title: A safe and effective dose of cisplatin in hepatic arterial infusion chemotherapy for hepatocellular carcinoma.
abstract: Cisplatin (CDDP) is an anticancer agent that is commonly used in hepatic arterial infusion (HAI) chemotherapy for hepatocellular carcinoma (HCC). This study aimed to clarify the safe and effective dose of CDDP in HAI for HCC. The hypervascular area was measured in 42 HCCs before and after HAI with CDDP. Serum platinum concentration was quantified in the peripheral and/or middle hepatic veins by atomic absorption spectrometry. The relation between the HCC response and CDDP dose was statistically analyzed. The multiple HCC nodules in an individual case generally demonstrated the same response to CDDP. The free-platinum concentration stayed relatively constant in the hepatic vein during HAI followed by a rapid decline, while total-platinum gradually increased then slowly disappeared over several days. After CDDP-HAI, 15 HCCs shrunk and 27 HCCs grew. The reduction rate in the shrunken nodules was tended to be correlated with CDDP dose after standardization with the target liver volume. On the other hand, the growth rate of the enlarged HCCs was significantly correlated with CDDP dose after normalization with creatinine clearance. These data support a recommendation of CDDP-HAI infusion where the amount of CDDP (mg) administered is less than patient creatinine clearance (mL/min/1.73 m(2)) upon an assumption of HCC doubling time of 90 days, and the targeted liver is smaller than 200 times the CDDP dose (mg). A further analysis is required to define appropriate injection speeds.
authors.affiliation: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University Niigata, Niigata 951-8510, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Osaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suda
authors.forename: Kenya
authors.initials: K
authors.lastname: Kamimura
authors.forename: Atsunori
authors.initials: A
authors.lastname: Tsuchiya
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tamura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takamura
authors.forename: Masato
authors.initials: M
authors.lastname: Igarashi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kawai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamagiwa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoyagi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010984:Platinum / Q000097:blood; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010984:Platinum; D002945:Cisplatin
keywords: Cisplatin; dose recommendation; hepatic arterial infusion chemotherapy; hepatocellular carcinoma