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Table of Contents Purpose of This PDQ Summary Overview General Information History Laboratory/Animal/Preclinical Studies Human/Clinical Studies
Adverse Effects Overall Level of Evidence for Antineoplastons Changes to This Summary (04/24/2008) More Information
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of antineoplastons as a treatment for cancer. The summary is reviewed regularly and updated as necessary by the PDQ Cancer Complementary and Alternative Medicine Editorial Board 1.
Information about the following is included in this summary:
- A brief history of antineoplastons research.
- The results of clinical studies of antineoplastons.
- Possible side effects of antineoplastons use.
This summary is intended as a resource to inform and assist clinicians and other health professionals who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help the readers assess the strength of the evidence supporting the use of specific interventions or treatment strategies. The PDQ Cancer Complementary and Alternative Medicine Editorial Board uses a formal evidence ranking system 2 in developing its level-of-evidence designations. These designations should not be used as a basis for reimbursement determinations.
This summary is also available in a patient version, which is written in less technical language. Overview
This complementary and alternative medicine (CAM) information summary provides an overview of the use of antineoplastons as treatments for patients 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:
- Antineoplastons are drugs composed of chemical compounds that are naturally present in the urine and blood. They are an experimental cancer therapy that is purported to provide a natural biochemical substance that is excreted and therefore lacking in people with cancer.
- Antineoplastons were first proposed as a possible cancer treatment in 1976.
- Antineoplastons were originally isolated from human urine but are now synthesized from readily available chemicals in the developer’s laboratory.
- Antineoplastons are not approved by the United States Food and Drug Administration for the prevention or treatment of any disease.
- No randomized controlled trials showing the effectiveness of antineoplastons have been published in the peer-reviewed scientific literature.
- Antineoplaston side effects can include serious neurologic toxicity.
- Nonrandomized clinical trials investigating the anticancer efficacy of antineoplastons are underway at the developer’s institute.
Many of the medical and scientific terms used in this summary are hypertext linked (at first use in each section) to the NCI Dictionary 3, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window. All linked terms and their corresponding definitions will appear in a glossary in the printable version of the summary.
Reference citations in some PDQ CAM information summaries may include links to external Web sites 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 Web sites, or of any treatment or product, by the PDQ Cancer CAM Editorial Board or the National Cancer Institute. General Information
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.[1-4] The developer originally isolated antineoplastons from human blood and later found the same peptides in urine. Urine was subsequently used because it was less expensive and easier to obtain. Since 1980, antineoplastons have been synthesized from commercially available chemicals at the Burzynski Research Institute.[2,4]
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.[1-3]
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.”[2]
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.”[2]
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.[2] The living cell is an autonomous cybernetic system connected to, and receiving, information from its environment through an energy pathway and an information pathway. It was postulated that a regulator within such a system would control the transfer of information and the expenditure of energy. Peptides were considered the information carriers in the body. Hypothesizing that peptides were the carriers of differentiation information to the cells, the developed began looking for peptides in the blood of cancer patients that might correct abnormal differentiation.[1-3,5]
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 their 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.[2]
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.[6] 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.[2]
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.[2]
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.[2-4]
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.[8] Presently, antineoplastons A10, AS2-5, AS2-1, A2, A3, and A5 are given orally or by injection.[8-20]
Critical opposition to antineoplaston therapy and its developer have appeared in the published literature.[4] A basic criticism of the developer’s work is that although he has put forth a theory of peptides inducing cell differentiation, there is no published evidence that he has experimentally tested the hypothesis that information-bearing peptides could normalize cancer cells. Although some articles attempt to demonstrate that antineoplastons (specifically, antineoplaston A10) can bind to DNA at certain sites, this is an extrapolation from three-dimensional molecular models of DNA and A10 and does not demonstrate that this binding actually occurs.[21-23]
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.[4]
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 neutralized.[4]
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.[24] The developer retains patents on antineoplaston compounds and their use when administered pharmaceutically to inhibit the growth of neoplastic cells.[6,25]
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.
There are currently several active clinical trials sponsored and administered by the developer of antineoplastons. Information on these trials can be accessed through the NCI Web site 4. None of these trials are randomized controlled trials.
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.[21,23] The theory is based on the manipulation of molecular models of DNA and A10; however, no published evidence of the creation of this actual molecule or evidence of the properties ascribed to it exists in the medical literature.
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.[21,26,27]
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.[28] Another theory proposes that phenylacetic acid, also a component of several antineoplastons, inhibits methylation of nucleic acids in cancer cells. The hypomethylation of DNA in cancer cells may lead to terminal differentiation and prevention of tumor growth or progression.[28]
References
-
Burzynski SR: Antineoplastons: biochemical defense against cancer. Physiol Chem Phys 8 (3): 275-9, 1976.
[PUBMED Abstract]
-
Burzynski SR: Antineoplastons: history of the research (I). Drugs Exp Clin Res 12 (Suppl 1): 1-9, 1986.
[PUBMED Abstract]
-
Burzynski SR: Potential of antineoplastons in diseases of old age. Drugs Aging 7 (3): 157-67, 1995.
[PUBMED Abstract]
-
Green S: 'Antineoplastons'. An unproved cancer therapy. JAMA 267 (21): 2924-8, 1992.
[PUBMED Abstract]
-
Burzynski SR: The present state of antineoplaston research (1). Integr Cancer Ther 3 (1): 47-58, 2004.
[PUBMED Abstract]
-
Burzynski SR: Purified Antineoplaston Fractions and Methods of Treating Neoplastic Disease. US Patent 4558057. December 10, 1985. Washington, DC: US Patent and Trademark Office, 1985. Available online 5. Last accessed October 16, 2007.
-
Revelle LK, D'Avignon DA, Wilson JA: 3-[(Phenylacetyl)amino]-2,6-piperidinedione hydrolysis studies with improved synthesis and characterization of hydrolysates. J Pharm Sci 85 (10): 1049-52, 1996.
[PUBMED Abstract]
-
Burzynski SR, Stolzmann Z, Szopa B, et al.: Antineoplaston A in cancer therapy. (I). Physiol Chem Phys 9 (6): 485-500, 1977.
[PUBMED Abstract]
-
Tsuda H, Hara H, Eriguchi N, et al.: Toxicological study on antineoplastons A-10 and AS2-1 in cancer patients. Kurume Med J 42 (4): 241-9, 1995.
[PUBMED Abstract]
-
Burzynski SR: Toxicology studies on antineoplaston AS2-5 injections in cancer patients. Drugs Exp Clin Res 12 (Suppl 1): 17-24, 1986.
[PUBMED Abstract]
-
Burzynski SR, Burzynski B, Mohabbat MO: Toxicology studies on antineoplaston AS2-1 injections in cancer patients. Drugs Exp Clin Res 12 (Suppl 1): 25-35, 1986.
[PUBMED Abstract]
-
Burzynski SR, Kubove E: Toxicology studies on antineoplaston A10 injections in cancer patients. Drugs Exp Clin Res 12 (Suppl 1): 47-55, 1986.
[PUBMED Abstract]
-
Burzynski SR, Kubove E, Burzynski B: Treatment of hormonally refractory cancer of the prostate with antineoplaston AS2-1. Drugs Exp Clin Res 16 (7): 361-9, 1990.
[PUBMED Abstract]
-
Burzynski SR, Kubove E, Burzynski B: Phase I clinical studies of antineoplaston A5 injections. Drugs Exp Clin Res 13 (Suppl 1): 37-43, 1987.
[PUBMED Abstract]
-
Burzynski SR, Kubove E: Phase I clinical studies of antineoplaston A3 injections. Drugs Exp Clin Res 13 (Suppl 1): 17-29, 1987.
[PUBMED Abstract]
-
Burzynski SR, Kubove E: Initial clinical study with antineoplaston A2 injections in cancer patients with five years' follow-up. Drugs Exp Clin Res 13 (Suppl 1): 1-11, 1987.
[PUBMED Abstract]
-
Sugita Y, Tsuda H, Maruiwa H, et al.: The effect of Antineoplaston, a new antitumor agent on malignant brain tumors. Kurume Med J 42 (3): 133-40, 1995.
[PUBMED Abstract]
-
Tsuda H, Sata M, Kumabe T, et al.: Quick response of advanced cancer to chemoradiation therapy with antineoplastons. Oncol Rep 5 (3): 597-600, 1998 May-Jun.
[PUBMED Abstract]
-
Kumabe T, Tsuda H, Uchida M, et al.: Antineoplaston treatment for advanced hepatocellular carcinoma. Oncol Rep 5 (6): 1363-7, 1998 Nov-Dec.
[PUBMED Abstract]
-
Buckner JC, Malkin MG, Reed E, et al.: Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma. Mayo Clin Proc 74 (2): 137-45, 1999.
[PUBMED Abstract]
-
Lehner AF, Burzynski SR, Hendry LB: 3-Phenylacetylamino-2,6-piperidinedione, a naturally-occurring peptide analogue with apparent antineoplastic activity, may bind to DNA. Drugs Exp Clin Res 12 (Suppl 1): 57-72, 1986.
[PUBMED Abstract]
-
Hendry LB, Muldoon TG, Burzynski SR, et al.: Stereochemical modelling studies of the interaction of antineoplaston A10 with DNA. Drugs Exp Clin Res 13 (Suppl 1): 77-81, 1987.
[PUBMED Abstract]
-
Michalska D: Theoretical investigations on the structure and potential binding sites of antineoplaston A10 and experimental findings. Drugs Exp Clin Res 16 (7): 343-9, 1990.
[PUBMED Abstract]
-
Choi BG, Seo HK, Chung BH, et al.: Synthesis of Mannich bases of antineoplaston A10 and their antitumor activity. Arch Pharm Res 17 (6): 467-9, 1994.
[PUBMED Abstract]
-
Burzynski SR: Purified Antineoplaston Fractions and Methods of Treating Neoplastic Disease. US Patent 4559325. December 17, 1985. Washington, DC: US Patent and Trademark Office, 1985. Available online 5. Last accessed October 16, 2007.
-
Wood JC, Copland JA, Muldoon TG, et al.: 3-phenylacetylamino-2,6-piperidinedione inhibition of rat Nb2 lymphoma cell mitogenesis. Proc Soc Exp Biol Med 197 (4): 404-8, 1991.
[PUBMED Abstract]
-
Tsuda H: Inhibitory effect of antineoplaston A-10 on breast cancer transplanted to athymic mice and human hepatocellular carcinoma cell lines. The members of Antineoplaston Study Group. Kurume Med J 37 (2): 97-104, 1990.
[PUBMED Abstract]
-
Sołtysiak-Pawłuczuk D, Burzyński SR: Cellular accumulation of antineoplaston AS21 in human hepatoma cells. Cancer Lett 88 (1): 107-12, 1995.
