title: Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma.
abstract: BACKGROUND
  In Japan and South Korea, transarterial chemoembolisation (TACE) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown effective and safe in patients with advanced HCC. This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE.
  
  
  METHODS
  Patients (n=458) with unresectable HCC, Child-Pugh class A cirrhosis and ≥25% tumour necrosis/shrinkage 1-3 months after 1 or 2 TACE sessions were randomised 1:1 to sorafenib 400mg bid or placebo and treated until progression/recurrence or unacceptable toxicity. Primary end-point was time to progression/recurrence (TTP). Secondary end-point was overall survival (OS).
  
  
  RESULTS
  Baseline characteristics in the two groups were similar; >50% of patients started sorafenib>9 weeks after TACE. Median TTP in the sorafenib and placebo groups was 5.4 and 3.7 months, respectively (hazard ratio (HR), 0.87; 95% confidence interval (CI), 0.70-1.09; P=0.252). HR (sorafenib/placebo) for OS was 1.06 (95% CI, 0.69-1.64; P=0.790). Median daily dose of sorafenib was 386 mg, with 73% of patients having dose reductions and 91% having dose interruptions. Median administration of sorafenib and placebo was 17.1 and 20.1 weeks, respectively. No unexpected adverse events were observed.
  
  
  CONCLUSIONS
  This trial, conducted prior to the reporting of registrational phase III trials, found that sorafenib did not significantly prolong TTP in patients who responded to TACE. This may have been due to delays in starting sorafenib after TACE and/or low daily sorafenib doses.
authors.affiliation: Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Japan. m-kudo@med.kindai.ac.jp
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
authors.forename: Kazuho
authors.initials: K
authors.lastname: Imanaka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Chida
authors.forename: Kohei
authors.initials: K
authors.lastname: Nakachi
authors.forename: Won-Young
authors.initials: WY
authors.lastname: Tak
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Takayama
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hori
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Suh
authors.forename: Junji
authors.initials: J
authors.lastname: Furuse
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Tanaka
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsui
authors.forename: Michihiko
authors.initials: M
authors.lastname: Wada
authors.forename: Iku
authors.initials: I
authors.lastname: Yamaguchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohya
authors.forename: Gerold
authors.initials: G
authors.lastname: Meinhardt
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Okita
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D007564:Japan; D008113:Liver Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage*; D056910:Republic of Korea; D000077157:Sorafenib; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib