. He got a license to practice medicine in 1973 and, with others, received a three-year grant to study the effect of urinary peptides on the growth of cancer cells in tissue culture. The grant was not renewed.”


“Burzynski's claim to a Ph.D. is questionable. Letters from the Ministry of Health, Warsaw, Poland, and from faculty at the Medical Academy at Lubin, Poland, say, respectively:

  1. At the time Burzynski was in school, medical schools did not give a Ph.D.

  2. Burzynski received the D.Msc. in 1968 after completing a one-year laboratory project and passing an exam. Burzynski did no independent research while in medical school.


“In 1976, with no preclinical or clinical cancer research experience, Burzynski announced a theory for the cure of cancer based on his assumption that spontaneous regression occurs because natural anticancer peptides, which he named antineoplastons, "normalize" cancer cells.”


At the time, Dr. Burzynski was working as a researcher at the Baylor College of Medicine under Georges Ungar in the Department of Anesthesia. Georges Ungar left Baylor shortly thereafter for the University of Tennessee. Burzynski wanted to research his peptides, now being dubbed ‘antineoplastons’ through Baylor’s Dept. of Anesthesia.

Dr. Gorski writes:

http://www.csicop.org/si/show/stanislaw_burzynski_four_decades_of_an_unproven_cancer_cure/

Baylor wanted Burzynski to sign away rights to his discoveries (a standard condition in academia), and Burzynski did not want to follow Ungar to Knoxville because he was afraid that the University of Tennessee would impose the same condition. There was another condition that rankled him as well. Shortly after he had obtained his Texas medical license in 1973, Burzynski started working part time at a private practice. There, he had apparently administered antineoplastons to cancer patients, the result being a twenty-one patient case series published in 1977...implying that he had likely been treating patients with ANPs as early as 1975.


“In 1976, Burzynski deemed antineoplastons ready to be tested against cancer in a clinical trial. Characteristically, despite having had no formal training in oncology and no experience in clinical trial design, Burzynski judged himself to be uniquely qualified to be principal investigator of such a trial.”


Dr. Burzynski opened a private practice in addition to establishing the Burzynski Clinic for treating patients with antineoplastons. The phase 1 publications listed above were mostly done independent of accredited university laboratories. However, things were not going so well with him, the FDA and oversight organizations.


Dr. Gorski continues:

“From the late 1970s to 1998, Burzynski was under nearly constant investigation by medical authorities, beginning with the Harris County Medical Society in 1979 and continuing with the Texas Medical Board and the FDA.”


“In the fall of 1995, a grand jury indicted Burzynski for seventy-five counts of insurance fraud and violations of the Food, Drug, and Cosmetics Act. As part of this process, Judge Simeon Lake of the U.S. District Court for the Southern District of Texas, ruled that Burzynski’s “continued pretrial release” was contingent upon his administering his drugs exclusively through FDA-approved clinical trials .“


Richard Jaffe, ESQ, provided Burzynski with legal representation. Jaffe is described on his own website thusly: “ He represents  practitioners, companies and health related organizations in complex health care matters throughout the United States, especially legal cases brought by federal and state government agencies. He has extensive experience in Medicare and insurance fraud defense, FDA litigation, professional licensure and criminal and civil scheduled drug prescribing problems, including medical marijuana and OxyContin. He also has represented doctors and companies involved in the clinical use of stem cells, and works on matters involving nutritional supplements.


By 1998, Burzynski was forbidden to treat any more patients with antineoplastons unless under the guise of a clinical trial. He created a large, retrospective “clinical trial”, called “CAN-1”.


The Cancer Letter states:

Patients who were getting antineoplastons at that time were placed into a protocol called CAN-1, a retrospective study in which data on non-Hodgkins lymphoma are reported alongside data on brain tumors, prostate cancer, and "adjuvant therapy." Michael Clark, former chief of the criminal division of US Attorney's Office for the Southern District of Texas, states, “CAN-1 is so distinctly unconventional that frustrated prosecutors promptly began to refer to it as "the garbage can." "When they put the patients into a large clinical trial unlike any other that we have been aware of, it made it very difficult to argue that the clinical trials process was very important in the case.


Burzynski’s attorney Richard Jaffe tellingly described CAN-1:


“. . . As far as clinical trials go, it [CAN-1] was a joke. Clinical trials are supposed to be designed to test the safety or efficacy of a drug for a disease. It is almost always the case that clinical trials treat one disease.

