NOTE: The information in this summary is no longer being updated and is provided for reference purposes only.
This cancer information summary provides an overview of the use of antineoplastons as treatments for people with cancer. The summary includes a brief history of the development of antineoplastons; a review of laboratory, animal, and human studies; and possible side effects associated with antineoplaston use.
This summary contains the following key information:
Many of the medical and scientific terms used in this summary are hypertext linked (at first use in each section) to the NCI Dictionary of Cancer Terms, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window.
Reference citations in some PDQ cancer information summaries may include links to external websites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the websites, or of any treatment or product, by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board or the National Cancer Institute.
Antineoplastons are an experimental cancer therapy developed by S.R. Burzynski, MD, PhD. Chemically, antineoplastons are a mixture of amino acid derivatives, peptides, and amino acids found in human blood and urine.[
According to the developer, antineoplastons are part of a biochemical surveillance system in the body and work as "molecular switches." For the developer, cell differentiation is the key to cancer therapy. At the molecular level, abnormal cells that are potential cancer cells need to be "switched" to normal mode. Antineoplastons are the surveillance system that directs cancer cells into normal channels of differentiation. According to statements published by the developer, people with cancer lack this surveillance system because they do not have an adequate supply of antineoplastons.[
The notion of controlling tumor growth through a naturally occurring biochemical mechanism in the body that directs cancer cells into normal channels of differentiation is one of the theoretical foundations of antineoplaston therapy. In a complex organism like the body, cells are continuously differentiating. Groups of abnormal cells can arise under the influence of carcinogenic factors from outside or inside the body. The body must have a mechanism for dealing with these abnormal cells, or the organism will not live very long. The proposed components in the body that correct the differentiation problems of abnormal cells and send them into normal pathways have been given the name "antineoplastons" by the developer.[
The developer defines antineoplastons as "substances produced by the living organism that protect it against development of neoplastic growth by a nonimmunological process which does not significantly inhibit the growth of normal tissues."[
The developer originally hypothesized the existence of antineoplastons by applying the cybernetic theory of information exchange in autonomous systems to the study of peptides in the blood.[
To begin the search for antineoplastons, the developer used human blood, separating and removing the peptides found there. Later it was discovered that the same peptide fractions existed in human urine. Each peptide fraction was tested in vitro against various normal and neoplastic cell lines to gauge its effect on DNA synthesis and growth. The fractions that had little or no inhibitory effect on normal cells but a substantial inhibitory effect on neoplastic cell lines were separated into two classes: those that were effective against a specific cell line and those that were active against a broad array of neoplastic cell lines. Those with a broad spectrum of activity were grouped together and called "antineoplaston A." Peptide fractions with specific antineoplastic activity were not investigated 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.[
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.[
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.
Antineoplastons are administered by different methods. Antineoplaston A has been given intravenously, intramuscularly, rectally, topically, intrapleurally, and by bladder instillation.[
Critical opposition to antineoplaston therapy and its developer have appeared in the published literature.[
Other criticism focuses on the form of antineoplastons. Although the active fraction, antineoplaston A10, is insoluble in aqueous solutions, the developer has stated that it is present in body fluids.[
Antineoplastons AS2-5 and AS2-1 are derived from A10. Antineoplaston AS2-5 is PAG, and AS2-1 is a 4:1 mixture of PA and PAG. Because it is a strong acid, PA would exhibit cytotoxicity in vitro if in high enough concentration and not in neutralized form.[
The active component of antineoplaston A10 is 3-phenylacetylamino-2,6-piperidinedione. Reagents necessary for the synthesis of this antineoplaston compound are readily available internationally from any chemical supply company.[
To conduct clinical drug research in the United States, researchers must file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA). The FDA's IND process is confidential, and the existence of an IND application can be disclosed only by an applicant.
Although several possible mechanisms of action and theories about the activity of antineoplastons have been proposed, specifically for antineoplaston A10, none of the theories has been conclusively demonstrated.
