title: High concentration of Daunorubicin and Daunorubicinol in human malignant astrocytomas after systemic administration of liposomal Daunorubicin.
abstract: The value of chemotherapy in patients with malignant astrocytoma remains controversial. In our laboratories in vitro experiments with organotypic spheroid cultures showed superior effectiveness of anthracyclines. Systemic administration did not provide in therapeutic concentrations so far. Because recent studies on Daunorubicin in liposomes in the treatment of Kaposi sarcoma have shown effectiveness with diminished systemic toxicity, we administered intravenously a single dose of Daunorubicin in liposomes in eight patients at different intervals prior to surgery (12-50 h). In samples taken from tumor, tumor-edge and where possible from adjacent brain, the levels of Daunorubicin and its active metabolite Daunorubicinol were assessed with high performance liquid chromatography. Here we report that high concentrations of Daunorubicin and Daunorubicinol were found in malignant gliomas after systemic administration of liposomal Daunorubicin.
authors.affiliation: Department of Neurosurgery, Graduate School of Neurosciences, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: K W
authors.initials: KW
authors.lastname: Albrecht
authors.forename: P C
authors.initials: PC
authors.lastname: de Witt Hamer
authors.forename: S
authors.initials: S
authors.lastname: Leenstra
authors.forename: P J
authors.initials: PJ
authors.lastname: Bakker
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: D
authors.initials: D
authors.lastname: Troost
authors.forename: P
authors.initials: P
authors.lastname: Kaaijk
authors.forename: A D
authors.initials: AD
authors.lastname: Bosch
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001254:Astrocytoma / Q000378:metabolism*; D003630:Daunorubicin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D013997:Time Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; C000847:daunorubicinol; D003630:Daunorubicin