Medline ® Abstract for Reference 249
of 'Chemotherapy hepatotoxicity and dose modification in patients with liver disease'
UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib.
Meza-Junco J, Chu QS, Christensen O, Rajagopalan P, Das S, Stefanyschyn R, Sawyer MB
Cancer Chemother Pharmacol. 2009 Dec;65(1):1-4. Epub 2009 Aug 12.
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 micromol/L (normal range<20 micromol/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 micromol/L). Unconjugated bilirubin was 38 micromol/L and conjugated was 10 micromol/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.
Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada. firstname.lastname@example.org