Increased frequency of uridine diphosphate glucuronosyltransferase 1A1 7/7 in patients experiencing severe irinotecan-induced toxicities.
BACKGROUND
Uridine diphosphate glucuronosyltransferase (UGT) 1A1 7/7 polymorphism has been linked with an increased risk of irinotecan-induced severe toxicities. We evaluated UGT1A1 polymorphism in patients developing grade 3/4 toxicity after initiation of irinotecan to determine the frequency of this polymorphism in this population.


METHODS
Twenty patients with grade 3/4 irinotecan-induced toxicity underwent UGT1A1 genotyping in an exploratory study. The frequency of UGT1A1 7/7 and the pattern of toxicity associated with this polymorphism were described.


RESULTS
Forty percent of patients with grade 3/4 toxicities had a UGT1A 7/7 polymorphism (vs. 10% in general population). Six of 7 patients requiring hospitalization, 7 of 10 patients with grade 4 neutropenia, and 3 of 3 patients with grade 4 diarrhea, had UGT1A1 7/7 polymorphism.


CONCLUSIONS
Uridine diphosphate glucuronosyltransferase 1A1 7/7 is prevalent in patients with irinotecan grade 3/4 toxicity, especially in patients with treatment-related hospitalizations and grade 4 toxicities. Our data support the need for more prospective studies that evaluate the predictive value of UGT1A1 as well as UGT1A1-based dosing in patients receiving irinotecan.
Fakih
Marwan G
MG
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. marwan.fakih@roswellpark.org
Ross
Mary Ellen
ME
Starostik
Petr
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011355:Prodrugs; D011401:Promoter Regions, Genetic; D000099148:UGT1A1 Enzyme
D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D011355:Prodrugs; D000099148:UGT1A1 Enzyme