One theoretical mechanism of action proposes that antineoplaston A10 is specifically capable of intercalating with DNA at specific base pairs and thereby might interfere with carcinogens binding to the DNA helix. This interweaving of A10 into the DNA helix may be capable of interfering with DNA replication, transcription, or translation.[
Another theoretical mechanism of action is based on the structural similarities of antineoplaston A10 to other experimental anticancer drugs such as carmustine and 5-cinnamoyl-6-aminouracil. A10 has been proposed to bind to chromatin and, therefore, relate to other anticancer drugs such as doxorubicin that interact directly with DNA.[
At the cellular level, two other mechanisms of action have been proposed to explain inhibition of tumor growth. One theory involves the activity of PAG, a component of some antineoplastons. PAG appears to compete with glutamine for access to the glutamine membrane transporter and may inhibit the incorporation of glutamine into the proteins of neoplastic cells. Because glutamine is essential for the cell cycle transition from G1 to S phase where DNA replication occurs, antineoplastons may arrest cell cycle progression and stop cell division.[
As noted in the General Information section, Burzynski first proposed antineoplastons as a naturally occurring biochemical defense against cancer in 1976 as a result of his study of cybernetic systems and information theory. The search for information-bearing peptides in body fluids led him to separate peptides from human blood and subsequently from human urine. He called these substances antineoplastons and categorized them according to their general and specific anticarcinogenic potential. In 1980, the developer characterized the chemical structures of antineoplastons and began preparing them synthetically rather than isolating them from human urine. Preparations now used in clinical studies to treat cancer are antineoplastons A10, AS2-5, AS2-1, A2, A3, and A5.
From 1991 to 1995, the National Cancer Institute (NCI) initiated phase II clinical trials of antineoplastons A10 and AS2-1. Protocols for two phase II clinical trials were originally developed by investigators from several cancer centers, with review and input from both the developer and NCI. The National Institutes of Health (NIH), Office of Alternative Medicine, now known as the National Center for Complementary and Integrative Health, provided funding for the trials. Three centers (Memorial Sloan-Kettering Cancer Center, the Mayo Clinic, and the Warren Grant Magnuson Clinical Center at NIH) began accruing participants for these NCI-sponsored studies in 1993. However, by August 1995 only nine patients had entered the trials. Despite efforts by the developer, NCI staff, and investigators to reach agreement on proposed changes to increase patient accrual and dose, these agreements could not be reached, and the studies were closed prematurely in August 1995.[
The developer and investigators in Japan have reported several case series showing varying results using antineoplastons as a clinical therapy against several different types of cancer, alone or in combination with standard chemotherapy.[
Other uses of antineoplastons suggested by the developer include treatment of conditions such as Parkinson's disease, sickle cell anemia, and thalassemia.[
In vitro studies using a variety of human cell lines have been used to assess the effectiveness of antineoplastons as antineoplastic agents. Burzynski states that antineoplaston A is species-specific because it had no therapeutic effect when the human preparation was tested on animal tumor systems. Although this finding limits the usefulness of animal model testing, the developer has suggested that a "marked" therapeutic effect was produced in a xenograft bearing human tumor tissue.[
Japanese scientists have tested antineoplastons A10 and AS2-1 in vitro for cell growth inhibition and progression in several human hepatocellular cell lines.[
Antineoplaston A10 was also shown to inhibit prolactin or interleukin-2 stimulation of mitogenesis in a dose-dependent manner in rat Nb2 lymphoma cell line. The addition of A10 (1–12 mM) to prolactin-stimulated cells inhibited growth but was reversible when A10 was removed, suggesting a cytostatic rather than cytotoxic mechanism of action. A10 also showed no toxicity in a chromium release assay. DNA synthesis was also inhibited by A10.[
The ability of antineoplaston A3, isolated from urine and not an analog, to inhibit the growth of the HBL-100 human breast cancer cell line in vitro was investigated in a study that also examined the toxicity of A3 in Swiss white mice. Antineoplaston A3 inhibited colony formation in a dose-dependent manner over a dose range of 0.05, 0.1, 0.2, and 0.4 µg/mL.[
A somewhat different approach to the use of A10 was taken by researchers in Egypt. Taking the developer's initial ideas about the presence of A10 in the urine of patients, this study looked for the amount of A10 in the urine of 31 breast cancer patients and compared this to the amount in 17 healthy controls. They found significantly (P < .001) less A10 in the urine of breast cancer patients than in controls, suggesting that the amount of A10 in urine has a potential use as a screening tool.[
The same researchers looked at the immunomodulating potential of A10 by examining the inhibition of neutrophil apoptosis induced by A10 in vitro. Neutrophils from 28 breast cancer patients and 28 controls were obtained from blood samples. Urine samples were obtained from the same patients and tested for the presence of A10. Cancer patients had significantly (P < .001) higher levels of neutrophil apoptosis and significantly lower levels of A10. Neutrophil apoptosis was assessed by adding A10 at a dose of 10 µg/mL to the cellular suspensions of 42 breast cancer patients. Nontreated samples were used as controls. A10 was found to significantly inhibit neutrophil apoptosis (P < .0001).[
In a 2014 study done in Japan, human colon cancer cells were exposed to antineoplaston AS2-1 at high concentration and reported to normalize hypermethylation status at the promoter region of various tumor suppressor genes that are silenced in colon cancer.[
Several analogs of antineoplaston A10 have been synthesized and their antineoplastic activity tested against various cell lines. These include aniline mustard analogs of antineoplaston A10 and Mannich bases of antineoplaston A10.[
No phase III, randomized, controlled trials of antineoplastons as a treatment for cancer have been conducted. Publications have taken the form of case reports, phase I clinical trials, toxicity studies, and phase II clinical trials. Phase I toxicity studies are the first group discussed below. The studies are categorized by the antineoplaston investigated. The second group of studies involves patients with various malignancies. Table 1 is a summary of dose regimens for all human studies. Table 2 summarizes the following clinical trials and appears at the end of this section.
