Sorafenib exposure and its correlation with response and safety in advanced hepatocellular carcinoma: results from an observational retrospective study



Severe adverse events frequently occur in patients treated with sorafenib, whereas some patients have suboptimal response to sorafenib. We aimed to evaluate the association of sorafenib-induced toxicities and clinical outcomes with the pharmacokinetics of sorafenib in patients with hepatocellular carcinoma (HCC).


This was a retrospective, observational study in which 26 HCC patients who had been treated with sorafenib were enrolled between September 2010 and March 2015. The association between trough sorafenib concentration and occurrence of grade ≥ 3 toxicities was evaluated. In addition, we estimated the association of trough sorafenib concentration with overall survival (OS).


The median sorafenib concentration was 2.91 μg/mL (range 0.74–8.8 μg/mL). Based on the receiver operating characteristic curve, the threshold value of the trough sorafenib concentration for predicting grade ≥ 3 toxicities and responder (complete response or partial response at best response, or stable disease for ≥ 3 months) was 3.45 μg/mL [area under the curve (AUC) 0.74, 95% confidence interval (CI) 0.54–0.93; p <0.05] and 1.40 μg/mL (AUC 0.97, 95% CI 0.97–1.00; p <0.05), respectively. OS of patients with sorafenib 1.40–3.45 µg/mL had a tendency to be longer than those of patients administered < 1.40 μg/mL and ≥ 3.45 μg/mL [median 17.8 months (1.40–3.45 μg/mL) vs. 5.3 months (< 1.40 μg/mL) and 9.5 months (≥ 3.45 μg/mL)].


From results of this study, we proposed that the target range of sorafenib may be a trough concentration of 1.40–3.45 μg/mL in patients with HCC.

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First of all, we thank all the patients that were willing to participate in this study. Furthermore, we would like to thank the hospital staff in acquiring the data.


This work was supported in part by grants from JSPS KAKENHI (Grant Numbers-JP18H00400), from the Research Foundation for Pharmaceutical Science, and from the Nakatomi Foundation.

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Correspondence to Satoshi Noda.

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This study protocol was approved by the Institutional Review Board of Shiga University of Medical Science. All patients gave written informed consent for the use of their blood sample and medical information for research.

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Noda, S., Hira, D., Osaki, R. et al. Sorafenib exposure and its correlation with response and safety in advanced hepatocellular carcinoma: results from an observational retrospective study. Cancer Chemother Pharmacol 86, 129–139 (2020).

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  • Sorafenib
  • Hepatocellular carcinoma
  • Pharmacokinetics
  • Personalized pharmacotherapy