Complete response and long-term survival (>20 years) of a child with tectal glioma: a case report.

Tectal glioma is a midbrain tumor. The patient generally presents with symptoms related to increased intracranial pressure and requires treatment for hydrocephalus. No effective pharmacological treatments have yet been introduced. This report discusses a case of a 13-year-old male diagnosed with tectal glioma who obtained a complete response and long-term survival after the treatment with antineoplastons (ANP) in phase II trial. Prior treatment consisted of placement of a ventriculoperitoneal shunt. After 6 years of stabilization there had been an increase in tumor size with signs of malignant transformation. The patient received treatment with ANP A10 and AS2-1 infusions for 20 months, obtained a complete response, and was switched to maintenance with ANP capsules. All treatments were discontinued in December 2003. Adverse events according to CTCAE v3.0 included: hypernatremia (two events of grade 3, one event of grade 2, four events of grade 1), one case of fatigue (grade 2), and one allergic reaction (grade 1). Currently, over 20 years from his diagnosis and over 13 years from treatment start he is symptom-free and leads a normal life. This report indicates that it is possible to obtain long-term survival of a child with tectal glioma with currently available investigational treatment.

Long-term survival (>13 years) in a child with recurrent diffuse pontine gliosarcoma: a case report.

Pediatric gliosarcoma (GS) is a rare variant of glioblastoma multiforme. The authors describe the case of an unusual pontine location of GS in a 9-year-old boy who was initially diagnosed with low-grade astrocytoma (LGA) that was successfully controlled for 4 years. Subsequently, his brain tumor transformed into a GS. Prior treatment of his LGA included subtotal tumor resection 3 times, standard radiation therapy, and Gamma Knife procedure twice. His LGA was also treated with a standard chemotherapy regimen of carboplatin and vincristine, and his GS with subtotal resection, high-dose cyclophosphamide, and thiotepa with stem cell rescue and temozolomide. Unfortunately, he developed disseminated disease with multiple lesions and leptomeningeal involvement including a tumor occupying 80% of the pons. Upon presentation at our clinic, he had rapidly progressing disease. He received treatment with antineoplastons (ANP) A10 and AS2-1 for 6 years and 10 months under special exception to our phase II protocol BT-22. During his treatment with ANP his tumor stabilized, then decreased, and, ultimately, did not show any metabolic activity. The patient's response was evaluated by magnetic resonance imaging and positron emission tomography scans. His pathology diagnosis was confirmed by external neuropathologists, and his response to the treatment was determined by central radiology review. He experienced the following treatment-related, reversible toxicities with ANP: fatigue, xerostomia and urinary frequency (grade 1), diarrhea, incontinence and urine color change (grade 2), and grade 4 hypernatremia. His condition continued to improve after treatment with ANP and, currently, he complains only of residual neurological deficit from his previous surgery. He achieved a complete response, and his overall and progression-free survival is in excess of 13 years. This report indicates that it is possible to obtain long-term survival of a child with a highly aggressive recurrent GS with diffuse pontine involvement with a currently available investigational treatment.

The response and survival of children with recurrent diffuse intrinsic pontine glioma based on phase II study of antineoplastons A10 and AS2-1 in patients with brainstem glioma.

BACKGROUND: Brainstem gliomas (BSG) are relatively rare tumors of which recurrent pediatric diffuse intrinsic pontine gliomas (RPDIPG) comprise a distinct group. Numerous trials have been conducted on RPDIPG, none of which have resulted in identifying any proven pharmacological treatment benefit. This study included 40 patients diagnosed with different types of BSG, but it was decided to describe first the encouraging results in the most challenging group of RPDIPG. MATERIALS AND METHODS: This single-arm phase II study evaluated the efficacy and safety of the combination of antineoplastons A10 and AS2-1 (ANP) in patients with RPDIPG. Seventeen patients (median age 8.8 years) were enrolled, and all were diagnosed with RPDIPG. ANP was administered intravenously daily. Efficacy analyses were conducted in this group of patients. RESULTS: In this group, complete responses were observed in 6 % of patients, partial responses in 23.5 %, and stable disease in 11.8 %. Six-month progression-free survival was 35.3 %. One-year overall survival was 29.4 %, 2 years 11.8 %, and 5, 10, and 15 years 5.9 %. One patient with DIPG is alive over 15 years post-treatment. Grade 3 and higher toxicities including hypokalemia and fatigue occurred in 6 %, hypernatremia in 18 %, fatigue and urinary incontinence in 6 %, and somnolence in 12 %. In a single patient, grade 4 hypernatremia occurred when he was on mechanical ventilation. He was disconnected from the ventilator and died from brain tumor according to the attending physician. Responding patients experienced improved quality of life. CONCLUSION: The results suggest that ANP shows efficacy and acceptable tolerability profile in patients with RPDIPG.

Targeted therapy with antineoplastons A10 and AS2-1 of high-grade, recurrent, and progressive brainstem glioma.

