Combined sorafenib and yttrium-90 radioembolization for the treatment of advanced hepatocellular carcinoma.
OBJECTIVE
In this pilot study, we assessed the safety and tolerability of combining sorafenib with90Y radioembolization for the treatment of unresectable hepatocellular carcinoma (hcc).


METHODS
The study, conducted prospectively during 2009-2012, included eligible patients with unresectable hcc and a life expectancy of at least 12 weeks. Each patient received sorafenib (400 mg twice daily) for 6-8 weeks before90Y treatment. Safety and tolerability were assessed.


RESULTS
Of the 40 patients enrolled, 29 completed treatment (combined therapy). In the initial cohort, the most common cause of hcc was hepatitis C (32.5%), and most patients were staged Child A (82.5%). The 29 patients who completed the study had similar baseline characteristics. Grades 1 and 2 toxicities accounted for 77.8% of all adverse events reported. The most common toxicities reported were fatigue (19.0%), alteration in liver function (7.9%), and diarrhea (6.3%). There were 12 grade 3 and 2 grade 4 toxicity events reported. One patient died of liver failure within 30 days after treatment. During the study, the sorafenib dose was reduced in 6 patients (20.7%), and sorafenib had to be interrupted in 4 patients (13.8%) and discontinued in 4 patients (13.8%). The disease control rate was 72.4% per the modified Response Evaluation Criteria in Solid Tumors, and tumour necrosis was observed in 82.8% of patients. Overall survival in patients undergoing combined therapy was 12.4 months.


CONCLUSIONS
Preliminary results demonstrate the safety and tolerability of combining90Y radioembolization and sorafenib for advanced hcc. A larger prospective study is needed to determine the extent of the survival benefit.
Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, McGill University, Montreal, QC.
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A
Salman
Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, McGill University, Montreal, QC.
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E
Simoneau
Department of Oncology, McGill University, Montreal, QC; Department of Surgery, King Saud University, Riyadh, Saudi Arabia.
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M
Hassanain
Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, McGill University, Montreal, QC; Department of Oncology, McGill University, Montreal, QC.
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P
Chaudhury
Department of Radiology, Division of Interventional Radiology, McGill University, Montreal, QC.
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LM
Boucher
Department of Radiology, Division of Interventional Radiology, McGill University, Montreal, QC.
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D
Valenti
Department of Radiology, Division of Interventional Radiology, McGill University, Montreal, QC.
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T
Cabrera
Department of Medicine, Division of Hepatology, McGill University, Montreal, QC.
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C
Nudo
Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, McGill University, Montreal, QC; Department of Oncology, McGill University, Montreal, QC.
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P
Metrakos
Hepatocellular carcinoma; radioembolization; sorafenib; unresectability