title: Phase 2 study of combined sorafenib and radiation therapy in patients with advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC).
  
  
  METHODS
  Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter.
  
  
  RESULTS
  Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal.
  
  
  CONCLUSIONS
  When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.
authors.affiliation: Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan; School of Medicine, Taipei Medical University, Taipei, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan. Electronic address: sjfchiou@gmail.com.
authors.forename: Shang-Wen
authors.initials: SW
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Chi-Mei Hospital, Tainan, Taiwan; School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Lin
authors.affiliation: Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan; Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Kuo
authors.affiliation: Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Ji-An
authors.initials: JA
authors.lastname: Liang
authors.affiliation: Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan; School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jeng-Fong
authors.initials: JF
authors.lastname: Chiou
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D003967:Diarrhea / Q000209:etiology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005355:Fibrosis / Q000473:pathology; D060831:Hand-Foot Syndrome; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011169:Portal Vein / Q000473:pathology; D011829:Radiation Dosage; D000077157:Sorafenib; D013997:Time Factors; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000473:pathology
chemical_list: D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib