Seventy-five
breast cancer patients scheduled to receive a first course (in a new cycle) of
cyclophosphamide,
fluorouracil, and
doxorubicin (FAC) or
epirubicin (FEC) participated in a double-blind crossover study to compare the
antiemetic efficacy and safety of
ondansetron (GR38032), a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, and
metoclopramide.
Ondansetron was given as an 8 mg loading dose (4 mg intravenously [IV] plus 4 mg orally) before
chemotherapy followed by 8 mg every 8 hours orally for 3 to 5 days.
Metoclopramide was given as an 80 mg loading dose (60 mg IV plus 20 mg orally) before
chemotherapy followed by 20 mg every 8 hours orally for 3 to 5 days. A "period" interaction in the analysis of
emetic response in the first 24 hours necessitated a parallel group analysis of first treatments only, 68 patients being assessable for this parameter. In the first 24 hours, complete or major control (zero to two
emetic episodes) of
emesis was achieved in 30 of 35 (86%) patients receiving
ondansetron and in 14 of 33 (42%) patients receiving
metoclopramide (P less than .001).
Ondansetron was also more effective in reducing acute
nausea. On days 2 to 3, the complete or major responses were significantly better with
ondansetron (81% v 65%; P = .033), but there was no statistical difference in the control of
nausea. There was a significant patient preference for
ondansetron (63% v 26%; P = .001). Extrapyramidal reactions were observed in two
metoclopramide treatments; both treatments were otherwise well tolerated. These results are consistent with
serotonin (5-HT), being a significant
neurotransmitter of
cyclophosphamide/
doxorubicin- or
epirubicin/
fluorouracil-induced
emesis.