4th edition

The role of your cancer health professional is to create an environment of openness and trust, and to help in making informed decisions about alternative/complementary therapies. Collaboration will improve the safe integration of all therapies during your experience with cancer. The "Summary" and "Professional Evaluation/ Critique" sections of this Unconventional manual are cited directly from the medical literature, and are intended to help in the objective evaluation of alternative/ complementary therapies.

Summary

"Because of very low response rates in breast cancer and in non-small cell lung cancer and in view of the significant toxicity experienced by some patients, the Agency [Food and Drug Administration] mandated that starting on Aug. 29, 1997 no additional patients with these tumors should be given antineoplastons as special exceptions." (Cancer Letter 1)

"The so-called five urinary antineoplastons (A-1 to A-5) have not been shown to be chemically, biologically, or pharmacologically distinct from each other, and none has been proven to have antineoplastic activity against experimental cancer." (Green)

Description/ Source/ Components

"Burzynski isolated about 120 peptide fragments, amino acid derivatives, and organic acids and termed them antineoplastons, suggesting that the activity of these compounds represents a biochemical adjunct to the immune system. He focused on 2 formulations, which were reproduced synthetically, as being the most active in tumor inhibition-antineoplaston A10 and antineoplaston AS2-1." (D'Epiro)

"The term 'antineoplastons' is used to describe mixtures of peptides, amino acid derivatives, and organic acids that serve as components of a theoretical natural defense system against human cancers and other human diseases. A10 (a 1:4 ratio of phenylacetylisoglutamine and phenylacetylglutamine [PAG]) and AS2-1 (a 1:4 ratio of PAG and phenylacetic acid) are two such antineoplastons used by Burzynski and associates in the treatment of patients with recurrent anaplastic astrocytoma or glioblastoma multiforme." (Buckner)

Antineoplastons are a group of synthetic compounds that were originally isolated from human blood and urine by Stanislaw Burzynski, M.D., Ph.D., in Houston, Texas. (Cancer Facts 2002)

"Antineoplastons are derived from glutamine, isoglutamine, and phenylacetate salts; antineoplaston AS5 is phenylacetate itself." (Burzynski 1995) (Spencer)

It is administered by injection or orally. (Green)

History

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. Since urine contains lots of peptides, he concluded that there he would find antineoplastons. Less than one year later and based only on these assumptions, Burzynski used an extract from human urine ("antineoplaston A") to treat 21 cancer patients at a clinic he opened. (Quackwatch)

Stanislaw R. Burzynski, M.D. and his associates have been working on antineoplastons as a treatment for cancer since 1967. He works from the Burzynski Research Institute, Houston, Texas; was educated in Poland and is licensed to practice in Texas. (CA)

During the past few years "many Phase I trials have been performed in the United States and Japan. …clinical Phase II studies would be needed to determine the likelihood of clinical usefulness." (Spencer, 1999)

Proponent / Advocate Claims

"Dr. Burzynski and his colleagues claim that these peptides are produced by individuals as part of a `biochemical defense system' that inhibits cancer cell growth. According to Dr. Burzynski, `The failure of the system and deficiency of antineoplastons will result in perpetuation of neoplastic growth and development of cancer.' Dr. Burzynski claims that his treatment restores this `defense system' by giving antineoplastons to people with cancer." (Cancer Facts 1995)

Burzynski claims that antineoplastons are able to reprogram cancer cells to restore errors in cellular differentiation to normal. (Burton Goldberg Group)

"Antineoplaston A10 is hydrolyzed in pancreatic juice when administered orally as phenylacetylglutamine and phenylacetylisoglutamine. The phenylacetylisoglutamine competes with L-glutamine which is an essential nitrogen source for tumor cell proliferation. Phenylacetylglutamine is further degraded to phenyl acetic acid. The combination of phenylacetylglutamine and phenyl acetic acid has been reported to have effects of inhibiting tumor growth and inducing cell terminal differentiation through the activation of tumor suppressor genes and inactivation of oncogenes." (Kumabe)

"Thibault and colleagues reported results of a phase I trial of intravenously administered PA [phenylacetate], including phamacokinetic data in patients with advanced cancer. In that trial, one of six patients with recurrent glioblastoma multiforme had symptomatic but not radiographic improvement." (Buckner)

"Dr. Burzynski wrote a letter which appeared in the Mayo Clinic Proceedings which noted that the antineoplaston dosages used in the NCI clinical trial were "known to be ineffective" and that plasma antineoplaston levels were very low in the NCI study patients. In contrast, Burzynski countered that 1 of his ongoing studies on protocol BT-9, 4 of 8 evaluable patients with astrocytoma had objective responses. The difference in outcomes is primarily due to the difference in dosage schedules." (D'Epiro)

