Mapping the evidence for opioid-mediated changes in malignancy and chemotherapeutic efficacy: A scoping review protocol (Preprint)

Author:

Constance JonathanORCID,McFarland Mary M,Casucci Tallie,Deininger Michael WORCID,Enioutina Elena Y,Job KathleenORCID,Lemons Richard SORCID,Lim Carol SORCID,Ward Robert M,Yellepeddi VenkataORCID,Watt Kevin MORCID

Abstract

BACKGROUND

Numerous reports contend opioids can augment or inhibit malignancy. At present, there is no consensus on the risk or benefit posed by opioids on malignancy or chemotherapeutic activity. Clinical studies typically lack opioid concentration data, and the interpretation of patient outcome is challenged by the inherent difficulty in separating and controlling for the role of pain and its management from that of opioid use. Preclinical data could augment information from clinical studies to better establish the potential for therapeutic opioids to influence tumor survival. Therefore, a scoping review approach inclusive of preclinical and clinical data will improve our understanding of the risk-benefit relationship concerning commonly prescribed opioids and cancer and cancer treatment.

OBJECTIVE

To map diverse studies spanning from preclinical to clinical regarding the intersection of opioids with malignancy and its treatment.

METHODS

This scoping review will employ the Arksey six stages framework to: 1) identify the research question, 2) identify relevant studies, 3) select studies meeting criteria, 4) extract and chart data, 5) collate, summarize and report results, and 6) conduct expert consultation. An initial pilot study was undertaken to: 1) parameterize the extent and scale of existing data for an evidence review, 2) identify key factors to be extracted in systematic charting efforts, and 3) assess opioid concentration as a variable for its relevance to the central hypothesis. Six databases will be searched with no filters: Medline, Embase, CINAHL Complete, Cochrane Library, Biological Sciences Collection, and International Pharmaceutical Abstracts. Trial registries will include ClinicalTrials.gov, Cochrane CENTRAL, ISRCTN Registry, EU Clinical Trials Register, and WHO International Clinical Trials Registry. Eligibility criteria will include preclinical and clinical study data on opioids effects on tumor growth or survival, or alteration on the antineoplastic activity of chemotherapeutics. We will chart data on: 1) opioid concentration data from human subjects with cancer, yielding a ‘physiologic range’ to better interpret available preclinical data, 2) patterns of opioid exposure with disease and treatment related patient outcomes, and 3) the influence of opioids on cancer cell survival, as well as opioid-related changes to cancer cell susceptibility for chemotherapeutics.

RESULTS

This scoping review will present results in narrative form as well as with the use of tables and diagrams. Initiated in February of 2021 at the University of Utah, this protocol is anticipated to generate a scoping review by August of 2023. The results of the scoping review will be disseminated through scientific conference proceedings and presentations, stakeholder meetings, and by publication in a peer-reviewed journal.

CONCLUSIONS

The findings of this scoping review will provide a comprehensive description of the consequences of prescription opioids on malignancy and its treatment. By incorporating preclinical and clinical data this scoping review will invite novel comparisons across study types that could inform new basic, translational, and clinical studies regarding risks and benefits of opioid use among patients with cancer.

CLINICALTRIAL

Publisher

JMIR Publications Inc.

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