Primary malignant brain tumors are a leading cause of cancer-related death in children. This Phase II study evaluated the efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in children who developed progressio...Primary malignant brain tumors are a leading cause of cancer-related death in children. This Phase II study evaluated the efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in children who developed progression during standard treatment. A total of 43 children were recruited to the study, but only 41 met eligibility criteria. There were twelve cases of glioblastoma multiforme (GBM), eight anaplastic astrocytomas (AA), twelve diffuse intrinsic pontine gliomas (DIPG), three supertentorial primitive neuroectodermal tumors (sPNET), three cases of medulloblastoma and one case each of anaplastic ependymoma (AE), atypical teratoid rhabdoid tumor (AT/RT), and disseminated pilocytic astrocytoma (PAD). ANP was administered intravenously daily every four hours (median dose of A10 8.74 g/kg/d and AS2-1 0.35 g/kg/d), until objective response (OR) was documented, and then a further eight months. All enrolled patients were included in safety, but only eligible patients in the efficacy evaluation. A total of 12.2% of patients obtained OR;2.4% complete response (CR) and 9.8% partial response (PR). Stable disease (SD) was determined in 17.1% and progressive disease (PD) in 43.9% of cases. There were 26.8% of nonevaluable (NE) cases due to premature discontinuation. Out of five OR cases, four patients were diagnosed with recurrent DIPG and one with recurrent AA. Median progression-free survival (PFS) was 2.5 months. Median overall survival was 4.8 months. OS at 6 months was 46.3%, one year was 12.2%, and 4.8% at two, five, and ten years. The longest survivor is a patient diagnosed with DIPG and gliosarcoma who remains alive more than 15 years. A group of eleven patients reported grade 3 and 4 toxicity including hypernatremia in eight cases, somnolence in two cases, and hypokalemia in one case. There were no chronic toxicities, and the quality of life was very good. The largest group of patients were represented by DIPG, GBM, and AA. The best results were obtained in the DIPG and AA groups. In the DIPG group, CR was in 8.3%,展开更多
Inoperable brainstem gliomas (BSG) are among the most difficult to treat malignancies. In the intent-to-treat (ITT) population of the BT-11 study for BSG, forty patients (median age 11.2 years old) were enrolled. Anti...Inoperable brainstem gliomas (BSG) are among the most difficult to treat malignancies. In the intent-to-treat (ITT) population of the BT-11 study for BSG, forty patients (median age 11.2 years old) were enrolled. Antineoplastons A10 and AS2-1 (ANP) were administered intravenously daily. The median daily dose of A10 was 8.70 g/kg/day and AS2-1 was 0.32 g/kg/day. Efficacy analyses were conducted in two subgroups: recurrent pediatric diffuse intrinsic pontine glioma (RPDIPG, N?= 17) and non-diffuse intrinsic pontine glioma (NDIPG, N?= 11). This paper reports the results of the study of the efficacy and safety of ANP in patients with NDIPG. The results in the RPDIPG group were reported before;complete response (CR) was 6%, partial response (PR) 23.5%, and stable disease (SD) 17.6%. One year overall survival (OS) was 29.4%, 2 years 11.8%, and 5, 10, and 15 years 6%. In the NDIPG group, there were 36% CR and 27.5% SD. OS at 1, 5, 10, and 15 years was 82%, 73%, 62%, and 50% correspondingly. There was only one serious adverse event (9%) reported in NDIPG represented by hypokalemia, Grade 4. The results suggest that ANP shows efficacy and an acceptable tolerability profile in patients with RPDIPG and NDIPG.展开更多
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...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. Thirty-two 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.展开更多
Brainstem glioma is rare tumour in adults accounting for 1% - 2% of intracranial gliomas. In this case study, a 28-year-old female diagnosed with BG, and lesions were observed in the pons and medulla region of the bra...Brainstem glioma is rare tumour in adults accounting for 1% - 2% of intracranial gliomas. In this case study, a 28-year-old female diagnosed with BG, and lesions were observed in the pons and medulla region of the brain stem. She was initially treated with radiotherapy (54 Gy in 30 fractions for 6 weeks) but no change in her clinical condition and size of tumor was observed. Temozolomide (250 mg/daily for 5 days) was prescribed as first line chemotherapy. After completion of three cycles of Temozolomide, patient presented with diplopia and MRI showed increase in the size of lesions. After unsatisfactory response to radiation and chemotherapy, the patient was treated with Nimotuzumab therapy. MRI scan demonstrated the reduction of lesion size after 8 cycles of Nimotuzumab (200 mg/week). This treatment continued for another 8 cycles and the MRI scan of patients showed a significant reduction in lesion size. Nimotuzumab was found to be an effective and safe treatment option for brainstem glioma patient who was resistant to radiotherapy and chemotherapy.展开更多
Diffuse intrinsic pontine glioma (DIPG) is the most common type of brainstem glioma and one of the most deadly brain tumors. DIPG in young adult patients is a rare disease for which treatment options are limited. Radi...Diffuse intrinsic pontine glioma (DIPG) is the most common type of brainstem glioma and one of the most deadly brain tumors. DIPG in young adult patients is a rare disease for which treatment options are limited. Radiation therapy remains the standard-of-care for newly-diagnosed DIPG, but no established therapies for recurrent disease are available. This paper describes the results of treatment of a young adult patient diagnosed with DIPG that progressed after radiation therapy. Therapy included sodium phenylbutyrate (PB) in combination with the targeted agents: pazopanib, everolimus, erlotinib, and bevacizumab. The patient achieved a rapid partial response, which persisted over a year and five months. The patient opted to discontinue the therapy and thereafter elected chemotherapy, which resulted in a subsequent rapid progression and death within one month. The targeted treatment was associated with minor toxicity that included a Grade 2 skin rash and Grade 1 elevation of transaminases. In conclusion, a combination of PB and currently available targeted drugs may offer extended survival in patients with recurrent DIPG.展开更多
