Central nervous system toxicity of high-dose systemic cytosine arabinoside.
Forty-nine adult patients with acute leukemia in relapse, refractory to conventional therapy, were studied. Increasing quantities of i.v. bolus high-dose cytosine arabinoside (cytarabine) were administered using the following schedules: 3 g/m2 every 12 hrs for 4-16 consecutive doses, or 4.5 g/m2 every 12 hrs for 12 consecutive doses. Patients ages ranged 16-76 year (median: 38). Thirty-seven patients had previously received either induction or maintainance therapy with conventional doses of cytarabine. Cerebral or cerebellar dysfunction attributable to cytarabine was observed in eight patients and appeared 6-8 days (mean: 6.6) after the first dose and lasted 3-7 days (mean: 4.7). None of 12 patients receiving up to 24 g/m2 total dose of 48 g/m2 developed reversible neurologic dysfunction. Four of six patients receiving 54 g/m2 developed CNS toxicity (irreversible in two cases), a significantly greater incidence compared to toxicity in patients receiving less than or equal to 48 g/m2 total dose (P less than 0.01). CNS toxicity was dose-related since patients treated for 12 consecutive doses of 4.5 g/m2 had significantly greater CNS toxicity than 12 consecutive doses at 3 g/m2 (P less than 0.04). Systemic cytarabine doses less than 54 g/m2 can be administered with minimal CNS side-effects.
D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000187:drug effects*; D001927:Brain Diseases / Q000139:chemically induced* / Q000473:pathology; D002524:Cerebellar Ataxia / Q000139:chemically induced; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011689:Purkinje Cells / Q000473:pathology
D003561:Cytarabine