| Abstract: | PurposeTo systematically review mechanism of action, pharmacokinetics (PKs), efficacy, and safety of ethiodized oil–based locoregional therapy (LRT) for liver cancer in preclinical models.Materials and MethodsA MEDLINE search was performed from 1988 to 2016. Search terms included hepatocellular carcinoma (HCC), HCC, liver-cell carcinoma, liver, hepatic, hepatocarcinoma, transarterial or chemoembolization, TACE, animal, Lipiodol, Ethiodol, iodized oil, and/or poppy-seed oil. Inclusion criteria were: publication in a peer-reviewed journal, an accepted animal model, and PK/safety/efficacy data reported. Exclusion criteria were: inadequate PK, safety, or efficacy data; anticancer drug name/dose not available; and article not in English. Outcomes included intratumoral anticancer drug uptake, PKs, tolerance, tumor response, and survival.ResultsOf 102 identified articles, 49 (49%) met the inclusion criteria. Seventeen, 35, and 2 articles used rat, rabbit, and pig models. Mechanism of action was investigated in 11 articles. Eleven articles reported drug uptake, PK, and tolerance data, showing 0.5%–9.5% of injected chemotherapy dose in tumor. Tumor-to-liver drug distribution ratios were 2–157. Toxicology data across 6 articles showed transient liver laboratory level elevations 1 day after LRT. There was no noteworthy liver or extrahepatic histologic damage. Nine articles reported tumor response, with 0%–30% viable tumor and –10% to –38% tumor growth at 7 days after LRT. Two articles reported survival, showing significantly longer survival after LRT vs untreated controls (56/60 d vs 33/28 d). Several articles described ethiodized oil mixed with radiopharmaceutical (n = 7), antiangiogenic (n = 6), gene (n = 6), nanoembolic (n = 5), immune (n = 2), or other novel (n = 1) agents.ConclusionsAnimal studies show preferential tumor uptake of anticancer agent, good hepatic/systemic tolerance, high tumor response, and enhanced survival after ethiodized oil–based LRT. |
