Mechanisms and latest clinical studies of new NK1 receptor antagonists for chemotherapy-induced nausea and vomiting: Rolapitant and NEPA (netupitant/palonosetron)

Research output: Contribution to journalArticle

Abstract

Many patients undergoing moderately or highly emetogenic chemotherapy experience chemotherapyinduced nausea/vomiting (CINV) and report reduced daily functioning, despite prophylaxis with antiemetic drugs. While modern antiemetics have largely alleviated acute emesis, management of nausea and delayed emesis remains particularly challenging. We briefly review the pathophysiologic mechanisms of CINV and the clinical impact of current antiemetics, i.e., the serotonin subtype 3 (5-HT3) receptor antagonists (RAs) and neurokinin-1 (NK1)RAs, before summarizing recent data from clinical trials of new agents. The new antiemetics reviewed include the two most recently approved drugs, the NK1RA rolapitant and the fixed-dose combination product, NEPA, which is composed of the NK1RA netupitant and the 5-HT3RA palonosetron. Phase 3 studies demonstrate improved control of CINV in the delayed and overall phases when rolapitant is added to a standard 5-HT3RA regimen. Phase 2 and phase 3 clinical trials with NEPA demonstrate improved control of CINV in the acute, delayed, and overall phases vs. 5-HT3RA regimens. These data suggest that delayed emesis can be substantially reduced via combined 5-HT3 and NK1 receptor neurotransmitter pathway inhibition.

Original languageEnglish (US)
Pages (from-to)904-913
Number of pages10
JournalCancer Treatment Reviews
Volume41
Issue number10
DOIs
StatePublished - 2015

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Neurokinin-1 Receptor Antagonists
Nausea
Vomiting
Antiemetics
Drug Therapy
Serotonin 5-HT3 Receptor Antagonists
Neurokinin-1 Receptors
Receptors, Serotonin, 5-HT3
Phase III Clinical Trials
Clinical Studies
8-((1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)methyl)-8-phenyl-1,7-diazaspiro(4,5)decan-2-one
netupitant
palonosetron
Neurotransmitter Agents
Serotonin
Clinical Trials

Keywords

  • 5-HT receptor antagonist
  • Chemotherapy-induced nausea and vomiting (CINV)
  • NEPA
  • NK receptor antagonist
  • Palonosetron
  • Rolapitant

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

Cite this

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title = "Mechanisms and latest clinical studies of new NK1 receptor antagonists for chemotherapy-induced nausea and vomiting: Rolapitant and NEPA (netupitant/palonosetron)",
abstract = "Many patients undergoing moderately or highly emetogenic chemotherapy experience chemotherapyinduced nausea/vomiting (CINV) and report reduced daily functioning, despite prophylaxis with antiemetic drugs. While modern antiemetics have largely alleviated acute emesis, management of nausea and delayed emesis remains particularly challenging. We briefly review the pathophysiologic mechanisms of CINV and the clinical impact of current antiemetics, i.e., the serotonin subtype 3 (5-HT3) receptor antagonists (RAs) and neurokinin-1 (NK1)RAs, before summarizing recent data from clinical trials of new agents. The new antiemetics reviewed include the two most recently approved drugs, the NK1RA rolapitant and the fixed-dose combination product, NEPA, which is composed of the NK1RA netupitant and the 5-HT3RA palonosetron. Phase 3 studies demonstrate improved control of CINV in the delayed and overall phases when rolapitant is added to a standard 5-HT3RA regimen. Phase 2 and phase 3 clinical trials with NEPA demonstrate improved control of CINV in the acute, delayed, and overall phases vs. 5-HT3RA regimens. These data suggest that delayed emesis can be substantially reduced via combined 5-HT3 and NK1 receptor neurotransmitter pathway inhibition.",
keywords = "5-HT receptor antagonist, Chemotherapy-induced nausea and vomiting (CINV), NEPA, NK receptor antagonist, Palonosetron, Rolapitant",
author = "Camilo Rojas and Barbara Slusher",
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AU - Rojas, Camilo

AU - Slusher, Barbara

PY - 2015

Y1 - 2015

N2 - Many patients undergoing moderately or highly emetogenic chemotherapy experience chemotherapyinduced nausea/vomiting (CINV) and report reduced daily functioning, despite prophylaxis with antiemetic drugs. While modern antiemetics have largely alleviated acute emesis, management of nausea and delayed emesis remains particularly challenging. We briefly review the pathophysiologic mechanisms of CINV and the clinical impact of current antiemetics, i.e., the serotonin subtype 3 (5-HT3) receptor antagonists (RAs) and neurokinin-1 (NK1)RAs, before summarizing recent data from clinical trials of new agents. The new antiemetics reviewed include the two most recently approved drugs, the NK1RA rolapitant and the fixed-dose combination product, NEPA, which is composed of the NK1RA netupitant and the 5-HT3RA palonosetron. Phase 3 studies demonstrate improved control of CINV in the delayed and overall phases when rolapitant is added to a standard 5-HT3RA regimen. Phase 2 and phase 3 clinical trials with NEPA demonstrate improved control of CINV in the acute, delayed, and overall phases vs. 5-HT3RA regimens. These data suggest that delayed emesis can be substantially reduced via combined 5-HT3 and NK1 receptor neurotransmitter pathway inhibition.

AB - Many patients undergoing moderately or highly emetogenic chemotherapy experience chemotherapyinduced nausea/vomiting (CINV) and report reduced daily functioning, despite prophylaxis with antiemetic drugs. While modern antiemetics have largely alleviated acute emesis, management of nausea and delayed emesis remains particularly challenging. We briefly review the pathophysiologic mechanisms of CINV and the clinical impact of current antiemetics, i.e., the serotonin subtype 3 (5-HT3) receptor antagonists (RAs) and neurokinin-1 (NK1)RAs, before summarizing recent data from clinical trials of new agents. The new antiemetics reviewed include the two most recently approved drugs, the NK1RA rolapitant and the fixed-dose combination product, NEPA, which is composed of the NK1RA netupitant and the 5-HT3RA palonosetron. Phase 3 studies demonstrate improved control of CINV in the delayed and overall phases when rolapitant is added to a standard 5-HT3RA regimen. Phase 2 and phase 3 clinical trials with NEPA demonstrate improved control of CINV in the acute, delayed, and overall phases vs. 5-HT3RA regimens. These data suggest that delayed emesis can be substantially reduced via combined 5-HT3 and NK1 receptor neurotransmitter pathway inhibition.

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