[PUBMED Abstract]
History
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 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, Office of Alternative Medicine, now known as the National Center for Complementary and Alternative Medicine, 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, the studies were closed prematurely in August 1995.[1-3]
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.[4-15] These studies are
described in more detail in the Human/Clinical Studies section of this document. Most of these studies were phase I trials or their equivalent; therefore, the only objective of these trials was safety.
Other uses of antineoplastons suggested by the developer include treatment of conditions such as Parkinson’s disease, sickle cell anemia, and thalassemia.[16]
References
-
The antineoplaston anomaly: how a drug was used for decades in thousands of patients, with no safety, efficacy data. The Cancer Letter 24 (36):1998 Also available online 6. Last accessed October 9, 2007.
-
Burzynski SR: Efficacy of antineoplastons A10 and AS2-1. Mayo Clin Proc 74 (6): 641-2, 1999.
[PUBMED Abstract]
-
Hammer MR, Jonas WB: Managing social conflict in complementary and alternative medicine research: the case of antineoplastons. Integr Cancer Ther 3 (1): 59-65, 2004.
[PUBMED Abstract]
-
Burzynski SR, Stolzmann Z, Szopa B, et al.: Antineoplaston A in cancer therapy. (I). Physiol Chem Phys 9 (6): 485-500, 1977.
[PUBMED Abstract]
-
Tsuda H, Hara H, Eriguchi N, et al.: Toxicological study on antineoplastons A-10 and AS2-1 in cancer patients. Kurume Med J 42 (4): 241-9, 1995.
[PUBMED Abstract]
-
Burzynski SR: Toxicology studies on antineoplaston AS2-5 injections in cancer patients. Drugs Exp Clin Res 12 (Suppl 1): 17-24, 1986.
[PUBMED Abstract]
-
Burzynski SR, Burzynski B, Mohabbat MO: Toxicology studies on antineoplaston AS2-1 injections in cancer patients. Drugs Exp Clin Res 12 (Suppl 1): 25-35, 1986.
[PUBMED Abstract]
-
Burzynski SR, Kubove E: Toxicology studies on antineoplaston A10 injections in cancer patients. Drugs Exp Clin Res 12 (Suppl 1): 47-55, 1986.
[PUBMED Abstract]
-
Burzynski SR, Kubove E, Burzynski B: Treatment of hormonally refractory cancer of the prostate with antineoplaston AS2-1. Drugs Exp Clin Res 16 (7): 361-9, 1990.
[PUBMED Abstract]
-
Burzynski SR, Kubove E, Burzynski B: Phase I clinical studies of antineoplaston A5 injections. Drugs Exp Clin Res 13 (Suppl 1): 37-43, 1987.
[PUBMED Abstract]
-
Burzynski SR, Kubove E: Phase I clinical studies of antineoplaston A3 injections. Drugs Exp Clin Res 13 (Suppl 1): 17-29, 1987.
[PUBMED Abstract]
-
Burzynski SR, Kubove E: Initial clinical study with antineoplaston A2 injections in cancer patients with five years' follow-up. Drugs Exp Clin Res 13 (Suppl 1): 1-11, 1987.
[PUBMED Abstract]
-
Sugita Y, Tsuda H, Maruiwa H, et al.: The effect of Antineoplaston, a new antitumor agent on malignant brain tumors. Kurume Med J 42 (3): 133-40, 1995.
[PUBMED Abstract]
-
Tsuda H, Sata M, Kumabe T, et al.: Quick response of advanced cancer to chemoradiation therapy with antineoplastons. Oncol Rep 5 (3): 597-600, 1998 May-Jun.
[PUBMED Abstract]
-
Kumabe T, Tsuda H, Uchida M, et al.: Antineoplaston treatment for advanced hepatocellular carcinoma. Oncol Rep 5 (6): 1363-7, 1998 Nov-Dec.
[PUBMED Abstract]
-
Burzynski SR: Potential of antineoplastons in diseases of old age. Drugs Aging 7 (3): 157-67, 1995.
[PUBMED Abstract]
Laboratory/Animal/Preclinical Studies
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.[1] This claim is made only for antineoplaston A. Other formulations of antineoplastons have not been tested in animal models.
Japanese scientists have tested antineoplastons A10 and AS2-1 in vitro for cell growth inhibition and progression in several human hepatocellular cell lines.[2,3] Tests were performed in a dose-dependent manner at concentrations varying from 0.5 to 8 µg/mL for A10 and AS2-1, and growth inhibition was generally observed at 6 to 8 µg/mL. This dose level is considered excessively high and generally reflects a lack of activity. Growth inhibition of one of the cell lines (KIM-1) was observed at low concentration for a mixture of cisplatin (CDDP) and A10, but this result was probably caused by the cisplatin, which was effective at concentrations of 0.5 to 2.0 μg/mL when tested alone.[4] AS2-1 was reported to induce apoptosis in three of the cell lines at concentrations of 2 and 4 μg/mL.
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.[5]
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.[6]
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.[7]
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).[8]
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.[9,10] These analogs showed improved in vitro antitumor activity over that of antineoplaston A10.
References
-
Burzynski SR, Stolzmann Z, Szopa B, et al.: Antineoplaston A in cancer therapy. (I). Physiol Chem Phys 9 (6): 485-500, 1977.
[PUBMED Abstract]
-
Tsuda H: Inhibitory effect of antineoplaston A-10 on breast cancer transplanted to athymic mice and human hepatocellular carcinoma cell lines. The members of Antineoplaston Study Group. Kurume Med J 37 (2): 97-104, 1990.
[PUBMED Abstract]
-
Tsuda H, Iemura A, Sata M, et al.: Inhibitory effect of antineoplaston A10 and AS2-1 on human hepatocellular carcinoma. Kurume Med J 43 (2): 137-47, 1996.
[PUBMED Abstract]
-
Tsuda H, Sugihara S, Nishida H, et al.: The inhibitory effect of the combination of antineoplaston A-10 injection with a small dose of cis-diamminedichloroplatinum on cell and tumor growth of human hepatocellular carcinoma. Jpn J Cancer Res 83 (5): 527-31, 1992.
[PUBMED Abstract]
-
Wood JC, Copland JA, Muldoon TG, et al.: 3-phenylacetylamino-2,6-piperidinedione inhibition of rat Nb2 lymphoma cell mitogenesis. Proc Soc Exp Biol Med 197 (4): 404-8, 1991.
[PUBMED Abstract]
-
Lee SS, Mohabbat MO, Burzynski SR: In vitro cancer growth inhibition and animal toxicity studies of antineoplaston A3. Drugs Exp Clin Res 13 (Suppl 1): 13-6, 1987.
[PUBMED Abstract]
-
Badria F, Mabed M, Khafagy W, et al.: Potential utility of antineoplaston A-10 levels in breast cancer. Cancer Lett 155 (1): 67-70, 2000.
[PUBMED Abstract]
-
Badria F, Mabed M, El-Awadi M, et al.: Immune modulatory potentials of antineoplaston A-10 in breast cancer patients. Cancer Lett 157 (1): 57-63, 2000.
[PUBMED Abstract]
-
Choi BG, Kim OY, Chung BH, et al.: Synthesis of antineoplaston A10 analogs as potential antitumor agents. Arch Pharm Res 21 (2): 157-63, 1998.
[PUBMED Abstract]
-
Hendry LB, Chu CK, Copland JA, et al.: Antiestrogenic piperidinediones designed prospectively using computer graphics and energy calculations of DNA-ligand complexes. J Steroid Biochem Mol Biol 48 (5-6): 495-505, 1994.
[PUBMED Abstract]
Human/Clinical Studies
To date, 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 7 is a summary of dose regimens for all human studies. Table 2 8 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.
Antineoplaston A
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.[1] Antineoplaston A was administered intravenously (IV), intramuscularly (IM), rectally, by bladder instillation, intrapleurally, and by application to the skin. Tolerance to antineoplaston A depended on the method of administration and the type of neoplasm.
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 7).
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.[1]
Antineoplaston A10
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.[2]
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.[2]
Antineoplaston AS2-1
A 1986 study examined the toxicity of injectable antineoplaston AS2-1.[3] Twenty patients ranging in age from 17 to 74 years received antineoplaston injections for 21 malignancies. Patients were followed for 5 years. Eight patients received antineoplaston AS2-1 alone. The remaining 12 received other antineoplastons in combination with AS2-1 at different times during treatment.
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.[3]
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.[4]
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.[4]
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.[4]
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 CT scan had confirmed no trace of tumor postoperatively.[4]
The addition of other therapies to the administration of antineoplastons is a confounding factor in assessing the results of antineoplaston treatment.
Information about ongoing clinical trials on A10 and AS2-1 9 is available from the NCI Web site 4.
Antineoplaston AS2-5
In a 1986 study, antineoplaston AS2-5 injections were administered to 13 patients with 15 various malignancies (two patients each had two different malignancies).[5] All patients had stage IV disease and ranged in age from 20 to 64 years. Only patients who had an expected survival longer than 1 month were eligible for the study.
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.[5]
Antineoplaston A2
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.[6]
Antineoplaston A3
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.[7]
Antineoplaston A5
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.[8]
Studies of Specific Malignancies Treated with Antineoplastons
Brain tumors
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.[9] Nine patients were diagnosed with the following brain tumors: three cases of glioblastoma, two cases of anaplastic astrocytoma, one pontine glioma, one medulloblastoma, one metastatic brain tumor, and one case of multiple brain metastases. All patients received some form of chemotherapy and radiation, with the exception of the patient with multiple brain metastases. Most patients underwent surgical resection of the tumor, with the exception of the cases of pontine glioma, multiple brain metastases, and metastatic brain tumor. Patients with glioma were treated with remission maintenance therapy. Nimustine or ranimustine was administered over intervals of several months; at 2-week intervals, the patients received interferon-beta and an antineoplaston. The study does not indicate which antineoplastons were used.[9]
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.[9]
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.[10] Slow patient accrual caused the trial to be closed early. Nine adult patients with anaplastic oligoastrocytoma, anaplastic astrocytoma, or glioblastoma multiforme that had recurred after radiation therapy received escalating doses of A10 and AS2-1, to a target daily dose of 1.0 g/kg for A10 and 0.4 g/kg for AS2-1. Six of the patients experienced a second tumor recurrence, while the remaining three patients experienced their first tumor recurrence.[10]
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.[10]
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.[10]
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.[11] However, in response, the study authors have stated that all patients in this study received treatment until either tumor progression or unacceptable toxic effects occurred.[11] The National Cancer Institute and the Burzynski Institute agreed to the dosage regimen and study plan before the study was initiated, and the tumor size in seven of the nine patients was within the specified limits.[11]
Steady-state plasma concentrations of phenylacetate and phenylacetylglutamine were measured during antineoplaston treatment in this study (refer to Table 1 7). High serum concentrations of phenylacetate were associated with central nervous system toxic effects.[11] Treatment-related neurologic toxicity included excessive somnolence, somnolence plus confusion, and increased frequency of underlying focal motor seizures. MRI scans also revealed increased cerebral edema in two patients. One of the nine patients had findings suggestive of a diffuse metabolic encephalopathic process; this patient and one other had antineoplaston treatment interrupted and received dexamethasone for their symptoms, which resolved within 48 hours. These patients resumed their treatment with a 25% decrease in dose and had no recurrence of neurologic toxicity. Another patient manifested persistent confusion that stopped after discontinuation of antineoplastons. Other toxicities included nausea and vomiting, headache, myalgia, and edema. These effects were reported as usually mild to moderate, except for headache, which was severe in two patients. The patient who experienced persistent confusion also developed severe cutaneous erythema, pruritus, and facial edema, at which time treatment was permanently discontinued. Another patient had treatment discontinued because of edema of the extremities and face that was unresponsive to diuretics. The edema resolved after discontinuation of antineoplastons.[10]
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.[12]
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.[13]
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.[14] Reported adverse effects included fever, granulocytopenia (reversible), and anemia.
