Phase I evaluation of crisnatol (BWA770U mesylate) on a monthly extended infusion schedule.
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.
Cobb
P W
PW
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884.
Havlin
K A
KA
Kuhn
J G
JG
Craig
J B
JB
Harman
G S
GS
Luther
J S
JS
Turner
J N
JN
Weiss
G R
GR
Tweedy
D A
DA
Koeller
J
J
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002911:Chrysenes / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009422:Nervous System Diseases / Q000139:chemically induced; D011409:Propylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D002911:Chrysenes; D011409:Propylene Glycols; C056722:crisnatol