Lysozyme-based spray for treatment of radiotherapy-induced oral mucositis

Abstract

Aim: The aim of this study was to examine the effectiveness and safety of lysozyme-based spray in the treatment of oral mucositis in patients undergoing head and neck radiotherapy.

Methods: A prospective, open-label study was conducted on patients with ulcerative inflammation of the oral cavity and pharynx mucous membranes clinically assessed for oral mucositis according to the World Health Organization (WHO) Oral Toxicity Scale. Patients were randomly divided into a lysozyme group (using a spray containing lysozyme + cetylpyridinium + lidocaine) and a control group (using a compounded preparation containing gentamicin + dexamethasone + lidocaine). The efficacy and safety of therapy were evaluated on the baseline and three follow-up visits (7, 14, and 21 days after the baseline visit).

Results: The total number of participants was 56, of which 26 were in lysozyme and 30 in the control group. The efficacy parameters were similar between the groups and there was no deterioration of symptoms during the follow-up period of 21 days. A significantly lower pain intensity when eating solid food was observed after 21 days in lysozyme compared to the control group. No adverse reactions were observed.

Conclusions: This study showed the efficacy and safety of lysozyme-based spray for treating radiotherapy-induced oral mucositis. The availability of new treatment options based on lysozyme, a natural enzybiotic present in the saliva of healthy subjects, could bring added value to the treatment of oral mucositis and the prevention of its complications. However, a larger randomized, blinded study is needed to confirm our results [the study was registered at the Agency for Medicinal Products and Medical Devices of Bosnia and Herzegovina (https://klinicka.almbih.gov.ba/pages/klinicka-registar-javni) under the protocol number LCS-OM-01].

Keywords

Oral mucositis / radiotherapy / lysozyme-based therapeutics / oral spray / oncology

References

[1] Pulito C, Cristaudo A, Porta CL, Zapperi S, Blandino G, Morrone A, et al. Oral mucositis: the hidden side of cancer therapy. J Exp Clin Cancer Res. 2020; 39: 210.

[2] Shetty SS, Maruthi M, Dhara V, Arruda JAAd, Abreu LG, Mesquita RA, et al. Oral mucositis: Current knowledge and future directions. Dis Mon. 2022; 68: 101300.

[3] Abusamak M, Abu—Samak A, Cai W, Al—Waeli H, Al—Hamed FS, Al—Tamimi M, et al. Chronotherapy in head and neck cancer: A systematic review and meta—analysis. Int J Cancer. 2024;[Epub ahead of print].

[4] Sieracki RL, Voelz LM, Johannik TM, Kopaczewski DM, Hubert K. Development and implementation of an oral care protocol for patients with cancer. Clin J Oncol Nurs. 2009; 13: 718—22.

[5] Yoshida K, Watanabe S, Hoshino N, Pak K, Hidaka N, Konno N, et al. Hospital pharmacist interventions for the management of oral mucositis in patients with head and neck cancer receiving chemoradiotherapy: a multicenter, prospective cohort study. Support Care Cancer. 2023; 31: 316.

[6] European Oral Care in Cancer Group. Oral Care Guidance and Support [Internet]. European Oral Care in Cancer Group ; [cited 2024 Apr 12]. Available from: https://www.eocc.co.uk/wp—content/uploads/2018/01/EOCC—Guidance—English.pdf

[7] WHO handbook for reporting results of cancer treatment [Internet]. World Health Organization; [cited 2024 Apr 12]. Available from: https://iris.who.int/handle/10665/37200

[8] Blanchard A, Yarom N, Levi L, Cheng KKF, Bossi P, Zadik Y, et al. ; Atask force of the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Clinicians’ experience with topical benzydamine and morphine for the management of oral mucositis: adverse effects and barriers. Support Care Cancer. 2022; 30: 10255-62.

[9] Lalla RV. Evidence—Based Management of Oral Mucositis. JCO Oncol Pract. 2020; 16: 111—2.

[10] Wang X, Zeng L, Feng X, Zhao N, Feng N, Du X. Did you choose appropriate mouthwash for managing chemoradiotherapy—induced oral mucositis? The therapeutic effect compared by a Bayesian network meta—analysis. Front Oral Health. 2023; 3: 977830.

[11] Shen B, Zhou Y, Wu D, Liu J. Efficacy of photobiomodulation therapy in the management of oral mucositis in patients with head and neck cancer: A systematic review and meta—analysis of randomized controlled trials. Head Neck. 2024; 46: 936-50.

