Ifosfamide-induced encephalopathy and concomitant use of netupitant/palonosetron in a patient with soft tissue sarcoma: a case report

A woman in her 30s diagnosed with high-grade soft tissue sarcoma with pulmonary metastases began treatment with ifosfamide-epirubicin, netupitant/palonosetron and dexamethasone. Shortly after, she developed dizziness and dysarthria, raising suspicion of ifosfamide-induced encephalopathy. Ifosfamide was immediately discontinued before the first dose was completed, and treatment with methylene blue was initiated the following day as the clinical condition continued to worsen. Due to her clinical condition, she was transferred to the intensive care unit, where she was started on thiamine and dexmedetomidine combined with methylene blue. Three days later, her neurological status improved, allowing methylene blue and thiamine to be discontinued. Several publications have reported cases of ifosfamide-related encephalopathy in patients receiving concomitant aprepitant, a CYP3A4 substrate and inhibitor that may increase the levels of ifosfamide's toxic metabolites. However, no cases of ifosfamide-induced encephalopathy have been reported with the use of netupitant/palonosetron for antiemetic prophylaxis. In light of our patient's condition, it is possible that the concomitant use of ifosfamide and netupitant/palonosetron contributed to an earlier onset and increased severity of ifosfamide-related neurotoxicity.