Glioblastoma (GBM), the most common malignant primary brain tumor in adults, has a poor prognosis, with a median survival of 12-15 months. The morbidity of standard therapy can be devastating in long-term survivors. Twenty-six patients with GBM and one with gliosarcoma (GS) were treated with Antineoplastons A10 and AS2-1 (ANP) in Phase II clinical studies at the Burzynski Clinic. The unusually long survival and lack of long-term negative sequelae in these patients are emphasized. Eligibility criteria for protocol ANP included a Karnofsky/Lansky (KPS/LPS) score of 60 or higher and a life expectancy of two months or more. IV ANP was given to all patients, while some also received oral ANP. Gradually increasing doses of IV ANP were administered via subclavian catheter and infusion pump until maximum tolerated doses of A10 and AS2-1 were achieved. Outcome criteria were tumor response, survival, and toxicity. The Kaplan-Meier survival analysis for 574 GBM/GC patients receiving protocol ANP yielded a median survival of 0.966 years. Twenty-seven of these patients (4.7%) survived from more than 3 years to more than 29 years. Seven of these 27 patients survived more than 12 years, a definition of cure. Age at admission to BC ranged from 6.5 to 68.0 years, with a median age of 38.4 years. KPS/ LPS ranged from 40 to 100 with a median of 50. Patients with a KPS/LPS score of less than 60 received treatment as Special Exceptions. One patient experienced a serious adverse event possibly related to treatment and recovered fully. ANP shows promise in the treatment of GBM/GC.

Rationale: With an incidence of 0.8 per 100,000 people, pilocytic astrocytoma (PCA) is the most common childhood brain tumor. There is no standard therapy for recurrent PCA. The case of a six-year-old child with a recurrent PCA is presented here to detail/discuss the efficacy of ANP therapy (Antineoplaston A10 {Atengenal} and Antineoplaston AS2-1 {Astugenal}) in the treatment of recurrent PCA and to permit a review of the Phase II Protocol BT-13. Objectives: This patient was treated at the Burzynski Clinic (BC), according to the Phase II Protocol, BT-13, which utilized IV ANP therapy in the treatment of patients with low-grade astrocytomas. ANP therapy was delivered via subclavian catheter and infusion pump. Tumor response was measured by sequential magnetic resonance imaging (MRI) of the brain utilizing gadolinium enhancement. Findings: At the age of 6 years, after gross total resection (GTR) of his PCA performed elsewhere, this male child presented to the BC with recurrent disease and some left-sided weakness. Baseline MRI of the brain performed on January 7, 1979, showed a left cerebellum hemisphere/pons enhancing lesion measuring 2.3 cm x 1.7 cm. On April 25, 1997, after 3 months of IV ANP therapy, the patient’s tumor showed a 53.5% decrease from baseline, indicating a partial response (PR). On December 5, 1997, no enhancing lesion was seen, indicating a complete response (CR). On December 6, 2002, the last follow-up MRI of the brain showed no residual tumor, indicating an enduring CR. The patient has had resolution of his left-sided weakness, has an OS of >27 years since the start of IV ANP therapy, and continues in excellent health. Conclusions: The utilization of ANP therapy to facilitate a cure in a patient with recurrent PCA is presented. We conclude that ANP therapy is an attractive therapeutic option for children with recurrent PCA.

