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.
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.
Authors: Li Gong; Marilyn M Giacomini; Craig Giacomini; Michael L Maitland; Russ B Altman; Teri E Klein Journal: Pharmacogenet Genomics Date: 2017-06 Impact factor: 2.089
Authors: Francis J Giles; Ophelia Q P Yin; William M Sallas; Philipp D le Coutre; Richard C Woodman; Oliver G Ottmann; Michele Baccarani; Hagop M Kantarjian Journal: Eur J Clin Pharmacol Date: 2012-10-05 Impact factor: 2.953