Antineoplaston

Overview
Antineoplaston (ANP) is a name used by Stanislaw Burzynski for a group of chemical compounds and mixtures for which he claims anti-cancer activity. These compounds have been sold and administered by Burzynski to cancer patients since 1986; clinical efficacy has not been demonstrated and several fatal side effects have occurred. The practice is considered quackery by critics. Burzynski maintains corporate offices and operates a clinic in Houston, Texas where he treats patients with antineoplastons. At a nearby facility in Stafford, Texas he conducts research and manufactures the pharmaceutical ingredients used in the medications and other products that he produces.

Background
In 1967 Stanislaw Burzynski began investigating the use of antineoplastons after noting significant peptide deficiencies in the blood of cancer patients as compared with a control group. Burzynski initially derived antineoplastons from human blood. Since similar peptides had been isolated from urine, in 1970 Burzynski switched to urine as a cheaper source of antinoeplastons. Since 1980 he has been reproducing his compounds synthetically. Since his initial discovery, Burzynski has isolated dozens of peptide fractions from urine, some of which have been reportedly found to be active against cancer with low toxicity.

The first active peptide fraction identified was called antineoplaston A-10 (3-phenylacetylamino-2,6-piperidinedione). From A-10, antineoplaston AS2-1, a 4:1 mixture of phenylacetic acid and phenylacetylglutamine, was derived. The active ingredient of antineoplaston A10-I is phenylacetylglutamine.

Phenylacetic acid is a toxic compound that the body produces during normal metabolism. It is detoxified in the liver to phenylacetyl glutamine. The "antineoplaston A-10" compound is an isolation artifact resulting from heating the urine under acidic conditions. The "antineoplaston AS2-1" mixture is the result of an alkaline hydrolysis of "antineoplaston A-10". All compounds are widely available cheap chemicals.

Treatment with Antineoplastons
For legal reasons Burzynski currently sells his treatments only in the context of clinical trials. Patients receiving cancer treatment with antineoplastons must first qualify for one of the currently available clinical trials. In order to qualify for most of the trials, a patient must have first failed standard treatment for the condition being treated, or it must be a condition that is unlikely to respond to currently available therapy and for which no curative therapy exists. Antineoplastons may be administered intravenously or orally. Patients who respond positively to initial treatment with intravenous antineoplastons sometimes transition to the oral form. Intravenous antineoplastons are administered continuously with a portable programmable pump that the patient carries on a shoulder strap in a canvas bag.

Treatment with antineoplastons can be very costly to patients without insurance coverage, exceeding $100,000 for the first year of intravenous treatment. Many insurance companies consider antineoplaston therapy to be investigational and unproven and will not cover the cost. The administered "antineoplastons" are very cheap and widely available chemicals that cost no more than 80 cents per treatment.

Proposed mechanisms
Antineoplastons have never shown to be effective in treating human cancer. Independent tests at at the National Cancer Institute have never been positive. The drug company Sigma-Tau Pharmaceuticals could not duplicate Burzynski's claims for AS-2.1 and A-10. The Japanese National Cancer Institute has reported that antineoplastons did not work in their studies. No scientific coauthor of Burzynski publications has endorsed his use of antineoplastons in cancer patients.

Burzynski suggest that antineoplastons A10 and AS2-1 both work by inhibiting oncogenes, promoting apoptosis, and activating tumor suppressor genes. Several other mechanism of action have been proposed.

One of the factors that allows some cancers to grow out of control is the presence of abnormal enzymes, a byproduct of DNA methylation. In the presence of these enzymes, the normal life cycle of the cells is disrupted and they replicate continuously. Antineoplastons have been shown in the laboratory to inhibit these enzymes.

Recent studies have shown that inhibiting histone deacetylase (HDAC) promotes the activation of tumor suppressor genes p21 and p53. Phenylacetic acid contained in the AS2-1 mixture has been shown to be a weak HDAC inhibitor.