UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib.
OBJECTIVE
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.
Meza-Junco
Judith
J
Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada. judimeza@cancerboard.ab.ca
Chu
Quincy S-C
QS
Christensen
Olaf
O
Rajagopalan
Prabhu
P
Das
Soma
S
Stefanyschyn
Ruslan
R
Sawyer
Michael B
MB
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D017321:Clinical Trials, Phase I as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D006932:Hyperbilirubinemia / Q000209:etiology* / Q000235:genetics; D008103:Liver Cirrhosis / Q000150:complications / Q000503:physiopathology; D008113:Liver Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011110:Polymorphism, Genetic; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D000077157:Sorafenib; D000099148:UGT1A1 Enzyme
D001557:Benzenesulfonates; D003520:Cyclophosphamide; D004317:Doxorubicin; D014453:Glucuronosyltransferase; D009536:Niacinamide; D010671:Phenylurea Compounds; D011725:Pyridines; D000077157:Sorafenib; D000099148:UGT1A1 Enzyme