Phase I study of flavone acetic acid (NSC 347512, LM975) in patients with pediatric malignant solid tumors.
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.
Pratt
C B
CB
Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Relling
M V
MV
Meyer
W H
WH
Douglass
E C
EC
Kellie
S J
SJ
Avery
L
L
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004341:Drug Evaluation; D005260:Female; D005419:Flavonoids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D005419:Flavonoids; C049328:flavone acetic acid