The CAN-1 protocol had almost two hundred patients in it and there were at least a dozen different types of cancers being treated. And since all the patients were already on treatment, there could not be any possibility of meaningful data coming out of the so-called clinical trial. It was all an artifice, a vehicle we and the FDA created to legally give the patients Burzynski’s treatment. The FDA wanted all of Burzynski’s patients to be on an IND, so that’s what we did.”


CAN-1 only covered the existing patients. Since it was retrospective, no new patients would be allowed unless they were entered into prospective trials. Richard Jaffe goes on to describe the creation of these trials:


“CAN-1 allowed Burzynski to treat all his existing patients. That solved the patients’ problems, but not the clinic’s. A cancer clinic cannot survive on existing patients. It needs a constant flow of new patients. So in addition to getting the CAN-1 trial approved, we had to make sure Burzynski could treat new patients. Mindful that he would likely only get one chance to get them approved, Burzynski personally put together seventy-two protocols to treat every type of cancer the clinic had treated and everything Burzynski wanted to treat in the future.”


According to The Cancer Letter, “In 1997, the government failed in two attempts to convict Burzynski. One trial ended in a hung jury. Another produced a not guilty verdict.


So, by the mid-nineties, the Burzynski Clinic was back in business and giving antineoplaston infusions to cancer patients who were enrolled in registered clinical trials. The bulk of the patients were enrolled in a trial described by prosecutors as “the garbage can”, and understood by Burzynski’s attorney as “a joke”,  “an artifice” and “a vehicle”. To this day, the 72 protocols and the 61 registered clinical trials have not resulted in the publication of any completed manuscripts.






Cost of the Clinical Trials

According to interviews with families of former patients of The Burzynski Clinic (see The Other Burzynski Patient Group), the cost to be enrolled and to begin treatment with antineoplastons is about $30,000, at least as of 2013. The monthly costs vary but are quoted as about $7,000.

Parents and families of children with brain tumors may face costs of about $300,000 out of pocket, as reported in USA Today.


It is likely that none of this cost will be covered by insurance as antineoplastons have not been approved by the FDA for the treatment of anything. It is unlikely that the FDA will approve antineoplastons in the future as no proper phase II or III trials have been completed and published.


Liz Szabo wrote in USA Today, “In fact, the FDA hasn't had a chance to approve Burzynski's drugs. He has never officially asked.”






Safety

The first thing that desperate cancer patients -- or the desperate parents of cancer patients -- who are searching for alternative treatment methods will do is to search the internet for information. Most people will enquire about the safety of any treatment. If one does an internet search for antineoplastons, they will likely end up seeing sites like Burzynskipatientgroup.org and read statements like these:


“Antineoplastons are nontoxic, naturally occurring peptides, amino acid derivatives, and organic acids that fight cancer with few if any side effects. Traditional radiation therapy and chemotherapies poison cancer cells and healthy cells as well; antineoplastons cause no harm to healthy cells.”


“Because these drugs are harmless to healthy cells the body can be flooded with antineoplastons, and only cancer cells are affected”


However, these statements are misleading. Cancer.org reports:


“These substances may have not been thoroughly tested to find out how they interact with medicines, foods, or dietary supplements. Even though some reports of interactions and harmful effects may be published, full studies of interactions and effects are not often available. Because of these limitations, any information on ill effects and interactions below should be considered incomplete.


Proponents claim that antineoplaston therapy is “nontoxic” However, reported side effects range from mild to serious, including fatigue (extreme tiredness), anemia (low red blood cell counts), headaches, numbness, skin rash, swelling of the hands and face, chills, fever, dizziness, changes in blood pressure, unpleasant body odor during treatment, and sleepiness. High levels of blood sodium and abnormal calcium levels can also cause significant problems with this therapy. Other serious side effects can involve the brain, and include confusion, seizures, and swelling in the brain. This has required that the treatment be stopped in some patients.


There is also a question of whether some of the unexpected effects in patients were unreported; the FDA noted in a March 2013 inspection report published on the FDA website that reports of serious events such as bleeding in the brain, high blood sodium levels, metabolic acidosis, confusion, and loss of consciousness were not made in a timely manner. Many of these events required hospitalization. After such events, the report noted, some of the patients who were supposed to have been removed from the investigation were not removed, but left in the study.


It is not known whether antineoplastons would cause any problems due to interactions with other medications.

Relying on this type of treatment alone and avoiding or delaying conventional medical care for cancer may have serious health consequences.”


