Critical opposition to antineoplaston therapy and its developer have appeared in the published literature. 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.[21,22,23]
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.
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.
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. 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. 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.