Research Article
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Year 2025, Volume: 11 Issue: 4, 809 - 820, 04.07.2025
https://doi.org/10.18621/eurj.1606165

Abstract

References

  • 1. Liu YQ, Wang XL, He DH, Cheng YX. Protection against chemotherapy- and radiotherapy-induced side effects: A review based on the mechanisms and therapeutic opportunities of phytochemicals. Phytomedicine. 2021;80:153402. doi: 10.1016/j.phymed.2020.153402.
  • 2. Toro López JR. Chemotherapy and radiotherapy: Could they contribute to the development of new tumors and metastases? Life Res. 2024;7(1)5. doi: 10.53388/lr20240005.
  • 3. Zhang QY, Wang FX, Jia KK, Kong LD. Natural Product Interventions for Chemotherapy and Radiotherapy-Induced Side Effects. Front Pharmacol. 2018;9:1253. doi: 10.3389/fphar.2018.01253.
  • 4. Lu Y, Luo X, Yang D, et al. Effects of probiotic supplementation on related side effects after chemoradiotherapy in cancer patients. Front Oncol. 2022;12:1032145. doi: 10.3389/fonc.2022.1032145.
  • 5. O'Reilly M, Mellotte G, Ryan B, O'Connor A. Gastrointestinal side effects of cancer treatments. Ther Adv Chronic Dis. 2020;11:2040622320970354. doi: 10.1177/2040622320970354.
  • 6. Alvariño-Martín C, Sarrión-Pérez MG. Prevention and treatment of oral mucositis in patients receiving chemotherapy. J Clin Exp Dent. 2014;6(1):e74-80. doi: 10.4317/jced.51313.
  • 7. Nicolatou-Galitis O, Sarri T, Bowen J, et al; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21(11):3179-3189. doi: 10.1007/s00520-013-1847-y.
  • 8. Peng TR, Tsai FP, Wu TW. Effects of various treatments for preventing oral mucositis in cancer patients: A network meta-analysis. PLoS One. 2022;17(12):e0278102. doi: 10.1371/journal.pone.0278102
  • 9. Çubukçu NÜ, Çınar S. [Can oral mucositis be prevented in patients receiving chemotherapy?]. 2012;2(4):155-163. [Article in Turkish]
  • 10. Miranda-Silva W, da Fonseca FP, Gomes AA, Mafra ABB, Rocha V, Fregnani ER. Oral mucositis in paediatric cancer patients undergoing allogeneic hematopoietic stem cell transplantation preventively treated with professional dental care and photobiomodulation: Incidence and risk factors. Int J Paediatr Dent. 2022;32(2):251-263. doi: 10.1111/ipd.12850.
  • 11. de Sousa Melo A, de Lima Dantas JB, Medrado ARAP, Lima HR, Martins GB, Carrera M. Nutritional supplements in the management of oral mucositis in patients with head and neck cancer: Narrative literary review. Clin Nutr ESPEN. 2021;43:31-38. doi: 10.1016/j.clnesp.2021.03.030.
  • 12. Ribeiro SB, de Araújo AA, Araújo Júnior RF, et al. Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters. PLoS One. 2017;12(10):e0186511. doi: 10.1371/journal.pone.0186511.
  • 13. Nugent M, Bryant V, Butcher C, et al. Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: The LiTEFORM RCT. Health Technol Assess (Winch Engl). 2022;26(46):1-172. doi: 10.3310/UWNB3375.
  • 14. Passali D, Arezzo MF, De Rose A, et al. Benzydamine hydrochloride for the treatment of sore throat and irritative/inflammatory conditions of the oropharynx: A cross-national survey among pharmacists and general practitioners. BMC Prim Care. 2022;23(1):154. doi: 10.1186/s12875-022-01762-3.
  • 15. Nicolatou-Galitis O, Bossi P, Orlandi E, René-Jean Bensadoun. The role of benzydamine in prevention and treatment of chemoradiotherapy-induced mucositis. Support Care Cancer. 2021;29(10):5701-5709. doi: 10.1007/s00520-021-06048-5.
  • 16. Ariyawardana A, Cheng KKF, Kandwal A, et al; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2019;27(10):3985-3995. doi: 10.1007/s00520-019-04888-w.
  • 17. Sheibani KM, Mafi AR, Moghaddam S, Taslimi F, Amiran A, Ameri A. Efficacy of benzydamine oral rinse in prevention and management of radiation-induced oral mucositis: A double-blind placebo-controlled randomized clinical trial. Asia Pac J Clin Oncol. 2015;11(1):22-27. doi: 10.1111/ajco.12288.
  • 18. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg. 2021;88:105906. doi: 10.1016/j.ijsu.2021.105906.
