Predictive factors for the development of irinotecan-related cholinergic syndrome using ordered logistic regression analysis

Cholinergic syndrome is an acute adverse reaction associated with irinotecan. Development of cholinergic syndrome can be ameliorated or prevented by administering various anticholinergics, including atropine sulfate or scopolamine butylbromide. Although many of the side effects are transient and non-life-threatening, their onset is painful and can lower a patient’s quality of life (QoL). This retrospective study was performed to identify predictive factors of the development of irinotecan-related cholinergic syndrome in order to develop future strategies for improving the QoL of patients undergoing chemotherapy. We enrolled 150 cancer patients who underwent chemotherapy, which included irinotecan, in our outpatient chemotherapy center between October 2014 and January 2017. For regression analysis, variables related to the development of irinotecan-related cholinergic syndrome were extracted from the patient’s clinical records. The degree of cholinergic syndrome was classified as follows: grade 0 = not developed; grade 1 = developed but did not require anticholinergic drugs; and grade 2 = developed and required anticholinergic drugs or stopping the chemotherapy due to cholinergic syndrome. Multivariate ordered logistic regression analysis was performed to identify predictive factors for the development of irinotecan-related cholinergic syndrome. Threshold measurements were determined using a receiver operating characteristic analysis (ROC) curve. Significant factors identified for the development of cholinergic syndrome included female sex [odds ratio (OR) 2.183, 95% confidence interval (CI) 1.010–4.717; P = 0.0471] and irinotecan dose (OR 1.014, 95% Cl 1.007–1.021; P = 0.0001). ROC curve analysis of the group likely to develop cholinergic syndrome indicated that the threshold for the irinotecan dose was 175 mg or above (area under the curve = 0.69). In conclusion, female sex and irinotecan dose were identified as significant predictors of the development of cholinergic syndrome.