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.

The development of an implanted pump that can locally and metronomically deliver drugs and biological agents is crucial in the treatment of cancer. For the last eight years, we have worked on an implanted pump that can deliver precisely at microliter doses. The Ipsum pump (Cognos Therapeutics) has three components: a double lumen catheter, a sampling reservoir, and a pump. The drug is pumped out of the bellows (5 ml) via a hermetically sealed MRI compatible piezoelectric pump. The drug is delivered via the delivery catheter lumen into the target. The sampling lumen can draw from the target to determine levels of drug delivered, allowing for in-vivo pharmacokinetic measurements. The reservoir is connected to the catheter and can be used to sample fluid. An optical sensor (embedded spectrophotometer) is set a specific frequency to determine absorbance for pharmacokinetic measurements of drug delivered. The pump is powered by a long term battery (good for up to five years) and is wirelessly controlled externally by the physician operator. Our first disease model will be delivery of methotrexate to the cerebrospinal fluid in the treatment of leptomeningeal carcinomatosis. Citation Format: Thomas C. Chen, Frank Adell, Joshua Schachar. Development of an implanted pump for metronomic delivery of chemotherapy and biological compounds: the virtue of local delivery. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B31.