title: Multicenter phase II study of sequential radioembolization-sorafenib therapy for inoperable hepatocellular carcinoma.
abstract: BACKGROUND
  The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies.
  
  
  METHODS
  Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS).
  
  
  RESULTS
  Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively.
  
  
  CONCLUSIONS
  This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00712790.
authors.affiliation: National Cancer Centre, Singapore, Singapore; Singapore General Hospital, Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Pierce K H
authors.initials: PK
authors.lastname: Chow
authors.affiliation: Singapore General Hospital, Singapore, Singapore.
authors.forename: Donald Y H
authors.initials: DY
authors.lastname: Poon
authors.affiliation: Yangon Gastrointestinal and Liver Centre, Yangon, Myanmar.
authors.forename: Maung-Win
authors.initials: MW
authors.lastname: Khin
authors.affiliation: Selayang Hospital, Selangor, Malaysia.
authors.forename: Harjit
authors.initials: H
authors.lastname: Singh
authors.affiliation: Seoul National University Bundang Hospital, Bundang, South Korea.
authors.forename: Ho-Seong
authors.initials: HS
authors.lastname: Han
authors.affiliation: National Cancer Centre, Singapore, Singapore.
authors.forename: Anthony S W
authors.initials: AS
authors.lastname: Goh
authors.affiliation: Singapore General Hospital, Singapore, Singapore.
authors.forename: Su-Pin
authors.initials: SP
authors.lastname: Choo
authors.affiliation: National Cancer Centre, Singapore, Singapore.
authors.forename: Hee-Kit
authors.initials: HK
authors.lastname: Lai
authors.affiliation: National Cancer Centre, Singapore, Singapore.
authors.forename: Richard H G
authors.initials: RH
authors.lastname: Lo
authors.affiliation: National Cancer Centre, Singapore, Singapore.
authors.forename: Kiang-Hiong
authors.initials: KH
authors.lastname: Tay
authors.affiliation: National Cancer Centre, Singapore, Singapore.
authors.forename: Teong-Guan
authors.initials: TG
authors.lastname: Lim
authors.affiliation: Duke-NUS Graduate Medical School, Singapore, Singapore; Singapore Clinical Research Institute, Singapore, Singapore.
authors.forename: Mihir
authors.initials: M
authors.lastname: Gandhi
authors.affiliation: Duke-NUS Graduate Medical School, Singapore, Singapore; Singapore Clinical Research Institute, Singapore, Singapore.
authors.forename: Say-Beng
authors.initials: SB
authors.lastname: Tan
authors.affiliation: National Cancer Centre, Singapore, Singapore; Singapore General Hospital, Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Khee-Chee
authors.initials: KC
authors.lastname: Soo
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000503:physiopathology / Q000532:radiotherapy* / Q000601:surgery; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004621:Embolization, Therapeutic / Q000009:adverse effects; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000532:radiotherapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D000077157:Sorafenib; D013997:Time Factors; D015021:Yttrium Radioisotopes / Q000627:therapeutic use
chemical_list: D010671:Phenylurea Compounds; D015021:Yttrium Radioisotopes; D009536:Niacinamide; D000077157:Sorafenib