Safety, tolerability, efficacy and plasma concentrations of tropisetron after administration at five dose levels to children receiving cancer chemotherapy.
In a double-blind, placebo-controlled, escalating dose study, 44 children receiving cancer chemotherapy of various degrees of emetogenicity were randomly allocated to once-daily treatment with tropisetron 0.05 mg/kg (6 patients), 0.10 mg/kg (5 patients), 0.20 mg/kg (6 patients), 0.33 mg/kg (6 patients), 0.50 mg/kg (6 patients) or placebo (15 patients). All doses of tropisetron were well tolerated; no tropisetron recipient discontinued treatment because of intolerance and no adverse effect could be plausibly correlated to tropisetron administration. Therapeutic plasma concentrations of tropisetron (> 3 ng/ml) were present for 9 h after administration of doses of 0.10 mg/kg or more. Tropisetron at doses of at least 0.20 mg/kg was significantly more effective in preventing vomiting than lower tropisetron doses or placebo, both in terms of treatment failure (> four vomits) (P = 0.015) and patient and investigator efficacy ratings (P = 0.04 for investigator rating; P = 0.035 for patient rating). Further comparative studies of the efficacy of tropisetron in chemotherapy-induced emesis in children are warranted.
Division of Pediatric Oncology, Institute Gustave Roussy, Villejuif, France.
A
A
Suarez
E R
ER
Stettler
E
E
Rey
G
G
Pons
C
C
Simonetta-Chateauneuf
K M
KM
de Bruijn
G
G
Olive
J
J
Lemerle
D000293:Adolescent; D000932:Antiemetics / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D008297:Male; D009325:Nausea / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D012702:Serotonin Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D000077526:Tropisetron; D014839:Vomiting / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D000970:Antineoplastic Agents; D007211:Indoles; D012702:Serotonin Antagonists; D000077526:Tropisetron