Irinotecan, a topoisomerase I inhibitor, is widely used in the treatment of numerous malignancies, such as gastric, colorectal, ovarian, cervical, and lung cancer. The principal dose-limiting toxicities of irinotecan are neutropenia and delayed diarrhea. Genetic variants (*6/*6, *28/*28, and *6/*28) of uridine diphosphate glucuronosyltransferase (UGT) 1A1 have been shown to be correlated with adverse events during irinotecan chemotherapy. However, irinotecan-induced adverse events may also occur in patients without a UGT1A1 polymorphism.
We conducted logistic regression analysis to determine the principal patient characteristics other than UGT1A1 polymorphism that are associated with severe irinotecan-induced neutropenia.
Ninety-six patients who received irinotecan therapy between June 2009 and May 2013 were analyzed. Our univariate analysis showed that smoking history, combined with oral fluoropyrimidines and platinum-containing drugs, weekly irinotecan schedule, was associated with irinotecan-induced severe neutropenia. The multivariate analysis showed that the following factors were also correlated with irinotecan-induced severe neutropenia: the patient's first cycle of irinotecan (at doses ≥ 133 mg/m2), prior chemotherapy history, smoking history (non-smoker), simultaneous treatment with a platinum-containing drug, and total serum bilirubin before treatment (at levels ≥ 0.5 mg/dL).
These findings suggest that it is valuable to identify patient characteristics other than UGT1A1 polymorphism assessing severe neutropenia in patients treated with irinotecan.
