PMID- 24631949
OWN - NLM
STAT- MEDLINE
DCOM- 20150831
LR  - 20240229
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Print)
IS  - 0923-7534 (Linking)
VI  - 25
IP  - 7
DP  - 2014 Jul
TI  - A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose 
      combination of netupitant and palonosetron, for prevention of 
      chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy.
PG  - 1333-1339
LID - S0923-7534(19)36687-6 [pii]
LID - 10.1093/annonc/mdu096 [doi]
AB  - BACKGROUND: Safe, effective and convenient antiemetic regimens that preserve 
      benefit over repeated cycles are needed for optimal supportive care during cancer 
      treatment. NEPA, an oral fixed-dose combination of netupitant, a highly selective 
      NK1 receptor antagonist (RA), and palonosetron (PALO), a distinct 5-HT3 RA, was 
      shown to be superior to PALO in preventing chemotherapy-induced nausea and 
      vomiting after a single cycle of highly (HEC) or moderately (MEC) emetogenic 
      chemotherapy in recent trials. This study was designed primarily to assess the 
      safety but also to evaluate the efficacy of NEPA over multiple cycles of HEC and 
      MEC. PATIENTS AND METHODS: This multinational, double-blind, randomized phase III 
      study (NCT01376297) in 413 chemotherapy-naive patients evaluated a single oral 
      dose of NEPA (NETU 300 mg + PALO 0.50 mg) given on day 1 with oral dexamethasone 
      (DEX). An oral 3-day aprepitant (APR) regimen + PALO + DEX was included as a 
      control (3:1 NEPA:APR randomization). In HEC, DEX was administered on days 1-4 
      and in MEC on day 1. Safety was assessed primarily by adverse events (AEs), 
      including cardiac AEs; efficacy by complete response (CR: no emesis, no rescue). 
      RESULTS: Patients completed 1961 total chemotherapy cycles (76% MEC, 24% HEC) 
      with 75% completing >/=4 cycles. The incidence/type of AEs was comparable for both 
      groups. Most frequent NEPA-related AEs included constipation (3.6%) and headache 
      (1.0%); there was no indication of increasing AEs over multiple cycles. The 
      majority of AEs were mild/moderate and there were no cardiac safety concerns 
      based on AEs and electrocardiograms. The overall (0-120 h) CR rates in cycle 1 
      were 81% and 76% for NEPA and APR + PALO, respectively, and antiemetic efficacy 
      was maintained over repeated cycles. CONCLUSIONS: NEPA, a convenient single oral 
      dose antiemetic targeting dual pathways, was safe, well tolerated and highly 
      effective over multiple cycles of HEC/MEC.
CI  - (c) The Author 2014. Published by Oxford University Press on behalf of the European 
      Society for Medical Oncology.
FAU - Gralla, R J
AU  - Gralla RJ
AD  - Department of Medical Oncology, Albert Einstein College of Medicine, Jacobi 
      Medical Center, Bronx, USA. Electronic address: richard.gralla@nbhn.net.
FAU - Bosnjak, S M
AU  - Bosnjak SM
AD  - Department of Supportive Oncology, Institute for Oncology and Radiology of 
      Serbia, Belgrade, Serbia.
FAU - Hontsa, A
AU  - Hontsa A
AD  - Chernivtsi Regional Cancer Hospital, Chernivtsi, Ukraine.
FAU - Balser, C
AU  - Balser C
AD  - OnkoNet Marburg GmbH, Marburg, Germany.
FAU - Rizzi, G
AU  - Rizzi G
AD  - Department of Statistics and Data Management.
FAU - Rossi, G
AU  - Rossi G
AD  - Department of Corporate Clinical Development, Helsinn Healthcare SA, Lugano, 
      Switzerland.
FAU - Borroni, M E
AU  - Borroni ME
AD  - Department of Corporate Clinical Development, Helsinn Healthcare SA, Lugano, 
      Switzerland.
FAU - Jordan, K
AU  - Jordan K
AD  - Department of Hematology and Oncology, University of Halle-Wittenberg, Halle, 
      Germany.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140314
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Drug Combinations)
RN  - 0 (Isoquinolines)
RN  - 0 (Pyridines)
RN  - 0 (Quinuclidines)
RN  - 5D06587D6R (Palonosetron)
RN  - 7732P08TIR (netupitant)
SB  - IM
CIN - Nat Rev Clin Oncol. 2014 Jul;11(7):377. PMID: 24889769
MH  - Antineoplastic Agents/*adverse effects
MH  - Double-Blind Method
MH  - Drug Combinations
MH  - Humans
MH  - Isoquinolines/*administration & dosage/adverse effects
MH  - Nausea/chemically induced/*prevention & control
MH  - Neoplasms/drug therapy
MH  - Palonosetron
MH  - Pyridines/*administration & dosage/adverse effects
MH  - Quinuclidines/*administration & dosage/adverse effects
MH  - Vomiting/chemically induced/*prevention & control
PMC - PMC4071753
OTO - NOTNLM
OT  - CINV
OT  - NEPA
OT  - multiple chemotherapy cycles
OT  - netupitant
OT  - neurokinin-1 receptor antagonist
OT  - palonosetron
EDAT- 2014/03/19 06:00
MHDA- 2015/09/01 06:00
PMCR- 2014/03/14
CRDT- 2014/03/18 06:00
PHST- 2014/03/18 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2015/09/01 06:00 [medline]
PHST- 2014/03/14 00:00 [pmc-release]
AID - S0923-7534(19)36687-6 [pii]
AID - mdu096 [pii]
AID - 10.1093/annonc/mdu096 [doi]
PST - ppublish
SO  - Ann Oncol. 2014 Jul;25(7):1333-1339. doi: 10.1093/annonc/mdu096. Epub 2014 Mar 
      14.