title: A randomized phase II trial of intra-arterial chemotherapy using SM-11355 (Miriplatin) for hepatocellular carcinoma.
abstract: BACKGROUND
  SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC) via administration into the hepatic artery as a sustained-release suspension in iodized oil. We conducted a multicenter phase II trial in patients with HCC to evaluate the efficacy and safety of SM-11355, using a Zinostatin stimalamer suspension in iodized oil as a reference.
  
  
  METHODS
  Patients with unresectable HCC were randomized 2:1 to receive administration of the SM-11355 or Zinostatin stimalamer suspension into the hepatic artery. A second injection was given 4-12 weeks later. Efficacy was evaluated by CT 3 months after treatment and categorized as therapeutic effect (TE) V to I, where TE V was defined as disappearance or 100% necrosis of all treated tumors.
  
  
  RESULTS
  A total of 122 patients were evaluated for efficacy and toxicity (SM-11355, n = 83; Zinostatin stimalamer, n = 39). Baseline characteristics were similar in the two groups. The TE V rates were 26.5% (22/83) and 17.9% (7/39) in the SM-11355 and Zinostatin stimalamer groups, respectively. In the SM-11355 group,the most frequent drug-related adverse events (AEs) of ≥ grade 3 were elevated AST, elevated ALT, thrombocytopenia, and hyperbilirubinemia. The AEs with the largest difference between the two groups (SM-11355 vs. Zinostatin stimalamer) were hepatic vascular injury (0 vs. 48.4%) and eosinophilia (84.3 vs. 41.0%). The 2-year and 3-year survival rates were 75.9% vs. 70.3% and 58.4% vs. 48.7%, respectively.
  
  
  CONCLUSIONS
  The results suggest that SM-11355 in iodized oil has similar efficacy to Zinostatin stimalamer and that repeated dosing of SM-11355 is possible without hepatic vascular injury in cases of relapse.
authors.affiliation: Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. tokusaka@ncc.go.jp
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kasugai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Shioyama
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.forename: Masaharu
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Toshihito
authors.initials: T
authors.lastname: Seki
authors.forename: Hidetugu
authors.initials: H
authors.lastname: Saito
authors.forename: Naoaki
authors.initials: N
authors.lastname: Hayashi
authors.forename: Keiko
authors.initials: K
authors.lastname: Shiratori
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Okita
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
authors.forename: Masao
authors.initials: M
authors.lastname: Honda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kusumoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsutsumi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakata
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial / Q000379:methods; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015996:Survival Rate
chemical_list: D009944:Organoplatinum Compounds; C406530:miriplatin