Phase I study of flavone acetic acid (NSC 347512, LM975) in patients with pediatric malignant solid tumors

Am J Clin Oncol. 1991 Dec;14(6):483-6. doi: 10.1097/00000421-199112000-00005.

Abstract

To evaluate the anticancer agent flavone acetic acid (FAA), we conducted a Phase I trial involving 17 pediatric patients with various malignant solid tumors. Dosages investigated included 5,120 and 6,144 mg/m2 given as 3-hour intravenous infusions; and 10,000, 12,500, 15,000, and 17,500 mg/m2 delivered in a 24-hour constant infusion with alkalinization. Grade 2 or worse toxicity was minimal, with 2 patients having nausea/vomiting, 2 having diarrhea, 1 becoming hypertensive, 1 becoming hypotensive, and 2 having myalgia. Three patients who received a 17,500 mg/m2 dose had no toxicity. Disease was stabilized for a brief period in 2 patients--1 with brain stem glioma and 1 with astrocytoma. The FAA pharmacokinetics varied with an average (SD) terminal half-life of 27.9 hr (18.7), clearance of 2.04 L/hr/m2 (0.37), and steady-state volume of 19.9 L/m2 (10.6). This study was discontinued because FAA caused no significant toxicity or therapeutic responses at doses 2.5 gm/m2 greater than had been tolerated by adults.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Evaluation
  • Female
  • Flavonoids / adverse effects
  • Flavonoids / pharmacokinetics
  • Flavonoids / therapeutic use*
  • Humans
  • Least-Squares Analysis
  • Male
  • Neoplasms / drug therapy*

Substances

  • Antineoplastic Agents
  • Flavonoids
  • flavone acetic acid