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Clinical and pharmacokinetic phase I trial with the diethylaminoester of flavone acetic acid (LM985, NSC 293015).

Abstract
The diethylaminoester of flavone acetic acid (LM985) is a new anticancer agent with curative effects against slow growing murine tumors. Thirty-one adult patients with solid tumors received a total of 57 courses of LM985 given on days 1 and 8 every 4 weeks. The drug was given as a short infusion (1-2 hr) at doses ranging from 120 to 1900 mg/sq.m/day. The dose-limiting toxicity consisted of acute expressive aphasia; this neurotoxicity usually appeared at the end of the infusion and resolved spontaneously within a few minutes to 1 hr after the end of the infusion. In some patients, neurotoxicity was avoided by reducing the infusion rate. Neurotoxicity was observed in 5 out of 6 patients receiving 960 mg/sq.m over 1 hr and in 3 out of 3 patients receiving 1900 mg/sq.m over 2 hr. The drug did not induce any significant myelosuppression. Other side-effects were very mild and consisted mainly of occasional nausea and/or vomiting at all dose levels. One patient with breast cancer resistant to several hormonal and chemotherapy regimens had stable disease for 6 months. LM985 was detected in plasma in very small concentrations (0-2.5 micrograms/ml) but there was extensive formation of flavone acetic acid (peak concentration ranging between 8.3 and 64 micrograms/ml). A dose of 1500 mg/sq.m on days 1 and 8 every 4 weeks could be recommended for phase II studies with LM985; however, since LM985 is a prodrug of flavone acetic acid, phase II studies with LM985 should not be activated prior to the completion of the ongoing phase I trials with flavone acetic acid, which may be devoid of the acute toxicity of LM985.
AuthorsP F Dodion, J Abrams, B Gérard, N Crespeigne, B Peeters, C Van Berchem, Y Kenis
JournalEuropean journal of cancer & clinical oncology (Eur J Cancer Clin Oncol) Vol. 23 Issue 6 Pg. 837-42 (Jun 1987) ISSN: 0277-5379 [Print] England
PMID3653200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Flavonoids
  • LM 985
Topics
  • Adult
  • Aged
  • Antineoplastic Agents (adverse effects, metabolism, therapeutic use)
  • Drug Evaluation
  • Female
  • Flavonoids (adverse effects, metabolism, therapeutic use)
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Neoplasms (drug therapy, metabolism)

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