Antitumor Activity of Ilmofosine (BM 41.440) in the 3Lewis-Lung Carcinoma Model

Herrmann, Dieter B.; Opitz, Hans-George; Munder, P. G.

doi:10.1201/9781439832042.ch97

Cited by 1 publication

(3 citation statements)

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“…In vitro testing of ilmofosine against human tumor explants in a colony-forming assay indicated concentration-dependent activity against nonsmall cell lung, breast, colorectal, gastric, renal cell, and ovarian carcinomas and melanoma (9). A dose-dependent response was observed in mice bearing xenografts of Lewis lung carcinoma and methylcholanthrene-induced fibrosarcoma (6,10). Schedules of frequent drug administration had activity superior to a single dose (10).…”

Section: Introductionmentioning

confidence: 88%

“…Determinations of the serum concentrations of ilmofosine and the sulfoxide metabolite were made using a validated high-pressure liquid chromatography method. 6 The analyses of ilmofosine and the sulfoxide metab-olite were conducted by the HPLC Department/Analytical Research Center, LAB GmbH & Co., New-Ulm, Germany. Kinetic Analysis.…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…The mechanism of cytotoxicity of this class of drugs is unknown, but they appear to act primarily at the cell membrane and can affect signal transduction pathways that are involved in cell differentiation and apoptosis (1,2). Ilmofosine has demonstrated dose-dependent in vivo and in vitro antitumor activity in various solid tumor models (3)(4)(5)(6)(7)(8). In vitro testing of ilmofosine against human tumor explants in a colony-forming assay indicated concentration-dependent activity against nonsmall cell lung, breast, colorectal, gastric, renal cell, and ovarian carcinomas and melanoma (9).…”

Section: Introductionmentioning

confidence: 99%

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Phase I and Pharmacokinetic Study of the Cytotoxic Ether Lipid Ilmofosine Administered by Weekly Two-Hour Infusion in Patients with Advanced Solid Tumors

Giantonio

Derry

McAleer

et al. 2004

Clinical Cancer Research

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Purpose: A Phase I trial was performed to determine the dose-limiting toxicity and maximum tolerated dose, and to describe the pharmacokinetics of the alkyl-lysophospholipid, ilmofosine, when administered as a weekly 2-h infusion in patients with solid tumors.Experimental Design: Thirty-nine patients were entered into a trial of ilmofosine administered weekly for 4 weeks followed by a 2-week rest period. Dose escalation occurred in 10 levels from 12 to 650 mg/m 2 . Results: Thirty-six patients were evaluable for toxicity. The median number of cycles per patient was 1 (range, 1-4). Dose-limiting gastrointestinal toxicity occurred at 650 mg/m 2 with grade 3 nausea in two patients and grade 3 vomiting and diarrhea in one patient. Grade 2 diarrhea was observed in four of six patients treated at 550 mg/m 2 . In addition, two patients treated at 550 mg/m 2 and two patients treated at 650 mg/m 2 experienced a decline in performance status of two or more levels that was determined to be due to treatment. There were no tumor responses. Stabilization of disease for at least 8 weeks occurred in six patients. Plasma concentrations of ilmofosine and its sulfoxide metabolite were evaluated by high-pressure liquid chromatography. The elimination of both compounds was biexponential with terminal half-lives of ϳ40 h for ilmofosine and 48 h for the sulfoxide. The area under the concentration-time curve was dose-proportional for each compound, and there was no evidence of saturable kinetics.Conclusions: The dose-limiting toxicity of ilmofosine is gastrointestinal and the recommended dose for Phase II trials is 450 mg/m 2 as a 2-h weekly infusion. The relatively long half-life of ilmofosine and its active metabolite support the use of this intermittent schedule.

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