Optic pathway glioma (OPG) is a low-grade tumor developing along the pre-cortical optic pathways and can involve the optic nerve, optic chiasm, optic tracts, and hypothalamus. Objective: A male child with newly diagnosed and unresectable OPG is presented to 1) review the earliest use of Antineoplastons A10 and AS2-1 for the treatment of brain tumors and 2) demonstrate the efficacy of Antineoplastons in the treatment of OPG. On April 18, 1988, a seven-year-old male child presented to the Burzynski Clinic (BC) with headaches. Based on prior, non-enhanced MRIs and biopsy, an unresectable suprasellar OPG was diagnosed. Antineoplaston therapy was started on a “proof of principle” basis. Tumor response was measured by magnetic resonance imaging (MRI) scans of the brain. Results: A brain MRI, performed on May 31, 1989, demonstrated an enhancing suprasellar nodule measuring 4.37 cm2. On August 24, 1990, brain MRI demonstrated a 0.96 cm2 enhancing nodule, indicating the achievement of a partial response (PR). Following higher dose intravenous (IV) and oral Antineoplastons, brain MRI performed on January 24, 1997, demonstrated a residual 0.4 cm2 enhancing nodule, indicating an enduring PR. All Antineoplaston therapy was discontinued on August 21, 2000. At last follow-up, > 35 years since the start of Antineoplaston therapy, the patient was healthy and showed no evidence of tumor progression. “Proof of principle” Antineoplaston therapy utilized in a seven-year-old male with unresectable OPG produced an objective response (OR) and prolonged overall survival. Antineoplaston therapy is an attractive therapeutic option for children with OPG.

Medulloblastomas arise in the posterior fossa, primarily in the region of the fourth ventricle. Recurrent medulloblastomas are high-risk and have a bad prognosis. Objectives: the case of a male child with recurrent, disseminated medulloblastoma is presented to detail the efficacy of ANP therapy (Antineoplaston A10 {Atengenal} and Antineoplaston AS2-1 {Astugenal}) in the treatment of high-risk medulloblastoma. This child was treated at the Burzynski Clinic (BC), as a Special Exception, according to Protocol BT-12, “Phase II Study of Antineoplastons A10 and AS2-1 in Children with Primitive Neuroectodermal Tumors”, with intravenous (IV) ANP therapy via a subclavian catheter and infusion pump. Tumor response was measured by sequential magnetic resonance imaging (MRI) of the brain with gadolinium enhancement. Findings: This child initially underwent tumor resection, placement of ventricular shunts, and chemotherapy, all performed elsewhere. Baseline MRI at the BC revealed recurrent, disseminated, and enhancing disease measuring 9.10 cm2 in total. IV ANP therapy began in March 2001 and ended in December 2002 after a complete response (CR) was achieved based on MRI criteria. Subsequently, the child received oral Antineoplastons as maintenance therapy, which were discontinued after eight months. At last follow-up, > 21 years and eight months since diagnosis and > 21 years and five months since the start of IV ANP therapy, the patient was well and showing no evidence of tumor recurrence. Conclusions: The utilization of ANP therapy to cure a patient with recurrent medulloblastoma is presented. We conclude that ANP therapy is an attractive therapeutic option for children with medulloblastoma

Rationale: Anaplastic astrocytoma (AA), a malignant brain tumor that arises from astrocytic cells, has a poor prognosis. It accounts for 6–7% of gliomas and 1-2% of brain tumors. Objectives: A 31-year and 11-month-old female with an AA is presented to discuss the efficacy of Antineoplastons A10 (Atengenal) and AS2-1 (Astugenal) in the treatment of AA. She presented to the Burzynski Clinic (BC) for treatment and was enrolled in Protocol BT-08, “Phase II Study of Antineoplastons A10 and AS2-1 in Adult Patients with Anaplastic Astrocytoma”, receiving both intravenous (IV) and oral Antineoplastons A10 and AS2-1 (ANP therapy). IV ANP therapy was delivered continuously via subclavian catheter and infusion pump. Tumor response was determined by comparison of baseline brain magnetic resonance imaging (MRI) to sequential brain MRIs during therapy. Findings: The patient presented to the BC with no prior treatment and a one-month history of right arm clumsiness and right leg weakness. Brain MRI and stereotactic biopsy performed elsewhere had demonstrated an AA. Baseline MRI at the BC showed a 2.0 cm2 nonenhancing lesion and two enhancing lesions (0.02 cm2 and 0.15 cm2 ) in the left parietal lobe. IV ANP therapy was given over 56 days, and a complete response (CR) was demonstrated after one month of therapy. Oral ANP therapy was subsequently provided for 17 months. At last follow-up, in June 2023, the patient was healthy and showed no evidence of recurrent disease. She had an overall survival (OS) of > 23 years and one month since diagnosis and an OS of > 23 years since the start of IV ANP therapy. Conclusions: The utilization of ANP therapy in an adult female patient with AA is presented. The patient achieved a CR and prolonged OS, suggesting that ANP therapy may be an effective therapeutic option for adults with AA.