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.[15] Patients were treated with a combination of AS2-1 and A10 for an average of 216 days (range, 1.53–18.36 months). Doses of A10 ranged from 0.78 g/kg daily to 19.44 g/kg daily; doses of AS2-1 ranged from 0.2 g/kg daily to 0.52 g/kg daily.
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.[16]
Prostate cancer
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.[17] Thirteen patients were diagnosed with stage IV prostate cancer, and one patient was diagnosed with stage II prostate cancer. Ages ranged from 54 to 88 years. Previous therapy included prostatectomy, orchiectomy, radiation therapy, and treatment with DES, luteinizing hormone-releasing hormone (LHRH) agonists, flutamide, aminoglutethimide, and immunotherapy. Patients all showed disease progression after initial response to treatment. During the study, all 14 patients received oral AS2-1 in doses ranging from 97 to 130 mg/kg daily and DES in doses ranging from 0.01 to 0.02 mg/kg daily. Patients exhibited few significant side effects.
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.[17] The use of DES in conjunction with AS2-1 is a confounding factor in interpreting any results of tumor response.
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.[18]
To date, no randomized controlled trials examining the use of antineoplastons in patients with cancer have been reported in the literature. Existing publications have taken the form of case reports or series, phase I clinical trials, and phase II clinical trials, conducted mainly by the developer and his associates. While these publications have reported on successful remissions with the use of antineoplastons, other investigators have been unable to duplicate these results [10] and suggest that interpreting effects of antineoplaston treatment in patients with recurrent gliomas may be confounded by pre-antineoplaston treatment as well as imaging artifacts.[11,14,16] Reports originating from Japan on the effect of antineoplaston treatment on brain and other types of tumors have been mixed, and in some Japanese studies the specific antineoplastons used are not named.[9] In many of the reported studies, several or all patients received concurrent or recent radiation therapy, chemotherapy, or both, confounding interpretability.
Table 1 summarizes the dose ranges of antineoplastons used in the studies discussed above.
Table 1. Dose Ranges for Clinical Studies of Antineoplastons
Reference
|
Cancer Types (No. Patients)
|
Antineoplaston
|
Dose
|
Administration
|
Treatment Duration
|
Single-Antineoplaston Therapy
|
[1]B*
|
Various advanced cancers or leukemia (12)
|
A
|
A was measured in units, the amount of preparation A that produces a cytostatic effect in 100 mL of 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 infusion of 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
|
[6]B* |
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 |
[7]B* |
Various advanced cancers (23) |
A3
|
Highest dose: 76 mg/kg/24 h |
|
44–478 d
|
[8]B* |
Various advanced cancers (15) |
A5 |
Highest dose range: 44 to 154 mg/kg/24 h |
IV: daily divided doses |
47–130 d |
[2]B* |
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 |
[3] |
Various advanced cancers
|
AS2-1
|
Highest dose: 160 mg/kg/24 h |
IV: every 6 h |
38–872 d |
[5] |
Various advanced cancers |
AS2-5 |
Highest dose: 167.6 mg/kg/24 h |
IV: daily divided doses |
41–436 d |
Combinations
|
[17]B* |
Hormonally refractive prostate (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 |
[9] |
Various brain tumors (9) |
AS2-1/A10 |
Highest dose range: 7 to 10 g/d |
Oral and IV |
|
[18] |
Hepatocellular (3) |
AS2-1/A10 (1 patient) |
3 to 10 g/d |
IV |
7–120 d (approx)
|
[10] |
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 |
[13]B* |
Pediatric recurrent progressive multicentric glioma (11) |
A10/AS2-1 |
Formation 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 by capsules followed. |
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 |
[12]B* |
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 |
[14]B* |
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 |
[16]B* |
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 |
bi-wk = bi-weekly; d = day; h = hour; IM = intramuscular; IV = intravenous; mo = month; No. = number; U = unit; wk = week.
|
*B indicates a study by Burzynski and associates.
|
Table 2 summarizes the clinical trials used in the studies discussed above.
Table 2. Antineoplastons Clinical Trials
Reference Citations
|
Type of Study
|
Type(s) of Antineoplaston
|
Type(s) of Cancer
|
No. of Patients
|
Strongest Benefit Reported
|
Concurrent Therapy
|
[1] |
Nonconsecutive case series
|
A |
Various types
|
21 |
Complete remission (2 grade III bladder cancers, stage IV breast cancer, ALL)a |
Nob
|
[3] |
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)
|
[5] |
Nonconsecutive case series
|
AS2-5 (11 pts)
|
Various types, advanced stages
|
13 |
Complete remission (stage II laryngeal, stage III NSCLC)e |
No |
AS2-5 plus AS2-1 (2 pts)
|
[2] |
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) |
[7] |
Nonconsecutive case series |
A3 |
Various types, advanced stages |
24 |
Complete remission (bladder carcinoma, basal cell epithelioma, and colon cancer)g |
No |
[8] |
Nonconsecutive case series |
A5 |
Various types, advanced stages |
15 |
Complete remission (grade III mixed bladder cancer)h |
Not specified |
[17] |
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 |
[9] |
Nonconsecutive case series/case reports |
AS2-1, A10 |
Brain tumors |
9 |
Partial response (1 pontine glioma, 1 metastatic brain tumor)k |
Yesl |
[19] |
Phase I clinical trial |
A10, AS2-1 (randomly chosen) |
Various types, advanced stages |
42m |
Complete response (3 tumors)k |
Yesn |
[4] |
Case reports |
A10, AS2-1 |
Various types |
3 |
Reduction in tumor size (stage IV breast, stage IIIB NSCLC) |
Yeso |
[18] |
Case reports |
A10, AS2-1 |
Advanced hepatocellular carcinoma |
2 |
Slight shrinkage of tumor thrombus in the portal vein p |
Yesq |
[10] |
Phase II clinical trial |
A10, AS2-1 |
Recurrent brain tumor (anaplastic astrocytoma or glioblastoma multiforme) |
9 (6 pts were assessable for efficacy) |
Noner |
No |
[13] |
Phase II study |
A10, AS2-1 |
Recurrent and progressive multicentric glioma in children |
12 |
Complete response 2 |
No |
Nonevaluable 1 |
[12] |
Phase II study |
A10, AS2-1 |
Recurrent diffuse intrinsic brain stem glioma |
12 |
Complete response 2 |
No |
[4] |
Case reports |
A10, AS2-1 |
Various types |
3 |
Reduction in tumor size (stage IV breast, stage IIIB NSCLC) |
Yess |
[18] |
Case reports |
A10, AS2-1 |
Advanced hepatocellular carcinoma |
2 |
Slight shrinkage of tumor thrombus in the portal veint |
Yesu |
[10] |
Phase II clinical trial |
A10, AS2-1 |
Recurrent brain tumor (anaplastic astrocytoma or glioblastoma multiforme) |
9 (6 assessable for efficacy) |
Nonev |
No |
[13] |
Phase II study |
A10, AS2-1 |
Recurrent and progressive multicentric glioma in children |
12 |
Complete response 2 |
No |
Nonevaluable 1 |
[12] |
Phase II study |
A10, AS2-1 |
Recurrent diffuse intrinsic brain stem glioma |
12 |
Complete response 2 |
No |
[14] |
Phase II study |
A10, AS2-1 |
Primitive neuroectodermal tumor |
13 |
Complete response 3 |
No |
[16] |
Summary of data, phase II trials |
A10, AS2-1 |
Recurrent diffuse intrinsic brainstem glioma |
18 (2 previously reported in [13]) |
Complete response 1 (1 previously reported) |
No |
No. = number; pt/pts = patient/patients.
|
aReported at 9 months of follow-up; patient with breast cancer had undergone radical mastectomy, radiation therapy, and chemotherapy and had subsequent metastases to ribs surgically resected prior to treatment with antineoplastons.
|
bOne patient with bladder cancer had surgery for removal of necrotic tumor.
|
cReported at 5 years of follow-up; patient with stage IA cervical cancer received prior radiation therapy; patient with breast cancer received prior radical mastectomy and had no measurable disease at the initiation of antineoplaston treatment.
|
dOne patient received 5-fluorouracil.
|
eReported at 5 years of follow-up; patient with stage II laryngeal cancer was 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 developed cervicallymph node recurrence 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.
|
fReported at 4 years of follow-up; 10 patients had died at the time of study publication.
|
gPatients reported to be in complete remission more than 5 years after beginning treatment; the patient with colon cancer had 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.
|
hLength of follow-up not specified.
|
iReported 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.
|
jDiethylstilbestrol (DES)
|
kLength of follow-up not specified.
|
lSurgery, chemotherapy, radiation, and biological response modifiers (beta-interferon).
|
mAuthors reported on the outcome of 46 tumors for complete or partial response and provided survival information for patients.
|
nChemotherapy and radiation.
|
oSurgery, chemotherapy, radiation, and interferon.
|
pBoth patients had died by the time of study publication.
|
qChemotherapy.
|
rAt the time of study publication, all patients had died.
|
sSurgery, chemotherapy, radiation, and interferon.
|
tBoth patients had died by the time of study publication.
|
uChemotherapy.
|
vAt the time of study publication, all patients had died.
|
References
-
Burzynski SR, Stolzmann Z, Szopa B, et al.: Antineoplaston A in cancer therapy. (I). Physiol Chem Phys 9 (6): 485-500, 1977.
