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Efficacy of oral and topical antioxidants in the prevention and management of oral mucositis in head and neck cancer patients: a systematic review and meta-analyses

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Abstract

Purpose

To evaluate the effectiveness of antioxidants in the prevention and management of oral mucositis in adults undergoing radiotherapy and/or chemotherapy with diagnosed head and neck cancer (HNC) compared to placebo intervention.

Methods

Cochrane, EMBASE, PubMed, and Web of Science databases were used to search for randomized controlled trials (RCTs) comparing oral or topical antioxidants with placebo in clinically diagnosed HNC adult patients receiving radiotherapy with/without chemotherapy. The primary outcome was to assess the efficacy of the antioxidant to prevent and decrease the incidence/prevalence and severity of oral/oropharyngeal mucositis. The risk of bias was assessed following Cochrane’s guidelines.

Results

The database search resulted in 203 records up to February 19, 2021. Thirteen RCTs were included with 650 HNC-diagnosed patients. Included studies showed a statistically significant improvement in mucositis severity score for all antioxidants except melatonin. However, further studies are needed as only one study reported outcomes for zinc, propolis, curcumin, and silymarin. Patients receiving vitamin E were 60% less likely to develop severe mucositis grade 2 or higher than those receiving placebo in one study (P = 0.040). Patients receiving zinc were 95% less likely to develop severe mucositis (grades 3–4) in one study compared to placebo (P = 0.031). One meta-analysis showed no statistical difference in the risk of having severe mucositis (grades 3–4) with 199 patients compared to placebo for honey (n = 2 studies, P = 0.403). Meta-analyses could not be conducted for zinc, propolis, curcumin, melatonin, silymarin, and selenium due to the lack of studies reporting similar outcomes for the same intervention.

Conclusion

Though oral and topical antioxidants significantly improved mucositis severity scores in HNC patients receiving radiotherapy with/without chemotherapy in individual studies, the quality of the evidence was low due to the small number of studies and unclear/high-risk bias. Additionally, large RCTs are needed to confirm these results.

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Availability of data and material

Results of the search and the meta-analyses are presented in tables and figures. Any intermediate data is available by email to renciso@usc.edu.

Code availability

Not applicable.

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Authors and Affiliations

  1. Orofacial Pain and Oral Medicine, Herman Ostrow School of Dentistry of USC, Los Angeles, CA, USA

    Afsheen Raza, Nelli Karimyan & Chitra P. Emperumal

  2. Providence Cancer Institute, Portland, ORE, USA

    Amber Watters

  3. Department of Diagnostic Sciences, Herman Ostrow School of Dentistry of USC, CA, Los Angeles, USA

    Kamal Al-Eryani

  4. Department of Geriatrics, Special Patients and Behavioral Science, Herman Ostrow School of Dentistry of University of Southern California, 925 West 34th Street, room #4268, Los Angeles, CA, USA

    Reyes Enciso

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  1. Afsheen Raza
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Contributions

Drs. Raza, Karimyan, Emperumal, Al-Eryani, and Enciso contributed to the study conception and design. Material preparation and data collection were performed by Drs. Raza, Karimyan, and Emperumal under the supervision of Drs. Enciso and Al-Eryani. Dr. Enciso performed all data analyses. Drs. Raza, Karimyan, Emperumal, Al-Eryani, Waters, and Enciso contributed to the first draft of the manuscript and multiple revisions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Reyes Enciso.

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Raza, A., Karimyan, N., Watters, A. et al. Efficacy of oral and topical antioxidants in the prevention and management of oral mucositis in head and neck cancer patients: a systematic review and meta-analyses. Support Care Cancer 30, 8689–8703 (2022). https://doi.org/10.1007/s00520-022-07190-4

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