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

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.

• Authors: Jens Ricke, Karsten Bulla, Frank Kolligs, Markus Peck-Radosavljevic, Peter Reimer, Bruno Sangro, Eckart Schott, Kerstin Schütte, Chris Verslype, Jerzy Walecki, Peter Malfertheiner, SORAMIC study group
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 35 Issue 2 Pg. 620-6 (Feb 2015) ISSN: 1478-3231 [Electronic] United States
• PMID: 24930619 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Phenylurea Compounds
• Niacinamide
• Yttrium
• Sorafenib

Topics

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