文摘Primary malignant brain tumors are a leading cause of cancer-related death in children. This Phase II study evaluated the efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in children who developed progression during standard treatment. A total of 43 children were recruited to the study, but only 41 met eligibility criteria. There were twelve cases of glioblastoma multiforme (GBM), eight anaplastic astrocytomas (AA), twelve diffuse intrinsic pontine gliomas (DIPG), three supertentorial primitive neuroectodermal tumors (sPNET), three cases of medulloblastoma and one case each of anaplastic ependymoma (AE), atypical teratoid rhabdoid tumor (AT/RT), and disseminated pilocytic astrocytoma (PAD). ANP was administered intravenously daily every four hours (median dose of A10 8.74 g/kg/d and AS2-1 0.35 g/kg/d), until objective response (OR) was documented, and then a further eight months. All enrolled patients were included in safety, but only eligible patients in the efficacy evaluation. A total of 12.2% of patients obtained OR;2.4% complete response (CR) and 9.8% partial response (PR). Stable disease (SD) was determined in 17.1% and progressive disease (PD) in 43.9% of cases. There were 26.8% of nonevaluable (NE) cases due to premature discontinuation. Out of five OR cases, four patients were diagnosed with recurrent DIPG and one with recurrent AA. Median progression-free survival (PFS) was 2.5 months. Median overall survival was 4.8 months. OS at 6 months was 46.3%, one year was 12.2%, and 4.8% at two, five, and ten years. The longest survivor is a patient diagnosed with DIPG and gliosarcoma who remains alive more than 15 years. A group of eleven patients reported grade 3 and 4 toxicity including hypernatremia in eight cases, somnolence in two cases, and hypokalemia in one case. There were no chronic toxicities, and the quality of life was very good. The largest group of patients were represented by DIPG, GBM, and AA. The best results were obtained in the DIPG and AA groups. In the DIPG group, CR was in 8.3%,
文摘Inoperable brainstem gliomas (BSG) are among the most difficult to treat malignancies. In the intent-to-treat (ITT) population of the BT-11 study for BSG, forty patients (median age 11.2 years old) were enrolled. Antineoplastons A10 and AS2-1 (ANP) were administered intravenously daily. The median daily dose of A10 was 8.70 g/kg/day and AS2-1 was 0.32 g/kg/day. Efficacy analyses were conducted in two subgroups: recurrent pediatric diffuse intrinsic pontine glioma (RPDIPG, N?= 17) and non-diffuse intrinsic pontine glioma (NDIPG, N?= 11). This paper reports the results of the study of the efficacy and safety of ANP in patients with NDIPG. The results in the RPDIPG group were reported before;complete response (CR) was 6%, partial response (PR) 23.5%, and stable disease (SD) 17.6%. One year overall survival (OS) was 29.4%, 2 years 11.8%, and 5, 10, and 15 years 6%. In the NDIPG group, there were 36% CR and 27.5% SD. OS at 1, 5, 10, and 15 years was 82%, 73%, 62%, and 50% correspondingly. There was only one serious adverse event (9%) reported in NDIPG represented by hypokalemia, Grade 4. The results suggest that ANP shows efficacy and an acceptable tolerability profile in patients with RPDIPG and NDIPG.
文摘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. Thirty-two 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.
文摘Brainstem glioma is rare tumour in adults accounting for 1% - 2% of intracranial gliomas. In this case study, a 28-year-old female diagnosed with BG, and lesions were observed in the pons and medulla region of the brain stem. She was initially treated with radiotherapy (54 Gy in 30 fractions for 6 weeks) but no change in her clinical condition and size of tumor was observed. Temozolomide (250 mg/daily for 5 days) was prescribed as first line chemotherapy. After completion of three cycles of Temozolomide, patient presented with diplopia and MRI showed increase in the size of lesions. After unsatisfactory response to radiation and chemotherapy, the patient was treated with Nimotuzumab therapy. MRI scan demonstrated the reduction of lesion size after 8 cycles of Nimotuzumab (200 mg/week). This treatment continued for another 8 cycles and the MRI scan of patients showed a significant reduction in lesion size. Nimotuzumab was found to be an effective and safe treatment option for brainstem glioma patient who was resistant to radiotherapy and chemotherapy.
文摘Diffuse intrinsic pontine glioma (DIPG) is the most common type of brainstem glioma and one of the most deadly brain tumors. DIPG in young adult patients is a rare disease for which treatment options are limited. Radiation therapy remains the standard-of-care for newly-diagnosed DIPG, but no established therapies for recurrent disease are available. This paper describes the results of treatment of a young adult patient diagnosed with DIPG that progressed after radiation therapy. Therapy included sodium phenylbutyrate (PB) in combination with the targeted agents: pazopanib, everolimus, erlotinib, and bevacizumab. The patient achieved a rapid partial response, which persisted over a year and five months. The patient opted to discontinue the therapy and thereafter elected chemotherapy, which resulted in a subsequent rapid progression and death within one month. The targeted treatment was associated with minor toxicity that included a Grade 2 skin rash and Grade 1 elevation of transaminases. In conclusion, a combination of PB and currently available targeted drugs may offer extended survival in patients with recurrent DIPG.
