5‑Fluorouracil‑induced severe hyperlactatemic encephalopathy during chemotherapy for advanced colorectal cancer: Case reports and literature review

Fluorouracil (5-FU) is a key drug in the treatment of advanced colorectal cancer (CRC).Although 5-FU is generally well tolerated, a small subset of patients may experience life-threatening neurotoxicity.Among these complications, 5-FU-induced encephalopathy accompanied by severe hyperlactatemia is a particularly serious metabolic emergency.Impaired drug clearance, especially due to underlying renal insufficiency, may substantially increase this risk.In the present study, the cases of three patients with advanced CRC who developed acute, severe impairment of consciousness 48 h after receiving 5-FU-based chemotherapy were retrospectively reviewed.Clinical presentations ranged from aphasia and confusion to deep coma.All patients exhibited marked hyperlactatemia, with peak blood lactate levels of 18.0, 18.19 and 15.56 mmol/l for Cases 1, 2 and 3, respectively.A total of two patients had marked baseline renal impairment (one with chronic kidney disease, the other with end-stage renal disease on maintenance hemodialysis).Neuroimaging (CT/CT perfusion/CT angiography/MRI) excluded acute cerebrovascular events in all cases.Chemotherapy was immediately discontinued and intensive supportive care was initiated.For the patient with anuric renal failure, early continuous venovenous hemofiltration was initiated.All three patients achieved complete neurological recovery and normalization of metabolic parameters.Notably, the hemodialysis-dependent patient subsequently underwent successful 5-FU rechallenge using a 50% dose reduction combined with prophylactic post-chemotherapy hemodialysis, without recurrence of neurotoxicity.5-FU-induced severe hyperlactatemic encephalopathy is a potentially fatal oncological emergency.Underlying renal impairment may lead to the accumulation of toxic metabolites.For patients presenting with extreme hyperlactatemia (>10 mmol/l) and profound impairment of consciousness, early initiation of continuous renal replacement therapy may be an effective strategy to resolve neurological dysfunction.In patients with end-stage renal disease requiring subsequent fluoropyrimidine therapy, substantial dose reduction combined with prophylactic hemodialysis may offer a feasible rechallenge approach.Furthermore, clinicians must consider genetic mutations related to hepatotoxicity and nephrotoxicity.Evaluation of these organ-vulnerability genes before chemotherapy warrants further clinical investigation to prevent severe toxicity.