Phase I Toxicity Studies for Specific Antineoplastons
The studies discussed below are phase I toxicity studies in patients with various types of malignancies, including bladder cancer, breast cancer, and leukemias. The studies are listed by the antineoplastons administered. The effect of a specific antineoplaston under investigation is difficult to ascertain because of the confounding effect of previous therapies. Unless specifically noted, all studies were conducted by the developer and his associates at his research institute.
A 1977 article reported on 21 patients with advanced cancer or leukemia who were treated with antineoplaston A and followed for up to 9 months. Patients ranged in age from 14 to 75 years and had cancers of various types. Eight patients received no previous therapies, and 13 patients had been previously treated with chemotherapy and radiation therapy.[
Fever and chills, the main side effects, occurred only after IV or IM administration at the beginning of treatment. Fever lasted for a few hours, followed by subnormal temperatures and lowered blood pressure. Premedication with salicylates, adrenocorticotrophic hormone, or corticosteroids were used to treat the fever or suppress it. Only patients with chronic lymphocytic leukemia, transitional cell carcinoma of the bladder, metastatic adenocarcinoma of the rectum, squamous cell carcinoma of the cervix, and synovial sarcoma reacted with fever to low doses of antineoplaston A. No severe adverse reactions were reported, even when patients were treated with very high doses of the formulation (refer to Table 1). No toxicities were reported in any patient. Platelet and white blood cell counts were elevated after a month of treatment but gradually returned to normal.
Four patients obtained complete tumor response (two cases of bladder cancer, one case of breast cancer, and one case of acute lymphocytic leukemia); four patients obtained partial tumor response (two cases of chronic lymphocytic leukemia, one case of rectosigmoid adenocarcinoma, and one case of synovial sarcoma); six patients had stable disease; and two patients discontinued treatment. There were five deaths during the study that were not attributed to antineoplaston A toxicity.[
In 1986, a toxicity study of antineoplaston A10 reported on 18 patients with 19 malignancies. Patients ranged in age from 19 to 70 years. Only patients who completed 6 or more weeks of antineoplaston A10 injections were included in the results. Six of the 18 patients received other antineoplastons in addition to A10. Four patients were administered additional drugs such as antibiotics, analgesics, and anticonvulsants.[
Treatment duration ranged from 52 to 640 days. No major toxicities were reported. As with the antineoplaston A study described above, chills and fever were reported in nine patients and occurred only once during the course of treatment. Other side effects noted were muscle and joint pain, abdominal pain, nausea, dizziness, and headache. Partial remission occurred in one patient with chondrosarcoma, and mixed response was obtained in three other cases. Eight patients attained stable disease, and six patients had disease progression. Ten patients discontinued treatment during the study; no reasons were reported. Ten of the 18 patients had died by the time of study publication, 4 years after the start of the study.[
A 1986 study examined the toxicity of injectable antineoplaston AS2-1.[
Side effects associated with AS2-1 treatment included nausea and vomiting, rash, moderate blood pressure elevation, mild electrolyte imbalance, and slightly lowered white blood cell count. Although complete remission was reported in six cases (one case each of stage IV lymphocytic lymphoma, glioma, myelocytic leukemia, intraductal carcinoma of the breast, stage IA uterine cervix carcinoma, and metastatic breast carcinoma), one patient with breast carcinoma could not be considered evaluable for response because she had undergone radical mastectomy and had no measurable disease at the beginning of treatment with AS2-1; the cervical cancer patient had received prior radiation therapy, which could not be ruled out as producing a beneficial effect.
