Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting

To examine pharmacologic and clinical characteristics of neurokinin 1 (NK(1))-receptor antagonists (RAs) for preventing chemotherapy-induced nausea and vomiting (CINV) following highly or moderately emetogenic chemotherapy, a literature search was performed for clinical studies in patients at risk of CINV with any approved NK(1) RAs in the title or abstract: aprepitant (capsules or oral suspension), HTX019 (intravenous [IV] aprepitant), fosaprepitant (IV aprepitant prodrug), rolapitant (tablets or IV), and fixed-dose tablets combining netupitant or fosnetupi-tant (IV netupitant prodrug) with the 5-hydroxytryptamine type 3 (5HT(3)) RA palonosetron (oral or IV). All NK(1) RAs are effective, but exhibit important differences in efficacy against acute and delayed CINV. The magnitude of benefit of NK(1)-RA-containing three-drug vs two-drug regimens is greater for delayed vs acute CINV. Oral rolapitant has the longest half-life of available NK(1) RAs, but as a consequence should not be administered more frequently than every 2 weeks. In general, NK(1) RAs are well tolerated; however, IV rolapitant was recently removed from US distribution, due to hypersensitivity and anaphylaxis, and IV fosaprepitant is associated with infusion-site reactions and hypersensitivity presumed related to its polysorbate 80 excipient. Also, available NK(1) RAs have potential drug–drug interactions. Adding an NK(1) RA to 5HT(3) RA and dexamethasone significantly improves CINV control vs the two-drug regimen. Newer NK(1) RAs offer more formulation options, higher acute-phase plasma levels, or improved tolerability, and increase clinicians’ opportunities to maximize benefits of this important class of antiemetics.