In this work, data from two phase III studies were pooled to further evaluate the NK(1) antagonist
aprepitant for prevention of
cisplatin induced
nausea and
vomiting. One thousand and forty three patients receiving
cisplatin (> or = 70 mg/m2) were randomised to receive either a control regimen (32 mg intravenous
ondansetron [O] and 20 mg oral
dexamethasone [D] on day 1; 8 mg D twice daily on days 2-4) or an
aprepitant (A) regimen (125 mg A plus 32 mg O and 12 mg D on day 1, 80 mg A and 8 mg D once daily on days 2-3, and 8 mg D on day 4). The primary endpoint was no
emesis and no rescue
therapy. Potential correlations between acute and delayed
emesis were assessed, as were frequency of
emetic episodes by time interval and effects on
nausea and quality of life as measured by the functional living index
emesis (FLIE) questionnaire. In the
aprepitant group, there was statistically significantly less
nausea over the study period as well as higher functioning on the FLIE questionnaire in both the
nausea and
vomiting domains. Patients without acute
emesis were more likely to have no
emesis in the delayed phase. Compared with control, the
aprepitant regimen improved prevention of delayed
emesis by 16% points in patients without acute
emesis, and by 17% points in patients with acute
emesis. Among patients who did not have complete response, the frequency of
emesis at various intervals over 5 days was consistently lower in patients receiving
aprepitant. Analyses of this combined Phase III population further characterized the clinical profile of the
aprepitant regimen, showing that delayed
emesis is correlated with, but not entirely dependent on, the presence of acute
emesis, and that
aprepitant has a favorable effect against
nausea throughout 5 days postchemotherapy. In addition, even among patients who had
emesis or needed rescue
therapy,
aprepitant was associated with a lower frequency of these events compared with the control regimen.