Partial remissions were reported in two cases, one each of stage III lung adenocarcinoma and chronic myelogenous leukemia in blastic phase. The patient with lung cancer had received prior radiation therapy; both patients developed disease progression and had died by the time of study publication. Seven cases were reported as having stable disease, and six patients had disease progression. Ten patients discontinued antineoplaston therapy during the study: two who were in complete remission, one in partial remission, and seven with stable disease.[
Antineoplastons A10 and AS2-1
A 1998 case series from Japan discussed three patients enrolled in a phase I study of antineoplastons A10 and AS2-1. Diagnoses included one case of breast cancer metastatic to the lung, one case of an anaplastic astrocytoma/thalamic glioma, and one case of large cell lung carcinoma (stage IIIB). All patients also received chemotherapy and radiation therapy.[
In the patient with metastatic breast cancer, A10 was added to a variety of chemotherapeutics. Rapid tumor growth was followed by the addition of antineoplaston AS2-1 and additional chemotherapy to the treatment regimen. Two weeks following this treatment, a chest x-ray showed marked reduction in size and number of metastatic tumors, and tumor sizes decreased further over the next 5 months.[
The patient with anaplastic astrocytoma received antineoplaston AS2-1 in addition to other chemotherapy and radiation. An MRI 6 weeks after diagnosis showed a 50% reduction in tumor diameters.[
The third patient with metastatic lung cancer received antineoplaston A10 in addition to chemotherapy followed by radiation. Although initially diagnosed as inoperable, after 1 month of this treatment the patient was reconsidered and underwent a middle and lower lobectomy. Follow-up showed the patient in good condition, and a computed tomography (CT) scan had confirmed no trace of tumor postoperatively.[
The addition of other therapies to the administration of antineoplastons is a confounding factor in assessing the results of antineoplaston treatment.
In a 1986 study, antineoplaston AS2-5 injections were administered to 13 patients with 15 various malignancies (two patients each had two different malignancies).[
In addition to antineoplaston AS2-5 injections, two patients also received injections of antineoplaston AS2-1, and one patient received antineoplaston A10 after surgical intervention for a recurrence. Patients received other drugs such as antibiotics, analgesics, anti-inflammatory agents, anti-emetics, bronchial dilators, diuretics, corticosteroids, antihistamines, and uricosuric agents.
Side effects included chills and fever in two patients; swelling of the joints, bone pain, and redness of hands and feet in one patient; increase in platelet count in one patient; and an increase in plasma globulin in one patient.
Two patients were classified as having achieved complete remission, four patients were classified as having stable disease, six had disease progression, and one patient had a mixed response. During the study, eight patients discontinued treatment and were lost to follow-up, and three patients died. At the time of study publication, one patient who was given A10 after surgical intervention for recurrence was reported to be free of cancer for a period of slightly more than 4 years.[
In a 1987 study, 15 patients received antineoplaston A2 through intravenous subclavian catheter. Minor side effects were noted in four patients: fever, chills, and muscle pain. Of the 15 patients, 9 had objective response to treatment: complete tumor response in 7 and partial tumor response in 2. Five patients had stable disease, and one had disease progression. Follow-up showed three patients with complete response were cancer-free 5 years after treatment, and three patients were known to have survived for 4 years from the beginning of the study. Three patients were followed for 2 years, at which time they discontinued AS2-1 therapy. Five patients died within 2 years of the start of the study, and one patient was lost to follow-up.[
In 1987, 24 patients with 25 various malignancies participated in a retrospective nonconsecutive case series study of antineoplaston A3. Patients who had more than 6 weeks' anticipated survival and who continued the treatment for more than 6 weeks were eligible. Antineoplaston A3 was administered through subclavian vein catheter in 23 patients. One patient received IM injections. Length of treatment was 44 to 478 days. Side effects, which occurred only once during treatment, included fever and chills in four patients, vertigo in two patients, headache in two patients, flushing of the face in one patient, nausea in one patient, and tachycardia in one patient. In addition, there was an increase in platelets, white blood cell counts, and reticulocyte counts. Tumor response was complete in five patients, and partial response was seen in five patients. Stable disease was reported in nine patients, while six patients had disease progression. One patient received radiation therapy before entering the study, so tumor response cannot be attributed solely to A3. Six patients discontinued treatment during the study; no reasons were reported.[
In 1987, patients with a variety of advanced malignancies participated in a retrospective selective case series study of antineoplaston A5. Patients ranged in age from 43 to 71 years. Only patients who were expected to survive for at least 6 weeks and who continued the treatment for at least 6 weeks were eligible. Patients received A5 through IV subclavian vein catheter. Treatment lasted from 47 to 130 days. Side effects included chills and fever in five patients, arthralgia in one patient, and premature heart beats and chest pressure in one patient. An increase in platelets and white blood cell counts were noted, as was hypertrophy of the epidermis. One patient had complete tumor response, and there were two partial responses. Stable disease was reported in seven patients. Disease progression occurred in four patients.[
Studies of Specific Malignancies Treated with Antineoplastons
A 1995 phase I study from Japan investigated the use of antineoplastons in conjunction with radiochemotherapy and surgical resection in patients with malignant brain tumors.[
