ONDANSETRON COMPARED WITH GRANISETRON IN THE PROPHYLAXIS OF CYCLOPHOSPHAMIDE-INDUCED EMESIS IN OUT-PATIENTS - A MULTICENTER, DOUBLE-BLIND, DOUBLE-DUMMY, RANDOMIZED, 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 a nd granisetron in the control of prolonged emesis after cyclophosphami de-containing chemotherapy (48% CMF, 35% EC) for breast cancer. A tota l of 514 patients were recruited. Of the 488 patients included in the intent-to-treat analyses, 167 were randomised to group A [8 mg ondanse tron intravenously (i.v.) + placebo by mouth (p.o.) before chemotherap y + 8 mg ondansetron p.o, twice daily (b.d.) until day 5], 155 to grou p 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 granisetro n i.v. + placebo p.o. before chemotherapy + placebo p.o. b.d. until da y 5). On study day 1, the groups were comparable with respect to the p roportion of patients experiencing up to 2 emetic episodes (group A: 8 9%; 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 Over the 5-day study period significantly more patients were rescued or withdrawn due to lack of response after the g ranisetron regimen (26%) than after the i.v. + p.o. ondansetron regime n (11%; p 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 a fter i.v. and p.o. ondansetron compared with granisetron was also obse rved 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 com pared with the granisetron regimen (no nausea; group A: 33%; B: 34%; C : 25%). Again these differences reflected differences in nausea contro l on days 2-5, since no differences were observed on day 1. Logistic r egression analyses adjusted for prognostic factors also revealed a sig nificant difference (p = 0.011) in favour of the i.v. + ondansetron gr oup compared with the granisetron group when complete plus major respo nse was compared over days 2-5. No significant differences in the safe ty profiles of the three treatment groups were observed. There were no severe or unexpected drug-related adverse events and as is well estab lished for the serotonin receptor antagonists, mild constipation (mean 8%) and mild headache (mean 8%) were most commonly reported.