Assessing cognitive toxicity in early phase trials - What are we missing?

Autor: Stapleton SE; Royal Marsden Hospital Drug Development Unit, Sutton, UK.; University of Southampton, Southampton, UK., Darlington AS; University of Southampton, Southampton, UK., Minchom A; Royal Marsden Hospital Drug Development Unit, Sutton, UK.; Institute of Cancer Research, Sutton, UK., Pal A; Royal Marsden Hospital Drug Development Unit, Sutton, UK.; Institute of Cancer Research, Sutton, UK., Raynaud F; Royal Marsden Hospital Drug Development Unit, Sutton, UK.; Institute of Cancer Research, Sutton, UK., Wiseman T; Royal Marsden Hospital, Sutton, UK.
Jazyk: angličtina
Zdroj: Psycho-oncology [Psychooncology] 2022 Mar; Vol. 31 (3), pp. 405-415. Date of Electronic Publication: 2021 Oct 29.
DOI: 10.1002/pon.5834
Abstrakt: 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.
(© 2021 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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