Improved stability of lipiodol-drug emulsion for transarterial chemoembolisation of hepatocellular carcinoma results in improved pharmacokinetic profile: Proof of concept using idarubicin.

Details

Serval ID
serval:BIB_3A8066ACD50D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Improved stability of lipiodol-drug emulsion for transarterial chemoembolisation of hepatocellular carcinoma results in improved pharmacokinetic profile: Proof of concept using idarubicin.
Journal
European Radiology
Author(s)
Boulin M., Schmitt A., Delhom E., Cercueil J.P., Wendremaire M., Imbs D.C., Fohlen A., Panaro F., Herrero A., Denys A., Guiu B.
ISSN
1432-1084 (Electronic)
ISSN-L
0938-7994
Publication state
Published
Issued date
02/2016
Peer-reviewed
Oui
Volume
26
Number
2
Pages
601-609
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
OBJECTIVES: To investigate the relationship between the improved stability of an anticancer drug-lipiodol emulsion and pharmacokinetic (PK) profile for transarterial chemoembolisation (TACE) of hepatocellular carcinoma (HCC).
METHODS: The stability of four doxorubicin- or idarubicin-lipiodol emulsions was evaluated over 7 days. PK and clinical data were recorded after TACE with the most stable emulsion in eight unresectable HCC patients, after institutional review board approval.
RESULTS: The most stable emulsion was the one that combined idarubicin and lipiodol (1:2 v:v). At 7 days, the percentages of aqueous, persisting emulsion and oily phases were 50-0-50, 33-0-67, 31-39-30, and 10-90-0 for the doxorubicin-lipiodol (1:1 v:v), doxorubicin-lipiodol (1:2 v:v), idarubicin-lipiodol (1:1 v:v), and the idarubicin-lipiodol (1:2 v:v) emulsion, respectively. After TACE, mean idarubicin Cmax and AUC0-24h were 12.5 ± 9.4 ng/mL and 52 ± 16 ng/mL*h. Within 24 h after injection, 40% of the idarubicin was in the liver, either in vessels, tumours, or hepatocytes. During the 2 months after TACE, no clinical grade >3 adverse events occurred. One complete response, five partial responses, one stabilisation, and one progression were observed at 2 months.
CONCLUSION: This study showed a promising and favourable PK and safety profile for the idarubicin-lipiodol (1:2 v:v) emulsion for TACE.
KEY POINTS: • Transarterial chemoembolisation (TACE) regimens that improve survival in hepatocellular carcinoma are needed. • Improved emulsion stability for TACE resulted in a favourable pharmacokinetic profile. • Preliminary safety and efficacy data for the idarubicin-lipiodol emulsion for TACE were encouraging.
Keywords
Aged, Antibiotics, Antineoplastic/administration & dosage, Antibiotics, Antineoplastic/pharmacokinetics, Carcinoma, Hepatocellular/therapy, Chemoembolization, Therapeutic/methods, Ethiodized Oil/administration & dosage, Female, Humans, Idarubicin/administration & dosage, Idarubicin/pharmacokinetics, Liver Neoplasms/therapy, Male, Prospective Studies, Treatment Outcome
Pubmed
Web of science
Create date
22/01/2016 10:18
Last modification date
20/08/2019 13:30
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