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UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib

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Abstract

Purpose

To report a single case of uridine glucuronosyltransferase 1A1 (UGT1A1) polymorphism and hyperbilirubinemia in a patient who received sorafenib.

Methods

A 63-year-old man with cirrhosis was diagnosed with hepatocellular carcinoma. His cirrhosis was categorized as Child-Pugh A, total bilirubin concentration was 24 μmol/L (normal range <20 μmol/L). The patient was enrolled in a phase I trial combination study of cyclophosphamide and doxorubicin combined with sorafenib.

Results

After a single infusion of doxorubicin and cyclophosphamide and 7 days of sorafenib, he presented with an elevated bilirubin concentration (48 μmol/L). Unconjugated bilirubin was 38 μmol/L and conjugated was 10 μmol/L. The patient was found to have one mutant allele (UGT1A1*28).

Conclusions

The isolated increase in serum bilirubin levels in our patient was probably due to sorafenib-induced UGT1A1 inhibition that manifested itself due both to the patient having one UGT1A1*28 allele and the presence of underlying liver disease. Bilirubin elevations in patients treated with sorafenib could indicate progression or drug toxicity; hence, these possibilities need to be ruled out. We would suggest that when patients develop hyperbilirubinemia while taking sorafenib for any indication, consideration be given to obtaining a fractionation of bilirubin and consideration of UGT1A1 genotyping in order to exclude a Gilbert’s syndrome as possible reason for the hyperbilrubinemia. Further studies are warranted to analyze the impact of sorafenib treatment on unconjugated bilirubin blood levels in patients with Gilbert’s syndrome.

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Authors and Affiliations

  1. Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada

    Judith Meza-Junco, Quincy S.-C. Chu, Ruslan Stefanyschyn & Michael B. Sawyer

  2. Bayer Healthcare Pharmaceuticals Inc, P.O. Box 1000, Montville, NJ, 07045-1000, USA

    Olaf Christensen & Prabhu Rajagopalan

  3. Department of Human Genetics, University of Chicago, 5841 South Maryland Avenue, Room L035/MC0077, Chicago, IL, 60637, USA

    Soma Das

Authors
  1. Judith Meza-Junco
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  2. Quincy S.-C. Chu
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  3. Olaf Christensen
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  4. Prabhu Rajagopalan
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  5. Soma Das
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  6. Ruslan Stefanyschyn
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  7. Michael B. Sawyer
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Correspondence to Judith Meza-Junco.

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Meza-Junco, J., Chu, Q.SC., Christensen, O. et al. UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib. Cancer Chemother Pharmacol 65, 1–4 (2009). https://doi.org/10.1007/s00280-009-1096-4

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  • DOI: https://doi.org/10.1007/s00280-009-1096-4

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