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

Ronald A. Fleming, Robert L. Capizzi, Gary L. Rosner, Lawrence K. Oliver, Stephen J. Smith, Charles A. Schiffer, Richard T. Silver, Bruce A. Peterson, Raymond B. Weiss, George A. Omura, Robert J. Mayer, David A. Van Echo, Clara D. Bloomfield, Richard L. Schilsky

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)425-430
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume36
Issue number5
DOIs
StatePublished - Sep 1 1995

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Keywords

  • Cytarabine
  • Leukemia

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Fleming, R. A., Capizzi, R. L., Rosner, G. L., Oliver, L. K., Smith, S. J., Schiffer, C. A., Silver, R. T., Peterson, B. A., Weiss, R. B., Omura, G. A., Mayer, R. J., Van Echo, D. A., Bloomfield, C. D., & Schilsky, R. L. (1995). Clinical pharmacology of cytarabine in patients with acute myeloid leukemia: a Cancer and Leukemia Group B study. Cancer Chemotherapy and Pharmacology, 36(5), 425-430. https://doi.org/10.1007/BF00686192