Crisnatol mesylate: Phase I dose escalation by extending infusion duration

Abstract

Crisnatol mesylate is a rationally designed cytotoxic arylmethylamino-propanediol with broad spectrum cytotoxic activity. A phase I study with an unconventional escalation scheme was developed using a constant drug infusion rate (mg/m2/hr) and prolonging the infusion duration from 6 to 96 hours. Sixty-five patients received crisnatol at doses from 18 mg/m2 in 6 hrs to 3400 mg/m2 in 72 hours. The dose-limiting toxicity in two of five patients at 2700 mg/m2 and two of three patients at 3400 mg/m2 was neurologic and consisted of a syndrome of confusion, agitation, and disorientation. Phlebitis mandated the use of a central line. The mean terminal phase half-life (T1/2β ) was 3.3 hours with a total body clearance (CL) of 22.8 L/hr/m2 and a volume of distribution (Vdss) of 53 L/m2. The median steady-state peak plasma concentration (Css) at 2700 mg/m2/72 hours was 2.7 μg/ml and at 3400 mg/m2/72 hours was 3.8 μg/ml. No responses were seen. The maximum tolerated dose (MTD) on this schedule is 2700 mg/m2/72 hours in patients with no liver disease and good performance status.

DOI: 10.1007/BF00194543

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@article{Poplin1991CrisnatolMP, title={Crisnatol mesylate: Phase I dose escalation by extending infusion duration}, author={Elizabeth A. Poplin and Guy G. Chabot and Richard L. Tuttle and Sol Lucas and William A Wargin and Laurence H. Baker}, journal={Investigational New Drugs}, year={1991}, volume={9}, pages={41-47} }