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

Massimo Zucchetti, Amerigo Boiardi, Antonio Silvani, Idria Parisi, Stefano Piccolrovazzi, Maurizio D'Incalci

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

DaunoXome is a liposome formulation containing daunorubicin (DM). Encapsulation of the drug in liposomes presents the advantage of low-level systemic exposure and better drug penetration into the tumor. We studied the distribution of DM and its 13-dihydro metabolite, daunorubicinol (DMol), in surgical biopsies from different parts of glioblastomas. The study was performed in eight patients with recurrent glioblastoma, all of whom had previously undergone surgery and been treated with radiotherapy and chemotherapy, who received 50 mg of DaunoXome as a 1-h infusion. Surgery was performed at 24 and 48 h after the infusion in seven cases and one case, respectively. Biopsies were divided into three parts: the central area of the tumor, peripheral tumor tissue, and brain-adjacent tumor (BAT) tissue. A complete plasma pharmacokinetics 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 fluorescence detection after solvent extraction. At 24 h, concentrations of DM and DMol in the central part of the tumor ranged between <0.005 and 0.80 μg/g and between 0.005 and 1.58 μ/g, respectively. Concentrations were similar in the peripheral tumor and in BAT tissue. From the data obtained on the 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 μg/g, respectively. DaunoXome was rapidly cleared from the body, with the plasma 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 clearance 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 systemic exposure. Further studies are therefore warranted. Although only preliminary and obtained in previously treated patients, these data suggest that DaunoXome merits investigation in CNS tumors.

Original languageEnglish
Pages (from-to)173-176
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Volume44
Issue number2
DOIs
Publication statusPublished - 1999

Fingerprint

Daunorubicin
Glioma
Tumors
Metabolites
Glioblastoma
Neoplasms
Tissue
Surgery
Brain Neoplasms
Liposomes
Biopsy
Plasmas
Brain
daunorubicinol
Pharmaceutical Preparations
Pharmacokinetics
Chemotherapy
Half-Life
Radiotherapy
High performance liquid chromatography

Keywords

  • Brain tumor
  • Liposomal daunorubicin
  • Pharmacokinetics
  • Tumor level

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Distribution of daunorubicin and daunorubicinol in human glioma tumors after administration of liposomal daunorubicin. / Zucchetti, Massimo; Boiardi, Amerigo; Silvani, Antonio; Parisi, Idria; Piccolrovazzi, Stefano; D'Incalci, Maurizio.

In: Cancer Chemotherapy and Pharmacology, Vol. 44, No. 2, 1999, p. 173-176.

Research output: Contribution to journalArticle

@article{11596166e1924c3eb6e5b5f46b24a029,
title = "Distribution of daunorubicin and daunorubicinol in human glioma tumors after administration of liposomal daunorubicin",
abstract = "DaunoXome is a liposome formulation containing daunorubicin (DM). Encapsulation of the drug in liposomes presents the advantage of low-level systemic exposure and better drug penetration into the tumor. We studied the distribution of DM and its 13-dihydro metabolite, daunorubicinol (DMol), in surgical biopsies from different parts of glioblastomas. The study was performed in eight patients with recurrent glioblastoma, all of whom had previously undergone surgery and been treated with radiotherapy and chemotherapy, who received 50 mg of DaunoXome as a 1-h infusion. Surgery was performed at 24 and 48 h after the infusion in seven cases and one case, respectively. Biopsies were divided into three parts: the central area of the tumor, peripheral tumor tissue, and brain-adjacent tumor (BAT) tissue. A complete plasma pharmacokinetics 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 fluorescence detection after solvent extraction. At 24 h, concentrations of DM and DMol in the central part of the tumor ranged between <0.005 and 0.80 μg/g and between 0.005 and 1.58 μ/g, respectively. Concentrations were similar in the peripheral tumor and in BAT tissue. From the data obtained on the 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 μg/g, respectively. DaunoXome was rapidly cleared from the body, with the plasma 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 clearance 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 systemic exposure. Further studies are therefore warranted. Although only preliminary and obtained in previously treated patients, these data suggest that DaunoXome merits investigation in CNS tumors.",
keywords = "Brain tumor, Liposomal daunorubicin, Pharmacokinetics, Tumor level",
author = "Massimo Zucchetti and Amerigo Boiardi and Antonio Silvani and Idria Parisi and Stefano Piccolrovazzi and Maurizio D'Incalci",
year = "1999",
doi = "10.1007/s002800050964",
language = "English",
volume = "44",
pages = "173--176",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "2",

