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

Rudolph M. Navari, Lee Schwartzberg

Research output: Contribution to journalReview article

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 fosnetupitant (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.

Original languageEnglish (US)
Pages (from-to)6459-6478
Number of pages20
JournalOncoTargets and Therapy
Volume11
DOIs
StatePublished - Jan 1 2018

Fingerprint

Neurokinin-1 Receptor Antagonists
Nausea
Vomiting
aprepitant
Drug Therapy
fosaprepitant
Receptors, Serotonin, 5-HT3
Prodrugs
Tablets
Hypersensitivity
Pharmaceutical Preparations
Antiemetics
Polysorbates
Excipients
Anaphylaxis
Dexamethasone
Capsules
Half-Life
Suspensions

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology (medical)

Cite this

Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting. / Navari, Rudolph M.; Schwartzberg, Lee.

In: OncoTargets and Therapy, Vol. 11, 01.01.2018, p. 6459-6478.

Research output: Contribution to journalReview article

@article{b1077b394d404cf2a860008859971571,
title = "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 fosnetupitant (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.",
author = "Navari, {Rudolph M.} and Lee Schwartzberg",
year = "2018",
month = "1",
day = "1",
doi = "10.2147/OTT.S158570",
language = "English (US)",
volume = "11",
pages = "6459--6478",
journal = "OncoTargets and Therapy",
issn = "1178-6930",
publisher = "Dove Medical Press Ltd.",

}

TY - JOUR

T1 - Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting

AU - Navari, Rudolph M.

AU - Schwartzberg, Lee

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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 fosnetupitant (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.

AB - 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 fosnetupitant (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.

UR - http://www.scopus.com/inward/record.url?scp=85057976241&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85057976241&partnerID=8YFLogxK

U2 - 10.2147/OTT.S158570

DO - 10.2147/OTT.S158570

M3 - Review article

VL - 11

SP - 6459

EP - 6478

JO - OncoTargets and Therapy

JF - OncoTargets and Therapy

SN - 1178-6930

ER -