"In a phase II study of antineoplaston A10 and AS2-1 in patients with recurrent diffuse intrinsic brain stem glioma. The median duration of treatment was 6 months and of the ten evaluable patients, complete response was determined in two cases, partial response in three, stable disease in three and progressive disease in two. Currently, of all 12 patients, two were alive and tumor 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… Two patients in the trial developed recurrence on lower dosages of antineoplaston A10, but responded again with a CR when the dosage of antineoplaston A10 was increased to approximately 10g/kg/day. In these two patients, antineoplaston AS2-1 did not seem to have an effect on their second response, which suggests that antineoplaston A10 rather than antineoplaston AS2-1 is the main active drug." (Burzynski, 2003)

"In Case 1, continuous infusion of antineoplaston A10-I, 10g/d, and oral administration of antineoplaston AS2-1, 10g/d, for the first 2 months did not result in reduction of the tumor sizes or a decrease in values of tumor markers. However, continuous infusion of antineoplaston A10-I to the hepatic artery for 5 days exhibited disappearance of tumor strain in the angiogram suggesting concentrated antineoplaston A10-I induces a rapid elimination of HCC [hepatocellular carcinoma]." (Kumabe)

"In Case 2, a continuous infusion of antineoplaston A10-I through the subclavian catheter, 10-30g/d, followed by oral administration of antineoplaston AS2-1, 10g/d. made it possible for the patient to be discharged from hospital and continue a normal life. Although the patient died from hepatic failure, marked shrinkage of the tumor thrombus in the portal vein found in CT on March 8, 1997 verifies the effectiveness of antineoplastons." (Kumabe)

"In addition to information from Burzynski and associates, certain preclinical data suggest that phenylacetate (PA) may inhibit proliferation of certain malignant cell lines and induce morphologic changes of differentiation." (Buckner)

"Tsuda and colleagues (Tsuda 1995, 1996) reported responses in patients with ovarian cytoadenoacarcinoma, anaplastic astrocytoma, recurrent renal cell carcinoma, brain metastases from prostatic carcinoma, brain metastases from breast cancer, lymphoma, and brainstem glioma. Their overall response rate was reported to be 32%. In a previous study in the same journal, Sugita and colleagues (Sugita) reported treatment success in a few patients with antineoplastons." (Spencer)

"We previously reported a quick response in 3 cases of advanced cancer to chemoradiation therapy with antineoplaston A10 and AS2-1 in 1998… We recently experienced 3 additional advanced cancer cases who responded well to combination therapy with chemotherapeutics and antineoplaston A10 and AS2-1. (Tsuda2)

"Antineoplaston AS2-1, the degradation products of Antineoplaston A10, induces differentiation in the HL-60, erythroleukemia, malignant melanoma and fibrosarcoma cells… Antineoplaston A10 and AS2-1 may be of value in preventing recurrence in HCC [hepatocellular carcinoma]." (Tsuda3)

Professional Evaluation/ Critique

"In a phase II trial, 9 patients with anaplastic astrocytoma or glioblastoma multiforme recurring after radiation were given increasing doses of iv antineoplastons A10 and AS2-1. Preclinical studies show that the phenylacetate component of the antineoplastons may be the active inhibitor of astrocytic tumors. Response was only assessable in 6 patients and none of them had tumor regression, with 3 patients requiring reoperation after AN [antineoplaston] treatment. The median survival time for all 9 patients was 5.2 months." (Buckner)

After reviewing these documents, I am unable to say what Dr. Burzynski's brain tumor data – or his work – are about. What I see is a waste of an opportunity to help people and advance the field. That's why you do clinical investigations: both to help people and to try to make the field move forward, and what he has done is present such a confusing morass of data that it's uninterpretable." (Cancer Letter2)

"Overall, half of the patients who responded to the treatment withdrew from the study due to patient request, worsening condition, or growth of tumor, the data summary said. The document states that last summer, FDA stopped issuing special exceptions for patients to receive Burzynski's treatment for breast cancer and non-small cell lung cancer." (Cancer Letter1)

The Ontario government sent two Toronto specialists to Burzynski's clinic - of 20 cases reviewed, no evidence was found that any had benefited from treatment. Of four patients Burzynski claimed had achieved complete remissions, three had died of recurrences and the fourth had undergone surgery for bladder cancer that was believed to be curative. (Dunlop) (Blackstein)

A 38-year-old woman received antineoplaston treatment for her recurrent rectal cancer involving the lower pelvis at the Burzynski clinic for nearly a year. During that period, her tumor progressed. "The patient succumbed to her disease some 6 months later." (Wanebo)

"Five fractions were produced from human urine by Burzynski, A-1, A-2, A-3, A-4, and A-5… Burzynski does not offer an explanation for the basis on which he chooses any one specific fraction for treatment of a patient, or why he has never reported using fractions A-1 or A-4 to treat patients... The so-called five urinary antineoplastons (A-1 to A-5) have not been shown to be chemically, biologically, or pharmacologically distinct from each other, and none has been proven to have antineoplastic activity against experimental cancer." (Green)

