title: Safety and toxicity of radioembolization plus Sorafenib in advanced hepatocellular carcinoma: analysis of the European multicentre trial SORAMIC.
abstract: OBJECTIVE
  The benefits of combined systemic and liver-directed treatments in inoperable intermediate- or advanced-stage hepatocellular carcinoma (HCC) have yet to be defined. This article presents the planned safety analyses for the first 40 patients randomized to radioembolization with yttrium-90 ((90) Y) resin microspheres followed by sorafenib (n = 20) or sorafenib only (n = 20) in the SORAMIC study.
  
  
  METHODS
  Patients identified for palliative treatment who were poor candidates for transarterial (chemo)embolization (including those failing TACE) with preserved liver function (Child-Pugh ≤B7) and ECOG performance status <2 were screened. Radioembolization was administered using a sequential lobar approach. On day 3 after the last radioembolization procedure, sorafenib 200 mg twice daily was initiated escalating to 400 mg twice daily 1 week later; a matching sorafenib dose schedule was initiated in the control arm.
  
  
  RESULTS
  Patients were followed up for a median of 8.3 months. Median total implanted activity of (90) Y was 1.87 (range: 0.54-2.35) GBq. Patients received a similar intensity and duration of sorafenib in the combination-treatment arm (median daily dose 614 mg over 8.5 months) and control arm (557 mg over 9.6 months). The incidence of total (196 vs. 222) and grade ≥3 (43 vs. 47) adverse events was similar in combination-treatment arm and control arm respectively (P > 0.05). No significant differences in the number of total or grade 3/4 toxicities were recorded for: total bilirubin, albumin, liver enzymes, ascites, Child-Pugh, fatigue, hand-foot skin reaction, blood pressure or diarrhoea.
  
  
  CONCLUSIONS
  Radioembolization followed by sorafenib appears to be as well tolerated as sorafenib alone.
authors.affiliation: Department of Radiology and Nuclear Medicine, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Ricke
authors.forename: Karsten
authors.initials: K
authors.lastname: Bulla
authors.forename: Frank
authors.initials: F
authors.lastname: Kolligs
authors.forename: Markus
authors.initials: M
authors.lastname: Peck-Radosavljevic
authors.forename: Peter
authors.initials: P
authors.lastname: Reimer
authors.forename: Bruno
authors.initials: B
authors.lastname: Sangro
authors.forename: Eckart
authors.initials: E
authors.lastname: Schott
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schütte
authors.forename: Chris
authors.initials: C
authors.lastname: Verslype
authors.forename: Jerzy
authors.initials: J
authors.lastname: Walecki
authors.forename: Peter
authors.initials: P
authors.lastname: Malfertheiner
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004621:Embolization, Therapeutic / Q000009:adverse effects / Q000379:methods*; D005060:Europe; D005500:Follow-Up Studies; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008863:Microspheres; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011169:Portal Vein / Q000473:pathology; D000077157:Sorafenib; D016896:Treatment Outcome; D015019:Yttrium / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D010671:Phenylurea Compounds; D009536:Niacinamide; D015019:Yttrium; D000077157:Sorafenib
keywords: HCC; SIRT; hepatocellular carcinoma; radioembolization; safety; sorafenib; survival; tolerability