This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Crews, K. R. Articles by Ribeiro, R. C. Search for Related Content PubMed PubMed Citation Articles by Crews, K. R. Articles by Ribeiro, R. C.

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.

This article has been cited by other articles:

				J. K. Lamba, K. Crews, S. Pounds, E. G. Schuetz, J. Gresham, V. Gandhi, W. Plunkett, J. Rubnitz, and R. Ribeiro Pharmacogenetics of Deoxycytidine Kinase: Identification and Characterization of Novel Genetic Variants J. Pharmacol. Exp. Ther., December 1, 2007; 323(3): 935 - 945. [Abstract] [Full Text] [PDF]

				G. J.L. Kaspers and C. M. Zwaan Pediatric acute myeloid leukemia: towards high-quality cure of all patients Haematologica, November 1, 2007; 92(11): 1519 - 1532. [Abstract] [Full Text] [PDF]

				S. Faderl, V. Gandhi, S. O'Brien, P. Bonate, J. Cortes, E. Estey, M. Beran, W. Wierda, G. Garcia-Manero, A. Ferrajoli, et al. Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias Blood, February 1, 2005; 105(3): 940 - 947. [Abstract] [Full Text] [PDF]

				M. E. Ross, R. Mahfouz, M. Onciu, H.-C. Liu, X. Zhou, G. Song, S. A. Shurtleff, S. Pounds, C. Cheng, J. Ma, et al. Gene expression profiling of pediatric acute myelogenous leukemia Blood, December 1, 2004; 104(12): 3679 - 3687. [Abstract] [Full Text] [PDF]

				S. Jeha, V. Gandhi, K. W. Chan, L. McDonald, I. Ramirez, R. Madden, M. Rytting, M. Brandt, M. Keating, W. Plunkett, et al. Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia Blood, February 1, 2004; 103(3): 784 - 789. [Abstract] [Full Text] [PDF]

				H. Kantarjian, V. Gandhi, J. Cortes, S. Verstovsek, M. Du, G. Garcia-Manero, F. Giles, S. Faderl, S. O'Brien, S. Jeha, et al. Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia Blood, October 1, 2003; 102(7): 2379 - 2386. [Abstract] [Full Text] [PDF]