Ondansetron compared with granisetron in the prophylaxis of cyclophosphamide-induced emesis in out-patients: a multicentre, double-blind, double-dummy, randomised, parallel-group study. Emesis Study Group for Ondansetron and Granisetron in Breast Cancer Patients.
This is the first double-blind clinical trial in a homogenous group of patients to compare the recommended dosing schedules of ondansetron and granisetron in the control of prolonged emesis after cyclophosphamide-containing chemotherapy (48% CMF, 35% EC) for breast cancer. A total of 514 patients were recruited. Of the 488 patients included in the intent-to-treat analyses, 167 were randomised to group A [8 mg ondansetron intravenously (i.v.) + placebo by mouth (p.o.) before chemotherapy + 8 mg ondansetron p.o. twice daily (b.d.) until day 5], 155 to group B (placebo i,.v. + 8 mg ondansetron p.o. before chemotherapy + 8 mg ondansetron p.o. b.d. until day 5) and 166 to group C (3 mg granisetron i.v. + placebo p.o. before chemotherapy + placebo p.o. b.d. until day 5). On study day 1, the groups were comparable with respect to the proportion of patients experiencing up to 2 emetic episodes (group A: 89%; B: 86%; C: 91%) and in the severity of nausea (no nausea; group A: 51%; B: 55%; C: 54%). Over the 5-day study period significantly more patients were rescued or withdrawn due to lack of response after the granisetron regimen (26%) than after the i.v. + p.o. ondansetron regimen (11%; p < 0.001). Since there was no difference in these parameters on day 1, this reflects differences on days 2-5 and was also reflected in the all-oral ondansetron group over this period (group B: 12%; C: 22% on days 2-5). A significant difference in the severity of nausea after i.v. and p.o. ondansetron compared with granisetron was also observed over the 5-day study period (p = 0.009). This was reflected in a numerical difference in favour of the all-p.o. ondansetron regimen compared with the granisetron regimen (no nausea; group A: 33%; B: 34%; C: 25%). Again these differences reflected differences in nausea control on days 2-5, since no differences were observed on day 1. Logistic regression analyses adjusted for prognostic factors also revealed a significant difference (p = 0.011) in favour of the i.v. + ondansetron group compared with the granisetron group when complete plus major response was compared over days 2-5. No significant differences in the safety profiles of the three treatment groups were observed. There were no severe or unexpected drug-related adverse events and as is well established for the serotonin receptor antagonists, mild constipation (mean 8%) and mild headache (mean 8%) were most commonly reported.
Stewart
A
A
Christie Hospital, Manchester, UK.
McQuade
B
B
Cronje
J D
JD
Goedhals
L
L
Gudgeon
A
A
Corette
L
L
Froger
X
X
Tubiana-Hulin
M
M
Laplaige
P
P
Roberts
J T
JT
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D017829:Granisetron / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D017294:Ondansetron / Q000008:administration & dosage / Q000627:therapeutic use*; D017060:Patient Satisfaction; D012107:Research Design; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D003520:Cyclophosphamide; D017829:Granisetron; D017294:Ondansetron