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.
Washington University, School of Medicine, Division of Oncology, 660 South Euclid Avenue, Campus Box 8069, St Louis, MO 63110, USA. smarsh@im.wustl.edu.
Sharon
S
Marsh
Howard L
HL
McLeod
D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D002166:Camptothecin / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D010597:Pharmacogenetics / Q000379:methods*
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin