Relation between irinotecan-induced cholinergic syndrome and prognosis of colorectal cancer patients.

Abstract

859 Background: It is well known that a cetuximab induced rash is strongly associated with improved survival of colorectal cancer patients. Irinotecan Induced Cholinergic Syndrome (IICS), manifesting in such events as early diarrhea and diaphoresis, is a notorious adverse effect of irinotecan. In this study, we reveal the relation between IICS and prognosis of colorectal cancer patients and examine the validity of IICS as a surrogate marker for the efficacy of irinotecan. Methods: We retrospectively reviewed data from 52 colorectal cancer patients who were treated with a chemotherapeutic regimen that included irinotecan at Kure Medical Center between 2012 and 2017. First, to assess the relation between adverse events and efficacy of irinotecan, patients who experienced IICS (n = 11) and did not experience IICS (n = 41) were analyzed from the aspect of overall survival (OS), progression-free survival (PFS), sex, age, dose, performance status (PS) and previous chemotherapy (PC). Kaplan-Meier survival curves were drawn for OS and PFS, and compared by means of a log-rank test. Secondly, to determine the response rate of butylscopolamine for IICS, we injected butylscopolamine 20mg into the irinotecan infusion bag and administered both agents through the intravenous line together to 11 patients who experienced IICS. Results: The presence of IICS was associated with a prolonged median OS (589 vs. 280 days, log-rank p = 0.0282; adjusted hazard ratio (HR) 0.27, 95% confidence interval [CI] 0.06-0.79, p = 0.0140), and prolonged median PFS (317 vs. 154 days, log-rank p = 0.1474; adjusted HR 0.56, 95% CI 0.22-1.25, p = 0.1635). There was no statistically significant difference between the two groups in terms of sex, age, dose, PS and PC. Ten patients of 11 patients who were administered butylscopolamine, experienced complete or partial improvement of IICS. The response rate was nearly 90%. Conclusions: The presence of IICS is associated with an improved OS for colorectal cancer patients and tends to have a positive correlation with PFS. IICS is a viable surrogate biomarker of the antitumor efficacy of irinotecan. As a prophylaxis of IICS, mixing butylscopolamine into the irinotecan infusion bag was remarkably effective.