Antineoplaston Therapy and Sodium Phenylbutyrate - CAM 024

Antineoplaston therapy is a complementary/alternative cancer treatment that involves using a group of synthetic chemicals called antineoplastons intended to protect the body from disease. Antineoplastons are made up mostly of peptides and amino acids originally taken from human blood and urine. Sodium phenylbutyrate is used together with a proper diet to help treat urea cycle disorders (including a specific liver enzyme deficiency) that help remove ammonia from the body.


  • Antineoplaston therapy (auto-urine therapy) and associated medical services is investigaional and/or unproven and therefore is considered NOT MEDICALLY NECESSARY because there is insufficient evidence published in the peer-reviewed medical literature validating the effectiveness of antineoplaston therapy for any indication.
  • Services associated with antineoplaston therapy are investigational and/or unproven and therefore are considered NOT MEDICALLY NECESSARY, including:
    • Ancillary diagnostic laboratory, X-rays, MRI or CT scans done to monitor antineoplaston therapy
    • Infusion pump and intravenous supplies for use with the infusion pump
    • Placement of Hickman catheter
  • Oral antineoplaston therapy or associated physician services for administering and monitoring oral antineoplaston therapy are investigational and/or unproven and are therefore considered NOT MEDICALLY NECESSARY
  • Sodium phenylbutyrate is investigational and/or unproven and therefore considered NOT MEDICALLY NECESSARY for the treatment of breast cancer and prostate cancer
  • Sodium phenylbutyrate is investigational and/or unproven and therefore considered NOT MEDICALLY NECESSARY for the treatment of amyotrophic lateral sclerosis, beta-thalassemia, insulin resistance and beta-cell dysfunction, maple syrup urine disease, sickle cell anemia, spinal muscular atrophy and for all other indications  

Antineoplastons are a group of naturally occurring peptides, which have been hypothesized to have anti-tumor activity. Antineoplaston treatment is offered by the Burzynski Research Institute in Houston, Texas, and has long been a controversial treatment for various types of malignancy. This therapy is not approved by the FDA for any indication. Of note, there are no controlled, peer-reviewed clinical trials indicating that antineoplaston therapy is effective for any indication.

Primitive neuroectodermal tumors (PNETs) are often treated with cranio-spinal radiation and chemotherapy. However, difficulties with conventional therapies can be encountered in very young children, in adult patients at high-risk of complication from standard treatment, as well as in patients with recurrent tumors.  In a phase II clinical trial, Burzynski et al. (2005) studied the effect of antineoplaston (ANP) therapy in 13 children, either with recurrent disease or high-risk disease (median age of five years and seven months, with a range of 1 to 11 years).  Medulloblastoma was diagnosed in eight patients, pineoblastoma in three patients and other PNET in two patients.  Prior therapies included surgery in 12 patients (1 had biopsy only, suboccipital craniotomy), chemotherapy in six patients and radiation therapy in six patients.  Six patients had not received chemotherapy or radiation. The treatment consisted of intravenous infusions of two formulations of ANP, A10 and AS2-1, and was administered for an average of 20 months. The average dosage of A10 was 10.3 g/kg/day and of AS2-1 was 0.38 g/kg/day. Complete response was accomplished in 23 percent, partial response in eight percent, stable disease in 31 percent and progressive disease in 38 percent of cases. Six patients (46 percent) survived more than five years from initiation of ANP; five were not treated earlier with radiation therapy or chemotherapy. Serious side effects included single occurrences of fever, anemia and granulocytopenia. Investigators noted that the percentage of patients' response is lower than for standard treatment of favorable PNET, but long-term survival in poor-risk cases and reduced toxicity makes ANP therapy promising for very young children, patients at high-risk of complication of standard therapy and patients with recurrent tumors.

Sodium phenylbutyrate (Buphenyl) taken orally metabolizes in the liver into a combination of phenylacetylglutamine and phenylacetate, which then enter the bloodstream. Those two chemicals are the prime ingredients of antineoplaston AS2-1.

Sodium phenylbutyrate removes ammonia from the bloodstream. It has been approved by the FDA for use in patients with urea cycle disorders and has also received an orphan drug designation by the FDA for treatment of acute promyelocytic leukemia. Sodium phenylbutyrate was given an orphan drug designation by the FDA for use as an adjunct to surgery, radiation therapy and chemotherapy for treatment of patients with primary or recurrent malignant glioma.

