Ondansetron compared with granisetron in the prophylaxis of cyclophosphamide-lnduced emesis in out-patients: A multicentre, double-blind, double-dummy, randomised, parallel-group study

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 Over the 5-day study period significantly more patients were rescued or withdrawn due to lack of response after the granisetron regimen (26%) than after the i.v. + p.o. ondansetron regimen (11%; p 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. © 1995 S. Karger AG, Basel.