  • 19. Thomas J, Kneale D, McKenzie JE, Brennan SE, Bhaumik S. Determining the scope of the review and the questions it will address. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editors. Cochrane Handbook for Systematic Reviews of Interventions version 6.4 (updated August 2023). Cochrane, 2023.
  • 20. Gümüş D, Yılmaz Z, Tuğrul F. The efficacy of benzydamine on cancer treatment-induced oral mucositis: Systematic review of randomised controlled trials. PROSPERO: International prospective register of systematic reviews. 2023. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023494747.
  • 21. Al-Taie A, Koseoglu A. Potential therapeutic effects of different mouthwashes for alleviation and treatment of oral complications of 5-fluorouracil-based chemotherapy in patients with colon cancer. Eur J Hosp Pharm. 2023;30(4):202-207. doi: 10.1136/ejhpharm-2021-002827.
  • 22. Ameri A, Poshtmahi S, Heydarirad G, et al. Effect of honey-lemon spray versus benzydamine hydrochloride spray on radiation-induced acute oral mucositis in head and neck cancer patients: a pilot, randomized, double-blind, active-controlled clinical trial. J Altern Complement Med. 2021;27(3):255-262. doi: 10.1089/acm.2020.0468.
  • 23. Erdem Ö, Güngörmüs Z. The effect of royal jelly on oral mucositis in patients undergoing radiotherapy and chemotherapy. Holist Nurs Pract. 2014;28(4):242-246. doi: 10.1097/HNP.0000000000000033.
  • 24. Hadjieva T, Cavallin-Stahl E, Linden M, Tiberg F. Treatment of oral mucositis pain following radiation therapy for head-and-neck cancer using a bioadhesive barrier-forming lipid solution. Support Care Cancer. 2014;22(6):1557-1562. doi: 10.1007/s00520-014-2117-3.
  • 25. Ahmed KM. The effect of olive leaf extract in decreasing the expression of two pro-inflammatory cytokines in patients receiving chemotherapy for cancer. A randomized clinical trial. Saudi Dent J. 2013;25(4):141-147. doi: 10.1016/j.sdentj.2013.09.001.
  • 26. Ameri A, Heydarirad G, Choopani R, et al. Sumac-rose water mouthwash versus benzydamine to prevent radiation-induced oral mucositis in head and neck cancers: a phase II randomized trial. J Cancer Res Clin Oncol. 2023;149(10):7427-7439. doi: 10.1007/s00432-023-04687-1.
  • 27. Chitapanarux I, Tungkasamit T, Petsuksiri J, et al. Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis. Support Care Cancer. 2018;26(3):879-886. doi: 10.1007/s00520-017-3904-4.
  • 28. Kannarunimit D, Chotirut A, Prayongrat A, et al. A prospective randomized study comparing the efficacy between povidone-iodine gargling and benzydamine hydrochloride for mucositis prevention in head and neck cancer patients receiving concurrent chemoradiotherapy. Heliyon. 2023;9(4):e15437. doi: 10.1016/j.heliyon.2023.e15437.
  • 29. Mohamed NH, Kamel AM, Edress MF, Mahmoud ASS, Gaafar AIAEH. Low level laser therapy versus benzydamin in prevention and treatment of oral mucositis induced by anticancer treatments (clinical and biochemical study). Braz Dent Sci. 2022;25(4):e3406. doi: 10.4322/bds.2022.e3406
  • 30. Rastogi M, Khurana R, Revannasiddaiah S, et al. Role of benzydamine hydrochloride in the prevention of oral mucositis in head and neck cancer patients treated with radiotherapy (>50 Gy) with or without chemotherapy. Support Care Cancer. 2017;25(5):1439-1443. doi: 10.1007/s00520-016-3548-9.
  • 31. Sahebjamee M, Mansourian A, Hajimirzamohammad M, et al. Comparative Efficacy of Aloe vera and Benzydamine Mouthwashes on Radiation-induced Oral Mucositis: A Triple-blind, Randomised, Controlled Clinical Trial. Oral Health Prev Dent. 2015;13(4):309-15. doi: 10.3290/j.ohpd.a33091.
  • 32. Shah S, Rath H, Sharma G, Senapati SN, Mishra E. Effectiveness of curcumin mouthwash on radiation-induced oral mucositis among head and neck cancer patients: A triple-blind, pilot randomised controlled trial. Indian J Dent Res. 2020;31(5):718-727. doi: 10.4103/ijdr.IJDR_822_18.
  • 33. Thomas PL, Kang HK, Rishi KS. Randomized Control Study of the Effects of Turmeric Mouthwash on Oral Health Status, Treatment-Induced Mucositis, and Associated Oral Dysfunctions Among Patients With Head and Neck Cancer. Cancer Nurs. 2023;46(1):36-44. doi: 10.1097/NCC.0000000000001149.

