PMID- 29722791
OWN - NLM
STAT- MEDLINE
DCOM- 20191118
LR  - 20200407
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 29
IP  - 7
DP  - 2018 Jul 1
TI  - Phase III safety study of intravenous NEPA: a novel fixed antiemetic combination 
      of fosnetupitant and palonosetron in patients receiving highly emetogenic 
      chemotherapy.
PG  - 1535-1540
LID - S0923-7534(19)32108-8 [pii]
LID - 10.1093/annonc/mdy169 [doi]
AB  - BACKGROUND: NEPA, an oral fixed combination of the NK1RA netupitant (300 mg) and 
      clinically/pharmacologically distinct 5-HT3RA palonosetron (PALO, 0.50 mg), is 
      the first fixed antiemetic combination to have been approved. A single oral NEPA 
      capsule plus dexamethasone (DEX) given before anthracycline-cyclophosphamide (AC) 
      and non-AC highly emetogenic chemotherapy (HEC) showed superior prevention of 
      chemotherapy-induced nausea and vomiting (CINV) over PALO plus DEX for 5 days 
      postchemotherapy. The safety of NEPA was well-established in the phase II/III 
      clinical program in 1169 NEPA-treated patients. An intravenous (i.v.) formulation 
      of the NEPA combination (fosnetupitant 235 mg plus PALO 0.25 mg) has been 
      developed. PATIENTS AND METHODS: This randomized, multinational, double-blind, 
      stratified (by sex and country) phase III study (NCT02517021) in 
      chemotherapy-naive patients with solid tumors assessed the safety of a single 
      dose of i.v. NEPA infused over 30 min before initial and repeated cycles of HEC. 
      Patients received either i.v. NEPA or oral NEPA, both with oral DEX on days 1-4. 
      Safety was assessed primarily by treatment-emergent adverse events (AEs) and 
      electrocardiograms. RESULTS: A total of 404 patients completed 1312 cycles. The 
      incidence and type of treatment-emergent AEs were similar for both treatment 
      groups with the majority of AEs as mild/moderate in intensity. There was no 
      increased incidence of AEs in subsequent cycles in either group. The incidence of 
      treatment-related AEs was similar and relatively low in both groups (12.8% i.v. 
      NEPA and 11.4% oral NEPA during the entire study), with constipation being the 
      most common (6.4% i.v. NEPA, 6.0% oral NEPA). No serious treatment-related AEs 
      occurred in either group. No infusion site or anaphylactic reactions related to 
      i.v. NEPA occurred. No clinically relevant changes in QTc and no cardiac safety 
      concerns were observed. CONCLUSIONS: Intravenous NEPA was well-tolerated with a 
      similar safety profile to oral NEPA in patients with various solid tumors 
      receiving HEC.
FAU - Schwartzberg, L
AU  - Schwartzberg L
AD  - Hematology & Oncology, West Cancer Center, Germantown, USA. Electronic address: 
      lschwartzberg@westclinic.com.
FAU - Roeland, E
AU  - Roeland E
AD  - Oncology & Palliative Care, Massachusetts General Hospital, Boston, USA.
FAU - Andric, Z
AU  - Andric Z
AD  - Division of Medical Oncology, Clinical Hospital Center Bezanijska Kosa, Belgrade, 
      Serbia.
FAU - Kowalski, D
AU  - Kowalski D
AD  - Lung Cancer and Chest Tumours, Maria Sklodowska-Curie Memorial Cancer Centre and 
      Institute of Oncology, Warsaw, Poland.
FAU - Radic, J
AU  - Radic J
AD  - Clinic of Oncology and Nuclear Medicine, Clinical Hospital Center 'Sestre 
      milosrdnice', Zagreb, Croatia.
FAU - Voisin, D
AU  - Voisin D
AD  - Clinical Research & Development, Helsinn Healthcare SA, Lugano, Switzerland.
FAU - Rizzi, G
AU  - Rizzi G
AD  - Statistics & Data Management, Helsinn Healthcare SA, Lugano, Switzerland.
FAU - Navari, R
AU  - Navari R
AD  - Division of Hematology Oncology, University of Alabama Comprehensive Cancer 
      Center, Birmingham.
FAU - Gralla, R J
AU  - Gralla RJ
AD  - Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, USA.
FAU - Karthaus, M
AU  - Karthaus M
AD  - Hematology, Oncology and Palliative Medicine, Staedt. Klinikum Neuperlach and 
      Harlaching, Munchen, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT02517021
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Anthracyclines)
RN  - 0 (Antiemetics)
RN  - 0 (Pyridines)
RN  - 5D06587D6R (Palonosetron)
RN  - 7732P08TIR (netupitant)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
CIN - Ann Oncol. 2018 Jul 1;29(7):1494-1496. PMID: 29790903
MH  - Administration, Intravenous
MH  - Anthracyclines/administration & dosage
MH  - Antiemetics/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/*adverse effects
MH  - Cyclophosphamide/administration & dosage
MH  - Dexamethasone/administration & dosage
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Induction Chemotherapy
MH  - Male
MH  - Middle Aged
MH  - Nausea/chemically induced/*prevention & control
MH  - Neoplasms/*drug therapy/pathology
MH  - Palonosetron/*therapeutic use
MH  - Prognosis
MH  - Pyridines/*therapeutic use
MH  - Survival Rate
MH  - Vomiting/chemically induced/*prevention & control
EDAT- 2018/05/04 06:00
MHDA- 2019/11/19 06:00
CRDT- 2018/05/04 06:00
PHST- 2018/05/04 06:00 [pubmed]
PHST- 2019/11/19 06:00 [medline]
PHST- 2018/05/04 06:00 [entrez]
AID - S0923-7534(19)32108-8 [pii]
AID - 10.1093/annonc/mdy169 [doi]
PST - ppublish
SO  - Ann Oncol. 2018 Jul 1;29(7):1535-1540. doi: 10.1093/annonc/mdy169.