[PUBMED Abstract]
-
Burzynski SR, Kubove E: Toxicology studies on antineoplaston A10 injections in cancer patients. Drugs Exp Clin Res 12 (Suppl 1): 47-55, 1986.
[PUBMED Abstract]
-
Burzynski SR, Burzynski B, Mohabbat MO: Toxicology studies on antineoplaston AS2-1 injections in cancer patients. Drugs Exp Clin Res 12 (Suppl 1): 25-35, 1986.
[PUBMED Abstract]
-
Tsuda H, Sata M, Kumabe T, et al.: Quick response of advanced cancer to chemoradiation therapy with antineoplastons. Oncol Rep 5 (3): 597-600, 1998 May-Jun.
[PUBMED Abstract]
-
Burzynski SR: Toxicology studies on antineoplaston AS2-5 injections in cancer patients. Drugs Exp Clin Res 12 (Suppl 1): 17-24, 1986.
[PUBMED Abstract]
-
Burzynski SR, Kubove E: Initial clinical study with antineoplaston A2 injections in cancer patients with five years' follow-up. Drugs Exp Clin Res 13 (Suppl 1): 1-11, 1987.
[PUBMED Abstract]
-
Burzynski SR, Kubove E: Phase I clinical studies of antineoplaston A3 injections. Drugs Exp Clin Res 13 (Suppl 1): 17-29, 1987.
[PUBMED Abstract]
-
Burzynski SR, Kubove E, Burzynski B: Phase I clinical studies of antineoplaston A5 injections. Drugs Exp Clin Res 13 (Suppl 1): 37-43, 1987.
[PUBMED Abstract]
-
Sugita Y, Tsuda H, Maruiwa H, et al.: The effect of Antineoplaston, a new antitumor agent on malignant brain tumors. Kurume Med J 42 (3): 133-40, 1995.
[PUBMED Abstract]
-
Buckner JC, Malkin MG, Reed E, et al.: Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma. Mayo Clin Proc 74 (2): 137-45, 1999.
[PUBMED Abstract]
-
Burzynski SR: Efficacy of antineoplastons A10 and AS2-1. Mayo Clin Proc 74 (6): 641-2, 1999.
[PUBMED Abstract]
-
Burzynski SR, Lewy RI, Weaver RA, et al.: Phase II study of antineoplaston A10 and AS2-1 in patients with recurrent diffuse intrinsic brain stem glioma: a preliminary report. Drugs R D 4 (2): 91-101, 2003.
[PUBMED Abstract]
-
Burzynski SR, Weaver RA, Lewy RI, et al.: Phase II study of antineoplaston A10 and AS2-1 in children with recurrent and progressive multicentric glioma : a preliminary report. Drugs R D 5 (6): 315-26, 2004.
[PUBMED Abstract]
-
Burzynski SR, Weaver RA, Janicki T, et al.: Long-term survival of high-risk pediatric patients with primitive neuroectodermal tumors treated with antineoplastons A10 and AS2-1. Integr Cancer Ther 4 (2): 168-77, 2005.
[PUBMED Abstract]
-
Burzynski SR, Conde AB, Peters A, et al.: A retrospective study of antineoplastons A10 and AS2-1 in primary brain tumors. Clin Drug Investig 18 (1): 1-10, 1999.
-
Burzynski SR, Janicki TJ, Weaver RA, et al.: Targeted therapy with antineoplastons A10 and AS2-1 of high-grade, recurrent, and progressive brainstem glioma. Integr Cancer Ther 5 (1): 40-7, 2006.
[PUBMED Abstract]
-
Burzynski SR, Kubove E, Burzynski B: Treatment of hormonally refractory cancer of the prostate with antineoplaston AS2-1. Drugs Exp Clin Res 16 (7): 361-9, 1990.
[PUBMED Abstract]
-
Kumabe T, Tsuda H, Uchida M, et al.: Antineoplaston treatment for advanced hepatocellular carcinoma. Oncol Rep 5 (6): 1363-7, 1998 Nov-Dec.
[PUBMED Abstract]
-
Tsuda H, Hara H, Eriguchi N, et al.: Toxicological study on antineoplastons A-10 and AS2-1 in cancer patients. Kurume Med J 42 (4): 241-9, 1995.
[PUBMED Abstract]
Adverse Effects
Adverse effects of antineoplaston therapy have ranged from mild and short-lasting symptoms to severe neurologic toxicity necessitating discontinuation of therapy in some patients.[1]
Table 3 summarizes the adverse effects in the referenced studies.
Table 3. Adverse Effects
Adverse Effect
|
Reference
|
*The most severe adverse effects occurred in this study, which reported neurologic toxic effects such as excessive somnolence, somnolence plus confusion, and increased frequency of underlying focalmotorseizures; increased cerebral edema; and persistent confusion. In addition, the study reported myalgia, severe cutaneouserythema, pruritus, and anasarca of the extremities and face.
|
Anemia
|
[2,3] |
Blood pressure elevation |
[4,5] |
Dizziness or vertigo |
[6,7] |
Excess abdominal gas |
[4,8] |
Fever and chills |
[2,5-7,9-11]
|
General malaise with and without anorexia |
[2,4] |
Headaches |
[1,4,6,7] |
Hypocalcemia and hypercalcemia |
[2,5] |
Increased thickness of epidermis associated with skin peeling and faster-than-usual growth of nails |
[11] |
Maculopapular or itchy skin rash |
[2,4,5,8] |
Mild myelosuppression |
[5,8,12] |
Nausea and vomiting |
[1,2,5-7] |
Neurocortical toxicity, severe |
[1]* |
Numbness |
[2] |
Palpitations, tachycardia, or pressure in the chest with irregular heartbeat |
[4,11,1,7]
|
Peripheral edema, facial edema, cerebral edema |
[1,4] |
Swelling, pain, or stiffness of small joints |
[4,8,10,11] |
References
-
Buckner JC, Malkin MG, Reed E, et al.: Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma. Mayo Clin Proc 74 (2): 137-45, 1999.
[PUBMED Abstract]
-
Burzynski SR, Lewy RI, Weaver RA, et al.: Phase II study of antineoplaston A10 and AS2-1 in patients with recurrent diffuse intrinsic brain stem glioma: a preliminary report. Drugs R D 4 (2): 91-101, 2003.
[PUBMED Abstract]
-
Burzynski SR, Janicki TJ, Weaver RA, et al.: Targeted therapy with antineoplastons A10 and AS2-1 of high-grade, recurrent, and progressive brainstem glioma. Integr Cancer Ther 5 (1): 40-7, 2006.
[PUBMED Abstract]
-
Tsuda H, Hara H, Eriguchi N, et al.: Toxicological study on antineoplastons A-10 and AS2-1 in cancer patients. Kurume Med J 42 (4): 241-9, 1995.
[PUBMED Abstract]
-
Burzynski SR, Burzynski B, Mohabbat MO: Toxicology studies on antineoplaston AS2-1 injections in cancer patients. Drugs Exp Clin Res 12 (Suppl 1): 25-35, 1986.
[PUBMED Abstract]
-
Burzynski SR, Kubove E: Toxicology studies on antineoplaston A10 injections in cancer patients. Drugs Exp Clin Res 12 (Suppl 1): 47-55, 1986.
[PUBMED Abstract]
-
Burzynski SR, Kubove E: Phase I clinical studies of antineoplaston A3 injections. Drugs Exp Clin Res 13 (Suppl 1): 17-29, 1987.
[PUBMED Abstract]
-
Sugita Y, Tsuda H, Maruiwa H, et al.: The effect of Antineoplaston, a new antitumor agent on malignant brain tumors. Kurume Med J 42 (3): 133-40, 1995.
[PUBMED Abstract]
-
Burzynski SR, Stolzmann Z, Szopa B, et al.: Antineoplaston A in cancer therapy. (I). Physiol Chem Phys 9 (6): 485-500, 1977.
[PUBMED Abstract]
-
Burzynski SR: Toxicology studies on antineoplaston AS2-5 injections in cancer patients. Drugs Exp Clin Res 12 (Suppl 1): 17-24, 1986.
[PUBMED Abstract]
-
Burzynski SR, Kubove E, Burzynski B: Phase I clinical studies of antineoplaston A5 injections. Drugs Exp Clin Res 13 (Suppl 1): 37-43, 1987.
[PUBMED Abstract]
-
Burzynski SR, Weaver RA, Janicki T, et al.: Long-term survival of high-risk pediatric patients with primitive neuroectodermal tumors treated with antineoplastons A10 and AS2-1. Integr Cancer Ther 4 (2): 168-77, 2005.
[PUBMED Abstract]
Overall Level of Evidence for Antineoplastons
To assist readers in evaluating the results of human studies of complementary and alternative medicine (CAM) treatments 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. 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 13 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 CAM treatments for cancer, refer to Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine 2. Changes to This Summary (04/24/2008)
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. More Information
Additional Information about CAM Therapies
About PDQ
Other PDQ Summaries
Important:
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). |
Glossary Terms
abdominal
Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs.
abnormal
Not normal. An abnormal lesion or growth may be cancerous, premalignant (likely to become cancer), or benign.
acute lymphocytic leukemia (uh-KYOOT LIM-foh-SIH-tik loo-KEE-mee-uh)
An aggressive (fast-growing) type of leukemia (blood cancer) in which too many lymphoblasts (immature white blood cells) are found in the bone marrow and blood. Also called ALL and acute lymphoblastic leukemia.
adenocarcinoma (A-den-oh-KAR-sih-NOH-muh)
Cancer that begins in cells that line certain internal organs and that have gland-like (secretory) properties.
administration (ad-MIH-nih-STRAY-shun)
In medicine, the act of giving a treatment, such as a drug, to a patient. It can also refer to the way it is given, the dose, or how often it is given.
advanced cancer (ad-VANST KAN-ser)
Cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment.
adverse effect
An unwanted side effect of treatment.
alternative medicine (all-TER-nuh-tiv MEH-dih-sin)
Practices used instead of standard treatments. They generally are not recognized by the medical community as standard or conventional medical approaches. Examples of alternative medicine include dietary supplements, megadose vitamins, herbal preparations, special teas, acupuncture, massage therapy, magnet therapy, spiritual healing, and meditation.
amino acid (uh-MEE-noh A-sid)
One of several molecules that join together to form proteins. There are 20 common amino acids found in proteins.
aminoglutethimide (a-MEE-no-gloo-TETH-ih-mide)
An anticancer drug that belongs to the family of drugs called nonsteroidal aromatase inhibitors. Aminoglutethimide is used to decrease the production of sex hormones (estrogen in women or testosterone in men) and suppress the growth of tumors that need sex hormones to grow.