In 2013, the FDA put a hold on the enrollment of new patients into antineoplaston trials after the reported death of a child with a brain tumor. The child died from severe hypernatremia (high sodium level). Antineoplastons require high sodium solutions for infusion. Hypernatremia can be expected as a consequence of infusing solutions with very high salt concentrations. Hypernatremia can cause severe brain damage and can be lethal. In The Skeptical Inquirer, Dr. Gorski writes:


[the child] died of hypernatremia, with USA Today reporting that he was recorded as having a serum sodium of 205 mEq/L, well into the lethal range (normal is between 135 and 145 mEq/L). Consistent with this, in a June 2013 report on the BBC series Panorama, the chief of the pediatric intensive care unit at nearby Texas Children’s Hospital related her experiences taking care of patients from the Burzynski Clinic suffering life-threatening toxicity from ANP treatment. In the same report, a parent who took her daughter to Texas Children’s Hospital after she had suffered such toxicity reported that the Burzynski Clinic had a very bad reputation there because of the frequency with which they had to care for critically ill and dying Burzynski patients.


In 2014, the FDA lifted its hold on the enrollment of patients into antineoplaston trials.






Propaganda

Dictionary.com defines propaganda as:

1. information, ideas, or rumors deliberately spread widely to help or harm a person, group, movement, institution, nation, etc.

2. the deliberate spreading of such information, rumors, etc.

3. the particular doctrines or principles propagated by an organization or movement.


It is said that the plural of anecdote is not data. Anecdotes are hand selected cases that are presented without the perspective of properly presented scientific analysis for the purpose of advancing a particular notion. When one organizes anecdotes and presents them to the public through various media outlets, the only really appropriate term for this is 'propaganda'.


So far, the only clinical evidence presented by Dr. Burzynski is anecdotal case reports which have been organized into a website and two movies. Think about that. No completed and published phase II or III clinical trials, but there are two movies headlining “successes”. Each were made by advertiser Eric Merola. The first one is called Burzynski The Movie: Cancer Is Serious Business and the second one is called Burzynski The Movie: Cancer Is Serious Business Part II. Each movie presents anecdotes and appeals to conspiracy theories to cast Dr. Burzynski as the brave lone maverick guru who is being suppressed by the FDA and “Big Pharma”. The website for the Burzynski movies states:


As with anything that changes current-day paradigms, Burzynski's ability to successfully treat incurable cancer with such consistency has baffled the industry. Ironically, this fact had prompted numerous investigations by the Texas Medical Board, who relentlessly took Dr. Burzynski as high as the state supreme court in their failed attempt to halt his practices. “


When Antineoplastons are approved for public use, it will allow a single scientist to hold an exclusive right to manufacture and sell these medicines on the open market—potentially leaving the pharmaceutical industry absent in profiting from the most effective gene-targeted cancer treatment the world has ever seen.


These propaganda pieces have been written about by other skeptics and anyone interested can look here: http://scienceblogs.com/insolence/tag/eric-merola/


The Burzynski Patient Group is a website created to showcase anecdotal stories as evidence. These stories are emotionally compelling and are very likely to convince many members of the lay public who are not aware of what constitutes scientific evidence. But the fact remains. No randomized, controlled phase II or III studies have been completed or appear to be near completion.


There is no scientific evidence that antineoplastons do anything. And that is not because the FDA is suppressing the lone maverick. It is because Dr. Burzynski has not, and likely will not, present any data in a way that is scientifically valid. Even if he has the “cure for cancer”, we will likely never have that knowledge due to scientific misconduct. And that should make any skeptic angry.






Misconduct

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2013/ucm378237.htm
For years, the FDA has been issuing warning after warning to Dr. Burzynski for misconduct. The most egregious of these (in many skeptics’ opinions) is the apparent loss of initial, key data on the status of patients’ tumors as they entered the trials.

This does not mean that antineoplastons are ineffective, but it does mean that we will likely never see the publication of any meaningful clinical trials, at least in the near future.


In 1995, Saul Green wrote, “U.S. Attorney Gaynelle Griffin Jones said that Stanislaw R. Burzynski and the Burzynski Research Institute introduced an unapproved anti-cancer drug into Interstate commerce, submitted false and misleading claims to health insurers for payment, and violated a federal court order prohibiting interstate trade in the drug without following FDA regulations.” And, “The FDA has never certified Burzynski's drug, which he calls "antineoplastins," as safe or effective. Trading in such unapproved drugs across state lines violates federal law.


