Neurokinin-1 receptor antagonists: review of their role for the prevention of chemotherapy-induced nausea and vomiting in adults

ABSTRACT

Introduction: The addition of neurokinin-1 receptor antagonists (NK₁RAs) to standard prophylaxis of 5-hydroxytryptamine-3 RA (5-HT₃RA) plus dexamethasone more effectively prevents chemotherapy-induced nausea and vomiting (CINV) associated with highly and moderately emetogenic chemotherapy.

Areas covered: This review presents the evidence base for the use of oral and intravenous (IV) NK₁RAs, focusing on the pharmacologic and clinical properties as a class, and highlighting differences between agents. A PubMed literature search was conducted from 2000 to 2018.

Expert opinion: Adherence to international antiemetic guidelines remains a clinical challenge. Strategies to simplify antiemetic regimens and facilitate their administration may improve compliance and treatment outcomes. The use of fixed-combination antiemetics offers clinical utility, in combining an NK₁RA with a 5-HT₃RA in a single oral dose. The use of long-lasting NK₁RAs and administering CINV prophylaxis closer to the time of chemotherapy may also assist with guideline and treatment compliance, diminishing the need for home-based administration, and potentially reducing resource utilization. The availability of IV and oral formulations of NK₁RAs and NK₁RA–5-HT₃RA fixed combinations offers further utility, particularly for those patients unsuited for oral administration. However, safety considerations with respect to injection site toxicity and hypersensitivity reactions of the new NK₁RA IV formulations deserve close attention.

KEYWORDS:

• Chemotherapy-induced nausea and vomiting (CINV)
• emesis
• antiemetics
• guidelines
• adherence

Article highlights

• It is suggested that clinicians should follow international antiemetic guidelines in order to minimize the negative impact of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer.

• Triplet regimens of neurokinin-1 receptor antagonist (NK₁RA), 5-hydroxytryptamine-3 receptor antagonist (5-HT₃RA), and dexamethasone provide superior control of CINV associated with highly emetogenic chemotherapy (HEC, including anthracycline plus cyclophosphamide) and carboplatin-based regimens compared with 5-HT₃RA–dexamethasone alone, and are therefore recommended by international guidelines.

• Strategies to simplify antiemetic regimens and facilitate their ease of administration are essential to improve clinician adherence to guidelines and patient treatment compliance.

• The fixed-combination agent NEPA, composed of the NK₁RA netupitant and the 5-HT₃RA palonosetron, targets in a single dose the two key signaling pathways involved in emesis via overlapping and synergistic mechanisms.

• NK₁RAs with prolonged half-life, such as netupitant and rolapitant, help reduce the number of doses needed.

• Achieving complete control of nausea remains a major obstacle in antiemetic treatment, and while the improvement in the control of delayed nausea of both aprepitant- and rolapitant-based regimens is not clear, NEPA plus dexamethasone has shown superiority over 5-HT₃RA–dexamethasone.

• Finally, the availability of intravenous (IV) formulations of antiemetics is of special value to patients who cannot swallow oral medications. IV NEPA has shown similar tolerability compared with the oral formulation. However, hypersensitivity reactions, including anaphylaxis and anaphylactic shock, may occur following fosaprepitant, IV aprepitant (injectable emulsion), or IV rolapitant (injectable emulsion) administration, and infusion site toxicities have been observed with fosaprepitant and IV rolapitant (injectable emulsion).

Declaration of interest

M Karthaus: advisory boards for Helsinn Healthcare, Merck Sharp & Dohme, RIEMSER Pharma, and Tesaro. CH Ruhlmann is the sponsor-investigator of a clinical research trial for which the institution has received a grant from Helsinn Healthcare. L Celio has received consulting fees from Italfarmaco. The authors are fully responsible for all content and editorial decisions for this manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Editorial support and medical writing assistance were provided by Iratxe Abarrategui from Aptitude Health, The Hague, The Netherlands, funded by Helsinn Healthcare SA, Lugano, Switzerland.