A phase 2 pharmacokinetic and pharmacodynamic dose-finding study of oral NEPA for chemotherapy-induced nausea and vomiting in pediatric patients with cancer.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	A phase 2 pharmacokinetic and pharmacodynamic dose-finding study of oral NEPA for chemotherapy-induced nausea and vomiting in pediatric patients with cancer.
Συγγραφείς:	Patel P; Pediatric Oncology Group of Ontario, Toronto, ON, Canada.; Department of Pharmacy, The Hospital for Sick Children, Toronto, ON, Canada., Arakaev O; Regional Children's Clinical Hospital #1, Ekaterinburg, Russia., Melnikov M; Children's Territorial Clinical Hospital, Krasnodar, Russia., Dementieva N; Dnipropetrovsk Regional Children's Clinical Hospital, Dnipro, Ukraine., Bernareggi A; Helsinn Healthcare SA, Lugano, Switzerland., Chen T; Helsinn Pharmaceuticals China, Shanghai, China., Spinelli T; Helsinn Healthcare SA, Lugano, Switzerland., Chaleff S; Maine Medical Center, Maine Children's Cancer Program, Scarborough, ME, 04074, USA. Stanley.Chaleff@mainehealth.org.
Πηγή:	Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer [Support Care Cancer] 2026 Sep 23; Vol. 34 (10). Date of Electronic Publication: 2026 Sep 23.
Τύπος έκδοσης:	Journal Article; Clinical Trial, Phase II; Multicenter Study; Randomized Controlled Trial
Γλώσσα:	English
Στοιχεία περιοδικού:	Publisher: Springer International Country of Publication: Germany NLM ID: 9302957 Publication Model: Electronic Cited Medium: Internet ISSN: 1433-7339 (Electronic) Linking ISSN: 09414355 NLM ISO Abbreviation: Support Care Cancer Subsets: MEDLINE
Imprint Name(s):	Original Publication: Berlin : Springer International, c1993-
Ιατρικοί όροι (MeSH):	Vomiting/chemically induced , Vomiting/drug therapy , Vomiting/prevention & control , Nausea/chemically induced , Nausea/drug therapy , Nausea/prevention & control , Palonosetron/administration & dosage , Palonosetron/pharmacokinetics , Antineoplastic Agents/adverse effects , Antineoplastic Agents/administration & dosage , Quinuclidines/administration & dosage , Quinuclidines/pharmacokinetics , Quinuclidines/therapeutic use , Pyridines/pharmacokinetics , Pyridines/administration & dosage , Pyridines/adverse effects , Pyridines/therapeutic use , Antiemetics/administration & dosage , Antiemetics/pharmacokinetics , Antiemetics/therapeutic use , Antiemetics/adverse effects , Isoquinolines/administration & dosage , Isoquinolines/pharmacokinetics , Isoquinolines/therapeutic use, Neoplasms/drug therapy ; Humans ; Female ; Child ; Male ; Child, Preschool ; Double-Blind Method ; Dose-Response Relationship, Drug ; Administration, Oral ; Adolescent ; Infant ; Piperazines ; Benzeneacetamides
Περίληψη:	Purpose: Chemotherapy-induced nausea and vomiting (CINV) remains a significant challenge in pediatric oncology, with limited data guiding optimal antiemetic regimens. This phase 2 study evaluated pharmacokinetics (PK), pharmacodynamics, efficacy, and safety of oral netupitant combined with oral palonosetron (NEPA) in pediatric patients receiving highly or moderately emetogenic chemotherapy. Methods: In this multicenter, randomized, double-blind, dose-finding study, pediatric patients (< 18 years) were stratified by age, chemotherapy emetogenicity, and schedule. Patients received one of two netupitant doses (1.33 or 4 mg/kg) with palonosetron (20 µg/kg). Efficacy was assessed via complete response (CR; no emesis and no rescue medication) during acute (0-24h), delayed (> 24-120h), and overall (0-120h) phases. PK parameters were derived from plasma concentrations of netupitant, its metabolites, and palonosetron. Safety was monitored through adverse events and clinical assessments. Results: Among 65 evaluable patients, CR rates were 85.3%, 70.6%, and 70.6% in the lower netupitant dose group, and 87.1%, 71.0%, and 67.7% in the higher dose group, for the acute, delayed, and overall phases, respectively. CR was mostly consistent across age groups and chemotherapy emetogenicity. A trend toward increased CR with higher netupitant exposure (AUC0-inf) was observed in the delayed phase. The safety profile was consistent with expectations for cytotoxic chemotherapy, and no new safety signals were observed. Conclusion: A single dose of 4 mg/kg oral netupitant with oral palonosetron was effective and well-tolerated for CINV prevention in pediatric patients, supporting further investigation of NEPA in this population. Trial Registration: NCT03204279 [2 July 2017 registration date]. (© 2026. The Author(s).)
Competing Interests:	Declarations. Ethics approval: The study was conducted in accordance with International Council for Harmonisation requirements and the Declaration of Helsinki. The study protocol was approved by the relevant independent ethics committees or institutional review boards. Consent to participate: For all patients, signed written informed consent by a parent/legal guardian was obtained before study initiation in compliance with the local laws and regulations, as well as signed children’s consent per local requirements. Consent for publication: Not applicable. Competing interests: P. Patel: Nothing to declare. O. Arakaev: Nothing to declare. M. Melnikov: Nothing to declare. N. Dementieva: Nothing to declare. A. Bernareggi: Clinical Pharmacology Consultant, Italy. Nothing to declare. T. Chen: Employee of Helsinn Healthcare. T. Spinelli: Employee of Helsinn Healthcare. S. Chaleff: Nothing to declare.
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Contributed Indexing:	Keywords: Chemotherapy-induced nausea and vomiting; NEPA; Netupitant; Palonosetron; Pediatric
Molecular Sequence:	ClinicalTrials.gov NCT03204279
Substance Nomenclature:	5D06587D6R (Palonosetron) 0 (Antineoplastic Agents) 0 (Quinuclidines) 0 (Pyridines) 0 (Antiemetics) 0 (Isoquinolines) 7732P08TIR (netupitant) 0 (Piperazines) 0 (Benzeneacetamides)
Entry Date(s):	Date Created: 20260923 Date Completed: 20260923 Latest Revision: 20261015
Update Code:	20261016
PubMed Central ID:	PMC13601078
DOI:	10.1007/s00520-026-11238-0
PMID:	42776270
Βάση Δεδομένων:	MEDLINE

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Περιγραφή
ISSN:	1433-7339
DOI:	10.1007/s00520-026-11238-0