Severe irinotecan-induced toxicities in a patient with uridine diphosphate glucuronosyltransferase 1A1 polymorphism.
Irinotecan is an analogue of camptothecin, a topoisomerase I inhibitor, that has an important role in the management of advanced colorectal cancer. It is approved as first-line therapy in combination with 5-fluorouracil and leucovorin or as monotherapy in the second-line setting. Its clinical use has been associated with variability in terms of pharmacokinetic behavior and toxicities, especially myelosuppression and diarrhea. Irinotecan is metabolized to the active compound SN-38; it is now known that the metabolism of irinotecan and the inactivation of SN-38 by glucuronidation are mediated by genetic differences, which contributes to the variability. In this article, a case is presented that illustrates this, and there is a brief discussion of the clinical pharmacology of irinotecan and some of the genetic variations that affect its cellular metabolism.
Mehra
Ranee
R
Department of Medical Oncology, Yale University Cancer Center, New Haven, CT 06520, USA.
Murren
John
J
Chung
Gina
G
Smith
Brian
B
Psyrri
Amanda
A
D000230:Adenocarcinoma / Q000188:drug therapy; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000378:metabolism* / Q000627:therapeutic use; D002166:Camptothecin / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000627:therapeutic use; D002430:Cecal Neoplasms / Q000188:drug therapy; D003967:Diarrhea / Q000139:chemically induced; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D000077146:Irinotecan; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D014453:Glucuronosyltransferase; D002166:Camptothecin