Rationale: Gangliogliomas are generally benign tumors and are classified by the World Health Organization (WHO) as grade I or II tumors. However, in 1-5% of cases, gangliogliomas can behave more aggressively (WHO grade III) and have a worse prognosis. Four children with a ganglioglioma are presented to detail and discuss the efficacy of Antineoplastons A10 (Atengenal) and AS2-1 (Astugenal) in the treatment of gangliogliomas. Objectives: The children were treated with Antineoplastons A10 and AS2-1 (ANP therapy) at the Burzynski Clinic (BC) according to the phase II Protocols, BT-10 and BT-11. ANP therapy was delivered via subclavian catheter and infusion pump. During ANP therapy, tumor response was determined by comparison of sequential magnetic resonance imaging (MRI) of the brain with a baseline brain MRI. Findings: Of the four children treated for gangliogliomas, all had prior surgery but none had radiation therapy (RT) or chemotherapy. Two had recurrent, and progressive tumors with possible high-grade transformation (thalamo-mesencephalic region; temporal lobe with leptomeningeal spread) while two had tumors of the brain stem (persistent multicentric ganglioglioma; persistent and progressive ganglioglioma of the inferior medulla and superior cervical spinal cord), which are more difficult to treat and have a worse prognosis. Physical findings corresponded with the location of each child’s tumor. IV ANP therapy continued for 6.4 to 24.8 months. The two children with possible high-grade transformation achieved a partial response (PR) while the two children with brain stem tumors maintained stable disease (SD). Overall survival for these four children ranged from 10.3 to 22.4 years. Conclusions: The utilization of ANP therapy in children with gangliogliomas is presented. We conclude that ANP therapy is an attractive therapeutic option for children with gangliogliomas who are ineligible for or refuse surgical resection and/or demonstrate persistent, recurrent, or progressive disease with or without high-grade transformation following surgical resection..

Rationale: Diffuse intrinsic pontine glioma (DIPG) is a lethal brain tumor and leading cause of brain tumor–related death in children. Over the past few decades, clinical trials have shown no improvement in outcome. Most DIPGs occur in the pediatric population. Adult brainstem gliomas are rare, constitute less than 2% of adult gliomas, and show a slight male predominance. The case of this 25-year-old female is presented to detail and discuss the use of Antineoplastons A10 (Atengenal) and AS2-1 (Astugenal) in the treatment of DIPG that persisted despite radiation therapy (RT) and temozolomide. Objectives: The patient described was treated at the Burzynski Clinic (BC), as a special exception, according to the phase II protocol, BT-09, which utilized Antineoplastons A10 and AS2-1 (ANP therapy) in the treatment of brain tumors. The delivery of ANP therapy was via a subclavian catheter and infusion pump. Tumor response to therapy was measured by sequential magnetic resonance imaging (MRI) of the brain. Overall Survival (OS) and Adverse Events (AES) were also documented. Findings: At her presentation to the BC, the patient complained of diplopia, left-sided weakness, and difficulty walking. On physical exam, she was alert and orientated. Her cranial nerves were intact. There was weakness of the left-sided extremities. Deep tendon reflexes were equal bilaterally with down-going toes bilaterally. Reports of the original brain MRIs in Argentina suggested a DIPG with extension to the medulla and cerebellum. In addition, tumor biopsy confirmed a grade 3 astrocytoma. Following radiation therapy (RT) and temozolomide in Argentina, the patient was treated at BC for persistent disease with ANP therapy. Sequential MRI imaging of the residual tumor, which was non-enhancing, showed no change in size during therapy. However, the patient did achieve resolution of her neurologic signs and symptoms and has survived more than nine years since first being seen at BC. Correspondence with the patient on September 9, 2021 indicated she was feeling fine, had a healthy child, and was enjoying life. Conclusions: We have presented here the case of an adult female with a DIPG who had resolution of signs and symptoms and survived more than nine years after ANP therapy. For patients with DIPG (or other high-grade astrocytoma), who do not qualify for/refuse RT or show persistent or progressive disease following RT and/or chemotherapy, ANP therapy is an effective therapeutic option. In collaboration with the FDA confirmatory Phase II and Phase III studies have been developed.

