DIFFERENCE IN COOP PENETRATION INTO CSF BETWEEN SELECTIVE INTRAARTERIAL CHEMOTHERAPY IN PATIENTS WITH MALIGNANT GLIOMA AND INTRAVENOUS OR INTRACAROTID ADMINISTRATION IN PATIENTS WITH METASTATIC BRAIN-TUMOR

Platinum (Pt) levels in plasma and cerebrospinal fluid (CSF) in patien ts with malignant glioma were determined after initiation of selective intraarterial chemotherapy with a combination of VP-16 (etoposide) an d CDDP (cisplatin), and were compared with the CSF Pt levels in patien ts with metastatic brain tumors after intravenous or intracarotid admi nistration of VP-16 and CDDP. CSF Pt levels were also compared for var ious administration routes, doses, CSF sampling routes and blood-CSF b arriers in metastatic brain tumor. Changes in the blood-CSF barrier to CDDP during treatment in a patient with meningeal lymphoma and in a p atient recovering from surgical removal of a metastatic brain tumor we re also examined by periodic administration of CDDP. All CSF samples w ere taken through Ommaya reservoirs placed in the anterior horn of the lateral ventricle or the postoperative cavity. The mean peak CSF/plas ma total Pt ratio (T/T ratio) and the mean CSF total Pt/plasma ultrafi ltrable Pt ratio (T/U ratio) were highest (15.0% and 24.4%, respective ly) following selective intraarterial infusion of CDDP in patients wit h malignant glioma, followed by intravenous infusion in meningeal carc inomatosis (11.5% and 18.9%), intracarotid administration (5.4% and 8. 7%) and intravenous infusion (60 mg/m(2) 2.5% and 100 mg/m(2) 2.9%; an d 60 mg/m(2) 3.5% and 100 mg/m(2) 7.7%) in patients with the solid typ e of metastatic brain tumor. In CSF obtained from the postoperative ca vity in cases of metastatic brain tumor, T/T and T/U ratios were extre mely high (40.9% and 62.4%). However, the CSF Pt level even after sele ctive intraarterial administration of CDDP in malignant glioma was 0.5 1-1.64 mu g/ml total Pt and 0.43-1.08 mu g/ml ultrafiltrable Pt. Even the CSF level obtained from the postoperative cavity was 1.0-4.7 mu g/ ml total Pt. These low levels of total and ultrafiltrable Pt are consi dered not to be cytotoxic to disseminated cells in the CSF space and t o normal brain cells. As for changes in the blood-CSF barrier, repeate d administration of CDDP showed that the rate of entry of Pt into the CSF decreased in parallel with improvements apparent on CT scans in th e patient with meningeal lymphoma, and also showed that the blood-CSF barrier to Pt was gradually repaired after the metastatic brain tumor had been removed.