Phase I clinical and pharmacokinetic trial of flavone acetic acid.


Journal Article

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. Pharmacokinetic studies revealed linear behavior in the eight patients studied, beginning at 3.9 g/m2. Peak plasma levels ranged from 125 to 630 micrograms/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.

Full Text

Cited Authors

  • Havlin, KA; Kuhn, JG; Craig, JB; Boldt, DH; Weiss, GR; Koeller, J; Harman, G; Schwartz, R; Clark, GN; Von Hoff, DD

Published Date

  • January 16, 1991

Published In

Volume / Issue

  • 83 / 2

Start / End Page

  • 124 - 128

PubMed ID

  • 1703237

Pubmed Central ID

  • 1703237

International Standard Serial Number (ISSN)

  • 0027-8874

Digital Object Identifier (DOI)

  • 10.1093/jnci/83.2.124


  • eng

Conference Location

  • United States