Assessing cognitive toxicity in early Phase Trials - What are we missing?

Abstract

OBJECTIVES\nNovel 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.\n\n\nMETHODS\nA 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.\n\n\nRESULTS\nDespite 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.\n\n\nCONCLUSION\nThe 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. This article is protected by copyright. All rights reserved.