Liz Szabo wrote in USA Today that in 1995 “a grand jury indicted Burzynski with 75 felony charges including mail fraud, violations of the Food, Drug and Cosmetics Act and contempt of court”. And, “The charges led to two trials. In 1997, one ended in a hung jury and the other in an acquittal.”


Dr. Stephen Barret documented:

“In 2011, the Texas Medical Board charged Stanislaw Burzynski, M.D. with (a) failure to meet standard of care, (b) negligence, (c) lack of diligence, (d) lack of informed consent, (e) unprofessional conduct, and (f) non-therapeutic prescribing. The charges were related to his management of two cancer patients. According to the complaint (shown below):

  • He treated a woman with breast cancer with a combination of five immunotherapy drugs that are not FDA-approved for treating breast cancer and that the combination plus a chemotherapy agent caused the woman to have unwarranted side effects.

  • He treated a neuroblastoma patient with a drug that lacks FDA approval for that cancer and continued it for an 11-month period even though the cancer kept growing.

In 2012, the Texas State Office of Administrative Hearings dismissed most of the charges and denied the board's request to reverse its ruling. In November 2012, the board decided to drop the case.”


In July, 2012, six weeks after the death of a child from severe hypernatremia (see above), the FDA  stopped Burzynski from giving antineoplastons to any new children.


In 2013, the FDA conducted an extensive inspection of the Burzynski Research Institute. Among the many problems uncovered, an unforgivable point of scientific misconduct was uncovered. 

The report states:

Your MRI tumor measurements initially recorded on worksheets at baseline and on-treatment MRI studies for all study subjects were destroyed and are not available for FDA inspectional review.”  (emphasis added)


Yes, that’s correct. The raw MRI data for the initial tumor measurements for all of the patients enrolled in his clinical trials are missing or destroyed. There is no possible way that any evidence on tumor regression can be verified. The Burzynski Research Institute destroyed the evidence! Since no phase II or III studies have been completed, let alone published in any peer reviewed journal, the world will likely never, ever, see any definitive clinical evidence for antineoplastons.


In December of that year, The FDA issued a warning letter citing the following claims and provided extensive detail about each claim::


1.      You failed to ensure that the investigation was conducted according to the investigational plan

2.      You failed to protect the rights, safety, and welfare of subjects under your care

3.      You failed to obtain informed consent in accordance with the provisions of 21 CFR part 50

4.      You failed to adhere to requirements for all expanded access uses with respect to maintaining accurate case histories and retaining records in a manner consistent with 21 CFR 312.62



https://s3.amazonaws.com/s3.documentcloud.org/documents/1234982/burzynski-2014-tmb.pdf
In July, 2014, the Texas Medical Board issued a 202 page complaint against Dr. Burzynski with over fifty serious charges. The document’s opening paragraph states:

Board Staff alleges that Respondent created a medical practice model based on marketing

his proprietary anti-cancer drugs to patients without adequate measures for patient safety and

therapeutic value. Respondent misled patients knowingly by promoting these drugs as an

attraction to bring patients to his medical practice when Respondent was aware that he could not

legally include most of those patients in FDA-approved Phase 2 clinical trials of his proprietary anti-cancer drugs. 

Respondent further misled patients into paying funds as a retainer prior to receiving any evaluation, diagnosis or treatment. 

Respondent further misled patients into:


(1) paying exorbitant charges for drugs and medical services;

(2) accepting care from unlicensed persons while Respondent and Respondent s employees misrepresented those unlicensed persons to be licensed medical doctors in Texas and the United States of America; and


(3) accepting care from health care providers who had little advanced education or training related to cancer treatment while Respondent and Respondent's employees misrepresented those health care providers to be doctors with significant advanced education or training related to cancer treatment.






Political Protection

But how can Dr. Burzynski continue to sidestep the FDA’s and the Texas Medical Board’s efforts to get him to comply with proper scientific procedure?


He has won the support of Representative Joe Barton of Texas. Over the years, Barton went to bat for Burzynski. Dr. Gorski writes:


Burzynski had cultivated powerful allies, in particular Representative Joe Barton (R-Texas), who held a series of hearings featuring cancer patients who were, quite understandably, terrified that Burzynski would be convicted. (Remember, these patients were completely convinced that Burzynski was the only person who could save them.) Between the cynical political theater, featuring weeping parents of children with brain tumors, national press stories of demonstrations featuring patients chanting “FDA go away! Let me live another day!” and the intense political pressure brought to bear by Barton, who dragged then-FDA Director David Kessler in front of his committee four times over two years to explain why the FDA was “harassing” Burzynski, the FDA ultimately relented and entered negotiations to let Burzynski set up clinical trials.





