Neurotoxic Effects of Oxaliplatin and Capecitabine in Colon Cancer Patients

Introduction We present a unique case of capecitabine and oxaliplatin (CAPOX) therapy presenting as dysarthria as an uncommon side effect in the context of a TIA and review relevant literature to highlight potential mechanisms and clinical implications. Case Presentation A 65‐year‐old male with colon adenocarcinoma (pT2N1aMX) on capecitabine (1000 mg/m 2 BID, 2 weeks on/1 week off) and oxaliplatin (130 mg/m 2 every 3 weeks) presented with a transient episode of acute dysarthria around 16:40, shortly after receiving chemotherapy earlier that day. His history included a remote left occipital hemorrhagic infarct (likely from paroxysmal atrial fibrillation), chronic left lower extremity DVT on apixaban 5 mg BID, hypertension, hyperlipidemia, and DM. His wife noted sudden slurred, unintelligible speech while he was preparing lunch; symptoms resolved within 15 minutes. He was asymptomatic upon ED arrival. Stroke workup, including brain MRI and MRA, was unremarkable. Given his vascular risk factors, cancer‐associated hypercoagulability, and temporal proximity to chemotherapy, a diagnosis of CAPOX‐induced transient ischemic attack was made. He was discharged on apixaban, and both he and his oncologist—who opted to continue the current regimen‐were counseled on the diagnosis. Discussion Chemotherapy‐induced neurotoxicity poses a frequent clinical challenge. Oxaliplatin is commonly associated with sensory peripheral neuropathy and pharyngolaryngeal dysesthesia, with occasional reports of headache, body pain, cranial nerve palsy, dysarthria, dysphagia, and rarely, posterior reversible encephalopathy syndrome (PRES). Capecitabine‐induced neurotoxicity occurs in ∼0.5% of cases, typically presenting as cerebellar syndrome with ataxia, dysarthria, and nystagmus, and more rarely, seizures or acute leukoencephalopathy. The underlying mechanisms remain unclear but may involve ammonia accumulation, capecitabine‐induced thiamine deficiency, or dihydropyrimidine dehydrogenase (DPD) deficiency, an enzyme essential for capecitabine metabolism. Animal studies suggest CAPOX may disrupt the blood‐brain barrier and increase extracellular ATP levels, potentially contributing to CNS toxicity. Dysarthria as an isolated chemotherapy‐related symptom is rare and may mimic acute cerebrovascular events, risking misdiagnosis. Early recognition is critical to avoid unnecessary treatment delays or dose modifications. Though typically self‐limiting, symptom severity varies. Slower infusion rates may help mitigate recurrence, and decisions on continuing chemotherapy should be guided by a careful risk‐benefit discussion with the patient. Conclusion Clinicians, pharmacists, and patients should be aware of the rare but significant neurotoxic effects of oxaliplatin and capecitabine. Nonetheless, a thorough evaluation for stroke remains essential, given the elevated risk from malignancy‐associated hypercoagulability.