IMPLANTED SYSTEM FOR INTRAVENTRICULAR DRUG INFUSION IN CENTRAL NERVOUS-SYSTEM TUMORS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 65  (5-6) , 401-411
Abstract
A totally implanted drug delivery system capable of maintaining constant cerebrospinal fluid (CSF) drug levels through continuous intraventricular infusion in outpatients was developed. This system was used to infuse methotrexate (MTX) intraventricularly in 7 patients with incurable CNS malignancies. One patient with meningeal diffuse histiocytic lymphoma, 5 patients with grade III-IV astrocytomas and 1 patient with melanoma metastatic to the brain were treated with this system for 4-40+ wk. The system consists of an Infusaid pump, implanted subcutaneously in the infraclavicular fossa, which delivers a drug-containing solution at a set rate (3-5 ml/day) through a subcutaneous silastic catheter to a Rickham ventriculostomy reservoir and into a lateral ventricle. System placement and maintenance were readily tolerated. Constant MTX infusion at rates of 0.5-10 mg/day generated corresponding constant CSF drug levels in the range of 2-30 .mu.M. Simultaneous serum MTX levels were undetectable (< 0.01 .mu.M), indicative of a 200- to 3000-fold selective regional concentration advantage for this approach. CNS toxic effects included transient meningism and fever (4 patients), transverse myelitis (1), and the development of a diffuse hypodensity of the white matter on computerized tomographic scan which was not associated with any neurologic deficit (2). The usual systemic toxic effects (myelosuppression and mucositis) of MTX were not seen. The patient with meningeal lymphoma has had a complete remission of meningeal disease continuing past 10 mo. Computerized tomography showed that 3 of the 5 high-grade astrocytomas had 25% size reductions in tumors lasting 2-6 mo. This system may provide a means for improved treatment of meningeal tumor although its role in the treatment of intraparenchymal brain tumors is less clear. Of greater consequence is the demonstrated ability of this system to maintain a controlled CSF drug level which should prove useful in many areas of therapeutic research.