One complete response was achieved in a patient with anaplastic astrocytoma. This response was seen within 4 weeks and lasted for 6 months, at which time the patient developed recurrence in another part of the brain. Two patients (one case of pontine glioma and one case of metastatic brain tumor) achieved a partial response. In two patients, no change in disease status was reported, while four patients had disease progression. Adverse effects of antineoplaston therapy included itchy skin rash, stiff finger joints, flatulence, and mild myelosuppression.[
A multicenter phase II study conducted by the departments of Oncology and Neurology at the Mayo Clinic attempted to assess the pharmacokinetics, toxicity, and efficacy of antineoplastons A10 and AS2-1.[
Of the nine patients enrolled in the trial, six could be evaluated for objective tumor response in accordance with the protocol. 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.[
Burzynski has stated that the results of this study were inconclusive because (1) the duration of treatment was too short and (2) researchers used a dosing regimen known to be ineffective against brain tumors as large as those of the study participants.[
Steady-state plasma concentrations of phenylacetate and phenylacetylglutamine were measured during antineoplaston treatment in this study (refer to Table 1). High serum concentrations of phenylacetate were associated with central nervous system toxic effects.[
A phase II study also conducted by the developer and his associates at his clinic reported on 12 patients with recurrent and diffuse intrinsic brain stem glioma. Of the ten patients who were evaluable, two achieved complete tumor response, three had partial tumor response, three had stable disease, and two had progressive disease. Patients ranged in age from 4 to 29 years. Treatment with escalating intravenous bolus injections of antineoplastons A10 and AS2-1 continued for 6 months. The average dose of A10 was 11.3 g/kg daily, and the average dose of AS2-1 was 0.4 g/kg daily. Adverse effects included skin allergy, anemia, fever and hypernatremia, agranulocytosis, hypocalcemia, hypoglycemia, numbness, tiredness, myalgia, and vomiting.[
A similar study of 12 pediatric patients with recurrent and progressive brain tumors was conducted by the developer and his associates at his clinic. Six patients were diagnosed with pilocytic astrocytoma, four had low-grade glioma, one had grade 2 astrocytoma, and one had visual pathway glioma. Both A10 and AS2-1 were administered intravenously and later orally, for an average duration of 16 months. The average dose of A10 was 7.95 g/kg daily, and the average dose of AS2-1 was 0.33 g/kg daily. Injections were discontinued after the patients showed stable disease or partial or complete tumor response. The patients then received oral administration of A10 and AS2-1 for an average duration of 19 months. Average doses for both A10 and AS2-1 were 0.28 g/kg daily. Of the 12 patients, one was nonevaluable, three were still in the study at the time of publication, and two achieved complete response. The remaining six patients requested removal from the study.[
Another study by the developer and associates reported on the long-term survival of high-risk pediatric patients with central nervous system primitive neuroectodermal tumors treated with a combination of AS2-1 and A10 for an average duration of 20 months (range, 1.2–67 months). The average dose of A10 was 10.3 g/kg daily, and the average dose of AS2-1 was 0.38 g/kg daily. Of 13 patients (age range, 1–11 years) with recurrent or high-risk disease given intravenous infusions of the antineoplaston combination, six patients survived more than 5 years from the start of antineoplaston therapy, and three of these six survived more than 7 years. These three patients received no chemotherapy or radiation after their initial partial tumor resection and before treatment with antineoplastons. A complete response was seen in two of the long-term survivors.[
A 2006 report from the developer and associates summarizes the results from four phase II trials of antineoplaston treatment for high-grade, recurrent, and progressive brainstem glioma. Two of the 18 patients in this report were included in a previously published study.[
Complete responses were observed in two cases, partial response in two cases, stable disease in seven cases, and progressive disease in seven cases. Reversible anemia, the only reported adverse effect, occurred in three patients. Survival from the start of antineoplaston treatment ranged from 2.6 months to 68.4 months among the newly reported cases.[
A phase II clinical trial using antineoplaston AS2-1 in conjunction with low-dose diethylstilbestrol (DES) was conducted by the developer and his associates in 14 patients with hormonally refractory prostate cancer.[
Overall, there were two complete remissions, three partial remissions, seven cases of stable disease, and two cases of disease progression. All patients were known to be alive 2 years after the beginning of the study. The two patients who showed disease progression discontinued AS2-1 treatment.[
Hepatocellular (liver) cancer
A case report from Japan discussed two patients with advanced hepatocellular carcinoma who received antineoplaston A10 in addition to other treatments. Although both patients died—one from hemorrhagic pancreatic necroses and the other from hepatic failure brought on by esophageal varices—both appeared to tolerate A10 with few serious side effects. CT scans indicated that one patient exhibited inhibition of tumor growth and slight shrinkage of the tumor after oral administration and infusion of A10.[
Comment on Studies
No randomized controlled trials examining the use of antineoplastons in patients with cancer have been reported in the literature. Existing published data have taken the form of case reports or series, phase I clinical trials, and phase II clinical trials, conducted mainly by the developer of the therapy and his associates. While these publications have reported successful remissions with the use of antineoplastons, other investigators have been unable to duplicate these results [
Table 1 summarizes the dose ranges of antineoplastons used in the studies discussed above.