Glioblastoma (GBM), with its very poor prognosis, accounts for 57% of gliomas and 48% of malignant central nervous system (CNS) tumors. After standard therapy, patients with GBM usually die within six months. The case of an adult male with a newly-diagnosed GBM is presented here to detail/discuss the efficacy of ANP therapy (Antineoplaston A10 {Atengenal} and Antineoplaston AS2-1 {Astugenal}) in the treatment of GBM and to permit a review of the Phase II Protocol BT-07. Objectives: This patient was treated at the Burzynski Clinic (BC), according to the Phase II Protocol, BT-07, which utilized IV ANP therapy in the treatment of patients with newly-diagnosed GBMs. ANP therapy was delivered via subclavian catheter and infusion pump. Tumor response was measured by sequential magnetic resonance imaging (MRI) of the brain utilizing gadolinium enhancement. Findings: At age 37, this patient was diagnosed with GBM of the right frontal lobe after subtotal tumor resection performed elsewhere. At age 37 years and six months, he presented to the BC with this newly diagnosed disease. He had a recent history of forgetfulness and personality change. Neurologic examination was otherwise normal. Baseline brain MRI at the BC revealed a measurable enhancing nodule (4.0 cm x 2.0 cm) in the right frontal lobe. Intravenous (IV) ANP therapy began in November 1995 and a partial response (PR) was achieved within three months. After another 5 months of IV ANP therapy, the patient underwent a complete tumor resection, then additional ANP therapy. Now, > 27 years later, the patient is doing well and showing no evidence of tumor recurrence. Conclusions: The utilization of ANP therapy to facilitate a cure in a patient with newly-diagnosed GBM is presented. We conclude that ANP therapy is an attractive therapeutic option for adults with a GBM who are ineligible for or refuse standard therapy.

Long-term survival in Diffuse Intrinsic Pontine Glioma (DIPG) is very rare. The purpose of this report is to detail the early (1988) use of IV Antineoplaston therapy (ANP {A-10 + AS2-1}) and its efficacy in DIPG while presenting the 27.7-year survival of a 36-year-old patient treated with ANP for progressive DIPG.

Individuals suffering from diffuse intrinsic pontine glioma (DIPG) face a dismal prognosis with a median overall survival of approximately 11 months, and a 2-year survival rate of 10%. Long-term survival is very rare. To date, radiotherapy remains the standard of care at diagnosis, but offers a survival benefit of approximately 3 months. Chemotherapy has not shown to be effective. There is no Standard of Care for progressive DIPG after radiation therapy (RT). The purpose of this case report is to present the 23-year survival of a 26-year-old male treated with Antineoplaston therapy A10 and AS2-1 (ANP) for progressive DIPG.

Rationale: Diffuse intrinsic pontine glioma (DIPG), a lethal brain tumor, is the leading cause of brain tumor–related death in children. Over the past few decades clinical trials have shown no improvement in outcome. The purpose of this case study is to detail and discuss the use of Antineoplastons A-10 (Atengenal) and AS2-1 (Astugenal) in the treatment of an eleven-year-old female with a newly diagnosed DIPG. Objectives: The patient described here was enrolled into BT-11, a Phase II protocol utilizing Antineoplastons A-10 and AS2-1 in the treatment of brainstem gliomas. The patient’s tumor response to therapy was measured by sequential MRIs of the brain, with and without gadolinium contrast. Findings: At her presentation to the Burzynski Clinic (BC), the patient was alert, and weighed 42.1 Kg. Physical examination showed dysfunction of the 6th and 7th cranial nerves, with lateral movement of the left eye being decreased by approximately 30% and with left-sided facial weakness being present. The patient obtained a baseline MRI, with and without gadolinium. Post-gadolinium T1-weighted axial images showed a 0.80 cm2 enhancing pontine mass and a 2.70 cm2 non-enhancing left-sided brainstem mass. Following Antineoplastons (ANP), the patient achieved a complete response (CR) of the enhancing pontine mass. At that time, physical examination, especially neurologic examination, showed no abnormalities. The patient was last seen at the BC on October 15, 2004 and she was in excellent health with no evidence of new/recurrent disease. On August 10, 2021, correspondence with the patient indicated that she continued in excellent health (>25 years survival). Conclusions: ANP is an effective treatment for DIPG and for a variety of low- and high-grade brain tumors. Multiple Phase II protocols utilizing ANP have now been completed and its impact on the treatment of brain tumors has been widely published.

