Description:
<jats:title>Abstract</jats:title>
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<jats:title>Lessons Learned</jats:title>
<jats:p>Recruitment of patients with advanced hepatocellular carcinoma and Child-Pugh B for sorafenib treatment and additional pharmacokinetic studies is challenging. Patients with Child-Pugh B liver cirrhosis have high rates of cirrhosis-related adverse events.</jats:p>
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<jats:title>Background</jats:title>
<jats:p>Few data are available on the pharmacokinetics (PK) of sorafenib in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh B liver cirrhosis. This study aimed to explore the sorafenib PK and its relationship with efficacy and toxicity in these patients.</jats:p>
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<jats:title>Methods</jats:title>
<jats:p>Patients with advanced HCC and Child-Pugh B7-8 liver function were prospectively recruited at a tertiary center. Adverse events (AEs), progression-free survival (PFS), and overall survival (OS) were recorded. Patients received a starting dose of 200 b.i.d. with toxicity-adjusted dose escalation to a target dose of 400 mg b.i.d. with PK sampling at fixed time points.</jats:p>
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<jats:title>Results</jats:title>
<jats:p>Between May 2014 and March 2017, 12 patients were screened, of whom 7 progressed to a terminal stage during the screening (n = 6) or shortly after recruitment (n = 1). The five included patients had median PFS of 3.8 months (range, 1.7–10.8) and OS of 7.4 months (range, 1.7–25.8). Three patients had severe AEs and one patient had a partial response with an OS of 25.8 months. In 2017, the trial was aborted for lack of accrual.</jats:p>
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<jats:title>Conclusion</jats:title>
<jats:p>Because of low accrual, no conclusion can be drawn on the sorafenib PK in patients with advanced HCC and Child-Pugh B liver cirrhosis. The poor survival and frequent cirrhosis-related AEs suggest limited benefit for most of these patients.</jats:p>
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