The efficacy of benzydamine on cancer treatment-induced oral mucositis: A systematic review of randomised controlled trials

Year 2025, Volume: 11 Issue: 4, 809 - 820, 04.07.2025
https://doi.org/10.18621/eurj.1606165

Abstract

Objectives: Mucositis is a well-known complication of oncological therapies, severely affecting the quality of life of patients. Benzydamine appears to be a promising option for the treatment of this condition, particularly in the management of oral mucositis. We can learn more about the potential use of benzydamine for oral mucositis by examining the available published research and what we know from clinical trials that have used this agent. This systematic review aims to evaluate the efficacy of benzydamine for the prevention and treatment of oral mucositis induced by cancer therapy through Randomized Controlled Trials.

Methods: A systematic literature review was performed across seven databases. After screening, this systematic review included nine articles that had been published between 2013 and 2023. The review was conducted in accordance with the Cochrane guidelines (2023). Bias risk is assessed using the Cochrane Collaboration Risk of Bias Assessment Tool. The studies differed in the number of participants, from 26 to 120, giving a total of 593 participants analyzed. The articles in the studies used Benzydamine, herbal formulation, sodium bicarbonate, povidone-iodine, and low-level laser.

Results: Results showed that benzydamine was effective to varying extents. Several studies provided statistically important improvements while others showed no statistically important variations.

Conclusions: This extensive literature review and clinical study offer insight into how benzydamine may work in the management of oral mucositis.

Ethical Statement

This systematic review was focused on previously published papers and did not involve any direct human or animal participants. Thus, ethical approval was not required.

