1. Aetna considers antineoplaston therapy (auto-urine therapy) and associated medical services experimental and investigational because there is insufficient evidence published in the peer-reviewed medical literature validating the effectiveness of antineoplaston therapy for any indication.

2. Aetna considers services associated with antineoplaston therapy experimental and investigational, including:

   • Placement of Hickman catheter
   • Infusion pump and intravenous supplies for use with the infusion pump

   • Ancillary diagnostic laboratory, x-rays, MRI or CT scans done to monitor antineoplaston therapy.

3. Aetna considers oral antineoplaston therapy or associated physician services for administering and monitoring oral antineoplaston treatment experimental and investigational.

4. Aetna considers sodium phenylbutyrate medically necessary for the treatment of acute promyelocytic leukemia and malignant glioma.

5. Aetna considers sodium phenylbutyrate experimental and investigational for the treatment of breast cancer, prostate cancer or cancers other than acute promyelocytic leukemia and malignant glioma. Sodium phenylbutyrate is considered experimental and investigational for 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.

Antineoplaston therapy is not FDA approved for any indication, and there are no controlled, peer-reviewed clinical trials to validate the effectiveness of antineoplaston therapy for any indication.

Primitive neuroectodermal tumors (PNETs) are often treated with craniospinal 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 (median age of 5 years and 7 months, with a range of 1 to 11 years).  Medulloblastoma was diagnosed in 8 patients, pineoblastoma in 3 patients, and other PNET in 2 patients.  Prior therapies included surgery in 12 patients (1 had biopsy only, suboccipital craniotomy), chemotherapy in 6 patients, and radiation therapy in 6 patients.  Six patients had not received chemotherapy or radiation.  The treatment consisted of intravenous infusions of 2 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%, partial response in 8 %, stable disease in 31%, and progressive disease in 38% of cases.  Six patients (46%) survived more than 5 years from initiation of ANP; 5 were not treated earlier with radiation therapy or chemotherapy.  The serious side effects included single occurrences of fever, anemia, and granulocytopenia.  These 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 is metabolized 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, and has been approved by the FDA for use in patients with urea cycle disorders.  It also has 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.

Brahe et al (2005) stated that spinal muscular atrophy (SMA) is caused by insufficient levels of survival motor neuron (SMN) protein.  These researchers found that sodium 4-phenylbutyrate enhances SMN gene expression in vitro, and that oral administration of sodium 4-phenylbutyrate significantly increases SMN expression in leukocytes of SMA patients.  They noted that this finding provides a rationale to further investigate the potential therapeutic effects of sodium 4-phenylbutyrate on patients with SMA.

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 produces full-length (FL)-SMN transcripts only, while the majority of SMN2 transcripts lacks exon 7.  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.