Regression of recurrent malignant gliomas with convection-enhanced delivery of topotecan.
Regression of recurrent malignant gliomas with convection-enhanced delivery of topotecan.
复制标题
DOI：
10.1227/neu.0b013e3182233e24
复制
发表时间：
2011-12
期刊：
影响因子：
4.8
通讯作者：
DeLaPaz RL
中科院分区：
文献类型：
--
作者：
Bruce JN;Fine RL;Canoll P;Yun J;Kennedy BC;Rosenfeld SS;Sands SA;Surapaneni K;Lai R;Yanes CL;Bagiella E;DeLaPaz RL
恶性胶质瘤化疗药物的对流增强输注是一种通过持续、低级别正压输注将药物直接输送到肿瘤和周围间质中的技术。这使得局部药物浓度高，同时克服了全身治疗中毒性和血脑屏障所带来的限制，这些限制阻止了许多潜在有效药物的使用。检查传统化疗药物拓扑替康的安全性，通过对流增强输送治疗复发性恶性胶质瘤，其次评估放射学反应和生存率。我们对拓扑异构酶i抑制剂拓扑替康进行了一项前瞻性、剂量递增的Ib期研究，通过对流增强输送给复发性恶性胶质瘤患者。通过影像学改变和延长总生存期，证明具有显著的抗肿瘤活性，并且具有最小的药物相关毒性。为未来的II期研究确定了最大耐受剂量。拓扑替康通过对流增强输送在对正常大脑无毒的浓度下具有显著的抗肿瘤活性。这种疗法作为恶性胶质瘤的一种普遍有效的治疗选择的潜力将在随后的II期和III期试验中进行测试。
Convection-enhanced delivery of chemotherapeutics for the treatment of malignant glioma is a technique that delivers drugs directly into a tumor and the surrounding interstitium through continuous, low-grade positive-pressure infusion. This allows high local concentrations of drug while overcoming the limitations imposed by toxicity and the blood-brain barrier in systemic therapies that prevent the use of many potentially effective drugs. To examine the safety profile of a conventional chemotherapeutic agent, topotecan, via convection-enhanced delivery in the treatment of recurrent malignant gliomas and secondarily to assess radiographic response and survival. We performed a prospective, dose-escalation phase Ib study of the topoisomerase-I inhibitor topotecan given by convection-enhanced delivery in patients with recurrent malignant gliomas. Significant antitumor activity as described by radiographic changes and prolonged overall survival with minimal drug-associated toxicity was demonstrated. A maximum tolerated dose was established for future phase II studies. Topotecan by convection-enhanced delivery has significant antitumor activity at concentrations that are nontoxic to normal brain. The potential for use of this therapy as a generally effective treatment option for malignant gliomas will be tested in subsequent phase II and III trials.