TY - JOUR
T1 - Severe irinotecan-induced toxicities in a patient with uridine diphosphate glucuronosyltransferase 1A1 polymorphism
AU - Mehra, Ranee
AU - Murren, John
AU - Chung, Gina
AU - Smith, Brian
AU - Psyrri, Amanda
PY - 2005/5
Y1 - 2005/5
N2 - 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.
AB - 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.
KW - Absolute neutrophil count
KW - Area under the curve
KW - Bilirubin
KW - Liver function tests
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U2 - 10.3816/CCC.2005.n.018
DO - 10.3816/CCC.2005.n.018
M3 - Article
C2 - 15929808
AN - SCOPUS:21844464083
SN - 1533-0028
VL - 5
SP - 61
EP - 64
JO - Clinical colorectal cancer
JF - Clinical colorectal cancer
IS - 1
ER -