|Reference||Cancer Types (No. Patients)||Antineoplaston||Dose||Administration||Treatment Duration|
|bi-wk = bi-weekly; d = day; DES = diethylstilbestrol; h = hour; IM = intramuscular; IV = intravenous; mo = month; No. = number; U = unit; wk = week.|
|a B indicates a study by Burzynski and associates.|
||Various advanced cancers or leukemia (12)||A||A was measured in units, the amount of preparation A that produces a cytostatic effect in 100mLof breast cancer cell line MDA-MB-231 determined by the stable number of cells counted after 24 h of incubation and persisting for at least an additional 48 h. Dose differed by type of administration.||IV: Range from 0.6 U/m²/24 h to 33 U/m²/24 h daily for 1 mo. IM: Range from 0.6 U/m²/24 h to 20 U/m²/24 h for up to 8 mo bi-wk. Rectal: Range from 15 U/m²/24 h to 23 U/m²/24 h daily divided into 2 or 3 doses/12–8 h post–IM treatment. Bladder instillation:Continuous infusionof 2.3 U/m²/24 h for 3 wk. Intrapleurally: 2 U to 4 U/injection. Highest tolerated dose: IV: 33 U/m²/24 h after initial febrile reaction subsided. IM: 10 U/m²/24 h.||IV: 1 mo; IM: bi-wk for up to 8 wk Rectal: daily Bladder Instillation: 3 wk Intrapleural: once/wk|
||Various advanced cancers (15)||A2||Highest dose: 147 mg/kg/24 h (A2 formulations: 50 mg/mL and 100 mg/mL)||IV: daily divided doses every 6 h or every 12 h.||52–358 d|
||Various advanced cancers (23)||A3||Highest dose: 76 mg/kg/24 h||44–478 d|
||Various advanced cancers (15)||A5||Highest dose range: 44 to 154 mg/kg/24 h||IV: daily divided doses||47–130 d|
||Various advanced cancers (18)||A10||Highest dose range: 70.0 to 2,210.5 mg/kg/24 h||IV: gradual increase every 3–6 h from 100 mg/mL to highest dose.||52–640 d|
|Typical dose range: 206.9 to 387 mg/kg/24 h|
||Various advanced cancers||AS2-1||Highest dose: 160 mg/kg/24 h||IV: every 6 h||38–872 d|
||Various advanced cancers||AS2-5||Highest dose: 167.6 mg/kg/24 h||IV: daily divided doses||41–436 d|
||Hormonally refractiveprostate(14)||AS2-1 and DES||AS2-1 dose range: 97 to 130 mg/kg/24 h||Oral||64–425 d|
|DES dose range: 0.01 to 0.02 mg/kg/24 h|
||Various brain tumors (9)||AS2-1/A10||Highest dose range: 7 to 10 g/d||Oral and IV|
||Hepatocellular (3)||AS2-1/A10 (1 patient)||3 to 10 g/d||IV||7–120 d (approx)|
||Recurrent glioma (9)||A10/AS2-1||Target dose: A10: 1.0 g/kg/24 h; AS2-1: 0.4 g/kg/24 h.||IV: daily divided doses||9–66 d|
|Steady-state plasma concentrations at target dose: phenylacetate, 177 ± 101 μg/mL; phenylacetylglutamine: 301 ± 102 μg/mL|
||Pediatric recurrent progressive multicentric glioma (11)||A10/AS2-1||Formulation dose: A10: 300 mg/mL; AS2-1: 80 mg/mL A10 and AS2-1||IV injection gradually increasing dose until max dose is reached. Oral administration bycapsulesfollowed.||IV: Average 16 mo; Oral: 19 mo|
|Max dose range: A10: 5.29 g/kg/d to 16.13 g/kg/d|
|Max dose range: AS2-1: 0.21 g/kg/d to 0.58 g/kg/d|
||Recurrent diffuse intrinsic brain stem glioma (12)||A10/AS2-1||Formulation dose: A10: 300 mg/mL; AS2-1: 80 mg/mL||IV injection of gradually increasing dose until max dose is reached.||Average 6 mo|
|A10 max dose range: 5.29 g/kg/d to 16.13 g/kg/d|
|AS2-1 max dose range: 0.21 g/kg/d to 0.58 g/kg/d|
||Primitive neuroectodermal tumor (13)||A10/AS2-1||Formulation dose: A10: 300 mg/mL; AS2-1: 80 mg/mL||IV injection of gradually increasing dose until max dose is reached.||Average 20 mo|
|Average dose: A10: 10.3 g/kg/d; AS2-1: 0.38 g/kg/d|
|Max dose: A10: 25 g/kg/d; AS2-1: 0.6 g/kg/d|
||Recurrent diffuse intrinsic brain stem glioma||A10/AS2-1||Average max dose: A10: 13.37g/kg/d; AS2-1: 0.49 g/kg/d||IV injection of gradually increasing dose until max dose is reached.||Average 5 mo|
Table 2 summarizes the clinical trials used in the studies discussed above.
