Abstract
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%, PR was 25%, median PFS was 4.8 months, median OS was 6.1 months, and OS at 6 months was 58.3%, at one year 25%, and 8.3% at two, five, and ten years. In the AA group, PR was 12.5%, median PFS was 3.7 months, median OS was 4.7 months, and OS at 6 months was 37.5%, and 12.5%, at one, two, five, and ten years. In conclusion, antineoplastons showed efficacy and acceptable toxicity in patients with recurrent, refractory or progressive primary brain tumors.
Highlights
Pediatric primary malignant brain tumors are a leading cause of cancer-related deaths in children [1]
Diagnosis made by magnetic resonance imaging (MRI) without the necessity of a biopsy is generally accepted for brainstem glioma (BSG)
As of May 15, 2013, all subjects were removed from the therapy due to a complete response (CR), partial response (PR), subject request, progressive disease (PD), or worsening clinical condition
Summary
Pediatric primary malignant brain tumors are a leading cause of cancer-related deaths in children [1]. Pediatric high-grade gliomas (HGG) are relatively uncommon and represent approximately 17% of all pediatric brain tumors [2]. Supratentorial HGG and diffuse intrinsic pontine glioma (DIPG) continue to be two main challenges for pediatric oncologists [3]. The standard of care for newly diagnosed HGG is surgical resection followed with daily temozolomide (TMZ) and radiation therapy (RT) with subsequent adjuvant TMZ [4] [5]. Standard RT continues to be the main treatment for newly diagnosed DIPG. There are no standard therapy recommendations after recurrence [5]-[7]
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