High concentration of daunorubicin and daunorubicinol in human malignant astrocytomas after systemic administration of liposomal daunorubicin

被引:21
作者
Albrecht, KW
Hamer, PCD
Leenstra, S
Bakker, PJM
Beijnen, JH
Troost, D
Kaaijk, P
Bosch, AD
机构
[1] Univ Amsterdam, Acad Med Ctr, Grad Sch Neurosci, Dept Neurosurg, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Grad Sch Neurosci, Dept Neuropathol, NL-1105 AZ Amsterdam, Netherlands
[3] Univ Amsterdam, Acad Med Ctr, Grad Sch Neurosci, Dept Med Oncol, NL-1105 AZ Amsterdam, Netherlands
[4] Slotervaart Hosp, Dept Pharmacol, Amsterdam, Netherlands
关键词
brain neoplasm; glioma; Daunorubicin; liposomes; pharmacokinetics; multidrug resistance;
D O I
10.1023/A:1012287212388
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页码:267 / 271
页数:5
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