PMID- 28327932
OWN - NLM
STAT- MEDLINE
DCOM- 20180129
LR  - 20240313
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Print)
IS  - 0923-7534 (Linking)
VI  - 28
IP  - 6
DP  - 2017 Jun 1
TI  - Integrated safety analysis of rolapitant with coadministered drugs from phase 
      II/III trials: an assessment of CYP2D6 or BCRP inhibition by rolapitant.
PG  - 1268-1273
LID - 10.1093/annonc/mdx073 [doi]
AB  - BACKGROUND: Rolapitant, a long-acting neurokinin (NK)1 receptor antagonist (RA), 
      has demonstrated efficacy in prevention of chemotherapy-induced nausea and 
      vomiting in patients administered moderately or highly emetogenic chemotherapy. 
      Unlike other NK1 RAs, rolapitant does not inhibit or induce cytochrome P450 (CYP) 
      3A4, but it does inhibit CYP2D6 and breast cancer resistance protein (BCRP). To 
      analyze potential drug-drug interactions between rolapitant and concomitant 
      medications, this integrated safety analysis of four double-blind, randomized 
      phase II or III studies of rolapitant examined adverse events (AEs) by use versus 
      non-use of drug substrates of CYP2D6 or BCRP. PATIENTS AND METHODS: Patients were 
      randomized to receive either 180 mg oral rolapitant or placebo  approximately 1-2 h before 
      chemotherapy in combination with a 5-hydroxytryptamine type 3 RA and 
      dexamethasone. Data for treatment-emergent AEs (TEAEs) and treatment-emergent 
      serious AEs (TESAEs) during cycle 1 were pooled across the four studies and 
      summarized in the overall population and by concomitant use/non-use of CYP2D6 or 
      BCRP substrate drugs. RESULTS: In the integrated safety population, 828 of 1294 
      patients (64%) in the rolapitant group and 840 of 1301 patients (65%) in the 
      control group experienced at least one TEAE. Frequencies of common TEAEs were 
      similar in the rolapitant and control populations. Overall, 53% of patients 
      received CYP2D6 substrate drugs, none of which had a narrow therapeutic index 
      (like thioridazine or pimozide), and 63% received BCRP substrate drugs. When 
      grouped by concomitant use versus non-use of CYP2D6 or BCRP substrate drugs, 
      TEAEs and TESAEs occurred with similar frequency in the rolapitant and control 
      populations. CONCLUSIONS: The results of this study support the safety of 
      rolapitant as part of an antiemetic triple-drug regimen in patients receiving 
      emetogenic chemotherapy, including those administered concomitant medications 
      that are substrates of CYP2D6 or BCRP, such as ondansetron, docetaxel, or 
      irinotecan.
CI  - (c) The Author 2017. Published by Oxford University Press on behalf of the European 
      Society for Medical Oncology.
FAU - Barbour, S
AU  - Barbour S
AD  - Department of Pharmacy, Duke University Hospital, Durham, USA.
FAU - Smit, T
AU  - Smit T
AD  - The Medical Oncology Center of Rosebank, Johannesburg, South Africa.
FAU - Wang, X
AU  - Wang X
AD  - TESARO, Inc., Waltham, USA.
FAU - Powers, D
AU  - Powers D
AD  - TESARO, Inc., Waltham, USA.
FAU - Arora, S
AU  - Arora S
AD  - TESARO, Inc., Waltham, USA.
FAU - Kansra, V
AU  - Kansra V
AD  - TESARO, Inc., Waltham, USA.
FAU - Aapro, M
AU  - Aapro M
AD  - IMO Clinique de Genolier, Genolier, Switzerland.
FAU - Herrstedt, J
AU  - Herrstedt J
AD  - Department of Oncology, Odense University Hospital, Odense, Denmark.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Spiro Compounds)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
RN  - NLE429IZUC (rolapitant)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cytochrome P-450 CYP2D6/*drug effects
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Spiro Compounds/*therapeutic use
MH  - Young Adult
PMC - PMC5452074
OTO - NOTNLM
OT  - breast cancer resistance protein
OT  - chemotherapy-induced nausea and vomiting
OT  - cytochrome P450
OT  - rolapitant
OT  - safety
EDAT- 2017/03/23 06:00
MHDA- 2018/01/30 06:00
PMCR- 2017/02/23
CRDT- 2017/03/23 06:00
PHST- 2017/03/23 06:00 [pubmed]
PHST- 2018/01/30 06:00 [medline]
PHST- 2017/03/23 06:00 [entrez]
PHST- 2017/02/23 00:00 [pmc-release]
AID - S0923-7534(19)32417-2 [pii]
AID - mdx073 [pii]
AID - 10.1093/annonc/mdx073 [doi]
PST - ppublish
SO  - Ann Oncol. 2017 Jun 1;28(6):1268-1273. doi: 10.1093/annonc/mdx073.