Phase I clinical and pharmacokinetic trial of flavone acetic acid.
 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.
