von Mehren M, Giantonio B J, McAleer C, Schilder R, McPhillips J, O'Dwyer P J
Fox Chase Cancer Center, Philadelphia, PA, USA.
Invest New Drugs. 1995;13(3):205-10. doi: 10.1007/BF00873801.
Ilmofosine, an ether lipid derivative of lysophosphatidylcholine has antineoplastic activity in vitro and in 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.
ilmofosine是溶血磷脂酰胆碱的醚脂衍生物，在体外和体内均具有抗肿瘤活性。临床前模型中的最大疗效与长时间接触该药物有关。在一项关于ilmofosine每周2小时输注方案的I期试验中，嗜睡、体能状态下降和轻度肝毒性综合征在550 mg/m²时成为剂量限制性因素。为避免与短时间输注相关的较高药物浓度，开展了一项关于每周24小时输注方案的I期研究，试图使剂量强度最大化。剂量从550 mg/m²逐步增加至800 mg/m²。毒性包括恶心、厌食、疲劳以及肝功能检查轻度升高。800 mg/m²时的剂量限制性毒性是严重腹痛综合征。除一名被发现患有骨髓增生异常综合征的患者外，未观察到中性粒细胞减少或血小板减少，且认为这与药物治疗无关。ilmofosine更长时间的输注方案并未导致可耐受剂量的大幅增加。
