Pharmacogenetics of irinotecan toxicity

Irinotecan is an anticancer drug approved in combination therapy for advanced colorectal cancer. Severe, life-threatening toxicities can occur from irinotecan treatment. Although multiple genes may play a role in irinotecan activity, the UDP glycuronosyltransferase 1 family, polypeptide A1 (UGT1A1) enzyme has been strongly associated with toxicity. A common dinucleotide repeat polymorphism in the UGT1A1 promoter region (UGT1A1*28) has been correlated with severe toxicity in cancer patients receiving irinotecan-containing therapy. Prospective screening of patients prior to chemotherapy selection may reduce the frequency of severe toxicities by allowing alternate therapy selections for patients carrying the UGT1A1*28 polymorphism.