Irinotecan-Induced Transient Dysarthria: Case Series and Updated Literature Review

Abstract

Irinotecan-based regimens are used worldwide for the treatment of several recurrent or advanced gastrointestinal malignancies. In this paper we describe the cases of four patients treated in our institution who developed acute dysarthria while receiving intravenous infusion of irinotecan. In all our cases, dysarthria occurred during the infusion of the first course of irinotecan, and then resolved rapidly without any sequelae. Imaging of the brain was performed, but failed to show any evidence of an acute neurological event. We also reviewed the literature on this very uncommon adverse event. The pathogenesis of irinotecan-induced dysarthria is still unknown and is not completely elucidated by the current pharmacodynamic or kinetic explanations; therefore, we could only hypothesize some assumptions.

Intrinsically Disordered Protein Micelles as Vehicles for Convection-Enhanced Drug Delivery to Glioblastoma Multiforme

“…The pro-drug form is 100–1000 times less cytotoxic than SN38 until it is activated via hydrolysis by carboxylesterase enzymes in the liver (Figure a). Although this releases SN38, its activation requires systemic administration at much larger dosages, significantly increasing the risk of toxicity and off-target effects. − Lipid-based nanoparticle formulations have been developed to encapsulate CPT-11 to reduce systemic toxicity and have shown promise for treating neuroblastoma brain tumors . Additionally, SN38 has been shown to increase survival and decrease tumor volume in animal glioma models using a hydrolyzable covalent linkage to a synthetic block copolymer consisting of PEG and poly­(glutamic acid) regions.…”

Investigating the Impact of SN-38 on Mouse Brain Metabolism Based on Metabolomics

“… 4 Rarer toxicities, including articulatory disorders, severe systemic weakness, paralysis, and aphasia induced by irinotecan, have also been reported. 5 However, research on SN-38’s effects on brain tissue is limited. Thus, the aim of this experiment is to thoroughly evaluate the neurotoxicity of SN-38 by examining its metabolite levels in the hippocampus and cerebral cortex, and to initially explore the specific mechanisms of SN-38-induced toxicity.…”