par Dodion, Pierre ;Abrams, Jeffrey S;Gerard, Béatrice;Crespeigne, Nadine;Peeters, Bernadette;Van Berchem, Christine;Kenis, Yvon
Référence European journal of cancer & clinical oncology, 23, 6, page (837-842)
Publication Publié, 1987
Article révisé par les pairs
Résumé : 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 ophasia; 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 μg/ml) but there was extensive formation of flavone acetic acid (peak concentration ranging between 8.3 and 64 μg/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 onging phase I trials with flavone acetic acid, which may be devoid of the acute toxicity of LM985. © 1987.

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