|Reference Citations||Type of Study||Type(s) of Antineoplaston||Type(s) of Cancer||No. of Patients||Strongest Benefit Reported||Concurrent Therapy|
|ALL = acute lymphoblastic leukemia; No. = number; NSLCC = non-small cell lung cancer; pt/pts = patient/patients.|
|a Reported at 9 months of follow-up; patient with breast cancer had undergone radicalmastectomy, radiation therapy, and chemotherapy and had subsequent metastases to ribs surgicallyresectedprior to treatment with antineoplastons.|
|b One patient with bladder cancer hadsurgeryfor removal of necrotic tumor.|
|c Reported at 5 years of follow-up; patient withstage IA cervical cancerreceived prior radiation therapy; patient with breast cancer received prior radical mastectomy and had nomeasurable diseaseat the initiation of antineoplaston treatment.|
|d One patient received 5-fluorouracil.|
|e Reported at 5 years of follow-up; patient withstage II laryngeal cancerwas reported to be in complete remission 730 days after beginning of treatment, but was lost to follow-up at time of study publication and his status was unknown; patient with stage III NSCLC was reported to be in complete remission after 62 days of treatment, but subsequently developedcervical lymph noderecurrence and lobular breast carcinoma. Both were treated surgically and patient received antineoplaston A10; at the time of study publication, the patient was reported to have been free of both cancers for more than 4 years.|
|f Reported at 4 years of follow-up; 10 patients had died at the time of study publication.|
|g Patients reported to be in complete remission more than 5 years after beginning treatment; the patient withcolon cancerhad undergone previous resection and was reported to have maintained complete remission during A3 treatment, however, developed recurrence with metastases after discontinuation of treatment. This patient subsequently received other antineoplaston formulations and chemotherapy.|
|h Length of follow-up not specified.|
|i Reported at 2 years of follow-up; at the time of study publication, one patient was reported to have been in complete remission for 17 months and off treatment for 16 months; the other patients were reported to have been disease-free for 9 months prior to study publication and to be continuing antineoplastons but not DES.|
|k Length of follow-up not specified.|
|l Surgery, chemotherapy, radiation, andbiological response modifiers(beta-interferon).|
|m Authors reported on theoutcomeof 46 tumors for complete or partial response and provided survival information for patients.|
|n Chemotherapy and radiation.|
|o Surgery, chemotherapy, radiation, and interferon.|
|p Both patients had died by the time of study publication.|
|r At the time of study publication, all patients had died.|
|s Surgery, chemotherapy, radiation, and interferon.|
|t Both patients had died by the time of study publication.|
|v At the time of study publication, all patients had died.|
||Nonconsecutive case series||A||Various types||21||Complete remission (2 grade III bladder cancers, stage IV breast cancer, ALL)a||Nob|
||Nonconsecutive case series||AS2-1 (8 pts)||Various types, most in advanced stages||20||Complete remission (stage IA cervical, intraductal breast carcinoma, stage IV lymphocytic lymphoma)c||Nod|
|AS2-1 plus other antineoplaston formulations (12 pts)|
||Nonconsecutive case series||AS2-5 (11 pts)||Various types, advanced stages||13||Complete remission (stage IIlaryngeal, stage III NSCLC)e||No|
|AS2-5 plus AS2-1 (2 pts)|
||Nonconsecutive case series||A10 (12 pts)||Various types, most in advanced stages||18||Partial remission (one case stage IB chondrosarcoma)f||No|
|A10 plus other antineoplaston formulations (6 pts)|
||Nonconsecutive case series||A3||Various types, advanced stages||24||Complete remission (bladder carcinoma,basal cellepithelioma, andcoloncancer)g||No|
||Nonconsecutive case series||A5||Various types, advanced stages||15||Complete remission (grade III mixed bladder cancer)h||Not specified|
||Consecutive case series(phase II trial)||AS2-1||Prostate cancer, hormone refractory (13 stage IV, 1 stage II)||14||Complete remission (2 pts)i||Yesj|
||Nonconsecutive case series/case reports||AS2-1, A10||Brain tumors||9||Partial response (1 pontine glioma, 1 metastatic brain tumor)k||Yesl|
||Phase I clinical trial||A10, AS2-1 (randomly chosen)||Various types, advanced stages||42m||Complete response (3 tumors)k||Yesn|
||Case reports||A10, AS2-1||Various types||3||Reduction in tumor size (stage IV breast, stage IIIB NSCLC)||Yeso|