Intimidation of Critics

Skeptics have been writing about Dr. Burzynski’s claims for years. Instead of dealing with criticism by addressing legitimate concerns (such as failing to publish any phase II or III trials, failing to inform patients of dangers, failure to adhere to proper scientific protocol, failure to comply with the FDA, destroying key data, etc, etc), Dr. Burzynski and his representatives have belittled and intimidated his critics.


The classic example is the intimidation of a 17 year-old blogger from Wales, Rhys Morgan in  2011. Rhys was very critical of Burzynski on his blog in response to a local fund-raising campaign to raise 200,000 pounds to send a four year-old girl with a brain tumor to the Burzynski Clinic. Rhys was stunned to find out that Burzynski had not completed or published any randomized controlled trials and that antineoplastons had not been approved. Soon after posting his blog, Rhys received a series of increasingly intimidating e-mails from a fellow named Marc Stephens, a then-employee of Dr. Burzynski. The letters accused Rhys of libel and sounded very legally threatening. To top it off, Stephens sent Rhys a Google Map picture of his family’s house in the U.K., as if to say, “We know where you live”.


Similarly, Mark Stephens sent increasingly intimidating letters to Andy Lewis of the Quackometer. His second letter ended thusly:


I am not playing games with you.  You have a history of being stubborn which will play right into my hands.  

Be smart and considerate for your family and new child, and shut the article down..Immediately.  FINAL WARNING.

Regards,

Marc Stephens”


After these e-mail intimidations became widely publicized on skeptic blogs, Dr. Burzynski quickly cut ties with Mark Stephens. In fact, it turns out that Mark Stephens is not an attorney. The Burzynski clinic issued another letter from its “Public Relations” director. It included this statement:


Marc Stephens was recently hired by the Burzynski Clinic as an independent contractor to provide web optimization services and to attempt to stop the dissemination of false and inaccurate information concerning Dr. Burzynski and the Clinic.


We understand that Marc Stephens sent a google map picture of a blogger’s house to the blogger and made personal comments to bloggers. Dr. Burzynski and the Clinic feel that such actions were not appropriate. Dr. Burzynski and the Burzynski Clinic apologize for these comments. Marc Stephens no longer has a professional relationship with the Burzynski Clinic.”


Many former patients and their families have come forward to tell of their negative experiences at the Burzynski Clinic. Many such stories have been documented at The OTHER Burzynski Patient Group. In response to such criticism, Dr. Burzynski essentially threw his former patients under the bus. Liz Szabo writes:


Burzynski remains combative, referring to his critics as “hooligans” and “hired assassins,” while describing the patients who complain about him thusly: “We see patients from various walks of life. We see great people. We see crooks. We have prostitutes. We have thieves. We have mafia bosses. We have Secret Service agents. Many people are coming to us, OK? Not all of them are the greatest people in the world. And many of them would like to get money from us. They pretend they got sick and they would like to extort money from us.





Occam’s Razor and The Apparent Successes

Many of the patients in Burzynski’s so-called clinical trials have received some form of conventional treatment -- such as surgery, radiation or chemotherapy -- prior to enrolling. It is reasonable to assume that this fact may have contributed to some of the apparent successes. But what about those who were not already treated?


As we have learned, Occam’s Razor is a philosophical and statistical tool that can be used to evaluate competing claims. It is a statistical fact that, when competing claims are offered to explain an observation, claims with the least number of unknown assumptions are simply more likely to be true than claims with a greater number. It is also known as the law of parsimony.


Since Dr. Burzynski destroyed or lost all of the initial, raw MRI data regarding the status of his patient’s tumors, we will never have objective science to evaluate his claims. We can, however, use some critical thinking and Occam’s Razor to evaluate his claims about curing certain brain tumors. First, let’s consider some facts.

- Gliomas

The tumors treated in his so-called trials are brain tumors. There are many types of brain tumors. Many of the tumors in question are called “gliomas”. The FDA granted antineoplastons with “orphan drug” status for the purposes of clinical trials for the treatment of gliomas. Indeed, many of Dr. Burzynski’s publications concern gliomas.

There are several different types of gliomas. Low-grade gliomas grow very slowly and do not spread (metastasize) like high-grade gliomas. Low-grade gliomas may be deadly due to their position within the brain and are often inoperable. There are differences in prognosis and treatments between adult brain tumors and pediatric brain tumors.


