Crisnatol mesylate: phase I dose escalation by extending infusion duration.
Invest New Drugs
; 9(1): 41-7, 1991 Feb.
Article
in En
| MEDLINE
| ID: mdl-2026483
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 (T1/2 beta) 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 micrograms/ml and at 3400 mg/m2/72 hours was 3.8 micrograms/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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Propylene Glycols
/
Chrysenes
/
Neoplasms
/
Antineoplastic Agents
Limits:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Invest New Drugs
Year:
1991
Document type:
Article