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 chemotherapy-induced 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.
authors.affiliation: Johns Hopkins Brain Science Institute, Johns Hopkins Medicine, Baltimore, MD, USA; Department of Molecular and Comparative Pathobiology, Johns Hopkins Medicine, Baltimore, MD, USA.
authors.forename: Camilo
authors.initials: C
authors.lastname: Rojas
authors.affiliation: Johns Hopkins Brain Science Institute, Johns Hopkins Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins Medicine, Baltimore, MD, USA; Department of Psychiatry, Johns Hopkins Medicine, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins Medicine, Baltimore, MD, USA. Electronic address: bslusher@jhmi.edu.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Slusher
mesh_terms: D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects; D004338:Drug Combinations; D006801:Humans; D007546:Isoquinolines / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy*; D064729:Neurokinin-1 Receptor Antagonists / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011812:Quinuclidines / Q000627:therapeutic use*; D013141:Spiro Compounds / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D004338:Drug Combinations; D007546:Isoquinolines; D064729:Neurokinin-1 Receptor Antagonists; D011725:Pyridines; D011812:Quinuclidines; D013141:Spiro Compounds; C000595957:netupitant, palosentron drug combination; C578834:rolapitant
keywords: 5-HT(3) receptor antagonist; Chemotherapy-induced nausea and vomiting (CINV); NEPA; NK(1) receptor antagonist; Palonosetron; Rolapitant