References

  • 1. Liu YQ, Wang XL, He DH, Cheng YX. Protection against chemotherapy- and radiotherapy-induced side effects: A review based on the mechanisms and therapeutic opportunities of phytochemicals. Phytomedicine. 2021;80:153402. doi: 10.1016/j.phymed.2020.153402.
  • 2. Toro López JR. Chemotherapy and radiotherapy: Could they contribute to the development of new tumors and metastases? Life Res. 2024;7(1)5. doi: 10.53388/lr20240005.
  • 3. Zhang QY, Wang FX, Jia KK, Kong LD. Natural Product Interventions for Chemotherapy and Radiotherapy-Induced Side Effects. Front Pharmacol. 2018;9:1253. doi: 10.3389/fphar.2018.01253.
  • 4. Lu Y, Luo X, Yang D, et al. Effects of probiotic supplementation on related side effects after chemoradiotherapy in cancer patients. Front Oncol. 2022;12:1032145. doi: 10.3389/fonc.2022.1032145.
  • 5. O'Reilly M, Mellotte G, Ryan B, O'Connor A. Gastrointestinal side effects of cancer treatments. Ther Adv Chronic Dis. 2020;11:2040622320970354. doi: 10.1177/2040622320970354.
  • 6. Alvariño-Martín C, Sarrión-Pérez MG. Prevention and treatment of oral mucositis in patients receiving chemotherapy. J Clin Exp Dent. 2014;6(1):e74-80. doi: 10.4317/jced.51313.
  • 7. Nicolatou-Galitis O, Sarri T, Bowen J, et al; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21(11):3179-3189. doi: 10.1007/s00520-013-1847-y.
  • 8. Peng TR, Tsai FP, Wu TW. Effects of various treatments for preventing oral mucositis in cancer patients: A network meta-analysis. PLoS One. 2022;17(12):e0278102. doi: 10.1371/journal.pone.0278102
  • 9. Çubukçu NÜ, Çınar S. [Can oral mucositis be prevented in patients receiving chemotherapy?]. 2012;2(4):155-163. [Article in Turkish]
  • 10. Miranda-Silva W, da Fonseca FP, Gomes AA, Mafra ABB, Rocha V, Fregnani ER. Oral mucositis in paediatric cancer patients undergoing allogeneic hematopoietic stem cell transplantation preventively treated with professional dental care and photobiomodulation: Incidence and risk factors. Int J Paediatr Dent. 2022;32(2):251-263. doi: 10.1111/ipd.12850.
  • 11. de Sousa Melo A, de Lima Dantas JB, Medrado ARAP, Lima HR, Martins GB, Carrera M. Nutritional supplements in the management of oral mucositis in patients with head and neck cancer: Narrative literary review. Clin Nutr ESPEN. 2021;43:31-38. doi: 10.1016/j.clnesp.2021.03.030.
  • 12. Ribeiro SB, de Araújo AA, Araújo Júnior RF, et al. Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters. PLoS One. 2017;12(10):e0186511. doi: 10.1371/journal.pone.0186511.
  • 13. Nugent M, Bryant V, Butcher C, et al. Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: The LiTEFORM RCT. Health Technol Assess (Winch Engl). 2022;26(46):1-172. doi: 10.3310/UWNB3375.
  • 14. Passali D, Arezzo MF, De Rose A, et al. Benzydamine hydrochloride for the treatment of sore throat and irritative/inflammatory conditions of the oropharynx: A cross-national survey among pharmacists and general practitioners. BMC Prim Care. 2022;23(1):154. doi: 10.1186/s12875-022-01762-3.
  • 15. Nicolatou-Galitis O, Bossi P, Orlandi E, René-Jean Bensadoun. The role of benzydamine in prevention and treatment of chemoradiotherapy-induced mucositis. Support Care Cancer. 2021;29(10):5701-5709. doi: 10.1007/s00520-021-06048-5.
  • 16. Ariyawardana A, Cheng KKF, Kandwal A, et al; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2019;27(10):3985-3995. doi: 10.1007/s00520-019-04888-w.
  • 17. Sheibani KM, Mafi AR, Moghaddam S, Taslimi F, Amiran A, Ameri A. Efficacy of benzydamine oral rinse in prevention and management of radiation-induced oral mucositis: A double-blind placebo-controlled randomized clinical trial. Asia Pac J Clin Oncol. 2015;11(1):22-27. doi: 10.1111/ajco.12288.
  • 18. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg. 2021;88:105906. doi: 10.1016/j.ijsu.2021.105906.