Despite dramatic progress over the last 50 years in the treatment of many childhood cancers, primary brain tumors remain the leading cause of death in pediatric oncology. This phase II study evaluated the efficacy and safety of Antineoplastons A10 and AS2-1 given in combination (ANP). Thirty-four patients, with a median age of 10.4 years, were enrolled in the study. Thirtytwo patients (94.1%), were Caucasians while 21 (61.8%) were female and 13 were male (38.2%). Twenty-four patients (70.6%) suffered from a brainstem glioma (BSG) or high-grade tumor. Ten patients (29.4%) suffered from a low-grade tumor. A distinct sub-group of three patients with low grade tumors had a ganglioglioma (GG). Eighty-two percent of patients had failed standard treatment. Daily ANP was administered by IV infusion, every four hours, until an objective response (OR) was documented, and then for an additional eight months. The median doses of A10 and AS2-1 were 11.64 g/kg/d and 0.45 g/kg/d, respectively. A complete response (CR) was documented in two patients (5.9%), a partial response (PR) in four patients (11.8%), and stable disease (SD) in six patients (17.6%). Objective responses were observed in diffuse intrinsic pontine glioma (DIPG), thalamic pilocytic astrocytoma with brainstem involvement, ganglioglioma and pilocytic astrocytoma. Six-month progression-free survival (PFS) was 35.3%. Overall survival (OS) at two and five years was 37.6% and 34.5%, respectively. Two patients experienced grade 4 hypernatremia while three experienced grade 3 hypokalemia. In this group of patients, ANP showed good efficacy and an acceptable toxicity profile.

Protocol BT-23, a Phase II study, was performed to determine the efficacy and safety of combination Antineoplaston A10 and Antineoplaston AS2-1 (ANP) in children with an optic pathway glioma (OPG). Sixteen patients (12 males, 4 females) ages 1 to 16 years (median age 4.5 years) were treated. The patients received ANP, by intravenous infusion, six times daily (i.e., every four hours). The length of treatment extended from a minimum of 4.1 weeks to a maximum of 210.0 weeks. The median dosage of A10 was 8.07 g/kg/d while for AS2-1 itwas 0.39 g/kg/d.Patients’ best response to ANP was determined: 12.5% of this patient population achieved a complete response, 18.8% achieved a partial response, and 31.3% maintained stable disease. The median overall survival was 78.5 months (95% CI: 37.6-92.3) while median progression-free survival was 45.4 months (95% CI: 7.1-71.4). ANPwas associated with a12% incidence of Grade 3 and a12% incidence of Grade 4 adverse drug experiences (ADEs). There were no Grade 5 ADEs. Grade 3 ADEs included somnolence and elevated SGOT; Grade 4 ADEsincluded hypernatremia and hypokalemia. Long-term quality of life was excellent with no chronic toxicity identified. Children with an OPG respond very well to ANP with good efficacy and toxicity profiles.