}

TY - JOUR

T1 - Distribution of daunorubicin and daunorubicinol in human glioma tumors after administration of liposomal daunorubicin

AU - Zucchetti, Massimo

AU - Boiardi, Amerigo

AU - Silvani, Antonio

AU - Parisi, Idria

AU - Piccolrovazzi, Stefano

AU - D'Incalci, Maurizio

PY - 1999

Y1 - 1999

N2 - DaunoXome is a liposome formulation containing daunorubicin (DM). Encapsulation of the drug in liposomes presents the advantage of low-level systemic exposure and better drug penetration into the tumor. We studied the distribution of DM and its 13-dihydro metabolite, daunorubicinol (DMol), in surgical biopsies from different parts of glioblastomas. The study was performed in eight patients with recurrent glioblastoma, all of whom had previously undergone surgery and been treated with radiotherapy and chemotherapy, who received 50 mg of DaunoXome as a 1-h infusion. Surgery was performed at 24 and 48 h after the infusion in seven cases and one case, respectively. Biopsies were divided into three parts: the central area of the tumor, peripheral tumor tissue, and brain-adjacent tumor (BAT) tissue. A complete plasma pharmacokinetics 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 fluorescence detection after solvent extraction. At 24 h, concentrations of DM and DMol in the central part of the tumor ranged between <0.005 and 0.80 μg/g and between 0.005 and 1.58 μ/g, respectively. Concentrations were similar in the peripheral tumor and in BAT tissue. From the data obtained on the 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 μg/g, respectively. DaunoXome was rapidly cleared from the body, with the plasma 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 clearance 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 systemic exposure. Further studies are therefore warranted. Although only preliminary and obtained in previously treated patients, these data suggest that DaunoXome merits investigation in CNS tumors.

AB - DaunoXome is a liposome formulation containing daunorubicin (DM). Encapsulation of the drug in liposomes presents the advantage of low-level systemic exposure and better drug penetration into the tumor. We studied the distribution of DM and its 13-dihydro metabolite, daunorubicinol (DMol), in surgical biopsies from different parts of glioblastomas. The study was performed in eight patients with recurrent glioblastoma, all of whom had previously undergone surgery and been treated with radiotherapy and chemotherapy, who received 50 mg of DaunoXome as a 1-h infusion. Surgery was performed at 24 and 48 h after the infusion in seven cases and one case, respectively. Biopsies were divided into three parts: the central area of the tumor, peripheral tumor tissue, and brain-adjacent tumor (BAT) tissue. A complete plasma pharmacokinetics 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 fluorescence detection after solvent extraction. At 24 h, concentrations of DM and DMol in the central part of the tumor ranged between <0.005 and 0.80 μg/g and between 0.005 and 1.58 μ/g, respectively. Concentrations were similar in the peripheral tumor and in BAT tissue. From the data obtained on the 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 μg/g, respectively. DaunoXome was rapidly cleared from the body, with the plasma 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 clearance 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 systemic exposure. Further studies are therefore warranted. Although only preliminary and obtained in previously treated patients, these data suggest that DaunoXome merits investigation in CNS tumors.

KW - Brain tumor

KW - Liposomal daunorubicin

KW - Pharmacokinetics

KW - Tumor level

UR - http://www.scopus.com/inward/record.url?scp=0032988632&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032988632&partnerID=8YFLogxK

U2 - 10.1007/s002800050964

DO - 10.1007/s002800050964

M3 - Article

C2 - 10412954

AN - SCOPUS:0032988632

VL - 44

SP - 173

EP - 176

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 2

ER -