Journal
HEPATOLOGY RESEARCH
Volume 42, Issue 5, Pages 473-481Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1872-034X.2011.00942.x
Keywords
cisplatin; drug delivery systems; hepatocellular carcinoma; suspension; transcatheter arterial chemoembolization; VX2 liver tumor
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Funding
- Ministry of Health, Labour and Welfare of Japan
- Nippon Medical School
- Grants-in-Aid for Scientific Research [23390306] Funding Source: KAKEN
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Aim: To evaluate the antitumor effects and hepatotoxicity of transcatheter arterial chemoembolization (TACE) with cisplatin-iodized oil suspension and emulsion in a rabbit tumor model. Methods: Transcatheter arterial chemoembolization was performed on 12 rabbits with hepatic VX2 tumors using a cisplatin suspension (1 mg/kg cisplatin and 0.1 mL/kg iodized oil, n = 6) or emulsion (1 mg/kg cisplatin, 0.1 mL/kg of iodized oil, and 0.1 mL/kg saline solution, n = 6). Time series changes in plasma platinum concentration were compared over 24 h. All rabbits were killed at 7 days after TACE, and the growth ratio and residual viable proportion of tumors were calculated on the basis of ultrasonographic and histopathological findings. Hepatotoxicity was also evaluated. Differences between the two groups were statistically assessed with the Mann-Whitney U-test. The animal care committee of our institute approved this study. Results: Plasma platinum concentrations were significantly higher in the suspension group than in the emulsion group at 0.5-24 h after TACE (P < 0.05). Growth ratios (-24.6 +/- 9.98% vs. 21.4 +/- 8.87%, respectively; P = 0.004) and residual viable proportions of tumors (25.8 +/- 5.02% vs. 51.1 +/- 11.4%, respectively; P = 0.009) were significantly lower in the suspension group than in the emulsion group. Hepatotoxicity was transient in all rabbits. Conclusion: Cisplatin-iodized oil suspensions facilitated the slow release of cisplatin at the tumor border. A suspension is preferable to an emulsion for drug delivery and the antitumor effect during the treatment of VX2 liver tumors with TACE.
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