It is estimated that as many as 30% of patients with primary CNS tumors have leptomeningeal, disseminated, and/or multicentric disease (LDM). These patients respond poorly to conventional therapy. Fifty-seven children with LDM (median age of 7.1 years) were treated in multiple prospective phase II clinical studies of high- and low-grade primary CNS tumors with Antineoplastons A10 and AS2-1 (ANP). Their inclusion in this analysis was based on MRI imaging. Patients with glioblastoma were excluded. The patients received ANP therapy 6 times daily; A10: 8.77 g/kg/d; AS2-1: 0.35 g/kg/d. The response to ANP was monitored by MRIs every 8 weeks. Patients evaluable for efficacy (N = 40) received 12 or more weeks of ANP or developed progressive disease (PD) before 12 weeks. 10 patients (17.5%) achieved an objective response (OR) with 4 (7%) achieving a complete response (CR) and 6 (10.5%) had a partial response (PR). Stable disease (SD) was maintained in 7 patients (12.3%) and PD developed in 23 patients (40.4%). Survival analysis of the 57 children showed 2- and 5-year overall survival (OS) were both 28% while 10- and 15-year OS were both 26%. One of the patients achieving an OR had atypical teratoid/rhabdoid tumor (AT/RT) while nine had low-grade gliomas (LGGs). Grade 3 and 4 toxicities included hypokalemia (14.0%); fatigue, anemia, hypernatremia and leukopenia (3.5% each); diarrhea, hypertension, joint pain, thrombocytopenia, and somnolence (1.8% each). These findings suggest the need for a single-arm, phase II study of ANP in children with LDM.

Nonresectable Low-Grade Astrocytomas (LGA) can compromise function and threaten life. For the majority of patients, the most appropriate strategy is initial chemotherapy followed by Radiation Therapy (RT). Since curative treatment is not available for most of these patients, it is reasonable to conduct clinical studies to evaluate new agents. This Phase II study evaluates efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in LGA. Sixteen children diagnosed with LGA were treated. They included 12 males and 4 females, ages 1.6 - 17.4 years (median 10.6). Efficacy was evaluated in 16 patients. The majority of patients were previously treated, but 1 patient had stereotactic biopsy only. Out of the remaining 15 patients, 6 patients received chemotherapy, and 7 patients had surgery, and 2 patients received RT and chemotherapy after surgery. The patients received treatment with ANP administered daily every 4 hours (median dose of A10 was 7.71 g/kg/d and AS2-1 was 0.26 g/kg/d) until objective response or stable disease was documented and for 8 months thereafter. The duration of ANP IV ranged from 1.4 to 286 weeks with a median of 83 weeks. A complete response was documented in 25.0%, partial response in 12.5%, and stable disease in 37.5%. Overall survival was 67.7% at 5 years, and 54.2% at 10 and 15 years. Progression-free survival was 48.1%, 34.4% and 34.4% at 5, 10, and 15 years respectively. The treatment was associated with grade 3 or grade 4 Adverse Drug Experiences (ADE) in 6 patients. There were two hypernatremias of grade 4 (12%). Grade 3 ADE included urinary frequency (6%), fatigue (6%) and hypernatremia (6%). There were no chronic toxicities, and there was a high quality of survival. ANP shows efficacy with a very good toxicity profile in this cohort of children with low-grade astrocytoma.

Most patients with recurrent glioblastoma (RGBM) die within 6 months regardless of treatment. In phase II studies of Antineoplaston A10 and AS2-1 injections (ANP), our investigators have reported objective responses and long-term survival in RGBM. Using a next-generation sequencing (NGS) based assay of 343 cancer-related genes and introns, comprehensive genomic profiling of tumor tissue obtained from a RGBM patient (who remains alive and well) was performed 11 years after diagnosis and permitted assignment of the patient’s RGBM to the classical subgroup. The most important genomic alterations included amplification of epidermal growth factor receptor (EGFR), cyclin-dependent kinase inhibitor 2A and 2B (CDKN2A/B), loss of phosphatase and tensin homolog (PTEN) and telomerase reverse transcriptase (TERT) mutation. An analysis of the signaling networks and other targets of ANP therapy was recently performed and presented in this publication. Based on our findings, patients with classical RGBM have a reasonable possibility of responding to ANP therapy and experiencing long-term survival. It is proposed that this subgroup of RGBM patients be enrolled in a genomics-driven clinical trial of ANP therapy.