title: Phase I study of miriplatin combined with transarterial chemotherapy using CDDP powder in patients with hepatocellular carcinoma.
abstract: BACKGROUND
  There is no standard therapeutic procedure for the hepatocellular carcinoma (HCC) in patients with poor hepatic reserve function. With the approval of newly developed chemotherapeutic agent of miriplatin, we have firstly conducted the phase I study of CDDP powder (DDP-H) and miriplatin combination therapy and reported its safety and efficacy for treating unresectable HCC in such cases. To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for the combination of transarterial oily chemoembolization (TOCE) and transarterial chemotherapy (TAC) using miriplatin and DDP-H for treating unresectable hepatocellular carcinoma (HCC).
  
  
  METHODS
  Transarterial chemotherapy using DDP-H was performed through the proper hepatic artery targeting the HCC nodules by increasing the dose of DDP-H (35-65 mg/m(2)) followed by targeting the HCC nodules by transarterial oily chemoembolization with miriplatin.
  
  
  RESULTS
  A total of nine patients were enrolled in this study and no DLT was observed with any dose of DDP-H in all cases in whom 80 mg (median, 18-120) miriplatin was administered. An anti-tumour efficacy rating for partial response was obtained in one patient, while a total of four patients (among eight evaluated) showed stable disease response, leading to 62.5% of disease control rate. The pharmacokinetic results showed no further increase in plasma platinum concentration following miriplatin administration.
  
  
  CONCLUSIONS
  Our results suggest that a combination of DDP-H and miriplatin can be safely administered up to their respective MTD for treating HCC.
  
  
  BACKGROUND
  This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR000003541).
authors.affiliation: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Kamimura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tamura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yokoo
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: Minoru
authors.initials: M
authors.lastname: Nomoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoyagi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002945:Cisplatin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007269:Injections, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011208:Powders
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011208:Powders; C406530:miriplatin; D002945:Cisplatin