Cancer.gov describes low-grade gliomas:

The tumor grows slowly, has cells that look a lot like normal cells, and rarely spreads into nearby tissues. Grade I brain tumors may be cured if they are completely removed by surgery.”


- Spontaneous Regression

When a tumor shrinks all on its own without intervention, we call this “spontaneous regression”. Some children with low-grade gliomas (brain stem and optic nerve) may actually undergo spontaneous regression of their tumor. This is relatively rare, however the actual incidence may not actually be known, since most patients undergo some sort of treatment through surgery, radiation or other targeted therapies.


Consider a pilocytic astrocytoma (a form of low-grade glioma). This case report demonstrates the spontaneous regression of such a tumor in a 15 year-old patient.


This tumor has a noteworthy benign biologic behavior that translates into an extremely high survival rate—94% at 10 years and a 20-year survival rate of 79%. Patients with gross total tumor resection have survival rates that approach 100%.  There are numerous reports of spontaneous regression of pilocytic astrocytomas arising in the optic pathway, diencephalon, and tectal region.


An article in the journal Pediatric Neurosurgery discusses low-grade gliomas;

Spontaneous regression of low-grade gliomas can occur for tumors in a diversity of anatomical locations, at varying ages and in both sexes. This may have implications for management. As such, spontaneous tumor regression is an important outcome to be considered for pediatric low-grade gliomas and pilocytic astrocytomas.


This case report of a patient with a diffuse pontine glioma diagnosed at age 2 (usually a poor prognosis) suggests complete spontaneous regression of the tumor by age 6. The authors report that the patient had also received some form of “unconventional treatment” as well and his parents apparently attributed the regression to this treatment. The authors stated:

The cause of the complete remission in our patient remains unknown. The effect which is to be attributed to the unconventional therapies applied is rated differently by the authors of this report according to their medical and philosophical background.


A 2001 article in the Archives of Ophthalmology entitled Spontaneous regression of optic gliomas: thirteen cases documented by serial neuroimaging states:

Large, clinically symptomatic optic gliomas may undergo spontaneous regression. Regression was seen in patients with and without NF-1 (Neurofibromatosis Type 1). Regression may manifest either as an overall shrinkage in tumor size, or as a signal change on magnetic resonance imaging. A variable degree of improvement in visual function may accompany regression. The possibility of spontaneous regression of an optic glioma should be considered in the planning of treatment of patients with these tumors.


- Pseudoprogression and Pseudoregression

These interesting phenomena have been described concerning the apparent increase in size on MRI scans of brain tumors after radiation treatment. This may be due to inflammation and does not represent true progression of the tumor size. This has been termed “pseudoprogression”. After a period of pseudoprogression, the tumor then will appear to regress in size as the inflammation decreases. Correspondingly, this has been called “pseudoregression”.


Dr. Gorski writes:

“Finally, one potential explanation for some of these seemingly miraculous responses to ANP therapy in brain cancers could come from a phenomenon known as pseudoprogression in which late effects of radiation therapy can produce enhancing lesions that mimic tumor recurrence on brain MRI (Stuplich 2012) and which can occur as much as 28 percent of the time after radiation therapy (Brandes et al. 2008). Such pseudoprogression “tumors” regress over the course of weeks to months, much as “recurrences” treated by Burzynski almost inevitably regress, and pseudoprogression can even persist as long as a year after radiation therapy (Stuplich 2012). While it must be conceded that it is possible that in some patients ANPs might exhibit antitumor effects, the more plausible and parsimonious explanation is that pseudoprogression likely explains many of Burzynski “miracle cures.”


- Applying Occam’s Razor

There are cases of patients that have been treated at the Burzynski Clinic with antineoplastons for their brain tumors that have survived to tell about it. We will likely never see the publication of uncontroversial randomized trials. Dr. Burzynski claims that he is curing brain tumors with antineoplastons. We have seen that the type of brain tumors that he claims to cure may, in fact, spontaneously regress sometimes. We also know that many of his patients have undergone traditional treatment with radiation, and therefore may have presented to Dr. Burzynski with inflated tumor measurements due to “pseudoprogression” (which in turn appear to regress due to “pseudoregression”).


We have two explanations for these successes. One is that perhaps antineoplastons actually work. This is a large assumption because we have no real knowledge for its validity -- and likely never will. The other is that some of the tumors that he treated either got better through spontaneous regression, or appeared to get better due to pseudeoregression. The second group of explanations require no new assumptions because they are based on known phenomenon. They represent the “Null Hypothesis”.


