title: Preclinical anticancer effects and toxicologic assessment of hepatic artery infusion of fine-powder cisplatin with lipiodol in vivo.
abstract: We conducted an in vivo study to evaluate the anticancer effect and toxicity of fine-powder cisplatin suspended in lipiodol (fCDDP/LPD suspension) after a single administration of three different doses to rats via the intrahepatic artery after transplantation of rat ascites hepatoma cells. The toxicity of the fCDDP/LPD suspension was also assessed in the same protocol in noncancer-bearing rats and the observed toxicologic changes were compared among groups administered saline (Sal), an aqueous solution of fCDDP (fCDDP/Sal solution), and LPD alone. In parallel with the toxicity test, plasma CDDP concentrations were compared between the fCDDP/LPD suspension and fCDDP/Sal solution. The mean weight of the tumors in the fCDDP/LPD suspension groups was significantly less than in the LPD-alone group. The pathologic changes in the liver observed in the fCDDP/LPD suspension group increased with dose, were more marked compared with those in the fCDDP/Sal solution and LPD-alone groups, and were reversible. No other toxicologic effects were observed. The concentration of CDDP in the plasma in the fCDDP/LPD suspension group was slightly lower than that in the fCDDP/Sal solution group. In conclusion, the results indicate that the fCDDP/LPD suspension has sufficient anticancer efficacy and tolerability for use in the clinical treatment of hepatocellular carcinoma.
authors.affiliation: Pharmaceutical Research Laboratories, Nippon Kayaku Co., Ltd., Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: N
authors.initials: N
authors.lastname: Nakajima
authors.forename: I
authors.initials: I
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Mashiba
authors.forename: T
authors.initials: T
authors.lastname: Kawashiro
authors.forename: K
authors.initials: K
authors.lastname: Ebara
authors.forename: E
authors.initials: E
authors.lastname: Ichimura
authors.forename: C
authors.initials: C
authors.lastname: Nishimura
authors.forename: K
authors.initials: K
authors.lastname: Okamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: T
authors.initials: T
authors.lastname: Ichida
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004998:Ethiodized Oil / Q000008:administration & dosage; D006499:Hepatic Artery; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009368:Neoplasm Transplantation; D010316:Particle Size; D011208:Powders; D051381:Rats; D018675:Toxicity Tests; D016896:Treatment Outcome
chemical_list: D011208:Powders; D004998:Ethiodized Oil; D002945:Cisplatin