Imperial College London
Alternate

ProfessorMariaBelvisi

Faculty of Medicine, National Heart & Lung Institute

Professor of Respiratory Pharmacology
 
 
 
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Contact

 

+44 (0)20 7594 7828m.belvisi

 
 
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Location

 

107Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Smith:2021:10.1164/rccm.202006-2359OC,
author = {Smith, JA and Harle, A and Dockry, R and Holt, K and Russell, P and Molassiotis, A and Yorke, J and Robinson, R and Birrell, MA and Belvisi, MG and Blackhall, F},
doi = {10.1164/rccm.202006-2359OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {737--745},
title = {Aprepitant for cough in lung cancer: a randomised placebo-controlled trial and mechanistic insights},
url = {http://dx.doi.org/10.1164/rccm.202006-2359OC},
volume = {203},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - RATIONALE: Effective cough treatments are a significant unmet need in lung cancer patients. Aprepitant is a licensed treatment for nausea and vomiting, which blocks substance P activation of Neurokinin 1 (NK-1) receptors, a mechanism also implicated in cough. OBJECTIVE: To assess aprepitant in lung cancer patients with cough and evaluate mechanisms in vagal nerve tissue. METHODS: Randomised double-blind crossover trial of lung cancer patients with bothersome cough. They received three days of aprepitant or matched placebo; following a three day wash out, patients crossed to the alternative treatment. The primary endpoint was awake cough frequency measured at screening and day 3 of each treatment; secondary endpoints included patient-reported outcomes. In vitro, the depolarization of isolated guinea pig and human vagus nerve sections in grease gap recording chambers, indicative of sensory nerve activation, was measured to evaluate mechanism. MEASUREMENTS AND MAIN RESULTS: Twenty lung cancer patients enrolled, mean age 66years (±7.7), 60% female, 80% non-small cell cancer, 50% advanced stage and 55% WHO performance status 1. Cough frequency improved with aprepitant, reducing by 22.2%(95%CI 2.8-37.7%) over placebo whilst awake (p=0.03), 30.3%(95%CI 12.7-44.3) over 24hours (p=0.002) and 59.8%(95%CI 15.1-86.0) during sleep (p=0.081). Patient-reported outcomes all significantly improved. Substance P depolarised both guinea pig and human vagus nerve. Aprepitant significantly inhibited substance P induced depolarisation by 78% in guinea pig (p=0.0145) and 94% in human vagus (p=0.0145). DISCUSSION: Substance P activation of NK-1 receptors appears to be an important mechanism driving cough in lung cancer, and NK-1 antagonists show promise as anti-tussive therapies. Clinical trial registration available at www.http://www.isrctn.com/, ID: ISRCTN16200035.
AU  - Smith,JA
AU  - Harle,A
AU  - Dockry,R
AU  - Holt,K
AU  - Russell,P
AU  - Molassiotis,A
AU  - Yorke,J
AU  - Robinson,R
AU  - Birrell,MA
AU  - Belvisi,MG
AU  - Blackhall,F
DO  - 10.1164/rccm.202006-2359OC
EP  - 745
PY  - 2021///
SN  - 1073-449X
SP  - 737
TI  - Aprepitant for cough in lung cancer: a randomised placebo-controlled trial and mechanistic insights
T2  - American Journal of Respiratory and Critical Care Medicine
UR  - http://dx.doi.org/10.1164/rccm.202006-2359OC
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32966755
UR  - https://www.atsjournals.org/doi/10.1164/rccm.202006-2359OC
UR  - http://hdl.handle.net/10044/1/83275
VL  - 203
ER  -
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