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COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss

COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss
COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss
Background:

Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy.

Methods:

A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears.

Results:

Although aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL.

Conclusions:

Aspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here.
Cisplatin, Chemotherapy, Aspirin
0959-8049
75-83
Crabb, Simon J.
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Martin, Karen
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Abab, Julia
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Ratcliffe, Ian
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Thornton, Roger
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Lineton, Ben
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Ellis, Mary
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Moody, Ronald
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Stanton, Louise
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Galanopoulou, Angeliki
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Maishman, Tom
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Geldart, Thomas
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Bayne, Mike
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Davies, Joe
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Lamb, Carolynn
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Popat, Sanjay
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Joffe, Johnathan K.
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Nutting, Chris
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Chester, John
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Hartley, Andrew
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Thomas, Gareth
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Ottensmeier, Christian
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Huddart, Robert
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King, Emma
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Crabb, Simon J.
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Martin, Karen
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Abab, Julia
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Ratcliffe, Ian
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Thornton, Roger
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Lineton, Ben
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Ellis, Mary
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Moody, Ronald
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Stanton, Louise
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Galanopoulou, Angeliki
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Maishman, Tom
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Geldart, Thomas
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Bayne, Mike
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Davies, Joe
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Lamb, Carolynn
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Popat, Sanjay
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Joffe, Johnathan K.
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Nutting, Chris
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Chester, John
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Hartley, Andrew
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Thomas, Gareth
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Ottensmeier, Christian
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Huddart, Robert
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King, Emma
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Crabb, Simon J., Martin, Karen, Abab, Julia, Ratcliffe, Ian, Thornton, Roger, Lineton, Ben, Ellis, Mary, Moody, Ronald, Stanton, Louise, Galanopoulou, Angeliki, Maishman, Tom, Geldart, Thomas, Bayne, Mike, Davies, Joe, Lamb, Carolynn, Popat, Sanjay, Joffe, Johnathan K., Nutting, Chris, Chester, John, Hartley, Andrew, Thomas, Gareth, Ottensmeier, Christian, Huddart, Robert and King, Emma (2017) COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss. European Journal of Cancer, 87, 75-83. (doi:10.1016/j.ejca.2017.09.033).

Record type: Article

Abstract

Background:

Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy.

Methods:

A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears.

Results:

Although aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL.

Conclusions:

Aspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here.

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More information

Accepted/In Press date: 25 September 2017
e-pub ahead of print date: 10 November 2017
Published date: December 2017
Keywords: Cisplatin, Chemotherapy, Aspirin

Identifiers

Local EPrints ID: 415580
URI: http://eprints.soton.ac.uk/id/eprint/415580
ISSN: 0959-8049
PURE UUID: ca3eb173-9c6d-482f-99b3-1601a1e7da6c
ORCID for Simon J. Crabb: ORCID iD orcid.org/0000-0003-3521-9064
ORCID for Karen Martin: ORCID iD orcid.org/0000-0002-6362-0501
ORCID for Julia Abab: ORCID iD orcid.org/0000-0002-5292-1042
ORCID for Louise Stanton: ORCID iD orcid.org/0000-0001-8181-840X

Catalogue record

Date deposited: 15 Nov 2017 17:30
Last modified: 13 Nov 2021 02:49

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Contributors

Author: Simon J. Crabb ORCID iD
Author: Karen Martin ORCID iD
Author: Julia Abab ORCID iD
Author: Ian Ratcliffe
Author: Roger Thornton
Author: Ben Lineton
Author: Mary Ellis
Author: Ronald Moody
Author: Louise Stanton ORCID iD
Author: Angeliki Galanopoulou
Author: Tom Maishman
Author: Thomas Geldart
Author: Mike Bayne
Author: Joe Davies
Author: Carolynn Lamb
Author: Sanjay Popat
Author: Johnathan K. Joffe
Author: Chris Nutting
Author: John Chester
Author: Andrew Hartley
Author: Gareth Thomas
Author: Robert Huddart
Author: Emma King

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