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Naltrexone’s Impact on Cancer Progression and Mortality: A Systematic Review of Studies in Humans, Animal Models, and Cell Cultures

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Abstract

Background

Naltrexone (NTX) is an opioid antagonist traditionally used as a treatment for alcohol and opioid use disorders, but various studies have documented its involvement in cancer progression, exploring possible anticancer potential, when administered at high doses or as low dose naltrexone (LDN). Herein we present a systematic review of cancer-related outcomes from case reports, clinical trials, and retrospective and prospective studies conducted using cell cultures, animal models, and human subjects receiving NTX/LDN.

Methods

A systematic search of NTX in cancer therapy was conducted. Outcomes including tumor size and number, latency to tumor development, survival duration, progression of disease, and scan results were assessed in clinical and animal studies, and cell number was used as the outcome measure of culture studies.

Results

Several case reports demonstrate notable survival durations and metastatic resolutions in patients with late stage cancer when administered an average LDN dose of 3–5 mg/day. Animal and cell culture studies suggest an overarching principle of NTX involvement in cancer pharmacophysiology, suggesting that high doses and continuous administration can foster cancer progression, whereas low doses and intermittent treatment may hinder cell proliferation, impede tumorigenesis, and have potential anticancer efficacy.

Conclusion

This review emphasizes the value of potential future research on NTX in cancer therapy, and warrants need for a better understanding of underlying mechanisms. Future controlled studies with more robust sample sizes, particularly in humans, are needed to fully elucidate its potential in cancer therapy.

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Acknowledgements

Funding

No funding or sponsorship was received for this study or publication of this article.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Authorship Contributions

Karina Liubchenko: data curation, investigation, project administration, visualization, writing – original draft. Kevin Kordbacheh: investigation, writing – original draft, visualization. Nika Khajehdehi: writing – original draft. Tanja Visnjevac: writing – review and editing. Frederick Ma: writing – review and editing. James Khan: writing – review and editing. Myles Storey: data curation, writing – review and editing. Alaa-Abd Elsayed: writing – review and editing. Ognjen Visnjevac: conceptualization, data curation, investigation, project administration, visualization, supervision, writing – review and editing

Disclosures

Dr. Abd-Elsayed is a consultant for Medtronic and Avanos. The remaining authors have nothing to disclose (Karina Liubchenko, Kevin Kordbacheh, Nika Khajehdehi, Tanja Visnjevac, Frederick Ma, James S. Khan, Myles Storey and Ognjen Visnjevac).

Compliance with Ethics Guidelines

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Data Availability

All data generated or analyzed during this study are included in this published article.

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Authors and Affiliations

  1. Schulich School of Medicine, Western University, London, ON, Canada

    Karina Liubchenko, Kevin Kordbacheh & Nika Khajehdehi

  2. Bloor Pain Specialists, Toronto, ON, Canada

    Tanja Visnjevac & Frederick Ma

  3. Department of Anesthesia and Pain Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada

    James S. Khan

  4. University of Wisconsin-Madison, Madison, WI, USA

    Myles Storey

  5. Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA

    Alaa Abd-Elsayed

  6. Department of Anesthesiology, Faculty of Health Sciences, McMaster University, Hamilton, Canada

    Ognjen Visnjevac

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  1. Karina Liubchenko
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Correspondence to Alaa Abd-Elsayed.

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Liubchenko, K., Kordbacheh, K., Khajehdehi, N. et al. Naltrexone’s Impact on Cancer Progression and Mortality: A Systematic Review of Studies in Humans, Animal Models, and Cell Cultures. Adv Ther 38, 904–924 (2021). https://doi.org/10.1007/s12325-020-01591-9

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