Abstract
CT-2584 HMS, 1-(11-dodecylamino-10-hydroxyundecyl)-3,7-dimethylxanthine-hydrogen methanesulphonate, is a modulator of intracellular phosphatidic acid. We treated 30 patients as part of a Phase I and pharmacokinetic study to determine the maximum-tolerated dose of CT-2584 HMS, toxicity profiles, pharmacokinetic profile and antitumour effects at escalating dose levels. CT-2584 HMS was given as a continuous infusion for 6 hours for 5 consecutive days every 3 weeks. Plasma samples for pharmacokinetic studies were analysed using a validated high-performance liquid chromatographic assay. Mean Cmaxand AUC values for each dose group were similar on days 1 and 5 and increases in plasma concentration (Cmaxand AUC) appeared proportional to the dose. CT-2584 HMS had a mean elimination half-life of 7.3 hours. Values of Vdand clearance were independent of dose and duration of treatment. Dose escalation was halted at 585 mg/m2 because of malaise and lethargy, which was sometimes accompanied by nausea and headache. 26 patients were evaluable for response, one patient with pleural mesothelioma achieved a partial response to treatment confirmed by CT scanning. A dose level of 520 mg/m2 daily × 5 days would be suitable for Phase II testing. Alternative schedules of CT-2584 HMS to overcome the limiting toxicity of malaise would be worthy of examination. © 2000 Cancer Research Campaign http://www.bjcancer.com
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Cheeseman, S., Brannan, M., McGown, A. et al. Phase I and pharmacologic study of CT-2584 HMS, a modulator of phosphatidic acid, in adult patients with solid tumours. Br J Cancer 83, 1599–1606 (2000). https://doi.org/10.1054/bjoc.2000.1503
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DOI: https://doi.org/10.1054/bjoc.2000.1503