Neurotoxicity
Cytarabine
Cytarabine is a pyrimidine analog that inhibits DNA polymerase commonly used in hematologic malignancies. 10-20% of patients who receive high dose intravenous cytarabine (greater than 3 gm/m2 administered every 12 hours) will experience neurotoxicity. Symptoms include cerebellar ataxia, somnolence and lethargy that present 3-8 days after an initial infusion.
Patients may experience neurotoxicity as early as the first course of therapy but can also present with symptoms upon subsequent courses. The elderly, patients with renal or hepatic insufficiency, and those receiving frequent drug administration or brain radiation, are at increased risk for experiencing these symptoms. Diagnosis consists of clinical manifestations as well as MRI, which may show white matter changes and cerebellar atrophy. EEG shows diffuse slowing consistent with encephalopathy.
Treatment should consist of immediate discontinuation of cytarabine, which leads to recovery in a few weeks in the majority of patients. 30% patients will not experience complete resolution of cerebellar symptoms. Once symptoms resolve, further cycles are not contraindicated, but neurotoxicity is likely to recur in patients with previous neurologic complications. The administration of IT cytarabine can also cause neurotoxicity, manifested as acute or subacute encephalopathy. Occasionally this is accompanied by seizures or aseptic meningitis. Seizures and meningitis are self-limiting and resolve upon discontinuation of therapy.
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