Dose-ranging antiemetic evaluation of the serotonin antagonist tropisetron in patients receiving anti-cancer chemotherapy.
BACKGROUND
Tropisetron (ICS 205-930) antagonizes the serotonin type 3 receptor and has antiemetic activity in animals given cisplatin. Its mean serum half-life in 11.1 hours.


METHODS
In this dose-ranging trial, 22 patients undergoing anti-cancer chemotherapy received 24 courses of a single intravenous infusion of tropisetron beginning 30 minutes before chemotherapy. Four dose levels were explored (range, 12-48 mg/m2).


RESULTS
Toxicities were mild and included headache, transient elevations of serum alanine transaminase and/or aspartate transaminase levels, and sedation. No akathisia or acute dystonic reactions were observed. Thirty-six percent of patients had no emesis, and 58% had two or fewer emetic episodes. Ten patients received high-dose cisplatin (dose, > or = 100 mg/m2) as initial chemotherapy. Of these, 30% had no emesis, and 60% had two or fewer episodes.


CONCLUSIONS
Tropisetron can be administered safely in the doses tested with no dose-limiting toxicities. The encouraging antiemetic efficacy, mild toxicities, lack of extrapyramidal effects, and convenience of a single 15-minute infusion regimen make this drug appropriate for study in additional trials.
Pisters
K M
KM
Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, New York 10021.
Kris
M G
MG
Tyson
L B
LB
Clark
R A
RA
Gralla
R J
RJ
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012702:Serotonin Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D000077526:Tropisetron; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000970:Antineoplastic Agents; D007211:Indoles; D012702:Serotonin Antagonists; D000077526:Tropisetron