Assessing cognitive toxicity in early phase trials - What are we missing?
Corresponding Author
Sarah E. Stapleton
Royal Marsden Hospital Drug Development Unit, Sutton, UK
University of Southampton, Southampton, UK
Correspondence
Sarah E. Stapleton, Drug Development Unit Royal Marsden Hospital Downs Rd Sutton Surrey SM2 5PT, Sutton, UK.
Email: [email protected]
Search for more papers by this authorAnne-Sophie Darlington
University of Southampton, Southampton, UK
Search for more papers by this authorAnna Minchom
Royal Marsden Hospital Drug Development Unit, Sutton, UK
Institute of Cancer Research, Sutton, UK
Search for more papers by this authorAbhijit Pal
Royal Marsden Hospital Drug Development Unit, Sutton, UK
Institute of Cancer Research, Sutton, UK
Search for more papers by this authorFlorence Raynaud
Royal Marsden Hospital Drug Development Unit, Sutton, UK
Institute of Cancer Research, Sutton, UK
Search for more papers by this authorCorresponding Author
Sarah E. Stapleton
Royal Marsden Hospital Drug Development Unit, Sutton, UK
University of Southampton, Southampton, UK
Correspondence
Sarah E. Stapleton, Drug Development Unit Royal Marsden Hospital Downs Rd Sutton Surrey SM2 5PT, Sutton, UK.
Email: [email protected]
Search for more papers by this authorAnne-Sophie Darlington
University of Southampton, Southampton, UK
Search for more papers by this authorAnna Minchom
Royal Marsden Hospital Drug Development Unit, Sutton, UK
Institute of Cancer Research, Sutton, UK
Search for more papers by this authorAbhijit Pal
Royal Marsden Hospital Drug Development Unit, Sutton, UK
Institute of Cancer Research, Sutton, UK
Search for more papers by this authorFlorence Raynaud
Royal Marsden Hospital Drug Development Unit, Sutton, UK
Institute of Cancer Research, Sutton, UK
Search for more papers by this authorAbstract
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.
CONFLICT OF INTEREST
The authors who are listed here certify that they have no conflict of interest to report relating to the subject matter discussed in this manuscript.
Open Research
DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no new data were created or analysed in this study.
Supporting Information
| Filename | Description |
|---|---|
| pon5834-sup-0001-suppl-data.docx65.8 KB | Supplementary Material |
| pon5834-sup-0002-table_s1.docx19.7 KB | Table S1 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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