title: A phase I study of hepatic arterial infusion chemotherapy with zinostatin stimalamer alone for hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatic arterial infusion of zinostatin stimalamer and lipiodol emulsion shows a moderate activity against hepatocellular carcinoma. However, the anti-tumor activity of zinostatin stimalamer alone is uncertain.
  
  
  METHODS
  The primary endpoint was to evaluate the frequency of dose-limiting toxicity and determine the maximum-tolerated dose of zinostatin stimalamer when used by intra-arterial infusion. The candidates for this study were patients with hepatocellular carcinoma no longer amenable to established forms of treatment. Hepatic arterial infusion chemotherapy was performed by selectively introducing a catheter into the hepatic artery with zinostatin stimalamer alone. Treatment was repeated at 4-8-week intervals until disease progression or the appearance of unacceptable toxicity. The starting dose of zinostatin stimalamer was 3 mg/m(2), and doses were increased in 1 mg/m(2) increments in successive cohorts. At least three patients were treated at each dose level and three additional patients were treated in the presence of dose-limiting toxicity.
  
  
  RESULTS
  Twelve patients were entered into this trial. Dose-limiting toxicity was observed in one of six patients at 3 mg/m(2), and in two of six patients at 4 mg/m(2). The maximum-tolerated dose was judged to be 3 mg/m(2) with liver dysfunction and serum creatinine increase as the dose-limiting toxicity. There was one early death suggested to be related to the protocol treatment. None of the 12 patients achieved an objective tumor response.
  
  
  CONCLUSIONS
  Hepatic arterial infusion with a zinostatin stimalamer of 3 mg/m(2) may be tolerated, but not active, in patients with far advanced hepatocellular carcinoma.
authors.affiliation: Division of Hepatobiliary and Pancreatic Medical Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. hirishii@east.ncc.go.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Junji
authors.initials: J
authors.lastname: Furuse
authors.forename: Michitaka
authors.initials: M
authors.lastname: Nagase
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Maru
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yoshino
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hayashi
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D007459:Iodized Oil / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008299:Maleic Anhydrides / Q000008:administration & dosage*; D008875:Middle Aged; D011137:Polystyrenes / Q000008:administration & dosage*; D009353:Zinostatin / Q000008:administration & dosage* / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D008299:Maleic Anhydrides; D011137:Polystyrenes; C035755:poly(maleic acid-styrene)neocarzinostatin; D007459:Iodized Oil; D009353:Zinostatin