title: Tissue levels of chemotherapeutic agents for hepatic metastasis during hepatic arterial and portal injection.
abstract: Hepatic metastasis is one of the most important prognostic factors in digestive organ cancer, and hepatic arterial infusion is aggressively performed for therapy of nonresectable metastatic liver cancer. Although comparatively high response rates have been attained in some cases, this treatment has been ineffective in not a few cases because these metastatic tumors are frequently hypovascular in nature. To develop better methods of administering chemotherapeutic agents, we performed basic experiments concerning intraportal administration which has been regarded as having a generally negative effect, focusing on a report indicating that portal supply is dominant along the borders of metastatic liver cancer tumors. VX2 carcinoma cells were inoculated into the hepatic parenchyma beneath the capsule of juvenile Japanese white rabbits. Drugs were infused 2 weeks after the inoculation, then tissue and blood were sequentially sampled. Mitomycin C (1.7 mg/kg) was infused either by bolus injection to the hepatic artery (arterial infusion group) or by bolus injection to the portal vein (portal infusion group). Five-fluorouracil (9.5 mg/kg) and Cisplatin (1.6 mg/kg) were likewise infused continuously over 60 min, and tissue levels of the drugs were compared between the two groups. Mitomycin C and 5-fluorouracil levels were measured by HPLC and Cisplatin levels were measured by atomic absorption spectrophotometry. As a result, the levels of every drug in VX2 tumor tissue did not significantly differ between the arterial infusion group and the portal infusion group, while the levels were significantly higher than those in the intravenous infusion group. Using portal infusion, we observed a drug transition which was not inferior to that of arterial infusion, suggesting that an imported antitumoral effect may be obtained with this method compared with intravenous infusion.
authors.affiliation: First Department of Surgery, Okayama University Medical School, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kaneko
authors.forename: Y
authors.initials: Y
authors.lastname: Naomoto
authors.forename: M
authors.initials: M
authors.lastname: Aoyama
authors.forename: N
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005472:Fluorouracil / Q000493:pharmacokinetics*; D006499:Hepatic Artery / Q000378:metabolism*; D007262:Infusions, Intravenous; D007269:Injections, Intra-Arterial; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary*; D008297:Male; D016685:Mitomycin / Q000493:pharmacokinetics*; D009368:Neoplasm Transplantation; D011169:Portal Vein / Q000378:metabolism*; D011817:Rabbits; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D016685:Mitomycin; D005472:Fluorouracil