Phase I evaluation of crisnatol (BWA770U mesylate) on a monthly extended infusion schedule

Sel Cancer Ther. 1991 Summer;7(2):85-91. doi: 10.1089/sct.1991.7.85.

Abstract

Crisnatol is an arylmethylaminopropanediol derivative that has shown promise as an antitumor agent in preclinical testing. In a phase I trial using a monthly six-hour infusion schedule the recommended dose for future phase II trials was found to be 388 mg/m2. Neurologic toxicity was dose-limiting in that trial and correlated with the attainment of a threshold plasma concentration of greater than 4.5 micrograms/ml. In this study we treated 15 patients with escalating doses of crisnatol from 450 mg/m2 to 900 mg/m2 administered at a rate of 50 mg/m2/hr over 9, 12, 15, and 18 hours. Toxicity was mild to moderate at all dose levels. However, serious central nervous system effects were noted in one patient at 900 mg/m2 over 18 hours whose plasma level was 6.5 micrograms/ml. This study has demonstrated higher total doses of crisnatol can be given if the drug is administered as a prolonged infusion in an attempt to avoid high plasma levels of the agent.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Chrysenes / adverse effects
  • Chrysenes / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Evaluation
  • Humans
  • Infusions, Intravenous
  • Middle Aged
  • Neoplasms / drug therapy*
  • Nervous System Diseases / chemically induced
  • Propylene Glycols / adverse effects
  • Propylene Glycols / therapeutic use*

Substances

  • Antineoplastic Agents
  • Chrysenes
  • Propylene Glycols
  • crisnatol