INTRODUCTION: FOLFIRINOX (fluorouracil, leucovorin, irinotecan and oxaliplatin) has increased survival rates for pancreatic cancer, but has adverse effects of febrile neutropenia, thrombocytopenia, and neuropathy. Transient dysarthria is a rare adverse effect associated with this regimen. We report a case of transient dysarthria as an isolated adverse effect associated with FOLFIRINOX.
CASE REPORT : A 45-year-old woman with stage 3 pancreatic adenocarcinoma was being treated with neoadjuvant FOLFIRINOX. She developed severe dysarthria and generalized weakness after completing Day 1 of her second cycle. Upon ED evaluation, she was given methylprednisolone and diphenhydramine with complete resolution of symptoms. At 3rd cycle, intravenous atropine was given prior to irinotecan infusion. Eight hours after initiation of the infusion, she developed slowed speech and dysarthria. Her vitals remained stable. On physical exam, she was drowsy and had slowed mentation, with slow and slurred speech. No other focal deficits were identified. Her symptoms resolved on follow up evaluation.
DISCUSSION: Acute cholinergic syndrome is a wellknown side effect associated with irinotecan containing chemotherapy regimens such as FOLFIRINOX. Symptoms include diarrhea, flushing, hypersalivation, lacrimation, abdominal cramping, diaphoresis, visual disturbances, bradycardia and shortness of breath. Self-limiting recurrent dysarthria is a rare adverse effect associated with both irinotecan and oxaliplatin. The exact mechanism contributing to dysarthria is unknown. According to Matsuoka et al, irinotecan is thought to bind to the active site of acetylcholinesterase, resulting in an increased cholinergic response. It is known that among the brainstem nuclei, hypoglossal nerve carries the highest density of cholinergic receptors. Hence irinotecan may cause overstimulation of hypoglossal nerve leading to dysarthria. Oxaliplatin is known to potentiate the cholinergic effects of irinotecan by causing neuronal hyperexcitation. Hence infusion of oxaliplatin prior to irinotecan may make dysarthria more prominent. Infusing irinotecan before oxaliplatin is shown to minimize dysarthria. Atropine is known to work well in preventing acute cholinergic syndrome but has shown mixed results in treating dysarthria. It is reassuring that irinotecan-induced dysarthria is self-limiting, but an increased awareness among physicians is needed so that this adverse effect is not misdiagnosed as a stroke.