Proper scientific conduct demands that we withhold support for an idea if the null hypothesis can explain an observation as well or better than the hypothesis in question. This is the crux of Occam’s Razor. We must withhold support for the notion that antineoplastons can cure brain tumors, let alone other cancers, until proper evidence is presented. 


And that looks like it will never happen.






Bait and Switch: “Gene Targeted Therapy”

Only patients with brain tumors may be enrolled in one of the registered clinical trials at the Burzynski Institute. Patients from around the world raise cash to be treated at the Burzynski Clinic because they heard the propaganda about antineoplastons. It has been documented that patients with cancers other than brain tumors are accepted, but then not treated with antineoplaston, but rather cocktails of chemotherapy. This switch was not apparent with patients like Kathy B. After great expense, patients seeking antineoplaston therapy for their non-brain-tumor cancers have found themselves the recipients of unproven, unapproved cocktails of individual FDA approved chemotherapy agents. These are given under the sciency-sounding guise of “personalized gene-targeted cancer therapy”.


Actually, there is legitimate research being done on personalized cancer treatments. The year of this writing is 2014. Perhaps in the future, such treatment will be a reality. So far, such strategies have not been shown in general to be superior to conventional treatment. Cancer.net states:


Despite the promises of personalized cancer treatments, not all types of cancer have personalized treatment options. Some of these are only available through a clinical trial and are not yet standard treatment options. Genetic testing of both the patient and the tumor sample may be costly and time-consuming, and many insurance plans may not cover the costs of these tests. Some personalized treatments, such as targeted treatments, can also be expensive. Finally, not enough is known yet for doctors to be able to make personalized recommendations for cancer screening and prevention.


Yet, the Burzynski Clinic claims to have an 85% response rate in treating all sorts of cancer by using genetic tests to determine which chemotherapeutic drugs to give to individuals. Dr. Gorski did a thorough job of unpacking this claim. The genetic testing that he apparently uses is not FDA approved for clinical use outside of a clinical trial. Yet, that is what he is apparently doing. This is followed by selling patients mixtures of immunologic and chemotherapy drugs mixed to treat the individual patient’s needs. However, these combinations have no proven efficacy or safety in well-designed trials. Dr. Gorski writes:


As we have seen, Dr. Burzynski does indeed give chemotherapy to his patients. 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.





Why Antineoplastons are Pseudoscience

As it stands, Dr. Burzynski’s claims about antineoplastons seem to meet a lot of our Hallmarks of Pseudoscience.


Antineoplaston research demonstrates stagnation and a failure to make progress. So-called clinical trials have been ongoing for decades without any meaningful publication of randomized, controlled studies.


There is a strong example of the Appeal to Tradition. Recall his 1986 abstract which states, “Medicinal use of urine and urine extracts has been known for centuries in ancient Egypt, Greece, Rome, India and North and Central America. In modern times, the first study of growth-inhibiting substances in urine was conducted in 1937. The research on urinary peptides has a long history and was initiated by a Polish researcher, S. Bondzynski, in 1897.”


We also see the Naturalistic Fallacy. Statements like these can be found on The Burzynski Patient Group: “Antineoplastons are naturally occurring peptides demonstrating ability to re-program cancer cells without destroying normal cells.  Due to their low-toxicity and anti-cancer activity antineoplastons represent a revolutionary avenue in cancer research.  According to Dr. Burzynski, antineoplastons are components of a complex biochemical defense system that controls cancer in the human body.  Antineoplastons occur naturally in human blood and are reproduced synthetically for medicinal use.


We have seen above that support for antineoplastons requires ignoring Occam’s Razor.


Vague language is used, including sciency-sounding words like toxicity.


Support for antineoplastons relies on anecdotes rather than controlled clinical trials. Supporters frequently point to the website The Burzynski Patient Group and the propaganda films mentioned above as if they represent scientific evidence. Anecdotes are not evidence. They are stories. Anecdotal evidence is fundamentally deceiving as it suffers from survivorship bias and represent cherry-picked data. No promoter of anything is going to pick cases of unambiguous failure to represent their nostrum. Anecdotal evidence can just as easily be used to build a case against a position. The Other Burzynski Patient Group is a collection of anecdotes that exemplify failures of antineoplaston therapy and misadventures at the Burzynski Clinic.

   

Burzynski avoids scrutiny by failing to interact with the academic medical community. He lost or destroyed the raw data of initial tumor MRI reports, and therefore final outcomes are based on his word only.


