Antineoplaston Therapy Form

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 approved by the Food and Drug Administration (FDA) 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 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 (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.

In an open label, non- blinded, randomized, phase II clinical trial, Ogata and colleagues (2015) compared the effectiveness of hepatic arterial infusion (HAI) with 5-fluorouracil,with or without antineoplastons as a post-operative therapy for colorectal metastasis to the liver. A total of 65 patients with histologically confirmed metastatic colon adenocarcinoma in liver, who had undergone hepatectomy, and/or thermal ablation for liver metastases were enrolled between 1998 to 2004. Patients were randomly assigned to receive systemic antineoplastons (A10-I infusion followed by per-oral AS2-1) plus HAI (AN arm) or HAI alone (control arm) based on the number of metastases and presence/absence of extra-hepatic metastasis at the time of surgery. Primary end-point was cancer-specific survival (CSS); secondary end-points were relapse-free survival (RFS), status and extent of recurrence, salvage surgery (rate) and toxicity. Overall survival was not statistically improved (p = 0.105) in the AN arm (n = 32). Relapse-free survival was not significant (p = 0.343). Nevertheless, the CSS rate was significantly higher in the AN arm versus the control arm (n = 33) with a median survival time 67 months (95 % confidence interval [CI]: 43 to not calculated) versus 39 months (95 % CI: 28 to 47) (p = 0.037) and 5 year CSS rate 60 % versus 32 % respectively. Cancer recurred more often in a single organ than in multiple organs in the AN arm versus the control arm. The limited extent of recurrent tumors in the AN arm meant more patients remained eligible for salvage surgery. Major adverse effects of antineoplastons were fullness of the stomach and phlebitis. No serious toxicity, including bone marrow suppression, liver or renal dysfunction, were found in the AN arm. The authors concluded that antineoplastons (A10 Injection and AS2-1) might be useful as adjunctive therapy in addition to HAI after hepatectomy in colorectal metastases to the liver.

Scope of Policy

This Clinical Policy Bulletin addresses antineoplaston therapy.

Experimental and Investigational

Aetna considers the following interventions experimental and investigational because the effectiveness of these approaches has not been established: