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Severe irinotecan-induced toxicities in a patient with uridine diphosphate glucuronosyltransferase 1A1 polymorphism
Ranee Mehra1, John Murren, Gina Chung
1Department of Medical Oncology, Yale University Cancer Center, New Haven, CT 06520, USA.
Abstract:
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.
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