The oral NK1 antagonist aprepitant for prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy

This paper reviews the clinical profile of the neurokinin-1 (NK 1) receptor antagonist aprepitant, the first approved antiemetic in its class, developed for use in the prevention of chemotherapy-induced nausea and vomiting (CINV). CINV, which ranges from mild nausea to protracted vomiting with dehydration, can significantly affect the wellbeing and quality of life of patients with cancer. CINV remains a problem despite recent advances in preventive measures, notably the introduction of the serotonin 5-HT3 receptor antagonists. With standard dual therapy (a 5-HT3 antagonist plus a corticosteroid) emesis still occurs in up to 50% of patients in the acute phase (0-24 hours following emetogenic chemotherapy), especially during multiple cycles of chemotherapy as the initial effectiveness of dual therapy is not sustained. For the same reasons, emesis still occurs in up to 80% of patients in the delayed phase (2-5 days following chemotherapy). Furthermore, the likelihood of CINV is increased among patients receiving multiple cycles of chemotherapy. Aprepitant has been evaluated clinically as a single agent and in combination with other antiemetic agents. The addition of a 3-day regimen of aprepitant to a 5-HT3 receptor antagonist and a corticosteroid was found to enhance antiemetic protection significantly in patients receiving highly emetogenic, cisplatin-based chemotherapy. This improvement was particularly robust in the delayed phase of CINV and was also well maintained over multiple cycles - two situations in which a need for better antiemetic prophylaxis had been especially conspicuous. Although care must be taken to use aprepitant according to the labeling guidelines to minimize the potential for drug interactions, aprepitant was generally well tolerated among the >3000 patients or participants exposed to it. Aprepitant has therefore emerged as an important clinical advance in the supportive care of patients with cancer.

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