Since sodium phenylbutyrate has been approved by the FDA for treatment of other indications, physicians can prescribe it for patients without any danger of legal sanctions or need for compassionate use exemptions. However, there is no adequate evidence in the peer-reviewed published medical literature demonstrating that the use of sodium phenylbutyrate improves the clinical outcomes of patients with cancers of the prostate, breast or cancers other than acute promyelocytic leukemia and malignant glioma. Current evidence is limited to in-vitro and in-vivo studies and phase I studies. Prospective phase III clinical outcome studies are necessary to determine the clinical effectiveness of sodium phenylbutyrate for cancer.

Wirth et al. (2006) stated that the molecular genetic basis of SMA is the loss of function of SMN1. The SMN2 gene, a nearly identical copy of SMN1, has been detected as a promising target for SMA therapy.  Both genes encode identical proteins, but differ markedly in their splicing patterns, with SMN1 producing full-length (FL)-SMN transcripts only, while the majority of SMN2 transcripts lack exon seven. Transcriptional SMN2 activation or modulation of its splicing pattern to increase FL-SMN levels is thought to benefit patients with SMA. Drugs such as valproic acid, phenylbutyrate, sodium butyrate, M344 and SAHA can stimulate the SMN2 gene transcription and/or restore the splicing pattern, thereby raising the levels of FL-SMN2 protein. Phase II clinical trials have shown promising results. However, phase III double-blind placebo-controlled studies are needed to prove the effectiveness of these drugs.

In a phase I clinical trial, Lin and associates (2009) determined the minimal effective dose and optimal dose schedule for 5-azacytidine (5-AC) in combination with sodium phenylbutyrate in patients with refractory solid tumors. The pharmacokinetics, pharmacodynamics and antineoplastic effects were also studied. Three dosing regimens were studied in 27 patients with advanced solid tumors, and toxicity was recorded. The pharmacokinetics of the combination of drugs was evaluated. Repeat tumor biopsies and peripheral blood mononuclear cells (PBMC) were analyzed to evaluate epigenetic changes in response to therapy. Epstein Barr virus titers were evaluated as a surrogate measure for gene re-expression of epigenetic modulation in PBMC.  The 3-dose regimens of 5-AC and phenylbutyrate were generally well-tolerated and safe. A total of 48 cycles was administrated to 27 patients. The most common toxicities were bone marrow suppression-related neutropenia and anemia, which were minor. The clinical response rate was disappointing for the combination of agents.  One patient showed stable disease for five months, whereas 26 patients showed progressive disease as the best tumor response.  The administration of sodium phenylbutyrate and 5-AC did not seem to alter the pharmacokinetics of either drug. Although there were individual cases of targeted DNA methyltransferase activity and histone H3/4 acetylation changes from paired biopsy or PBMC, no conclusive statement can be made based on these limited correlative studies. The authors concluded that the combination of 5-AC and sodium phenylbutyrate across 3-dose schedules was generally well-tolerated and safe, yet lacked any real evidence for clinical benefit.


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Coding Section

Codes Number Description
CPT 96549 Unlisted chemotherapy procedure (when specified as administration of antineoplaston therapy)
HCPCS  J3490 Unclassified drugs (when specified as antineoplastons)
  J8999 Prescription drug, oral, chemotherapeutic, NOS (when specified as antineoplastons)
  J9999 Not otherwise classified, antineoplastic drugs (when specified as antineoplastons)
ICD-9 Diagnosis   All diagnoses
ICD-10-CM (effective 10/01/15)   All diagnoses

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

"Current Procedural Terminology © American Medical Association. All Rights Reserved" 

History From 2014 Forward     


Annual review, no change to policy intent. 


Annual review, no change to policy intent. 


Annual review, updating policy verbiage from stating investigational to all uses of these treatments to be investigational and/or unproven and are therefore considered not medically necessary. No other changes. 


Annual review, no change to policy intent. 


Annual review, no change to policy intent. 


Annual review, no change to policy intent. 


Change Category from Medicine to Prescription Drug.


Annual review, no change to policy intent. Addied coding.


Annual review, no changes made.


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