Burzynski "offers no explanation of how or where this insoluble substance [antineoplaston A-10] is made or how it gets from the blood, through the kidneys, and into the urine. Being insoluble, A-10 is obviously not suitable for intravenous administration." (Green)

"The investigators at the Mayo Clinic, Memorial Sloan-Kettering Cancer Centre and the Clinical Pharmacology Branch of the NCI, found no evidence of tumor regression in any of the patients. They concluded that evidence of beneficial activity of antineoplastons in patients with recurrent high-grade astrocytoma was insufficient to recommend their use outside of clinical trials." (D'Epiro)

"Burzynski did not follow the accepted scientific method of testing his products on animals - he claims that extracts from human urine worked only in humans and that animal testing would be pointless." (Dunlop)

"It is not clear from Dr. Burzynski's work what response rate he is actually claiming. Of the 11 BC Cancer Agency (BCCA) patients known to have been treated with antineoplastons, 9 have died with no evidence of therapeutic effect. One remains alive and well after having received treatment at BCCA that we fully expected to be curative. The remaining patient, who Dr. Burzynski referred to in Vancouver as his "best case", also received radiation therapy to all known sites of disease. While the response to radiation was better than expected, such responses have been seen before and cannot be fairly attributed to antineoplastons." (Silver 1986)

Toxicity/ Risks

"Toxicity included elevated levels of serum sodium, a condition that `contributed to the death of at least seven patients' enrolled in the trials". "Other adverse effects described in the annual report include nausea, vomiting, allergic skin reactions, dizziness, fatigue, drowsiness, joint pain, muscle pains, and other blood electrolyte abnormalities such as low potassium." (Cancer Letter1)

PA [phenylacetic acid] may not be safe. In 1919, it was shown that PA can be toxic when ingested by normal individuals. It can also reach toxic levels in patients with phenylketonuria (PKU); and in a pregnant woman, it can cause the child in utero to suffer brain damage. (Green)

"Reversible grade 2 or 3 neurocortical toxicity, consisting of transient somnolence, confusion, and exacerbation of an underlying seizure disorder, was noted in five patients."(Buckner)

"...hives developed in one pharmacy technician in the evening after her first exposure to antineoplastons. The drug did contact her skin. Because she had never experienced hives previously, we concluded that the skin reaction was a possible adverse effect of contact with the compounds." (Buckner)

"Side effects included weakness, drowsiness, febrile [pertaining to fever] reactions, nausea and vomiting, skin rash, and leukopenia [reduction in the number of white blood cells in the blood] and thrombocytopenia [decrease in the number of blood platelets]." (Spencer)

"...two Ontario patients developed septicemia after returning from Texas and one of them died of septicemia" (Dunlop)

"Some patients have experienced stomach gas, skin rashes, increased blood pressure, chills, fever and unpleasant body odors." (Ontario)

"PA [phenylacetate] has known to be toxic in humans since 1919. Exposure to PA has been associated with brain damage, which occurs in patients with phenylketonuria. PA is detoxified by conversion to PAG [phenylacetylglutamine], the urinary metabolite of PA." (Buckner)

Costs

The BC Cancer Agency has compiled information available to provide an estimate of the cost of this therapy. This information is limited by the resources available and may not reflect actual costs.

Before consultation with Dr. Burzynski, an initial deposit of $6000 is required from all patients. Treatment costs run between $7,000 and $9,500 a month. The duration is usually between four and twelve months depending on the patient's response. Treatment with antineoplastons occurs at the Burzynski Clinic in Houston, TX on an outpatient basis. Travel and housing costs are not included in the treatment fee. A few insurance companies will pay for treatment with antineoplastons but the majority does not. (Harwood 2000)

"For intravenous therapy, approximately $5,000 per month." (Fink 1997)

"Initial consultation is $125. Treatment is given on an outpatient basis at a cost of approximately $135 to $685 U.S. per day. Diagnostic tests are not included." (Fink 1988) (Ontario)

In 1982, Dr. Burzynski charged $180 a day for treatments lasting from six weeks to a year, plus other charges that brought the cost of treatment to about $4000 a month. Travel costs are not included. A deposit of $5000 is required. (CA 1983)

An Ontario patient, Stephanie Kusan, aged 20 was unsuccessfully treated by Dr. Burzynski. Cost to the patient was $75,000. (Dunlop 1985)

References

Blackstein ME, Bervgsagel DE. Report to the Ministry of Health, Province of Ontario based on a preliminary review of Dr. Burzynski's publications, a site visit on 15 November 1982, and a follow-up review of some patients treated by Dr. Burzynski.

Buckner JC, et al. Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma. Mayo Clin Proc 1999;74:137-45.

