Cannabinoids for Cancer Treatment-Related Symptoms and Side Effects: Investigating the Interplay Between Clinical Trial Design and Outcomes
Date
2024
Authors
Cao, Katrina
Editors
Advisors
Salter, Amy
Wardill, Hannah
Wardill, Hannah
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Thesis
Citation
Statement of Responsibility
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Abstract
Introduction: Most cancer treatments are associated with adverse symptoms that impact quality of life, adherence, and survival. Recently, cannabinoids have gained popularity for their potential to alleviate these treatment-related symptoms. However, although many people with cancer report self-medicating with cannabinoids, few healthcare providers feel adequately equipped to prescribe due to a lack of conclusive evidence. The contradictory evidence base likely reflects the inconsistent approaches to studying cannabinoids in supportive oncology. This systematic review aims to comprehensively synthesise all existing evidence on cannabinoids as a supportive care intervention and explore the interplay between study design and outcomes, with the overarching goal of identifying key attributes to inform future cannabinoid trials. Methods: Six databases were searched from inception of database to January 2023. Study screening, selection, and data extraction were conducted using Covidence systematic review management software by two independent reviewers. Studies were included if they were primary research comparing the effects of cannabinoids on cancer treatment-related symptoms with a control or comparison group, in all people undergoing cancer therapy, regardless of type, stage, treatment status, or age. The quality of the evidence was assessed using the Cochrane risk of bias (RoB 2) tool. The systematic review protocol was registered on PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID = CRD42022373000. Results: A total of 87 studies with 93 separately extracted primary outcomes involving 15,773 participants were included; 76 had a ‘high risk’ of bias, and the remaining 11 had ‘some concerns.’ Across all cancer treatment-related symptoms, there were a greater number of studies indicating the benefits of cannabinoids, although none were significant except for chemotherapy-induced nausea and vomiting (p = 0.004). Cannabinoids were associated with a higher incidence of adverse events compared to both placebo and active comparators, as well as a higher dropout rate (36.1% vs. 26.71%), although this was not significant (p = 0.223). Regarding trial design, cannabinoids were found to be most effective in studies that administered cannabinoids prophylactically before symptom occurrence (p = 0.028). Conclusions: The evidence base was highly variable and limited by the predominance of studies published before CONSORT and COSMIN guidelines. Moving forward, trials should adopt pragmatic design approaches that prioritise patient-centred methodological decisions. This will help expand the range of potential benefits (i.e., across multiple symptoms/side effects), as well as translational applications. Further research is needed to personalise cannabinoid treatment and determine the optimal products, self-titration/dosing schedules, formulations, and administration methods to meet individual patient goals. Additional research is required to determine the effects of individual endocannabinoid system (ECS) expression and the "entourage effect" on cannabinoid effectiveness and safety. More research is required on outcome assessment, particularly the use of patient-reported outcome measures (PROMs), the effect of response-shift, and strategies to improve PROM implementation to minimise participant burden. These findings underscore the need to establish guidelines to ensure that cannabinoid trials reflect real-world supportive oncology settings. This systematic review offers recommendations to support the translation of cannabinoid research findings into clinical practice.
School/Discipline
School of Public Health
Dissertation Note
Thesis (MPhil) -- University of Adelaide, School of Public Health, 2024
Provenance
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