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Interim Comparison of a Continuous Infusion Versus a Short Daily Infusion of Cytarabine Given in Combination With Cladribine for Pediatric Acute Myeloid Leukemia

From the Departments of Pharmaceutical Sciences, Biostatistics, Hematology-Oncology, and Pathology, St Jude Children’s Research Hospital, Memphis, TN, and Departments of Experimental Therapeutics and Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX.

Address reprint requests to Kristine R. Crews, Department of Pharmaceutical Sciences, St Jude Children’s Research Hospital, 332 N Lauderdale, Memphis, TN 38105-2794; email: kristine.crews{at}stjude.org

PURPOSE: To identify the optimal schedule for infusion of cytarabine (ara-C) given with cladribine (2-CdA) to pediatric patients with acute myeloid leukemia (AML), and to compare the effects of the two schedules on the pharmacokinetics of ara-C triphosphate (ara-CTP) in leukemic cells.

PATIENTS AND METHODS: Forty-nine pediatric patients with newly diagnosed primary AML received a 5-day course of ara-C 500 mg/m²/d and 2-CdA 9 mg/m²/d. They were randomly assigned to receive ara-C as either a 2-hour daily infusion (arm A) or a continuous infusion (arm B). Cellular pharmacokinetics were studied on days 1 and 2. All patients then received two courses of remission induction chemotherapy with daunorubicin, ara-C, and etoposide (DAV).

RESULTS: Thirty-two percent of patients (seven of 22) in arm A and 63% (17 of 27) in arm B entered complete remission (P = .045) after ara-C and 2-CdA therapy. Coadministration of 2-CdA increased the intracellular concentration of ara-CTP in 20 of 36 patients, although we found no statistically significant difference between the treatment arms in this effect (P = .63). The incidence of toxicity did not differ significantly between the two treatment arms (P = .53). After two courses of DAV, the rate of complete remission was 91% in arm A and 96% in arm B (P = .58).

CONCLUSION: Intracellular accumulation of ara-CTP is increased when 2-CdA is given with ara-C, but no schedule-dependent differences in this effect were seen. The combination of 2-CdA and ara-C seems to be effective therapy for pediatric AML.

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