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

Abstract: 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 fosnetupitant (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. Keywords: aprepitant, chemotherapy-induced nausea and vomiting, fosaprepitant, netupitant, neurokinin 1-receptor antagonists, rolapitant