Chen Thomas C, Napolitano Gina R, Adell Frank, Schönthal Axel H, Shachar Yehoshua
Departments of 1 Neurosurgery and Pathology, and.
Pharmaco-Kinesis Corporation, Inglewood; and.
J Neurosurg. 2015 Aug;123(2):362-72. doi: 10.3171/2014.10.JNS14343. Epub 2015 May 8.
Patients with leptomeningeal carcinomatosis face a particularly grim prognosis. Current treatment consists of intrathecal delivery of methotrexate (MTX) or cytosine arabinoside (Ara-C) via Ommaya reservoir or lumbar puncture. Yet despite these interventions, the median survival after diagnosis is only 4-7 months. To address inherent shortcomings of current treatments and provide a more effective therapeutic approach, the Pharmaco-Kinesis Corporation has developed a novel type of implantable pump capable of delivering intrathecal chemotherapy (i.e., MTX) in a metronomic fashion with electronic feedback. The Metronomic Biofeedback Pump (MBP) consists of 3 components: 1) a 2-lumen catheter; 2) a microfluidic delivery pump with 2 reservoirs; and 3) a spectrophotometer monitoring MTX concentrations in the CSF. Using an animal model of intraventricular drug delivery, the authors demonstrate that the MBP can reliably deliver volumes of 500 μl/min, consistently measure real-time intrathecal MTX concentrations via CSF aspiration, and provide biofeedback with the possibility of instant control and delivery adjustments. Therefore, this novel approach to chemotherapy minimizes toxic drug levels and ensures continuous exposure at precisely adjusted, individualized therapeutic levels. Altogether, application of the MBP is expected to increase survival of patients with leptomeningeal carcinomatosis, and appropriate Phase I and II trials are pending.
柔脑膜癌病患者面临着特别严峻的预后。目前的治疗方法包括通过奥马亚贮液器或腰椎穿刺鞘内注射甲氨蝶呤（MTX）或阿糖胞苷（Ara-C）。然而，尽管采取了这些干预措施，诊断后的中位生存期仅为4至7个月。为了克服当前治疗方法的固有缺点并提供更有效的治疗方法，药代动力学公司开发了一种新型的可植入泵，能够以节律性方式并通过电子反馈进行鞘内化疗（即MTX）。节律性生物反馈泵（MBP）由3个组件组成：1）双腔导管；2）带有2个贮液器的微流体输送泵；3）监测脑脊液中MTX浓度的分光光度计。作者使用脑室内给药的动物模型证明，MBP能够可靠地以500微升/分钟的速度输送药物，通过抽取脑脊液持续测量鞘内MTX的实时浓度，并提供生物反馈，有可能即时控制和调整给药。因此，这种新型化疗方法可将药物毒性水平降至最低，并确保在精确调整的个体化治疗水平上持续给药。总体而言，预计MBP的应用将提高柔脑膜癌病患者的生存率，相应的I期和II期试验正在筹备中。
