CHRONIC CONVECTION ENHANCED DELIVERY (CED) OF TOPOTECAN FOR GLIOBLASTOMA

描述（由申请人提供）：无法达到足够的肿瘤内化疗药物浓度是胶质母细胞瘤患者治疗失败的主要原因之一。我们已经在一项1期临床试验中表明，拓扑异构酶抑制剂拓扑替康可以安全有效地通过对流增强递送给复发性恶性胶质瘤患者，作为克服全身递送限制的一种手段。在本提案中，我们将通过验证一种无创监测药物分布的创新方法来改进这种治疗策略，并通过创新使用植入式微输液泵来延长输液时间。在这些研究的结论中，预期的结果将是一种新的、可测量的策略，通过可植入的泵来治疗复发性胶质母细胞瘤患者，该泵可以长期将高剂量的拓扑替康输送到肿瘤和周围的大脑中，以避免传统全身输送带来的限制。在更广泛的层面上，我们将首次在人类身上证明，长期实现药物直接进入脑实质的局部-区域分布的能力。

DESCRIPTION (provided by applicant): The inability to achieve sufficient intratumoral concentrations of chemotherapeutic drugs in is one of the primary causes of treatment failure in patients with glioblastoma. We have shown in a Phase 1 clinical trial that a topoisomerase inhibitor, topotecan, can be safely and effectively delivered by convection enhanced delivery into patients with recurrent malignant gliomas as a means of overcoming systemic delivery limitations. In this proposal, we will improve this treatment strategy by validating an innovative method for non-invasive monitoring of drug distribution and expanding the duration of infusion by innovating the use of an implantable microinfusion pump. At the conclusion of these studies, the expected outcome will be a novel, measureable strategy to treat patients with recurrent glioblastoma via an implantable pump that can chronically deliver high doses of topotecan into the tumor and surrounding brain to avoid the limitations imposed by conventional systemic delivery. On a broader level, we will have demonstrated, for the first time in humans, the ability to chronically achieve a local-regional distribution of a drug directly into the brain parenchyma.