Safety and toxicity of radioembolization plus Sorafenib in advanced hepatocellular carcinoma: analysis of the European multicentre trial SORAMIC

Liver Int. 2015 Feb;35(2):620-6. doi: 10.1111/liv.12622. Epub 2014 Jul 8.

Abstract

Background & aims: 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.

Keywords: HCC; SIRT; hepatocellular carcinoma; radioembolization; safety; sorafenib; survival; tolerability.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / radiotherapy*
  • Combined Modality Therapy
  • Embolization, Therapeutic / adverse effects
  • Embolization, Therapeutic / methods*
  • Europe
  • Follow-Up Studies
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / radiotherapy*
  • Microspheres
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / therapeutic use*
  • Portal Vein / pathology
  • Sorafenib
  • Treatment Outcome
  • Yttrium / adverse effects
  • Yttrium / therapeutic use*

Substances

  • Phenylurea Compounds
  • Niacinamide
  • Yttrium
  • Sorafenib