Central nervous system toxicity of high‐dose systemic cytosine arabinoside

Abstract

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/m2every 12 hrs for 4‐16 consecutive doses, or 4.5 g/m2every 12 hrs for 12 consecutive doses. Patients ages ranged 16‐76 years (median: 38). Thirty‐seven patients had previously received either induction or maintanance 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/m2total dose exhibited CNS toxicity; three of 19 receiving a total dose of 36 g/m2and one of 12 patients given a total dose of 48 g/m2developed reversible neurologic dysfunction. Four of six patients receiving 54 g/m2developed CNS toxicity (irreversible in two cases), a significantly greater incidence compared to toxicity in patients receiving ≤48 g/m2total dose (P< 0.01). CNS toxicity was dose‐related since patients treated for 12 consecutive doses of 4.5 g/m2had significantly greater CNS toxicity than 12 consecutive doses at 3 g/m2(P< 0.04). Systemic cytarabine doses less than 54 g/m2can be administered with minimal CNS side‐effects. Copyright © 1981 American Cancer Society