Increased cytotoxicity and stability of Lipiodol-pirarubicin emulsion compared to classical doxorubicin-Lipiodol: potential advantage for chemoembolization of unresectable hepatocellular carcinoma.
There is no well-defined curative treatment for advanced and unresectable hepatocellular carcinoma. The widely used transarterial chemoembolization (TACE) with a doxorubicin-Lipiodol emulsion has not been shown to improve survival in randomized studies. Further, obstruction of the hepatic artery used in the procedure is badly tolerated in patients with cirrhosis. Drugs with a more rapid penetration into the cancer cells are likely to eliminate the need for obstruction of the hepatic artery. We therefore compared the cytotoxicity of another anthracycline pirarubicin with that of the commonly used doxorubicin. In this report, we show that pirarubicin has a greater in vitro cytotoxic effect than doxorubicin on the HepG2 and Hu-H7 human hepatoma cell lines. Pirarubicin emulsion with Lipiodol is more stable at 37 degrees C than doxorubicin-Lipiodol. Moreover, pirarubicin accumulates at a greater extent in the oil phase, permitting Lipiodol to act as a slow-releasing vector for the anthracycline. Further, amiodarone, a multidrug resistance inhibitor, was shown to decrease the intrinsic resistance of HepG2 and Hu-H7 cells to both anthracyclines, and the presence of polysorbate 80 in the amiodarone preparation increased the stability of the anthracycline-Lipiodol emulsions. We therefore conclude that pirarubicin is a better candidate for TACE than doxorubicin. The rapid and increased cytotoxicity of pirarubicin on hepatoma cancer cells and the stability of the pirarubicin-Lipiodol amiodarone emulsion could avoid the complete obstruction of the hepatic artery by Gelfoam sponges, and provide a better tolerated method of TACE in patients with latent liver insufficiency.
Favoulet
P
P
Faculty of Medicine, Unité INSERM 517, 21000 Dijon, France.
Cercueil
J P
JP
Faure
P
P
Osmak
L
L
Isambert
N
N
Beltramo
J L
JL
Cognet
F
F
Krause
D
D
Bedenne
L
L
Chauffert
B
B
D000638:Amiodarone / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D004355:Drug Stability; D004655:Emulsions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007459:Iodized Oil / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D004655:Emulsions; D004791:Enzyme Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D007459:Iodized Oil; D004317:Doxorubicin; C027260:pirarubicin; C022616:thiazolyl blue; D000638:Amiodarone