||Case reports||A10, AS2-1||Advanced hepatocellular carcinoma||2||Slight shrinkage of tumorthrombusin theportal vein p||Yesq|
||Phase II clinical trial||A10, AS2-1||Recurrent brain tumor (anaplastic astrocytoma or glioblastoma multiforme)||9 (6 pts were assessable for efficacy)||Noner||No|
||Phase II study||A10, AS2-1||Recurrent and progressive multicentric glioma in children||12||Complete response 2||No|
||Phase II study||A10, AS2-1||Recurrent diffuse intrinsic brain stem glioma||12||Complete response 2||No|
||Case reports||A10, AS2-1||Various types||3||Reduction in tumor size (stage IV breast, stage IIIB NSCLC)||Yess|
||Case reports||A10, AS2-1||Advanced hepatocellular carcinoma||2||Slight shrinkage of tumor thrombus in the portal veint||Yesu|
||Phase II clinical trial||A10, AS2-1||Recurrent brain tumor (anaplastic astrocytoma or glioblastoma multiforme)||9 (6 assessable for efficacy)||Nonev||No|
||Phase II study||A10, AS2-1||Recurrent and progressive multicentric glioma in children||12||Complete response 2||No|
||Phase II study||A10, AS2-1||Recurrent diffuse intrinsic brain stem glioma||12||Complete response 2||No|
||Phase II study||A10, AS2-1||Primitive neuroectodermal tumor||13||Complete response 3||No|
||Summary of data, phase II trials||A10, AS2-1||Recurrent diffuse intrinsic brainstem glioma||18 (2 previously reported in[
||Complete response 1 (1 previously reported)||No|
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Adverse effects of antineoplaston therapy have ranged from mild and short-lasting symptoms to severe neurologic toxicity necessitating discontinuation of therapy in some patients.[
Table 3 summarizes the adverse effects in the referenced studies.
|a The most severe adverse effects occurred in this study, which reported neurologictoxiceffects such as excessive somnolence, somnolence plusconfusion, and increased frequency of underlyingfocal motor seizures; increasedcerebraledema; and persistent confusion. In addition, the study reportedmyalgia, severecutaneous erythema,pruritus, and anasarca of the extremities and face.|
|Dizziness or vertigo||[
|General malaise with and withoutanorexia||[
|Increased thickness ofepidermisassociated with skin peeling and faster-than-usual growth of nails||[
|Maculopapular or itchy skin rash||[
|Neurocortical toxicity, severe||[
|Palpitations,tachycardia, or pressure in the chest with irregular heartbeat||[
|Peripheraledema, facial edema, cerebral edema||[
|Swelling, pain, or stiffness of small joints||[
To assist readers in evaluating the results of human studies of integrative, alternative, and complementary therapies for cancer, the strength of the evidence (i.e., the "levels of evidence") associated with each type of treatment is provided whenever possible. To qualify for a level of evidence analysis, a study must:
Antineoplaston therapy has been studied as a complementary and alternative therapy for cancer. Case reports, phase I toxicity studies, and some phase II clinical studies examining the effectiveness of antineoplaston therapy have been published. For the most part, these publications have been authored by the developer of the therapy, Dr. S.R. Burzynski, in conjunction with his associates at the Burzynski Clinic. Although these studies often report remissions, other investigators have not been successful in duplicating these results. (Refer to the Human/Clinical Studies section of this summary for more information.) The evidence for use of antineoplaston therapy as a treatment for cancer is inconclusive. Controlled clinical trials are necessary to assess the value of this therapy.
Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. For additional information about levels of evidence analysis of integrative, alternative, and complementary therapies for cancer, refer to Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of antineoplastons in the treatment of people with cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Integrative, Alternative, and Complementary Therapies Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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The preferred citation for this PDQ summary is:
PDQ® Integrative, Alternative, and Complementary Therapies Editorial Board. PDQ Antineoplastons. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/cam/hp/antineoplastons-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389311]
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Last Revised: 2019-08-15
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