Prevention of Acute / Delayed Nausea and Vomiting (Emesis)
In two randomized, double-blind, parallel, multicenter, controlled studies (520 patients in each study), patients received cisplatin (≥70 mg/m2) and were randomly assigned to receive either standard therapy with a 5-HT3 receptor antagonist (ondansetron) and dexamethasone prechemotherapy and dexamethasone postchemotherapy (days 2–4) or standard therapy plus aprepitant prechemotherapy and on days 2 and 3 postchemotherapy.[30,58][Level of evidence: I] The CR (no emesis, no rescue) of the aprepitant group in both studies was significantly higher in both the acute period (83%–89%) and the delayed period (68%–75%), compared with the CR of the standard therapy group in the acute period (68%–78%) and delayed period (47%–56%). Nausea was improved in the aprepitant group for some, but not all of the various specific measures of nausea. The studies discussed above formed the basis for the approval of aprepitant by the FDA in March 2003. In combination with other antiemetics, aprepitant is indicated for the prevention of acute and delayed N&V associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin. An additional study confirmed the efficacy of aprepitant in the delayed period, when it was compared with ondansetron.[Level of evidence: I]
All of the initial studies using aprepitant were conducted in patients receiving highly emetogenic chemotherapy such as cisplatin-based chemotherapy regimens. Subsequently, one group [Level of evidence: I] presented a study on the use of aprepitant in 862 breast cancer patients receiving moderately emetogenic chemotherapy (e.g., cyclophosphamide, doxorubicin). Two regimens were compared. Because the chemotherapy was moderately emetogenic, steroids were omitted from both arms, as illustrated in Table 2.
Table 2. Comparison of Aprepitant and Standard Regimens
|Regimen||Day 1||Days 2 and 3|
|bid = twice a day.|
|Aprepitant||Prechemotherapy: aprepitant (125 mg), ondansetron (8 mg), dexamethasone (12 mg)||Aprepitant (80 mg/d)|
|After 8 h: ondansetron (8 mg)|
|Standard||Prechemotherapy: ondansetron (8 mg), dexamethasone (20 mg)||Ondansetron (8 mg bid)|
|After 8 h: ondansetron (8 mg)|
There was a significant improvement in CR (no emesis, no rescue) in the 24 hours after chemotherapy in the patients receiving aprepitant; however, there was no significant improvement in CR on days 2 to 5 in the postchemotherapy period when aprepitant alone was compared with ondansetron alone. The overall (days 1–5) CR was significantly improved for the aprepitant-containing regimen, most likely because of the improvement in the first 24 hours. The control of nausea in moderately emetogenic chemotherapy was not improved with the use of aprepitant without steroids on days 2 and 3 postchemotherapy. These results were consistent for multiple cycles of chemotherapy. The role of aprepitant in moderately emetogenic chemotherapy remains undetermined. One open-label study demonstrated that in the 5 days postchemotherapy, aprepitant in combination with palonosetron and dexamethasone is safe and highly effective in preventing CINV in patients receiving moderately emetogenic chemotherapy.[Level of evidence: II] Another study reported that aprepitant combined with ondansetron and dexamethasone provided superior efficacy in the prevention of acute and delayed CINV in a broad range of patients receiving moderately emetogenic chemotherapy (both anthracycline-cyclophosphamide regimens and nonanthracycline-cyclophosphamide regimens). It is not known whether aprepitant is necessary in all moderately emetogenic regimens.