Incidence and Risk Factors of Cholinergic Syndromes Induced by FOLFIRINOX in Advanced Pancreatic Adenocarcinoma

FOLFIRINOX is a novel chemotherapy that has been approved for the treatment of advanced pancreatic adenocarcinoma. In comparison with the conventional gemcitabine single agent therapy, FOLFIRINOX is advanced for objective responses, progression-free survival, and median overall survival. Cholinergic syndromes are frequently observed in patients receiving FOLFIRINOX and have been suggested to occur due to the inhibition of acetylcholinesterase by irinotecan (CPT-11). However, no research has been performed on the incidence and risk factors of cholinergic syndromes under FOLFIRINOX. This study aimed to evaluate the incidence and risk factors of cholinergic syndromes induced by FOLFIRINOX in retrospective investigation. Forty-eight patients who were treated with the first cycle of FOLFIRINOX were analyzed and 33 (68.8％) of those experienced cholinergic syndromes including diaphoresis (50.0％), acute diarrhea (33.3％), abdominal pain (29.2％), dysarthria (8.3％), and one for each case of bradycardia, nasal flow, miosis and numbness in the hands. Diaphoresis was experienced more frequently in younger patients (P = 0.029). Other characteristics of patients had no significant relationship with the induction of cholinergic syndrome; sex, stage of cancer, performance status, prior chemotherapy, dose of CPT-11, use of opioid, use of NSAIDs and/or acetaminophen and UGT1A1 genotype. This study indicated for the first time that cholinergic syndromes are observed in almost 70％ of patients treated with FOLFIRINOX, and it might be due to the combination of CPT-11 and oxaliplatin. Since cholinergic syndromes can deteriorate the quality of life, patients should be monitored carefully regardless of their characteristics under FOLFIRINOX.