Abstract
Ilmofosine, an ether lipid derivative of lysophosphatidylcholine has antineoplastic activityin vitro andin vivo. Maximum efficacy in preclinical models is associated with prolonged exposure to the drug. In a Phase I trial of a weekly 2 hour infusion schedule of ilmofosine, a syndrome of lethargy, diminished performance status, and mild hepatotoxicity was dose-limiting at 550 mg/m2. To avoid the higher drug concentrations 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/m2. Toxicities included nausea, anorexia, fatigue, and minor elevations of liver function tests. The dose limiting toxicity at 800 mg/ m2 was a syndrome of severe abdominal pain. No neutropenia or thrombocytopenia was observed except in one patient who was found to have a myelodysplastic syndrome, thought not to be related to drug therapy. The more prolonged infusion schedule of ilmofosine did not result in a substantial increase in the tolerable dose.
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von Mehren, M., Giantonio, B.J., McAleer, C. et al. Phase I trial of ilmofosine as a 24 hour infusion weekly. Invest New Drugs 13, 205–210 (1995). https://doi.org/10.1007/BF00873801
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DOI: https://doi.org/10.1007/BF00873801