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Crisnatol mesylate: phase I dose escalation by extending infusion duration
E A Poplin1, G G Chabot, R L Tuttle
1Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48202-0188.
Investigational New Drugs
|February 1, 1991
Summary
This Phase I study found that crisnatol mesylate, a cytotoxic drug, caused dose-limiting neurologic toxicities at high doses. The maximum tolerated dose was determined to be 2700 mg/m2 over 72 hours.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Crisnatol mesylate is a novel cytotoxic agent with broad-spectrum activity.
- Phase I clinical trials are essential for evaluating new cancer therapies.
Purpose of the Study:
- To determine the safety and maximum tolerated dose (MTD) of crisnatol mesylate.
- To characterize the pharmacokinetic profile of crisnatol mesylate.
- To assess preliminary efficacy of crisnatol mesylate in cancer patients.
Main Methods:
- A Phase I clinical trial with an unconventional dose escalation scheme.
- Constant drug infusion rate (mg/m2/hr) with prolonged infusion duration (6 to 96 hours).
- Sixty-five patients received crisnatol mesylate at escalating doses.
Main Results:
- Dose-limiting neurologic toxicities (confusion, agitation, disorientation) observed at higher doses.
- Phlebitis necessitated central line use.
- Pharmacokinetics: T1/2 beta = 3.3 hrs, CL = 22.8 L/hr/m2, Vdss = 53 L/m2.
- Median Css at 2700 mg/m2/72h was 2.7 µg/ml; at 3400 mg/m2/72h was 3.8 µg/ml.
- No objective responses were observed.
Conclusions:
- The MTD of crisnatol mesylate on this schedule is 2700 mg/m2/72 hours in patients without liver disease and with good performance status.
- Neurologic toxicity is the dose-limiting factor.
- Further investigation may be needed to optimize dosing or combination strategies, as no responses were seen.