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Case Reports
. 2021 Jan 9;14(1):46.
doi: 10.3390/ph14010046.

Combining Sorafenib and Immunosuppression in Liver Transplant Recipients with Hepatocellular Carcinoma

Koen G A M Hussaarts  1 , Leni van Doorn  1 , Sander Bins  1 , Dave Sprengers  2 , Peter de Bruijn  1 , Roelof W F van Leeuwen  1   3 , Stijn L W Koolen  1   3 , Teun van Gelder  3 , Ron H J Mathijssen  1
Affiliations
Case Reports

Combining Sorafenib and Immunosuppression in Liver Transplant Recipients with Hepatocellular Carcinoma

Koen G A M Hussaarts et al. Pharmaceuticals (Basel). .

Abstract

Hepatocellular carcinoma (HCC) recurrence after liver transplantation occurs in approximately 20% of patients. Most of these patients use immunosuppressant drugs. Meanwhile, patients with HCC recurrence are frequently treated with the small molecule kinase inhibitor (SMKI) sorafenib. However, sorafenib and many immunosuppressants are substrates of the same enzymatic pathways (e.g., CYP3A4), which may potentially result in altered SMKI or immunosuppressant plasma levels. Therefore, we investigated changes in drug exposure of both sorafenib and immunosuppressants over time in four patients with systemic immunosuppressant and sorafenib treatment after HCC recurrence. In this study, sorafenib exposure declined over time during combined treatment with immunosuppressants, while two patients also experienced declining tacrolimus plasma levels. Importantly, patients were unable to increase the sorafenib dose higher than 200 mg b.i.d. without experiencing significant toxicity. We recommend to treat patients using both sorafenib and immunosuppressants with a sorafenib starting dose of 200 mg b.i.d.

Keywords: HCC; liver transplantation; sorafenib.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Sorafenib and tacrolimus Ctrough concentrations over time for Subject 1: The Ctrough levels are displayed over time after the start of sorafenib treatment. Furthermore the optimal Ctrough levels of both sorafenib and tacrolimus are provided.
Figure 2
Figure 2
Sorafenib and tacrolimus Ctrough concentrations over time for Subject 2: The Ctrough levels over time after the start of sorafenib treatment. Furthermore the optimal Ctrough levels of both sorafenib and tacrolimus are provided.
Figure 3
Figure 3
Sorafenib and tacrolimus Ctrough concentrations over time for Subject 3: The Ctrough levels are displayed over time after the start of sorafenib treatment. Furthermore the optimal Ctrough levels of both sorafenib and sirolimus are provided. Case 3 was initially treated with both sirolimus and tacrolimus but stopped tacrolimus short after start of sorafenib as was shown in this figure.
Figure 4
Figure 4
Sorafenib and tacrolimus Ctrough concentrations over time for Subject 4: The Ctrough levels are displayed over time after the start of sorafenib treatment. Furthermore the optimal Ctrough levels of both sorafenib and tacrolimus are provided.
See this image and copyright information in PMC

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