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

Abstract

To examine pharmacologic and clinical characteristics of neurokinin 1 (NK1)-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 NK1 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 (5HT3) RA palonosetron (oral or IV). All NK1 RAs are effective, but exhibit important differences in efficacy against acute and delayed CINV. The magnitude of benefit of NK1-RA-containing three-drug vs two-drug regimens is greater for delayed vs acute CINV. Oral rolapitant has the longest half-life of available NK1 RAs, but as a consequence should not be administered more frequently than every 2 weeks. In general, NK1 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 NK1 RAs have potential drug–drug interactions. Adding an NK1 RA to 5HT3 RA and dexamethasone significantly improves CINV control vs the two-drug regimen. Newer NK1 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.

Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy

“…Rolapitant IV contains the synthetic surfactant polyoxyl 15 hydroxystearate , and HTX‐019 (IV aprepitant) contains potentially allergenic excipients including egg lecithin, soybean oil, and ethanol but does not contain either polysorbate 80 or synthetic surfactants . Unlike these IV NK 1 RAs, the IV NEPA combination solution does not require any surfactant, emulsifier, or solubility enhancer and contains no allergenic excipients .…”

“…In general, the NK 1 RAs as a class are considered safe and well tolerated . However, hypersensitivity reactions and infusion‐site AEs have been associated with fosaprepitant, most likely due to the polysorbate 80 surfactant .…”

Expert Consensus on Effective Management of Chemotherapy-Induced Nausea and Vomiting: An Indian Perspective

“…Furthermore, scientific literature has provided good evidence on the effectiveness and safety of netupitant-palonosetron combination in both HEC and MEC settings (59)(60)(61)(62). The NCCN guideline recommends NK1 RA to be added to a 5-HT3/dexamethasone regimen for patients receiving MEC anticancer therapy who have additional risk factors, or previous treatment failure with the two-drug regimen.…”

Use of dexamethasone and a 5-HT3 receptor antagonist with or without aprepitant to prevent chemotherapy-induced nausea and vomiting among patients with lung cancer who are treated with platinum-based chemotherapy: a systematic review and meta-analysis of randomized controlled trials

“…Aprepitant is a neurokinin-1 (NK-1) RA that functions in both the gut and the central nervous system by antagonizing the interaction of substance P (chemotherapyrelated increase) and NK-1 receptors to prevent CINV (7). Some clinical trials have suggested that adding aprepitant (ADH) to DH has achieved excellent effects (8).…”