Defenders of Burzynski claim that he is persecuted by a hostile establishment

They often claim that there is a conspiracy of Big Pharma and the FDA to suppress his work because they know that he has the cure for cancer and that it would destroy the profits of the pharmaceutical industry. The promotional page for Merola’s movie states, 

When Antineoplastons are approved for public use, it will allow a single scientist to hold an exclusive right to manufacture and sell these medicines on the open market—potentially leaving the pharmaceutical industry absent in profiting from the most effective gene-targeted cancer treatment the world has ever seen.

http://theotherburzynskipatientgroup.wordpress.com/2014/03/20/burzynski-patient-claire-f-s-story/

Burzynski has been known to demonize his enemies (see Intimidation of Critics above).


Dr. Burzynski has questionable credentials. He is not a board certified oncologist, nor has he any particular training in oncology. As stated above (and worth repeating here) Saul Green writes:


Burzynski's claim to a Ph.D. is questionable. When I investigated, I found:

  • An official from the Ministry of Health in Warsaw informed me that when Burzynski was in school, medical schools did not give a Ph.D.

  • Faculty members from at the Medical Academy at Lubin informed me that Burzynski received his D.Msc. in 1968 after completing a one-year laboratory project and passing an exam [2] and that he had done no independent research while in medical school.

  • In 1973, when Burzinski applied for a federal grant to study "antineoplaston peptides from urine," he identified himself as "Stanislaw Burzynski, M.D, D.Msc."


Dr. Burzynski works in isolation. He cut his ties with Baylor University and set up his own research institute to “study” antineoplastons. This enabled him to enroll patients in clinical trials for large fees and keep total control of the data (much of the key data was reported as destroyed or missing by the 2013 FDA investigation).


This brings us to ulterior motives. If he has the cure for cancer, then he should be doing proper research. Since the mid-nineties when his 72 trial protocols were established, many properly done trials for cancer treatments have been done by other institutions resulting in numerous FDA approvals for new, successful drugs. Why have none of these trial protocols resulted in meaningful evidence for antineoplaston therapy?


The words of Richard A. Jaffe, Burzynski’s former lawyer, deserve reprinting here:


“As far as clinical trials go, it [CAN-1] was a joke. Clinical trials are supposed to be designed to test the safety or efficacy of a drug for a disease. It is almost always the case that clinical trials treat one disease. The CAN-1 protocol had almost two hundred patients in it and there were at least a dozen different types of cancers being treated. And since all the patients were already on treatment, there could not be any possibility of meaningful data coming out of the so-called clinical trial. It was all an artifice, a vehicle we and the FDA created to legally give the patients Burzynski’s treatment. The FDA wanted all of Burzynski’s patients to be on an IND, so that’s what we did.


“CAN-1 allowed Burzynski to treat all his existing patients. That solved the patients’ problems, but not the clinic’s. A cancer clinic cannot survive on existing patients. It needs a constant flow of new patients. So in addition to getting the CAN-1 trial approved, we had to make sure Burzynski could treat new patients. Mindful that he would likely only get one chance to get them approved, Burzynski personally put together seventy-two protocols to treat every type of cancer the clinic had treated and everything Burzynski wanted to treat in the future.”



Could it be that the Burzynski Research Institute is making a lot of cash by charging patients to enroll in these trials and that this gravy train would end if the trials ended without meaningful support for antineoplastons? It is not a far stretch of the imagination.





Conclusion

Cancer is a collection of terrible diseases. Treatment is difficult at best and miserable at worst. Over the last few decades, we have seen a proliferation of science-based treatments approved and implemented. We have seen the death rates from cancer decrease as a result. When research is conducted properly, society wins.


Antineoplatons, like any novel idea, could have been properly researched through phase I, II, and III clinical trials. 


But they weren't. They may have some role to play in cancer treatment, however, because of one doctor's refusal to conduct the research through proper scientific protocols, we may never actually know. The limited, properly-obtained scientific knowledge that we actually have on antineoplatons is uniformly negative.


If Dr. Burzynski's claims for the success of antineoplastons and his personalized gene-targeted treatments were actually true, cancer treatment would be revolutionized. He would be awarded the Nobel Prize. He and his supporters explain this away by appealing to conspiracies of the FDA and the pharmaceutical industry. Yet, despite all of the claims, hand-waving and anecdotes, he never published any randomized controlled trials to properly demonstrate efficacy of any of his treatments. It is unlikely that such evidence will ever be established because of the destruction of key data.


Dr. Burzynski's behavior regarding his antineoplastons provides us with a classic picture of the evolution of a modern pseudoscience.



John Byrne, MD




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