PHASE-I TRIAL OF ILMOFOSINE AS A 24-HOUR INFUSION WEEKLY

Ilmofosine, an ether lipid derivative of lysophosphatidylcholine has a ntineoplastic activity in vitro and in vivo. Maximum efficacy in precl inical models is associated with prolonged exposure to the drug. In a Phase I trial of a weekly 2 hour infusion schedule of ilmofosine, a sy ndrome of lethargy, diminished performance status, and mild hepatotoxi city was dose-limiting at 550 mg/m(2). To avoid the higher drug concen trations associated with a brief infusion, a Phase I study of a weekly 24 hour infusional schedule was undertaken in an attempt to maximize dose-intensity. Doses were escalated from 550 to 800 mg/m(2). Toxiciti es included nausea, anorexia, fatigue, and minor elevations of liver f unction tests. The dose limiting toxicity at 800 mg/m(2) was a syndrom e of severe abdominal pain. No neutropenia or thrombocytopenia was obs erved except in one patient who was found to have a myelodysplastic sy ndrome, thought not to be related to drug therapy. The more prolonged infusion schedule of ilmofosine did not result in a substantial increa se in the tolerable dose.