analgesic
A drug that reduces pain. Analgesics include aspirin, acetaminophen, and ibuprofen.
analog
In chemistry, a substance that is similar, but not identical, to another.
analysis
A process in which anything complex is separated into simple or less complex parts.
anaplastic (an-ah-PLAS-tik)
A term used to describe cancer cells that divide rapidly and have little or no resemblance to normal cells.
anemia (a-NEE-mee-a)
A condition in which the number of red blood cells is below normal.
animal model
An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models.
animal study (AN-ih-mul STUH-dee)
A laboratory experiment using animals to study the development and progression of diseases. Animal studies also test how safe and effective new treatments are before they are tested in people.
anorexia
An abnormal loss of the appetite for food. Anorexia can be caused by cancer, AIDS, a mental disorder (i.e., anorexia nervosa), or other diseases.
anti-inflammatory
Having to do with reducing inflammation.
antibiotic (an-tih-by-AH-tik)
A drug used to treat infections caused by bacteria and other microorganisms.
anticarcinogenic (AN-tee-KAR-sin-o-JEN-ik)
Having to do with preventing or delaying the development of cancer.
anticonvulsant (AN-tee-kon-VUL-sant)
A drug or other substance used to prevent or stop seizures or convulsions. Also called an antiepileptic.
antineoplastic
A substance that blocks the formation of neoplasms (growths that may become cancerous).
antineoplaston
A substance isolated from normal human blood and urine that is being tested as a type of treatment for some tumors and AIDS.
antitumor (AN-tee-TOO-mer)
Having to do with stopping abnormal cell growth.
apoptosis (A-pop-TOH-sis)
A type of cell death in which a series of molecular steps in a cell leads to its death. This is the body’s normal way of getting rid of unneeded or abnormal cells. The process of apoptosis may be blocked in cancer cells. Also called programmed cell death.
aqueous
Having to do with water.
aromatic (A-ruh-MA-tik)
Having an odor, which often is pleasant or spicy.
arthralgia (ar-THRAL-juh)
Joint pain.
assay (AS-say)
A laboratory test to find and measure the amount of a specific substance.
assessment (uh-SESS-ment)
In healthcare, a process used to learn about a patient’s condition. This may include a complete medical history, medical tests, a physical exam, a test of learning skills, tests to find out if the patient is able to carry out the tasks of daily living, a mental health evaluation, and a review of social support and community resources available to the patient.
astrocytoma (AS-troh-sy-TOH-muh)
A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes.
basal cell (BAY-sul SEL)
A small, round cell found in the lower part (or base) of the epidermis, the outer layer of the skin.
biological response modifier therapy (BY-oh-LAH-jih-kul reh-SPONTS MAH-dih-FY-er THAYR-uh-pee)
BRM therapy. Treatment to boost or restore the ability of the immune system to fight cancer, infections, and other diseases. Also used to lessen certain side effects that may be caused by some cancer treatments. Agents used in biological response modifier therapy include monoclonal antibodies, growth factors, and vaccines. These agents may also have a direct antitumor effect. Also called immunotherapy, biological therapy, biotherapy, and BRM therapy.
bladder (BLA-der)
The organ that stores urine.
bladder cancer (BLA-der KAN-ser)
Cancer that forms in tissues of the bladder (the organ that stores urine). Most bladder cancers are transitional cell carcinomas (cancer that begins in cells that normally make up the inner lining of the bladder). Other types include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). The cells that form squamous cell carcinoma and adenocarcinoma develop in the inner lining of the bladder as a result of chronic irritation and inflammation.
blastic phase chronic myelogenous leukemia (BLAS-tik FAYZ KRAH-nik MY-eh-LAH-jeh-nus loo-KEE-mee-uh)
A phase of chronic myelogenous leukemia in which 20% or more of the cells in the blood or bone marrow are blast cells (immature blood cells). When tiredness, fever, and an enlarged spleen occur during the blastic phase, it is called blast crisis.
blood
A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.
blood cell count
A test to check the number of red blood cells, white blood cells, and platelets in a sample of blood. Also called complete blood count and CBC.
blood pressure (blud PREH-sher)
The force of circulating blood on the walls of the arteries. Blood pressure is taken using two measurements: systolic (measured when the heart beats, when blood pressure is at its highest) and diastolic (measured between heart beats, when blood pressure is at its lowest). Blood pressure is written with the systolic blood pressure first, followed by the diastolic blood pressure (for example 120/80).
bolus
A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion.
brain metastasis (...meh-TAS-tuh-sis)
Cancer that has spread from the original (primary) tumor to the brain.
brain stem glioma (...glee-OH-muh)
A tumor located in the part of the brain that connects to the spinal cord (the brain stem). It may grow rapidly or slowly, depending on the grade of the tumor.
brain tumor
The growth of abnormal cells in the tissues of the brain. Brain tumors can be benign (non-cancerous) or malignant (cancerous).
breast (brest)
Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.
breast cancer (brest KAN-ser)
Cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare.
bronchial (BRON-kee-ul)
Having to do with the bronchi, which are the larger air passages of the lungs, including those that lead from the trachea (windpipe) to the lungs and those within the lungs.
CAM
Complementary and alternative medicine. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices generally are not considered standard medical approaches. Standard treatments go through a long and careful research process to prove they are safe and effective, but less is known about most types of CAM. CAM may include dietary supplements, megadose vitamins, herbal preparations, special teas, acupuncture, massage therapy, magnet therapy, spiritual healing, and meditation. Also called complementary and alternative medicine.
cancer (KAN-ser)
A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.
capsule (KAP-sool)
In medicine, a sac of tissue and blood vessels that surrounds an organ, joint, or tumor. A capsule is also a form for medicine that is taken by mouth. It usually has a shell made of gelatin with the medicine inside.
carcinogen (kar-SIN-o-jin)
Any substance that causes cancer.
carcinoma (KAR-sih-NOH-muh)
Cancer that begins in the skin or in tissues that line or cover internal organs.
carmustine
An anticancer drug that belongs to the family of drugs called alkylating agents.
case report
A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin).
case series
A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment.
catheter (KA-theh-ter)
A flexible tube used to deliver fluids into or withdraw fluids from the body.
cell (sel)
The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
cell differentiation
The process during which young, immature (unspecialized) cells take on individual characteristics and reach their mature (specialized) form and function.
central nervous system (SEN-trul NER-vus SIS-tem)
CNS. The brain and spinal cord. Also called CNS.
cerebral hemisphere (seh-REE-bral HEM-is-feer)
One half of the cerebrum, the part of the brain that controls muscle functions and also controls speech, thought, emotions, reading, writing, and learning. The right hemisphere controls the muscles on the left side of the body, and the left hemisphere controls the muscles on the right side of the body.
cervical (SER-vih-kul)
Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck. Cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the “neck”) of the uterus.
cervical cancer (SER-vih-kul KAN-ser)
Cancer that forms in tissues of the cervix (the organ connecting the uterus and vagina). It is usually a slow-growing cancer that may not have symptoms but can be found with regular Pap tests (a procedure in which cells are scraped from the cervix and looked at under a microscope).
cervix (SER-viks)
The lower, narrow end of the uterus that forms a canal between the uterus and vagina.
chemotherapy (KEE-moh-THAYR-uh-pee)
Treatment with drugs that kill cancer cells.
chest x-ray
An x-ray of the structures inside the chest. An x-ray is a type of high-energy radiation that can go through the body and onto film, making pictures of areas inside the chest, which can be used to diagnose disease.
chondrosarcoma (KON-droh-sar-KOH-muh)
A type of cancer that forms in bone cartilage. It usually starts in the pelvis (between the hip bones), the shoulder, the ribs, or at the ends of the long bones of the arms and legs. A rare type of chondrosarcoma called extraskeletal chondrosarcoma does not form in bone cartilage. Instead, it forms in the soft tissues of the upper part of the arms and legs. Chondrosarcoma can occur at any age but is more common in people older than 40 years. It is a type of bone cancer.
chronic lymphocytic leukemia (KRAH-nik LIM-foh-SIH-tik loo-KEE-mee-uh)
CLL. A slow-growing type of leukemia (blood cancer) in which too many lymphoblasts (immature white blood cells) are found in the blood and bone marrow. Also called chronic lymphoblastic leukemia and CLL.
chronic myelogenous leukemia (KRAH-nik MY-eh-LAH-jeh-nus loo-KEE-mee-uh)
CML. A slowly progressing disease in which too many white blood cells (not lymphocytes) are made in the bone marrow. Also called CML, chronic granulocytic leukemia, and chronic myeloid leukemia.
cisplatin (sis-PLA-tin)
A drug used to treat many types of cancer. Cisplatin contains the metal platinum. It kills cancer cells by damaging their DNA and stopping them from dividing. Cisplatin is a type of alkylating agent.
clinical
Having to do with the examination and treatment of patients.
clinical study
A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical trial.
clinical trial
A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical study.
colon (KOH-lun)
The longest part of the large intestine, which is a tube-like organ
connected to the small intestine at one end and the anus at the other. The
colon removes water and some nutrients and electrolytes from partially
digested food. The remaining material, solid waste called stool, moves
through the colon to the rectum and leaves the body through the anus.
colon cancer (KOH-lun KAN-ser)
Cancer that forms in the tissues of the colon (the longest part of the large intestine). Most colon cancers are adenocarcinomas (cancers that begin in cells that make and release mucus and other fluids).
complementary and alternative medicine (KOM-pleh-MEN- tuh-ree... all-TER-nuh-tiv MEH-dih-sin)
CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices generally are not considered standard medical approaches. Standard treatments go through a long and careful research process to prove they are safe and effective, but less is known about most types of CAM. CAM may include dietary supplements, megadose vitamins, herbal preparations, special teas, acupuncture, massage therapy, magnet therapy, spiritual healing, and meditation. Also called CAM.
complete remission
The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete response.
complete response (kum-PLEET reh-SPONTS)
The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission.
complication (kom-plih-KAY-shun)
In medicine, a medical problem that occurs during a disease, or after a procedure or treatment. The complication may be caused by the disease, procedure, or treatment or may be unrelated to them.
compound (KOM-pownd)
In science, a substance that is made up of more than one ingredient.
computed tomography scan (kum-PYOO-ted toh-MAH-gruh-fee skan)
CT scan. A series of detailed pictures of areas inside the body taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CT scan, computerized tomography, computerized axial tomography scan, and CAT scan.
confusion (kun-FYOO-zhun)
A mental state in which one is not thinking clearly.
consecutive case series
A clinical study that includes all eligible patients identified by the researchers during the study registration period. The patients are treated in the order in which they are identified. This type of study usually does not have a control group.
continuous infusion (kon-TIN-yoo-us in-FYOO-zhun)
The administration of a fluid into a blood vessel, usually over a prolonged period of time.
controlled clinical trial
A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all.
corticosteroid (KOR-tih-koh-STAYR-oyd)
Any steroid hormone made in the adrenal cortex (the outer part of the adrenal gland). They are also made in the laboratory. Corticosteroids have many different effects in the body, and are used to treat many different conditions. They may be used as hormone replacement, to suppress the immune system, and to treat some side effects of cancer and its treatment. Corticosteroids are also used to treat certain lymphomas and lymphoid leukemias.
