title: Phase I/II multicenter study of transarterial chemoembolization with a cisplatin fine powder and porous gelatin particles for unresectable hepatocellular carcinoma: Japan Interventional Radiology in Oncology Study Group Study 0401.
abstract: OBJECTIVE
  A multicenter phase I/II study of transarterial chemoembolization with a fine cisplatin powder and gelatin particles (GPs) for multifocal hepatocellular carcinoma (HCC) was conducted. Primary endpoints were dose-limiting toxicity (DLT) and recommended dose (RD). Secondary endpoints were the incidence and severity of adverse events and tumor response.
  
  
  METHODS
  Nonselective transarterial chemoembolization was performed until all tumor enhancement disappeared. Lipiodol was not used. In the phase I study, the cisplatin dose was escalated from 35 mg/m(2) to 65 mg/m(2) in 15-mg/m(2) increments to determine DLT and RD. In the phase II study, 40 patients were treated with the RD. Toxicity was assessed by Common Toxicity Criteria for Adverse Effects (version 3.0), and tumor response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST; version 1.0) and European Association for the Study of the Liver (EASL) criteria.
  
  
  RESULTS
  A total of 46 patients were enrolled. As no DLT occurred at any dose level in the phase I study, RD was determined as 65 mg/m(2). In the phase II study, the treatment was discontinued in one patient as a result of vasovagal response. Toxicities of grade 3 or higher included nausea (2.2%), pancreatitis (2.2%), cholecystitis (2.2%), thrombocytopenia (8.7%), hyperbilirubinemia (2.2%), and increased aspartate aminotransferase (28.3%) and alanine aminotransferase (21.7%) levels. Tumor response rates under RD were 25.6% and 64.1% by RECIST and EASL criteria, respectively.
  
  
  CONCLUSIONS
  Nonselective transarterial chemoembolization with fine cisplatin powder and GPs was well tolerated and effective in patients with multifocal HCC at the RD of 65 mg/m(2).
authors.affiliation: Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. osuga@radiol.med.osaka-u.ac.jp
authors.forename: Keigo
authors.initials: K
authors.lastname: Osuga
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Arai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Anai
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Aramaki
authors.forename: Eiji
authors.initials: E
authors.lastname: Sugihara
authors.forename: Takanobu
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Inaba
authors.forename: Fumikiyo
authors.initials: F
authors.lastname: Ganaha
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Seki
authors.forename: Shunichi
authors.initials: S
authors.lastname: Sadaoka
authors.forename: Mikio
authors.initials: M
authors.lastname: Sato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kodama
authors.forename: Shinichi
authors.initials: S
authors.lastname: Inoh
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yamakado
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005780:Gelatin / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D016062:Porosity; D011208:Powders; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D011208:Powders; D005780:Gelatin; D002945:Cisplatin