Burton Goldberg Group, compilers. Alternative medicine: the definitive guide. Puyallup, Washington : Future Medicine Publishing, Inc., 1993:571-574.

Burzynski SR. Potential antineoplastons in disease of old age. Drugs Aging 1995;7:157.

Burzynski S. Antineoplastons: an investigational cancer therapy. Townsend Letter, 1993;115/116:150-3.

Burzynski S., et al. Phase II Study of Antineoplaston A10 and AS2-1 in Patients with Recurrent Diffuse Intrinsic Brain Stem Glioma: A Preliminary Report. Drugs in R & D, 2003. 4(2): p.91-101.

Cancer Letter1 (Anonymous). FDA discloses responses, toxicities for Burzynski's "antineoplastons". Cancer Letter 1998;24:1-4.

Cancer Letter2 (Anonymous). The Antineoplaston anomaly: how a drug was used for decades in thousands of patients, with no safety, efficacy data. Cancer Letter 1998;24(36):12.

CA (Anonymous). Unproven methods of cancer management: antineoplastons. CA: a Cancer Journal for Clinicians 1983;33(1):57-59.

Cancer Facts. National Cancer Institute. Antineoplastons. [Date reviewed: 07/13/2001 Editorial changes made: 05/20/2002] http://cis.nci.nih.gov/fact/7_43.htm

Cancer Facts. National Cancer Institute. National Cancer Institute-sponsored clinical trials of antineoplastons. Cancer Facts 11/28/95.

Choi, B.G., et al., Synthesis of antineoplaston A10 analogs as potential antitumor agents. Archives of Pharmacol Research 1998;21(2):157-63.

D'Epiro, N.W., Integrative medicine. Alternative treatments in cancer: a growing source of hope. Patient Care 2000;34(13):85-90.

Dunlop M. Understanding cancer: an invaluable book for cancer patients and their families. Toronto : Irwin, 1985. p.99-101.

Fink JM. Third opinion: an international directory to alternative therapy centers for the treatment and prevention of cancer and other degenerative diseases. 2nd ed. Garden City Park, New York : Avery Publishing Group Inc. 1988. p.36-39.

Fink JM. Third opinion: an international directory to alternative therapy centers for the treatment and prevention of cancer and other degenerative diseases. 3rd ed. Garden City Park, New York : Avery Publishing Group Inc., 1997. p.49.

Green S. 'Antineoplastons': an unproved cancer therapy. JAMA 1992 Jun 3;267(21):2924-2928.

Kumabe T, et al. Antineoplaston treatment for advanced hepatocellular carcinoma. Oncology Reports 1998;5:1363-1367.

Harwood K, Pickett C. A Cancer Patient's Guide to Complementary and Alternative Medicine, 2nd edition. See the web-based version for current updates at http://cancer.duke.edu/PatEd [Dated 12/2000; cited June 23, 2004]

Quackwatch [homepage on the Internet]. Green S. Stanislaw Burzynski and "Antineoplastons". Available from: http://www.quackwatch.org/01QuackeryRelatedTopics/Cancer/burzynski1.html [Dated June 25, 2001; cited March 24, 2004].

Kumabe T., et al. Antineoplaston treatment for advanced hepatocellular carcinoma. Oncology Reports 1998;5(6):1363-7.

Piscitelli SC, et al. Disposition of phenylbutyrates and its metabolites, phenylacetate and phenylglutamine. J Clin Pharmacol 1995;35:368.

Silver HKB. Memorandum on Burzynski. Vancouver: BC Cancer Agency, 1986. (BCCA Cancer Information Centre search file 983)

Soltysiak-Pawluczuk D, et al. Cellular accumulation of antineoplaston AS21 in human hepatoma cells. Cancer Lett 1995;88:107.

Spencer JW, Jacobs JJ. Complementary/alternative medicine: an evidence based approach. Toronto : Mosley 1999. p. 138-9.

Sugita Y, et al. The effect of antineoplaston: a new antitumor agent on malignant brain tumors. Karume Med J 1995;42:133.

Tsuda H, et al. Quick response of advanced cancer to chemoradiation therapy with antineoplastons. Oncology reports 1998;5:597-600.

Tsuda, H., et al. A novel strategy for remission induction and maintenance in cancer therapy. Oncology Reports 2002;9(1):65-8.

Tsuda, H., et al. Inhibitory effect of antineoplaston A10 and AS2-1 on human hepatocellular carcinoma. Kurume Medical Journal 1996;43(2):137-47.

Tsuda H, et al. Toxicological study on antineoplaston A-10 and AS2-1 in cancer patients. Karume Med J 1995;42:241.

Wanebo HJ. Antineoplastons: the controversy continues [letter; comment]. JAMA 1993;269(4):476.

4th edition - Revised June 2004