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J Neurosurg. 2015 Aug;123(2):362-72. doi: 10.3171/2014.10.JNS14343. Epub 2015 May 8.

Development of the Metronomic Biofeedback Pump for leptomeningeal carcinomatosis: technical note.

Author information

1
Departments of 1 Neurosurgery and Pathology, and.
2
Pharmaco-Kinesis Corporation, Inglewood; and.
3
Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California, Los Angeles;
4
Magnetecs Corporation, Inglewood, California.

Abstract

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.

KEYWORDS:

Ara-C = cytosine arabinoside; BBB = blood-brain barrier; GUI = graphical user interface; ICP = intracranial pressure; LC = leptomeningeal carcinomatosis; MBP = Metronomic Biofeedback Pump; MTX = methotrexate; biofeedback; intrathecal; leptomeningeal carcinomatosis; metronomic delivery; oncology

PMID:
25955873
DOI:
10.3171/2014.10.JNS14343
[Indexed for MEDLINE]

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