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Clinical pharmacology of cytarabine in patients with acute myeloid leukemia: a Cancer and Leukemia Group B study

  • Original Article
  • Cytarabine, Leukemia
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Abstract

The pharmacokinetics of cytarabine (ara-C) were determined in 265 patients with acute myeloid leukemia (AML) receiving ara-C (200 mg/m2 per day for 7 days as a continuous infusion) and daunorubicin during induction therapy. The mean (standard deviation) ara-C concentration at steady-state (Css) and systemic clearance (Cl) were 0.30 (0.13) μM and 134 (71) l/h per m2 respectively. Males had a significantly faster ara-C Cl (139 vs 131 l/h per m2,P=0.025) than females. Significant correlations were noted between ara-C Cl and the pretreatment, peripheral white blood cell count (P=0.005) and pretreatment blast count (P=0.020). No significant differences in ara-C Css or Cl were noted in patients achieving complete remission compared with those failing therapy (P=0.315,P=0.344, respectively). No significant correlations were observed between ara-C pharmacokinetic parameters and several indices of patient toxicity. Our findings indicate that variability in ara-C disposition in plasma at this dosage level does not correlate with remission status or toxicity in patients with AML receiving initial induction therapy with ara-C and daunorubicin.

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Author notes

  1. Robert L. Capizzi

    Present address: US Bioscience, West Conshohocken, PA, USA

Authors and Affiliations

  1. Medical Center Boulevard, Comprehensive Cancer Center of Wake Forest University, 27157-1082, Winston-Salem, NC, USA

    Ronald A. Fleming, Robert L. Capizzi & Stephen J. Smith

  2. Duke University Medical Center, Durham, NC, USA

    Gary L. Rosner

  3. The Upjohn Company, Kalamazoo, MI, USA

    Lawrence K. Oliver

  4. University of Maryland Cancer Center, Baltimore, MD, USA

    Charles A. Schiffer & David A. Van Echo

  5. The New York Hospital, New York, NY, USA

    Richard T. Silver

  6. University of Minnesota Medical School, Minneapolis, MN, USA

    Bruce A. Peterson

  7. Walter Reed Army Medical Center, Washington DC, USA

    Raymond B. Weiss

  8. The University of Alabama at Birmingham, Birmingham, AL, USA

    George A. Omura

  9. Dana-Farber Cancer Institute, Boston, MA, USA

    Robert J. Mayer

  10. Roswell Park Cancer Institute, Buffalo, NY, USA

    Clara D. Bloomfield

  11. Cancer Research Center, University of Chicago, Chicago, IL, USA

    Richard L. Schilsky

Authors
  1. Ronald A. Fleming
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  2. Robert L. Capizzi
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  3. Gary L. Rosner
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  4. Lawrence K. Oliver
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  5. Stephen J. Smith
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  6. Charles A. Schiffer
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  7. Richard T. Silver
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  8. Bruce A. Peterson
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  9. Raymond B. Weiss
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  10. George A. Omura
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  11. Robert J. Mayer
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  12. David A. Van Echo
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  14. Richard L. Schilsky
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Additional information

This study was supported in part by grants from the National Cancer Institute (CA-03927, CA-37027, CA-59518, CA-47577, CA-32291, CA-07968, CA-16450, CA-16450, CA-26806, CA-47545, CA-12197, and CA-41287), the Upjohn Company, and the Coleman Leukemia Research Fund

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Fleming, R.A., Capizzi, R.L., Rosner, G.L. et al. Clinical pharmacology of cytarabine in patients with acute myeloid leukemia: a Cancer and Leukemia Group B study. Cancer Chemother. Pharmacol. 36, 425–430 (1995). https://doi.org/10.1007/BF00686192

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  • DOI: https://doi.org/10.1007/BF00686192

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