Assessing cognitive toxicity in early Phase Trials ‐ what are we missing?
Assessing cognitive toxicity in early Phase Trials ‐ what are we missing?
Objectives: novel therapies, such as, small protein molecule inhibitors and immunotherapies are first tested clinically in Phase I trials. Moving on to later phase trials and ultimately standard practice. A key aim of these early clinical trials is to define a toxicity profile; however, the emphasis is often on safety. The concern is cognitive toxicity is poorly studied in this context and may be under-reported. The aim of this review is to map evidence of cognitive assessment, toxicity, and confounding factors within reports from Phase I trials and consider putative mechanisms of impairment aligned with mechanisms of novel therapies.
Methods: a scoping review methodology was applied to the search of databases, including Embase, MEDLINE, Clinicaltrials.gov. A [keyword search was conducted, results screened for duplication then inclusion/exclusion criteria applied. Articles were further screened for relevance; data organised into categories and charted in a tabular format]. Evidence was collated and summarised into a narrative synthesis.
Results: despite the availability of robust ways to assess cognitive function, these are not routinely included in the conduct of early clinical trials. Reports of cognitive toxicity in early Phase I trials are limited and available evidence on this shows that a proportion of patients experience impaired cognitive function over the course of participating in a Phase I trial. Links are identified between the targeted action of some novel therapies and putative mechanisms of cognitive impairment.
Conclusion: the review provides rationale for research investigating cognitive function in this context. A study exploring the cognitive function of patients on Phase I trials and the feasibility of formally assessing this within early clinical trials is currently underway at the Royal Marsden.
anti-cancer therapies, attention, cancer, clinical trial phase I, cognitive dysfunction, drug development, immunotherapies, memory, oncology, pi3 kinase, poly (ADP-ribose) polymerase inhibitors, psycho-oncology
Stapleton, Sarah. E.
13e4d829-f059-42c8-bce7-4ce4875394c9
Darlington, Anne‐sophie
472fcfc9-160b-4344-8113-8dd8760ff962
Minchom, Anna
a89e1a87-6d5c-4df7-87da-a8421acb5239
Pal, Abhijit
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Raynaud, Florence
55c86c86-dd61-46be-9834-c3a4993c7ddb
Wiseman, Theresa
e3ff42ae-97ef-4640-af3d-40eeae830df9
14 October 2021
Stapleton, Sarah. E.
13e4d829-f059-42c8-bce7-4ce4875394c9
Darlington, Anne‐sophie
472fcfc9-160b-4344-8113-8dd8760ff962
Minchom, Anna
a89e1a87-6d5c-4df7-87da-a8421acb5239
Pal, Abhijit
fcbacbdb-904b-4bfe-ad96-4c6d35a5ef6e
Raynaud, Florence
55c86c86-dd61-46be-9834-c3a4993c7ddb
Wiseman, Theresa
e3ff42ae-97ef-4640-af3d-40eeae830df9
Stapleton, Sarah. E., Darlington, Anne‐sophie, Minchom, Anna, Pal, Abhijit, Raynaud, Florence and Wiseman, Theresa
(2021)
Assessing cognitive toxicity in early Phase Trials ‐ what are we missing?
Psycho-Oncology.
(doi:10.1002/pon.5834).
Abstract
Objectives: novel therapies, such as, small protein molecule inhibitors and immunotherapies are first tested clinically in Phase I trials. Moving on to later phase trials and ultimately standard practice. A key aim of these early clinical trials is to define a toxicity profile; however, the emphasis is often on safety. The concern is cognitive toxicity is poorly studied in this context and may be under-reported. The aim of this review is to map evidence of cognitive assessment, toxicity, and confounding factors within reports from Phase I trials and consider putative mechanisms of impairment aligned with mechanisms of novel therapies.
Methods: a scoping review methodology was applied to the search of databases, including Embase, MEDLINE, Clinicaltrials.gov. A [keyword search was conducted, results screened for duplication then inclusion/exclusion criteria applied. Articles were further screened for relevance; data organised into categories and charted in a tabular format]. Evidence was collated and summarised into a narrative synthesis.
Results: despite the availability of robust ways to assess cognitive function, these are not routinely included in the conduct of early clinical trials. Reports of cognitive toxicity in early Phase I trials are limited and available evidence on this shows that a proportion of patients experience impaired cognitive function over the course of participating in a Phase I trial. Links are identified between the targeted action of some novel therapies and putative mechanisms of cognitive impairment.
Conclusion: the review provides rationale for research investigating cognitive function in this context. A study exploring the cognitive function of patients on Phase I trials and the feasibility of formally assessing this within early clinical trials is currently underway at the Royal Marsden.
Text
Assessing cognitive toxicity in early Phase Trials
- Accepted Manuscript
More information
Accepted/In Press date: 29 September 2021
e-pub ahead of print date: 14 October 2021
Published date: 14 October 2021
Additional Information:
Funding Information:
The first author's post is funded by Cancer Research UK.
Publisher Copyright:
© 2021 John Wiley & Sons Ltd.
Keywords:
anti-cancer therapies, attention, cancer, clinical trial phase I, cognitive dysfunction, drug development, immunotherapies, memory, oncology, pi3 kinase, poly (ADP-ribose) polymerase inhibitors, psycho-oncology
Identifiers
Local EPrints ID: 452561
URI: http://eprints.soton.ac.uk/id/eprint/452561
ISSN: 1057-9249
PURE UUID: c41df13b-15f2-4632-b6c2-eb53c8467250
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Date deposited: 11 Dec 2021 11:27
Last modified: 17 Mar 2024 06:54
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Contributors
Author:
Sarah. E. Stapleton
Author:
Anna Minchom
Author:
Abhijit Pal
Author:
Florence Raynaud
Author:
Theresa Wiseman
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