Ondansetron compared with high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting. A multicenter, randomized, double-blind, crossover study.
OBJECTIVE
To compare the efficacy and side effects of ondansetron with those of high-dose metoclopramide in treating acute and delayed cisplatin-induced nausea and vomiting.


METHODS
Randomized, double-blind, crossover trial.


METHODS
Conducted at two university hospitals, a cancer institute, and six community hospitals.


METHODS
Of 125 patients, 95 were evaluable for the acute phase and 79 for the delayed phase. Major reasons for not being evaluable were no second course (14 patients), protocol violation (5 patients), and change in cisplatin dose (3 patients) for the acute phase, and rescue medication on day 1 (7 patients), protocol violation (3 patients), and inadequate data (4 patients) for the delayed phase.


METHODS
All patients received cisplatin, 50 to 100 mg/m2 body surface area (median, 75 mg/m2); none had previously received chemotherapy. Thirty minutes before the cisplatin administration, ondansetron was given intravenously over 15 minutes, at a loading dose of 8 mg followed by a continuous infusion of 1 mg/h for 24 hours. Metoclopramide was given at a loading dose of 3 mg/kg body weight, followed by a continuous infusion for 8 hours (4 mg/kg). For the delayed phase (days 2 through 6), the first oral dose was given as soon as the infusion was completed; the oral dose consisted of either metoclopramide, 20 mg three times daily, or ondansetron, 8 mg three times daily for another 5 days.


RESULTS
In the acute phase, a major or complete response was seen in 72% of the ondansetron-treated and 41% of the metoclopramide-treated patients (P less than 0.001). Nausea was significantly better controlled among the ondansetron-treated patients (P = 0.04). In the delayed phase, no statistically significant difference was seen between ondansetron- and metoclopramide-treated patients. Nausea was significantly better controlled with metoclopramide (P = 0.016).


CONCLUSIONS
Ondansetron is significantly more effective than metoclopramide in preventing acute nausea and vomiting. In the delayed phase, the results of both drugs were disappointing, although metoclopramide's effect on delayed nausea was superior. Patients preferred ondansetron.
De Mulder
P H
PH
University Hospital, Nijmegen, The Netherlands.
Seynaeve
C
C
Vermorken
J B
JB
van Liessum
P A
PA
Mols-Jevdevic
S
S
Allman
E L
EL
Beranek
P
P
Verweij
J
J
D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008787:Metoclopramide / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D017294:Ondansetron; D012737:Sex Factors; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control
D000932:Antiemetics; D007093:Imidazoles; D017294:Ondansetron; D008787:Metoclopramide; D002945:Cisplatin