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

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.

• Authors: C B Pratt, M V Relling, W H Meyer, E C Douglass, S J Kellie, L Avery
• Journal: American journal of clinical oncology (Am J Clin Oncol) Vol. 14 Issue 6 Pg. 483-6 (Dec 1991) ISSN: 0277-3732 [Print] United States
• PMID: 1957836 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Flavonoids
• flavone acetic acid

Topics

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