BACKGROUND: Brainstem glioma carries the worst prognosis of all malignancies of the brain. Most patients with brainstem glioma fail standard radiation therapy and chemotherapy and do not survive longer than 2 years. Treatment is even more challenging when an inoperable tumor is of high-grade pathology (HBSG). The objective of this report is to summarize the outcome of patients with HBSG treated with antineoplastons in 4 phase 2 trials. PATIENTS: The following group of 18 patients was evaluable: 4 patients with glioblastomas and 14 patients with anaplastic HBSG. Fourteen patients had diffuse intrinsic tumors. Twelve patients suffered from recurrence, and 6 patients did not have radiation therapy or chemotherapy. METHODS: Antineoplastons, which consist of antineoplaston A10 (A10I) and AS2-1 injections, were given in escalating doses by intravenous injections. The median duration of antineoplaston administration was 5 months, and the average dosage of A10I was 9.22 g/kg/d and of AS2-1 was 0.31 g/kg/d. Responses were assessed by gadolinium-enhanced magnetic resonance imaging and positron emission tomography. RESULTS: The overall survival at 2 and 5 years was 39% and 22%, respectively, and maximum survival was more than 17 years for a patient with anaplastic astrocytoma and more than 5 years for a patient with glioblastoma. Progression-free survival at 6 months was 39%. Complete response was achieved in 11%, partial response in 11%, stable disease in 39%, and progressive disease in 39% of patients. Antineoplastons were tolerated very well with 1 case of grade 4 toxicity (reversible anemia). CONCLUSION: Antineoplastons contributed to more than a 5-year survival in recurrent diffuse intrinsic glioblastomas and anaplastic astrocytomas of the brainstem in a small group of patients.

Phase II study of antineoplaston A10 and AS2-1 in children with recurrent and progressive multicentric glioma : a preliminary report.

OBJECTIVE: To evaluate the response rates, survival and toxicity of treatment with antineoplaston A10 and AS2-1 (ANP) in the first 12 children enrolled in our studies diagnosed with incurable recurrent and progressive multicentric glioma. PATIENTS AND METHODS: The patients' median age was 9 years. Six patients were diagnosed with pilocytic astrocytoma, four with low-grade astrocytoma and one with astrocytoma grade 2. In one case of visual pathway glioma, a biopsy was not performed due to a dangerous location. Patients received ANP intravenously initially and subsequently orally. The average duration of intravenous ANP therapy was 16 months and the average dosage of A10 was 7.95 g/kg/day and of AS2-1 was 0.33 g/kg/day. The average duration of oral ANP was 19 months and the average dosage of A10 and AS2-1 was 0.28 g/kg/day. Responses were assessed by MRI according to the National Cancer Institute's criteria and confirmed by PET scans in some cases. RESULTS: Complete response was accomplished in 33%, partial response in 25%, and stable disease in 33% of patients, and there was no progressive disease. One patient was non-evaluable due to only 4 weeks of ANP and lack of follow-up scans. One patient who had stable disease discontinued ANP against medical advice and died 4.5 years later. Ten patients are alive and well from 2 to >14 years post-diagnosis. Only one case of serious toxicity of reversible tinnitus, of one day's duration, was described. The study continues with accrual of additional patients. CONCLUSION: The results of the present study are favourable in comparison with radiation therapy and chemotherapy. We believe that confirmation of these results through further studies may introduce a new promising treatment for incurable paediatric brain tumours.

Phase II study of antineoplaston A10 and AS2-1 in patients with recurrent diffuse intrinsic brain stem glioma: a preliminary report.

OBJECTIVE: A phase II study of antineoplaston A10 and AS2-1 was conducted to evaluate the antineoplastic activity in patients with recurrent diffuse intrinsic brain stem glioma. PATIENTS AND METHODS: This report describes the results of treatment of the first 12 patients admitted to the study. Patients received escalating doses of antineoplaston A10 and AS2-1 by intravenous bolus injections. The median duration of treatment was 6 months and the average dosage of antineoplaston A10 was 11.3 g/kg/day and of antineoplaston AS2-1 0.4 g/kg/day. Responses were assessed by gadolinium-enhanced magnetic resonance imaging of the head. RESULTS: Of ten evaluable patients, complete response was determined in two cases (20%), partial response in three (30%), stable disease in three (30%) and progressive disease in two (20%). Survival at 2 years was 33.3%. Currently, of all 12 patients, two (17%) were alive and tumour free for over 5 years since initial diagnosis; one was alive for more than 5 years, and another for more than 4 years from the start of treatment. Only mild and moderate toxicities were observed, which included three cases of skin allergy, two cases of anaemia, fever and hypernatraemia, and single cases of agranulocytosis, hypoglycaemia, numbness, tiredness, myalgia and vomiting. CONCLUSION: The results of this study compared favourably with the responses of patients treated with radiation therapy and chemotherapy. The study continues with accrual of additional patients.