CT scan
Computed tomography scan. A series of detailed pictures of areas inside the body taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computed tomography scan, computerized tomography, computerized axial tomography scan, and CAT scan.
culture (KUL-chur)
The beliefs, values, and behaviors that are shared within a group, such as a religious group or a nation. Culture includes language, customs, and beliefs about roles and relationships.
cultured cell line
Cells of a single type (human, animal, or plant) that have been adapted to grow continuously in the laboratory and are used in research.
cutaneous (kyoo-TAY-nee-us)
Having to do with the skin.
cytotoxic (SY-toh-TOK-sik)
Cell-killing.
derivative
In chemistry, a compound produced from or related to another.
dexamethasone
A synthetic steroid (similar to steroid hormones produced naturally in the adrenal gland). Dexamethasone is used to treat leukemia and lymphoma and may be used to treat some of the problems caused by other cancers and their treatment.
diagnosis (DY-ug-NOH-sis)
The process of identifying a disease, such as cancer, from its signs and symptoms.
diethylstilbestrol (dye-EH-thul-stil-BES-trol)
DES. A synthetic form of the hormone estrogen that was prescribed to pregnant women between about 1940 and 1971 because it was thought to prevent miscarriages. DES may increase the risk of uterine, ovarian, or breast cancer in women who took it. DES also has been linked to an increased risk of clear cell carcinoma of the vagina or cervix in daughters exposed to DES before birth. Also called DES.
differentiation
In cancer, refers to how mature (developed) the cancer cells are in a tumor. Differentiated tumor cells resemble normal cells and tend to grow and spread at a slower rate than undifferentiated or poorly differentiated tumor cells, which lack the structure and function of normal cells and grow uncontrollably.
diffuse
Widely spread; not localized or confined.
disease progression
Cancer that continues to grow or spread.
diuretic
A drug that increases the production of urine.
DNA
Deoxyribonucleic acid. The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.
dose
The amount of medicine taken, or radiation given, at one time.
dose-dependent
Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose-dependent.
doxorubicin (DOK-soh-ROO-bih-sin)
A drug that is used to treat many types of cancer and is being studied in the treatment of other types of cancer. Doxorubicin comes from the bacterium Streptomyces peucetius. It damages DNA (the molecules inside cells that carry genetic information) and stops cells from growing. Rapidly growing tumor cells that take up doxorubicin may die. It is a type of anthracycline antitumor antibiotic. Also called doxorubicin hydrochloride, Adriamycin PFS, Adriamycin RDF, and Rubex.
drug
Any substance, other than food, that is used to prevent, diagnose,
treat or relieve symptoms of a disease or abnormal condition. Also refers
to a substance that alters mood or body function, or that can be
habit-forming or addictive, especially a narcotic.
edema (eh-DEE-ma)
Swelling caused by excess fluid in body tissues.
efficacy
Effectiveness. In medicine, the ability of an intervention (for example, a drug or surgery) to produce the desired beneficial effect.
electrolyte (ee-LEK-troh-lite)
A substance that breaks up into ions (electrically charged particles) when it is dissolved in body fluids or water. Some examples of electrolytes are sodium, potassium, chloride, and calcium. Electrolytes are primarily responsible for the movement of nutrients into cells and the movement of wastes out of cells.
endpoint
In clinical trials, an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial. The endpoints of a clinical trial are usually included in the study objectives. Some examples of endpoints are survival, improvements in quality of life, relief of symptoms, and disappearance of the tumor.
epidermis (ep-i-DER-mis)
The upper or outer layer of the two main layers of tissue that make up the skin.
erythema (ER-ih-THEE-muh)
Redness of the skin.
esophageal (ee-SAH-fuh-JEE-ul)
Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach.
experimental (ek-SPER-ih-men-tul)
In clinical trials, refers to a drug (including a new drug,
dose, combination, or route of administration) or procedure that has
undergone basic laboratory testing and received approval from the U.S. Food
and Drug Administration (FDA) to be tested in human subjects. A drug or
procedure may be approved by the FDA for use in one disease or condition,
but be considered experimental in other diseases or conditions. Also called
investigational.
fatty acid
A major component of fats that is used by the body for energy and tissue development.
fever (FEE-ver)
An increase in body temperature above normal (98.6 degrees F), usually caused by disease.
fluid
Liquid.
flutamide (FLOO-ta-mide)
An anticancer drug that is a type of antiandrogen.
focal
In terms of cancer, limited to a specific area.
follow-up
Monitoring a person's health over time after treatment. This includes keeping track of the health of people who participate in a clinical study or clinical trial for a period of time, both during the study and after the study ends.
Food and Drug Administration
FDA. An agency in the U.S. federal government whose mission is to protect public health by making sure that food, cosmetics, and nutritional supplements are safe to use and truthfully labeled. The Food and Drug Administration also makes sure that drugs, medical devices, and equipment are safe and effective, and that blood for transfusions and transplant tissue are safe. Also called FDA.
glioblastoma (GLEE-oh-blas-TOH-muh)
A fast-growing type of central nervous system tumor that forms from glial (supportive) tissue of the brain and spinal cord and has cells that look very different from normal cells. Glioblastoma usually occurs in adults and affects the brain more often than the spinal cord. Also called grade IV astrocytoma, glioblastoma multiforme, and GBM.
glioblastoma multiforme (GLEE-oh-blas-TOH-muh MUL-tih-form)
GBM. A fast-growing type of central nervous system tumor that forms from glial (supportive) tissue of the brain and spinal cord and has cells that look very different from normal cells. Glioblastoma multiforme usually occurs in adults and affects the brain more often than the spinal cord. Also called grade IV astrocytoma, glioblastoma, and GBM.
glioma (glee-OH-muh)
A cancer of the brain that begins in glial cells (cells that surround and support nerve cells).
glutamine
An amino acid used in nutrition therapy. It is also being studied for the treatment of diarrhea caused by radiation therapy to the pelvis.
grade
The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer.
granulocytopenia (GRAN-yoo-loh-SY-toh-PEE-nee-uh)
A deficiency in the number of granulocytes, a type of white blood cell.
hepatic (hih-PA-tik)
Refers to the liver.
hepatocellular carcinoma (HEP-a-toe-SEL-yoo-ler KAR-sih-NOH-muh)
A type of adenocarcinoma, the most common type of liver tumor.
high grade
When referring to cancerous and precancerous growths, a term used to describe cells that look abnormal under a microscope. These cells are more likely to grow and spread quickly than cells in low-grade cancerous and precancerous growths.
hormone (HOR-mone)
One of many chemicals made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs. Some hormones can also be made in the laboratory.
hypercalcemia (HY-per-kal-SEE-mee-uh)
Higher than normal levels of calcium in the blood. Some types of cancer increase the risk of hypercalcemia.
hypoglycemia
Abnormally low blood sugar.
hypothesis
A tentative proposal made to explain certain observations or facts that requires further investigation to be verified.
imaging (IH-muh-jing)
In medicine, a process that makes pictures of areas inside the body. Imaging uses methods such as x-rays (high-energy radiation), ultrasound (high-energy sound waves), and radio waves.
immunotherapy (IH-myoo-noh-THAYR-uh-pee)
Treatment to boost or restore the ability of the immune system to fight cancer, infections, and other diseases. Also used to lessen certain side effects that may be caused by some cancer treatments. Agents used in immunotherapy include monoclonal antibodies, growth factors, and vaccines. These agents may also have a direct antitumor effect. Also called biological therapy, biotherapy, biological response modifier therapy, and BRM therapy.
in vitro (in VEE-troh)
In the laboratory (outside the body). The opposite of in vivo (in the body).
in vivo
In the body. The opposite of in vitro (outside the body or in the laboratory).
infusion (in-FYOO-zhun)
A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion.
injection
Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."
inoperable
Describes a condition that cannot be treated by surgery.
instillation
In medicine, a method used to put a liquid into the body slowly or drop by drop.
interferon (in-ter-FEER-on)
A biological response modifier (a substance that can improve the body's natural response to infections and other diseases). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and -gamma. The body normally produces these substances. They are also made in the laboratory to treat cancer and other diseases.
interleukin-2 (in-ter-LOO-kin)
IL-2. A type of biological response modifier (a substance that can improve the body's natural response to infection and disease) that stimulates the growth of certain disease-fighting blood cells in the immune system. These substances are normally produced by the body. Aldesleukin is IL-2 that is made in the laboratory for use in treating cancer and other diseases.
intervention (IN-ter-VEN-shun)
In medicine, a treatment or action taken to prevent or treat disease, or improve health in other ways.
intraductal carcinoma (IN-truh-DUK-tul KAR-sih-NOH-muh)
A noninvasive condition in
which abnormal cells are found in the lining of a breast duct. The abnormal
cells have not spread outside the duct to other tissues in the breast. In
some cases, intraductal carcinoma may become invasive cancer and spread to other tissues,
although it is not known at this time how to predict which lesions will
become invasive. Also called ductal carcinoma in situ and DCIS.
intramuscular (IN-truh-MUS-kyoo-ler)
IM. Within or into muscle. Also called IM.
intrapleural
Within the pleural cavity.
intravenous (IN-truh-VEE-nus)
Into or within a vein. Intravenous usually refers to a way of giving a drug or other substance through a needle or tube inserted into a vein. Also called I.V.
investigational drug (in-VES-tih-GAY-shuh-nul drug)
A substance that has been tested in a laboratory and has gotten approval from the U.S. Food and Drug Administration (FDA) to be tested in people. A drug may be approved by the FDA for use in one disease or condition but be considered investigational in other diseases or conditions. Also called experimental drug.
joint (joynt)
In medicine, the place where two or more bones are connected. Examples include the shoulder, elbow, knee, and jaw.
laboratory study
Research done in a laboratory. These studies may use test tubes or animals to find out if a drug, procedure, or treatment is likely to be useful. Laboratory studies take place before any testing is done in humans.
large cell carcinoma (...KAR-sih-NOH-muh)
Lung cancer in which the cells are large and look abnormal when viewed under a microscope.
laryngeal (luh-RIN-jee-ul)
Having to do with the larynx.
leukemia (loo-KEE-mee-uh)
Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.
levels of evidence (LEH-vulz uv EH-vih-dents)
A ranking system used to describe the strength of the results measured in a clinical trial or research study. The design of the study (such as a case report for an individual patient or a randomized double-blinded controlled clinical trial) and the endpoints measured (such as survival or quality of life) affect the strength of the evidence.
