Distribution of daunorubicin and daunorubicinol in human glioma tumors after administration of liposomal daunorubicin

DaunoXome is a liposome formulation containing daunorubicin (DM). Encapsula tion of the drug in liposomes presents the advantage of low-level systemic exposure and better drug penetration into the tumor. We studied the distrib ution of DM and its 13-dihydro metabolite. daunorubicinol (DMol), in surgic al biopsies from different parts of glioblastomas. The study was performed in eight patients with recurrent glioblastoma, all of whom had previously u ndergone surgery and been treated with radiotherapy and chemotherapy, who r eceived 50 mg of DaunoXome as a 1-h infusion. Surgery was performed at 24 a nd 48 h after the infusion in seven cases and one case, respectively. Biops ies were divided into three parts: the central area of the tumor. periphera l tumor tissue, and brain-adjacent tumor (BAT) tissue. A complete plasma ph armacokinetics study was conducted in seven cases, with samples being taken for up to 48 h after the end of the infusion. DM and DMol were determined in plasma and tissue by high-performance liquid chromatography with fluores cence detection after solvent extraction. At 24 hi concentrations of DM and DMol in the central part of the tumor ranged between <0.005 and 0.80 mu g/ g and between 0.005 and 1.58 mu g/g, respectively. Concentrations were simi lar in the peripheral tumor and in BAT tissue. From the data obtained on th e patient who underwent surgery at 48 h it appears that DM and DMol remain in tumor tissue for a long time, the concentrations being 0.4 and 2.8 mu g/ g, respectively. DaunoXome was rapidly cleared from the body, with the plas ma levels of DM and DMol determined at 48 h lying in the range of <5-50 and <5-20 ng/ml, respectively. The mean (+/-SD) half-life and plasmatic cleara nce of DM were 4.8 +/- 1.0 h and 0.2 +/- 0.06 l h(-1) m(-2). In conclusion, DaunoXome achieved and maintained potentially cytotoxic levels of both DM and DMol in glioblastoma for a long time in association with low-level syst emic exposure. Further studies are therefore warranted. Although only preli minary and obtained in previously treated patients, these data suggest that DaunoXome merits investigation in CNS tumors.