[12] Rupel K, Cornacchia A, Poiani M, Mohamed S, Bellis ED, Ballerini M, et al. Preventive versus curative photobiomodulation for oral mucositis in patients with multiple myeloma undergoing hematopoietic stem cell transplantation: which approach is more effective? Support Care Cancer. 2024; 32: 208.

[13] Parra—Rojas S, Spanemberg JC, Díaz—Robayna NDM, Peralta—Mamani M, Cayón RTV. Assessing the Cost—Effectiveness of Photobiomodulation for Oral Mucositis Prevention and Treatment: A Systematic Review. Biomedicines. 2024; 12: 2366.

[14] Chan J, Filippi F, Filippi C. Clinical guidance for maintaining oral hygiene in patients undergoing chemotherapy or radiation therapy: a scoping review. Swiss Dent J. 2023; 133: 368-79.

[15] Eminagić D, Lokvančić A, Hasanbegović B, Mekić—Abazović A, Avdičević A, Marijanović I, et al. Efficacy and safety of local lysozyme treatment in patients with oral mucositis after chemotherapy and radiotherapy. Acta Pharm. 2019; 69: 695-704.

[16] Rasic A, Kapo B, Avdicevic A, Mekic—Abazovic A, Jankovic SM, Lokvancic A. Efficacy and Safety of Lysozyme, Cetylpyridinium and Lidocaine Fixed Combination for Treatment of Chemotherapy— and Radiotherapy—Induced Oral Mucositis: a Pilot Study. Mater Sociomed. 2019; 31: 166-71.

[17] Ragland SA, Criss AK. From bacterial killing to immune modulation: Recent insights into the functions of lysozyme. PLoS Pathog. 2017; 13: e1006512.

[18] Bergamo A, Sava G. Lysozyme: A Natural Product with Multiple and Useful Antiviral Properties. Molecules. 2024; 29: 652.

[19] Carrillo W, Spindola H, Ramos M, Recio I, Carvalho JE. Anti—Inflammatory and Anti—Nociceptive Activities of Native and Modified Hen Egg White Lysozyme. J Med Food. 2016; 19: 978-82.

[20] Ogundele MO. A novel anti—inflammatory activity of lysozyme: modulation of serum complement activation. Mediators Inflamm. 1998; 7: 363-5.

[21] Bianchi C. Is Fleming’s lysozyme an analgesic agent? An experimental reappraisal of clinical data. Eur J Pharmacol. 1981; 71: 211—21.

[22] Zhao M, Huang M, Li Z. Exploring the therapeutic potential of recombinant human lysozyme: a review on wound management system with antibacterial. Front Bioeng Biotechnol. 2023; 11: 1292149.

[23] randomizr: Easy—to—Use Tools for Common Forms of Random Assignment and Sampling. [Internet]. Coppock A ; [cited 2024 Apr 23]. Available from: https://cran.r—project.org/web/packages/randomizr/index.html

[24] R: The R Project for Statistical Computing [Internet]. The R Foundation; [cited 2024 Oct 2]. Available from: https://www.r—project.org/

[25] Basic Functions for Power Analysis [Internet]. Champely S ; [cited 2024 Jun 3]. Available from: https://CRAN.R—project.org/package=pwr

[26] Wickham H. ggplot2: Elegant Graphics for Data Analysis. Cham: Springer; 2016.

[27] Olsen MF, Bjerre E, Hansen MD, Hilden J, Landler NE, Tendal B, et al. Pain relief that matters to patients: systematic review of empirical studies assessing the minimum clinically important difference in acute pain. BMC Med. 2017; 15: 35.

[28] Zhang X, Lei Y, Xiao Y, Cao X, Tian X, Zhu Y, et al. Hen Egg Lysozyme Alleviates Static Mechanical Pain Via NRF1—Parkin—TACAN Signaling Axis in Sensory Neurons. Neuroscience. 2022; 502: 52-67.

[29] Hukić M, Seljmo D, Ramovic A, Ibrišimović MA, Dogan S, Hukic J, et al. The Effect of Lysozyme on Reducing Biofilms by Staphylococcus aureus, Pseudomonas aeruginosa, and Gardnerella vaginalis: An In Vitro Examination. Microb Drug Resist. 2018; 24: 353—8.

[30] Bergamo A, Sava G. Pharmacological Modulation of Host Immunity with Hen Egg White Lysozyme (HEWL)—A Review. Molecules. 2023; 28: 5027.

[31] Lin CTS, Raman R. Comparison of the efficacy between oral rinse, oral gargle, and oral spray. J Prim Care Community Health. 2012; 3: 80-2.