LH-RH
Luteinizing hormone-releasing hormone. A hormone that stimulates the production of sex hormones in men and women. Also called luteinizing hormone-releasing hormone.
lobectomy (loh-BEK-toh-mee)
Surgery to remove a whole lobe (section) of an organ (such as the lungs, liver, brain, or thyroid gland).
low grade
When referring to cancerous and precancerous growths, a term used to describe cells that look nearly normal under a microscope. These cells are less likely to grow and spread quickly than cells in high-grade cancerous or precancerous growths.
lung
One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.
lung cancer (lung KAN-ser)
Cancer that forms in tissues of the lung, usually in the cells lining air passages. The two main types are small cell lung cancer and non-small cell lung cancer. These types are diagnosed based on how the cells look under a microscope.
lymph node (limf node)
A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Lymph nodes filter lymph (lymphatic fluid), and they store lymphocytes (white blood cells). They are located along lymphatic vessels. Also called lymph gland.
lymphocytic (LIM-foh-SIH-tik)
Refers to lymphocytes (a type of white blood cell).
lymphoma (lim-FOH-muh)
Cancer that begins in cells of the immune system.
There are two basic categories of lymphomas. One kind is Hodgkin
lymphoma, which is marked by the presence of a type of cell called the
Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which
includes a large, diverse group of cancers of immune system cells.
Non-Hodgkin lymphomas can be further divided into cancers that have an
indolent (slow-growing) course and those that have an aggressive
(fast-growing) course. These subtypes behave and respond to
treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur
in children and adults, and prognosis and treatment depend on the stage and
the type of cancer.
magnetic resonance imaging (mag-NEH-tik REH-zuh-nunts IH-muh-jing)
A procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue. Magnetic resonance imaging makes better images of organs and soft tissue than other scanning techniques, such as computed tomography (CT) or x-ray. Magnetic resonance imaging is especially useful for imaging the brain, the spine, the soft tissue of joints, and the inside of bones. Also called MRI, nuclear magnetic resonance imaging, and NMRI.
maintenance therapy (...THAYR-uh-pee)
Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission.
malignant (muh-LIG-nunt)
Cancerous. Malignant tumors can invade and destroy nearby tissue and spread to other parts of the body.
mastectomy (ma-STEK-toh-mee)
Surgery to remove the breast (or as much of the breast tissue as possible).
mean
A statistics term. The average value in a set of measurements. The mean is the sum of a set of numbers divided by how many numbers are in the set.
mean survival time
The average time that patients in a clinical study remained alive. The time is measured beginning either at diagnosis or the start of treatment.
measurable disease
A tumor that can be accurately measured in size. This information can be used to judge response to treatment.
median survival time
The time from either diagnosis or treatment at which half of the patients with a given disease are found to be, or expected to be, still alive. In a clinical trial, median survival time is one way to measure how effective a treatment is.
medulloblastoma (MED-yoo-loh-blas-TOH-muh)
A malignant brain tumor that begins in the lower part of the brain and that can spread to the spine or to other parts of the body. Medulloblastomas are a type of primitive neuroectodermal tumor (PNET).
membrane
A very thin layer of tissue that covers a surface.
metabolic (MEH-tuh-BAH-lik)
Having to do with metabolism (the total of all chemical changes that take place in a cell or an organism to produce energy and basic materials needed for important life processes).
metastasis (meh-TAS-tuh-sis)
The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).
metastatic (meh-tuh-STA-tik)
Having to do with metastasis, which is the spread of cancer from one part of the body to another.
methodology (MEH-thuh-DAH-loh-jee)
In medicine, the rules and procedures for doing research and evaluating results.
milliliter
A measure of volume for a liquid. A milliliter is approximately 950 times smaller than a quart and 30 times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same.
molecule
The smallest particle of a substance that has all of the physical
and chemical properties of that substance. Molecules are made up of one or
more atoms. If they contain more than one atom, the atoms can be the same
(an oxygen molecule has two oxygen atoms) or different (a water molecule has
two hydrogen atoms and one oxygen atom). Biological molecules, such as
proteins and DNA, can be made up of many thousands of atoms.
motor
In medicine, having to do with the movement of body parts.
MRI
A procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue. MRI makes better images of organs and soft tissue than other scanning techniques, such as computed tomography (CT) or x-ray. MRI is especially useful for imaging the brain, the spine, the soft tissue of joints, and the inside of bones. Also called magnetic resonance imaging, nuclear magnetic resonance imaging, and NMRI.
myalgia (my-AL-juh)
Pain in a muscle or group of muscles.
myelosuppression (MY-eh-loh-suh-PREH-shun)
A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. When myelosuppression is severe, it is called myeloablation.
National Cancer Institute
The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.
National Center for Complementary and Alternative Medicine (NA-shuh-nul SEN-ter ... KOM-pleh-MEN-tuh-ree ... all-TER-nuh-tiv MEH-dih-sin)
NCCAM. A federal agency that uses science to explore complementary and alternative medicine (CAM) practices, trains CAM researchers, and provides authoritative information about CAM to professionals and the public. NCCAM awards grants for research projects, training, and career development in CAM; sponsors conferences, educational programs, and exhibits; studies ways to use proven CAM practices along with conventional medical practice; and supports adding CAM to medical, dental, and nursing school programs. NCCAM is part of the National Institutes of Health. Also called NCCAM.
National Institutes of Health
NIH. A federal agency in the U.S. that conducts biomedical research in its own laboratories; supports the research of non-Federal scientists in universities, medical schools, hospitals, and research institutions throughout the country and abroad; helps in the training of research investigators; and fosters communication of medical information. Access the National Institutes of Health Web site at http://www.nih.gov. Also called NIH.
nausea
A feeling of sickness or discomfort in the stomach that may come with an urge to vomit. Nausea is a side effect of some types of cancer therapy.
NCI
NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. It conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://www.cancer.gov. Also called National Cancer Institute.
neoplasm (NEE-oh-PLA-zum)
An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Neoplasms may be benign (not cancerous), or malignant (cancerous). Also called tumor.
nervous system (NER-vus SIS-tem)
The organized network of nerve tissue in the body. It includes the central nervous system (the brain and spinal cord), the peripheral nervous system (nerves that extend from the spinal cord to the rest of the body), and other nerve tissue.
neurologic (NOOR-oh-LAH-jik)
Having to do with nerves or the nervous system.
neutrophil (NOO-tro-fil)
A type of white blood cell.
NIH
National Institutes of Health. A federal agency in the U.S. that conducts biomedical research in its own laboratories; supports the research of non-Federal scientists in universities, medical schools, hospitals, and research institutions throughout the country and abroad; helps in the training of research investigators; and fosters communication of medical information. Access the NIH Web site at http://www.nih.gov. Also called National Institutes of Health.
nimustine (NY-mus-tine)
A substance that is being studied in the treatment of brain cancer. It belongs to the family of drugs called nitrosoureas.
nonconsecutive case series
A clinical study that includes some, but not all, of the eligible patients identified by the researchers during the study registration period. This type of study does not usually have a control group.
nonrandomized clinical trial
A clinical trial in which the participants are not assigned by chance to different treatment groups. Participants may choose which group they want to be in, or they may be assigned to the groups by the researchers.
objective response (ub-JEK-tiv reh-SPONTS)
A measurable response.
observation (OB-ser-VAY-shun)
Closely monitoring a patient's condition but withholding treatment until symptoms appear or change. Also called watchful waiting, active surveillance, and expectant management.
oligoastrocytoma (AH-lih-goh-AS-troh-sy-TOH-muh)
A brain tumor that forms from both oligodendrocytes and astrocytes, which are types of glial cells (cells that cover and protect nerve cells in the brain and spinal cord and help them work the way they should). An oligoastrocytoma is a type of mixed glioma.
oral (OR-ul)
By or having to do with the mouth.
orchiectomy (or-kee-EK-toh-mee)
Surgery to remove one or both testicles. Also called orchidectomy.
organism
A living thing, such as an animal, a plant, a bacterium, or a fungus.
outcome
A specific result or effect that can be measured. Examples of outcomes include decreased pain, reduced tumor size, and improvement of disease.
pancreatic
Having to do with the pancreas.
partial remission
A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial response.
partial response (PAR-shul reh-SPONTS)
A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission.
PDQ
PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, complementary and alternative medicine, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information, and more specific information about PDQ, can be found on the NCI's Web site at http://www.cancer.gov/cancertopics/pdq. Also called Physician Data Query.
pediatric (pee-dee-A-trik)
Having to do with children.
peer-reviewed scientific journal
A publication that contains original articles that have been written by scientists and evaluated for technical and scientific quality and correctness by other experts in the same field.
peptide
Any compound consisting of two or more amino acids, the building blocks of proteins.
pharmacokinetics (FAR-muh-koh-kih-NEH-tix)
The activity of drugs in the body over a period of time, including the processes by which drugs are absorbed, distributed in the body, localized in the tissues, and excreted.
phase I trial
The first step in testing a new treatment in humans. These studies test the best way to give a new treatment (for example, by mouth, intravenous infusion, or injection) and the best dose. The dose is usually increased a little at a time in order to find the highest dose that does not cause harmful side effects. Because little is known about the possible risks and benefits of the treatments being tested, phase I trials usually include only a small number of patients who have not been helped by other treatments.
phase II trial
A study to test whether a new treatment has an anticancer effect (for example, whether it shrinks a tumor or improves blood test results) and whether it works against a certain type of cancer.
phase III trial
A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.
phenylacetate
A substance that is being studied in the treatment of cancer.
pilocytic (PI-lo-SIT-ik)
Made up of cells that look like fibers when viewed under a microscope.
plasma (PLAZ-muh)
The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma.
platelet (PLATE-let)
A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called a thrombocyte.
pontine
Having to do with the pons (part of the central nervous system, located at the base of the brain, between the medulla oblongata and the midbrain).
portal vein
A blood vessel that carries blood to the liver from the stomach, small and large intestines, spleen, pancreas, and gallbladder. Also called hepatic portal vein.
prevention (pree-VEN-shun)
In medicine, action taken to decrease the chance of getting a disease or condition. For example, cancer prevention includes avoiding risk factors (such as smoking, obesity, lack of exercise, and radiation exposure) and increasing protective factors (such as getting regular physical activity, staying at a healthy weight, and having a healthy diet).
primitive neuroectodermal tumor (PRI-muh-tiv NOOR-oh-EK-toh-DER-mul TOO-mer)
One of a group of cancers that
develop from the same type of early cells, and share certain biochemical and
genetic features. Some primitive neuroectodermal tumors develop in the brain and central nervous
system (CNS-PNET), and others develop in sites outside of the brain such as
the limbs, pelvis, and chest wall (peripheral PNET).
