Combined sorafenib and yttrium-90 radioembolization for the treatment of advanced hepatocellular carcinoma

Abstract

Background and aims: In this pilot study, we assessed the safety and tolerability of combining sorafenib with ⁹⁰Y 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 before ⁹⁰Y 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 combining ⁹⁰Y radioembolization and sorafenib for advanced hcc. A larger prospective study is needed to determine the extent of the survival benefit.

Keywords: Hepatocellular carcinoma; radioembolization; sorafenib; unresectability.

FIGURE 1

Timeline and study design. CT = computed tomography.

FIGURE 2

Patient accrual and progress through the study, 2009–2012.

FIGURE 3

The burden of disease trended smaller in therapy responders than in non-responders, although the difference was nonsignificant. PR = partial response; CR = complete response; PD = progressive disease; SD = stable disease.

FIGURE 4

Kaplan–Meier survival curve for 29 patients completing the sorafenib plus ⁹⁰Y regimen.