title: A randomised phase II study of TSU-68 in patients with hepatocellular carcinoma treated by transarterial chemoembolisation.
abstract: BACKGROUND
  TSU-68 is an antitumour drug that acts by inhibiting angiogenesis. We evaluated the efficacy and safety of TSU-68 in combination with transarterial chemoembolisation (TACE) in patients with intermediate-stage hepatocellular carcinoma (HCC).
  
  
  METHODS
  In this multicenter, open-label phase II study, we randomised patients with HCC who had been treated with a single session of TACE to receive either 200mg TSU-68 twice daily or no medication. The primary end-point was progression-free survival (PFS).
  
  
  RESULTS
  A total of 103 patients were enrolled. Median PFS was 157.0days (95% confidence interval [CI], 124.0-230.0days) in the TSU-68 group and 122.0days (95% CI, 73.0-170.0days) in the control group. The hazard ratio was 0.699 (95% CI, 0.450-1.088). Fatigue, elevated aspartate aminotransferase (AST), elevated alkaline phosphatase, oedema and anorexia were more frequent in the TSU-68 group than in the control group. The most frequent grade 3/4 adverse events were AST elevation (46% of patients in the TSU-68 group and 12% of controls) and alanine aminotransferase elevation (26% of patients in the TSU-68 group and 8% of controls). Two deaths, grade 5 hepatic failure and melena were noted in the TSU-68 group.
  
  
  CONCLUSIONS
  This exploratory study shows a trend towards prolonged PFS with TSU-68 treatment after a single session of TACE, but this observation was not statistically significant. The two deaths were related to the study treatment. These results suggest that further examination of the study design is necessary to determine whether TSU-68 has any clinical benefits when combined with TACE.
authors.affiliation: Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Japan. 105824@aichi-cc.jp
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Inaba
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kanai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Aramaki
authors.forename: Takanobu
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yamakado
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
authors.forename: Kazuho
authors.initials: K
authors.lastname: Imanaka
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kora
authors.forename: Norifumi
authors.initials: N
authors.lastname: Nishida
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kawai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Seki
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsui
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Arioka
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Arai
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007564:Japan; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D000078183:Oxindoles; D011422:Propionates / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011758:Pyrroles; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D000078183:Oxindoles; D011422:Propionates; D011758:Pyrroles; C412603:orantinib
keywords: Hepatocellular carcinoma; Platelet-derived growth factor; TSU-68; Transarterial chemoembolisation