Also called PNET.
progression (proh-GREH-shun)
In medicine, the course of a disease, such as cancer, as it becomes worse or spreads in the body.
progressive disease
Cancer that is growing, spreading, or getting worse.
prolactin (proh-LAK-tin)
A hormone that is made by the pituitary gland (a pea-sized organ in the center of the brain). Prolactin causes a woman’s breasts to make milk during and after pregnancy, and has many other effects in the body.
prostate (PROS-tayt)
A gland in the male reproductive system. The prostate surrounds the part of the urethra (the tube that empties the bladder) just below the bladder, and produces a fluid that forms part of the semen.
prostate cancer (PROS-tayt KAN-ser)
Cancer that forms in tissues of the prostate (a gland in the male reproductive system found below the bladder and in front of the rectum). Prostate cancer usually occurs in older men.
prostatectomy (PROS-tuh-TEK-toh-mee)
An operation to remove part or all of the prostate. Radical (or total) prostatectomy is the removal of the entire prostate and some of the tissue around it.
protein (PRO-teen)
A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.
protocol
An action plan for a clinical trial. The plan states what the study will do, how, and why. It explains how many people will be in it, who is eligible to participate, what study agents or other interventions they will be given, what tests they will receive and how often, and what information will be gathered.
pruritus (proo-RY-tus)
Itching. Severe itching may be a side effect of some cancer treatments and a symptom of some types of cancers.
quality of life
The overall enjoyment of life. Many clinical trials assess the effects of cancer and its treatment on the quality of life. These studies measure aspects of an individual’s sense of well-being and ability to carry out various activities.
radiation therapy (RAY-dee-AY-shun THAYR-uh-pee)
The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called radiotherapy and irradiation.
radical mastectomy (RA-dih-kul ma-STEK-toh-mee)
Surgery for breast cancer in which the breast, chest muscles, and all of the lymph nodes under the arm are removed. For many years, this was the breast cancer operation used most often, but it is used rarely now. Doctors consider radical mastectomy only when the tumor has spread to the chest muscles. Also called Halsted radical mastectomy.
randomized clinical trial
A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.
rectal (REK-tul)
By or having to do with the rectum. The rectum is the last several inches of the large intestine closest to the anus.
rectum (REK-tum)
The last several inches of the large intestine closest to the anus.
recur
To come back or to return.
recurrence (ree-KER-ents)
Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrent cancer.
recurrent cancer (ree-KER-ent KAN-ser)
Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrence.
refractory
In medicine, describes a disease or condition that does not respond to treatment.
regimen
A treatment plan that specifies the dosage, the schedule, and the duration of treatment.
regression
A decrease in the size of a tumor or in the extent of cancer in the body.
resected
Removed by surgery.
resection (ree-SEK-shun)
A procedure that uses surgery to remove tissue or part or all of an organ.
response (reh-SPONTS)
In medicine, an improvement related to treatment.
response rate (reh-SPONTS...)
The percentage of patients whose cancer shrinks or disappears after treatment.
retrospective
Looking back at events that have already taken place.
sarcoma
A cancer of the bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.
scan
A picture of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body.
scientist
A person who has studied science, especially one who is active in a particular field of investigation.
screening (SKREEN-ing)
Checking for disease when there are no symptoms. Since screening may find diseases at an early stage, there may be a better chance of curing the disease. Examples of cancer screening tests are the mammogram (breast), colonoscopy (colon), Pap smear (cervix), and PSA blood level and digital rectal exam (prostate). Screening can also include checking for a person’s risk of developing an inherited disease by doing a genetic test.
seizure (SEE-zhur)
Convulsion; a sudden, involuntary movement of the muscles.
sepsis (SEP-sis)
The presence of bacteria or their toxins in the blood or tissues.
serum
The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed.
sickle cell anemia (SIH-kul sel uh-NEE-mee-uh)
An inherited disease in which the red blood cells have an abnormal crescent shape, block small blood vessels, and do not last as long as normal red blood cells. Sickle cell anemia is caused by a mutation (change) in one of the genes for hemoglobin (the substance inside red blood cells that binds to oxygen and carries it from the lungs to the tissues). It is most common in people of West and Central African descent. Also called sickle cell disease.
side effect
A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.
squamous cell carcinoma (SKWAY-mus sel KAR-sih-NOH-muh)
Cancer that begins in squamous cells, which are thin, flat cells that look like fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma.
stable disease
Cancer that is neither decreasing nor increasing in extent or severity.
stage
The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.
stage I cervical cancer (... SER-vih-kul KAN-ser)
Cancer is found in the cervix only. Stage I is divided into stages IA and IB, based on the amount of cancer that is found. In stage IA, a very small amount of cancer that can only be seen with a microscope is found in the tissues of the cervix. The cancer is not deeper than 5 millimeters and not wider than 7 millimeters. In stage IB, the cancer is still within the cervix and either (1) can only be seen with a microscope and is deeper than 5 millimeters or wider than 7 millimeters; or (2) can be seen without a microscope and may be larger than 4 centimeters.
stage II laryngeal cancer (...luh-RIN-jul...)
Cancer that is found in the larynx. The exact definition of stage II depends on where the cancer started. If it started in the supraglottis, then cancer is in more than one area of the supraglottis or glottis or region near the supraglottis. If it started in the glottis, then cancer has spread to the supraglottis and/or the subglottis, and/or the vocal cords do not move normally. If it started in the subglottis, then cancer has spread to the vocal cords, which may not move normally.
stage II prostate cancer (...PROS-tayt KAN-ser)
Cancer that began in the prostate and is more advanced than stage I, but has not grown outside the prostate. The Gleason score (a number that describes how abnormal the cells look under a microscope) can be any level.
stage IV breast cancer
Cancer has spread to other organs of the body, most often the bones, lungs, liver, or brain.
stage IV prostate cancer (...PROS-tayt KAN-ser)
Cancer that began in the prostate and has spread to lymph nodes near or far from the prostate, or to other parts of the body, often to the bones. The Gleason score (a number that describes how abnormal the cells look under a microscope) can be any level.
surgery (SER-juh-ree)
A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.
surveillance (ser-VAY-lents)
In medicine, the ongoing collection of information about a disease, such as cancer, in a certain group of people. The information collected may include where the disease occurs in a population and whether it affects people of a certain gender, age, or ethnic group.
survivor (ser-VY-ver)
One who remains alive and continues to function after overcoming difficulties or life-threatening diseases like cancer.
symptom
An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.
synovial sarcoma
A malignant tumor that develops in the synovial membrane of the joints.
tachycardia
Rapid beating of the heart, usually defined as greater than 100 beats per minute.
therapeutic (THAYR-uh-PYOO-tik)
Having to do with treating disease and helping healing take place.
therapy (THAYR-uh-pee)
Treatment.
thrombus (THROM-bus)
A blood clot that forms on the wall of a blood vessel or in the heart when blood platelets, proteins, and cells stick together. A thrombus may block the flow of blood.
tissue (TISH-oo)
A group or layer of cells that work together to perform a specific function.
topical
On the surface of the body.
toxic (TOK-sik)
Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects.
toxicity (tok-SIH-sih-tee)
The extent to which something is poisonous or harmful.
transcription
In biology, the process by which a cell makes an RNA copy of a sequence of DNA that is a gene.
transitional cell
A cell that varies in shape depending on whether the tissue is being stretched. Transitional cells may be stretched without breaking apart. They line hollow organs such as the bladder.
tumor (TOO-mer)
An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancerous), or malignant (cancerous). Also called neoplasm.
urine (YOOR-in)
Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra.
uterus (YOO-ter-us)
The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a baby grows. Also called the womb.
vein (vayn)
A blood vessel that carries blood to the heart from tissues and organs in the body.
visual pathway glioma (...glee-OH-muh)
A rare, slow-growing tumor that usually forms in the optic nerve, optic chiasm, or optic tract. These are parts of the nervous system that carry messages from the eye to the brain. Also called optic pathway glioma.
vomit
To eject some or all of the contents of the stomach through the mouth.
white blood cell
Refers to a blood cell that does not contain hemoglobin. White blood cells include lymphocytes, neutrophils, eosinophils, macrophages, and mast cells. These cells are made by bone marrow and help the body fight infections and other diseases. Also called WBC.
xenograft
The cells of one species transplanted to another species.
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Table of Links
1 | http://www.cancer.gov/cancerinfo/pdq/cancer-cam-board |
2 | http://cancer.gov/cancertopics/pdq/levels-evidence-cam/HealthProfessional |
3 | http://www.cancer.gov/dictionary |
4 | http://www.cancer.gov/clinicaltrials |
5 | http://www.uspto.gov/patft/index.html |
6 | http://www.cancerletter.com/vol24n36.html |
7 | http://cancer.gov/cancertopics/pdq/cam/antineoplastons/healthprofessional/140.c dr#Section_140 |
8 | http://cancer.gov/cancertopics/pdq/cam/antineoplastons/healthprofessional/142.c dr#Section_142 |
9 | http://www.cancer.gov/search/ResultsClinicalTrialsAdvanced.aspx?protocolsearchi d=3550605 |
10 | http://cancer.gov/cancertopics/pdq/cam/antineoplastons/healthprofessional/Table1 |
11 | http://cancer.gov/cancertopics/pdq/cam/antineoplastons/healthprofessional/Table2 |
12 | http://cancer.gov/cancertopics/pdq/cam/antineoplastons/healthprofessional/Table3 |
13 | http://cancer.gov/cancertopics/pdq/cam/antineoplastons/healthprofessional/47.cd r#Section_47 |
14 | http://nccam.nih.gov |
15 | http://www.cancer.gov/cam |
16 | http://www.nlm.nih.gov/nccam/camonpubmed.html |
17 | http://cancer.gov/cancerinfo/pdq/cancerdatabase |
18 | http://cancer.gov/cancerinfo/pdq/adulttreatment |
19 | http://cancer.gov/cancerinfo/pdq/pediatrictreatment |
20 | http://cancer.gov/cancerinfo/pdq/supportivecare |
21 | http://cancer.gov/cancerinfo/pdq/screening |
22 | http://cancer.gov/cancerinfo/pdq/prevention |
23 | http://cancer.gov/cancerinfo/pdq/genetics |
24 | http://cancer.gov/cancerinfo/pdq/cam |
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