Phase I clinical and pharmacokinetic trial of flavone acetic acid

A. Kathleen Havlin, John G. Kuhn, John B. Craig, David H. Boldt, Geoffrey R. Weiss, James Koeller, Glenn Harman, Rowena Schwartz, Gary N. Clark, Daniel D. Von Hoff

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    21 Scopus citations

    Abstract

    Flavone acetic acid is a synthetic benzopyrone derivative with an unknown mechanism of action. Thirty-eight patients (30 men and 8 women) were treated once a week for 4 weeks every 5 weeks with doses of flavone acetic acid ranging from 0.33 to 12.5 g/m2. At doses less than or equal to 3.9 g/m2, the drug was administered intravenously over 1 hour; at doses greater than or equal to 5.28 g/m2, the infusion period was lengthened to 6 hours. Treatment of all patients included hydration before and after treatment and alkalization to maintain urine pH at greater than or equal to 6.5. A dose-limiting toxic effect was hypotension at 10 g/m2. Pharmaco-kinetic studies revealed linear behavior in the eight patients studied, beginning at 3.9 g/m2. Peak plasma levels ranged from 125 to 630 μg/mL, with a mean terminal half-life of 22.4 hours. Immunologic monitoring was performed in three patients at 10 g/m2. A transient increase in CD16- and/or Leu-19-positive cells was noted in all three patients. In one patient, this increase correlated with a 10-fold increase in K562 cell killing. There were no objective tumor responses seen in this trial. The recommended phase II dose on this schedule is 8 g/m2. Further studies to elucidate the drug's mechanism of action and to define its immunologic properties are recommended. [J Natl Cancer Inst 83: 124-128, 1991]

    Original languageEnglish (US)
    Pages (from-to)124-128
    Number of pages5
    JournalJournal of the National Cancer Institute
    Volume83
    Issue number2
    DOIs
    StatePublished - Jan 16 1991

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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