CHRONIC CONVECTION ENHANCED DELIVERY (CED) OF TOPOTECAN FOR GLIOBLASTOMA

描述（由申请方提供）：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。我们在1期临床试验中表明，拓扑异构酶抑制剂拓扑替康可以通过对流增强递送安全有效地递送到复发性恶性胶质瘤患者中，作为克服全身递送限制的一种手段。在这项提案中，我们将通过验证一种创新的方法来改善这种治疗策略，该方法用于无创监测药物分布，并通过创新植入式微输注泵的使用来延长输注时间。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，通过植入式泵治疗复发性胶质母细胞瘤患者，该植入式泵可以长期将高剂量的拓扑替康递送到肿瘤和周围大脑中，以避免传统全身递送的限制。在更广泛的层面上，我们将首次在人类身上证明，能够长期实现药物直接进入脑实质的局部区域分布。 公共卫生相关性：脑肿瘤的化疗是无效的，因为过多的副作用限制了多少药物可以输送到大脑。在我们的提案中，我们描述并严格测试了一种创新的植入式导管和泵系统，用于将化疗药物直接输送到肿瘤中，以避免与标准口服或静脉内输送相关的副作用。

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. PUBLIC HEALTH RELEVANCE: Chemotherapy for brain tumors is ineffective because excessive side effects limit how much drug can be delivered into the brain. In our proposal we describe and critically test an innovative implantable catheter and pump system for delivering chemotherapy directly into the tumor for over extended time periods to avoid the side effects associated with standard oral or intravenous delivery.