Irinotecan-based chemotherapy regimens are used worldwide in the treatment of recurrent or advanced gastrointestinal (GI) cancers, in combination with other cytotoxic drugs or monoclonal antibodies. The most common side effects include acute cholinergic syndrome (ACS) mediated through the inhibition of acetylcholinesterase (AchE), delayed diarrhoea, nausea and vomiting, myelosuppression, alopecia, stomatitis and abdominal pain.

Dysarthria, defined as an impairment of speech caused by an alteration of the strength and control of speech muscles, is a very uncommon central nervous system (CNS) adverse event occurring rarely during or shortly following irinotecan (CPT-11) infusion. Its pathogenesis is not completely elucidated by current pharmacodynamic or kinetic explanations. In all the cases previously reported in the literature, it occurred during the first cycle within 90 min of drug infusion, and was not accompanied by any other signs on clinical examination and imaging.

Dysarthria was transient and resolved within 24 h independently of any adopted strategies.

The aim of our study is to add to the scientific literature our institution’s experience of four patients who experienced transient dysarthria related to CPT-11. We also performed a literature review reporting the different pathogenic mechanisms that have been previously hypothesized by several authors, in terms of pharmacodynamic or pharmacokinetic explanations.

In order to better understand the pathogenesis of this rare adverse event, we propose to investigate the potential role of UGT1A1 gene polymorphisms, which are also related to an increased rate of severe haematological and/or gastrointestinal toxicities.

Lastly, we remind the importance of being aware of the recommended guidelines about the irinotecan administration (in terms of preparation of infusion solution and pre-medication with antiemetic drugs, steroids and atropine) and we highlighted the need to agree recommendations and/or protocols regarding the management of neurological adverse events.