[Cis-diamminedichloroplatinum penetration into the cerebrospinal fluid of the lateral ventricle, postoperative cavity, and lumbar subarachnoid space with or without pre-intravenous mannitol administration in patients with brain metastasis from lung cancer].

We have previously reported that repeated intravenous administration of cis-diamminedichloroplatinum(CDDP)prevented local recurrence of metastatic brain tumors after surgical total excision; however, data on CDDP distribution in the postoperative cavity after intravenous CDDP administration are not available. In the present study, we evaluated the penetration of total platinum(Pt)into the cerebrospinal fluid(CSF)and the effect of intravenous administration of 20%mannitolon total Pt distribution in the plasma and CSF. Total Pt levels in the plasma and CSF were determined immediately after intravenous infusion of CDDP(80mg/m2)for 1 hour, with or without pre-intravenous infusion of 20% mannitol(200mL), in 11 patients with brain metastasis from lung cancer. CSF samples were obtained via Ommaya reservoirs placed in the anterior horn of the lateral ventricle(CSF-V)and the postoperative cavity(CSF-C). Spinal CSF (CSF-L)was also obtained in the last 4 patients of the series via spinal drainage. CDDP was administered intravenously without mannitol 10 days after brain tumor excision, and 1 week after the initial administration of CDDP, CDDP was intravenously administered again after intravenous mannitol administration. CDDP was always administered intravenously at 1:00 PM to rule out the influence of circadian variation. Plasma and CSF were sequentially sampled after intravenous CDDP administration, and their Pt levels were analyzed for Pt content by using atomic absorption spectroscopy. The area under the concentration time curve(AUC)was calculated for plasma and CSF using the moment method. The AUC for total Pt in plasma showed a significantly higher level with the administration of mannitol than without the administration of mannitol(p<0.01, paired t-test). Total Pt levels(AUCs and peak concentrations)in CSF-C were much higher than were those in CSF-V and CSF-L both with and without the administration of mannitol. The ratio(%)of CDDP penetration into CSF(CSF AUC/plasma AUC)was much higher for CSF-C than for CSF-V(p<0.0001)both with and without mannitol administration. However, the CSF penetration ratio with mannitol administration did not differ significantly from that without mannitol administration. Thus, the administration of mannitol did not significantly increase the penetration ratio of total Pt. Creatinine clearance was moderately reduced in all patients during the first administration of CDDP. However, 7 of the 11 patients showed an increase in creatinine clearance after the second administration of CDDP with mannitol.