Standard treatment for high-grade glioma involves surgical resection followed by radiation therapy and temozolomide. Unfortunately, there are no standard treatment recommendations after recurrence and new therapies ar...Standard treatment for high-grade glioma involves surgical resection followed by radiation therapy and temozolomide. Unfortunately, there are no standard treatment recommendations after recurrence and new therapies are needed for patients whose tumor recurs after first-line treatment. This single-arm, two-stage, interventional Phase II study evaluated the efficacy and safety of a combination of antineoplastons A10 and AS2-1. Nineteen patients were enrolled in the study (safety population), but fifteen patients with a median age of 9.4 years who met eligibility criteria were evaluated. The majority of subjects (12/15) were Caucasian and 8/15 (53%) were female. More than half (53%) of patients were diagnosed with glioblastoma and 33% with anaplastic astrocytoma. All patients had failed standard therapy including surgery, radiation, and chemotherapy. Antineoplastons were administered intravenously every four hours (median dose of A10 6.9 g/kg/d and AS2-1 0.30 g/kg/d) until objective response was documented and thereafter for a further 8 months. Clinical evaluations were performed every 8 weeks. All patients enrolled in the study were included in the safety analysis but only patients fulfilling the inclusion criteria were included in the efficacy evaluation. The duration of treatment with antineoplastons ranged from 2 weeks to 120 weeks. A complete response was documented in 2/15 (13%), partial response in 2/15 (13%), stable disease in 3/15 (20%). Progression-free survival at six months was 47% and overall survival (OS) at one year was 33.3%. One patient (6.7%) survived 10 years from treatment start. A small group of patients suffered reversible Grade 3 and 4 toxicities including hypernatremia 2/19 (11%) and decrease of neutrophils 1/19 (5%). There were no chronic toxicities. There was improvement of quality of life in patients who had objective response. It is concluded that antineoplastons show efficacy with an acceptable profile in this cohort of patients with recurrent high-grade glioma.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
文摘Standard treatment for high-grade glioma involves surgical resection followed by radiation therapy and temozolomide. Unfortunately, there are no standard treatment recommendations after recurrence and new therapies are needed for patients whose tumor recurs after first-line treatment. This single-arm, two-stage, interventional Phase II study evaluated the efficacy and safety of a combination of antineoplastons A10 and AS2-1. Nineteen patients were enrolled in the study (safety population), but fifteen patients with a median age of 9.4 years who met eligibility criteria were evaluated. The majority of subjects (12/15) were Caucasian and 8/15 (53%) were female. More than half (53%) of patients were diagnosed with glioblastoma and 33% with anaplastic astrocytoma. All patients had failed standard therapy including surgery, radiation, and chemotherapy. Antineoplastons were administered intravenously every four hours (median dose of A10 6.9 g/kg/d and AS2-1 0.30 g/kg/d) until objective response was documented and thereafter for a further 8 months. Clinical evaluations were performed every 8 weeks. All patients enrolled in the study were included in the safety analysis but only patients fulfilling the inclusion criteria were included in the efficacy evaluation. The duration of treatment with antineoplastons ranged from 2 weeks to 120 weeks. A complete response was documented in 2/15 (13%), partial response in 2/15 (13%), stable disease in 3/15 (20%). Progression-free survival at six months was 47% and overall survival (OS) at one year was 33.3%. One patient (6.7%) survived 10 years from treatment start. A small group of patients suffered reversible Grade 3 and 4 toxicities including hypernatremia 2/19 (11%) and decrease of neutrophils 1/19 (5%). There were no chronic toxicities. There was improvement of quality of life in patients who had objective response. It is concluded that antineoplastons show efficacy with an acceptable profile in this cohort of patients with recurrent high-grade glioma.
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.