  • 19. Thomas J, Kneale D, McKenzie JE, Brennan SE, Bhaumik S. Determining the scope of the review and the questions it will address. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editors. Cochrane Handbook for Systematic Reviews of Interventions version 6.4 (updated August 2023). Cochrane, 2023.
  • 20. Gümüş D, Yılmaz Z, Tuğrul F. The efficacy of benzydamine on cancer treatment-induced oral mucositis: Systematic review of randomised controlled trials. PROSPERO: International prospective register of systematic reviews. 2023. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023494747.
  • 21. Al-Taie A, Koseoglu A. Potential therapeutic effects of different mouthwashes for alleviation and treatment of oral complications of 5-fluorouracil-based chemotherapy in patients with colon cancer. Eur J Hosp Pharm. 2023;30(4):202-207. doi: 10.1136/ejhpharm-2021-002827.
  • 22. Ameri A, Poshtmahi S, Heydarirad G, et al. Effect of honey-lemon spray versus benzydamine hydrochloride spray on radiation-induced acute oral mucositis in head and neck cancer patients: a pilot, randomized, double-blind, active-controlled clinical trial. J Altern Complement Med. 2021;27(3):255-262. doi: 10.1089/acm.2020.0468.
  • 23. Erdem Ö, Güngörmüs Z. The effect of royal jelly on oral mucositis in patients undergoing radiotherapy and chemotherapy. Holist Nurs Pract. 2014;28(4):242-246. doi: 10.1097/HNP.0000000000000033.
  • 24. Hadjieva T, Cavallin-Stahl E, Linden M, Tiberg F. Treatment of oral mucositis pain following radiation therapy for head-and-neck cancer using a bioadhesive barrier-forming lipid solution. Support Care Cancer. 2014;22(6):1557-1562. doi: 10.1007/s00520-014-2117-3.
  • 25. Ahmed KM. The effect of olive leaf extract in decreasing the expression of two pro-inflammatory cytokines in patients receiving chemotherapy for cancer. A randomized clinical trial. Saudi Dent J. 2013;25(4):141-147. doi: 10.1016/j.sdentj.2013.09.001.
  • 26. Ameri A, Heydarirad G, Choopani R, et al. Sumac-rose water mouthwash versus benzydamine to prevent radiation-induced oral mucositis in head and neck cancers: a phase II randomized trial. J Cancer Res Clin Oncol. 2023;149(10):7427-7439. doi: 10.1007/s00432-023-04687-1.
  • 27. Chitapanarux I, Tungkasamit T, Petsuksiri J, et al. Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis. Support Care Cancer. 2018;26(3):879-886. doi: 10.1007/s00520-017-3904-4.
  • 28. Kannarunimit D, Chotirut A, Prayongrat A, et al. A prospective randomized study comparing the efficacy between povidone-iodine gargling and benzydamine hydrochloride for mucositis prevention in head and neck cancer patients receiving concurrent chemoradiotherapy. Heliyon. 2023;9(4):e15437. doi: 10.1016/j.heliyon.2023.e15437.
  • 29. Mohamed NH, Kamel AM, Edress MF, Mahmoud ASS, Gaafar AIAEH. Low level laser therapy versus benzydamin in prevention and treatment of oral mucositis induced by anticancer treatments (clinical and biochemical study). Braz Dent Sci. 2022;25(4):e3406. doi: 10.4322/bds.2022.e3406
  • 30. Rastogi M, Khurana R, Revannasiddaiah S, et al. Role of benzydamine hydrochloride in the prevention of oral mucositis in head and neck cancer patients treated with radiotherapy (>50 Gy) with or without chemotherapy. Support Care Cancer. 2017;25(5):1439-1443. doi: 10.1007/s00520-016-3548-9.
  • 31. Sahebjamee M, Mansourian A, Hajimirzamohammad M, et al. Comparative Efficacy of Aloe vera and Benzydamine Mouthwashes on Radiation-induced Oral Mucositis: A Triple-blind, Randomised, Controlled Clinical Trial. Oral Health Prev Dent. 2015;13(4):309-15. doi: 10.3290/j.ohpd.a33091.
  • 32. Shah S, Rath H, Sharma G, Senapati SN, Mishra E. Effectiveness of curcumin mouthwash on radiation-induced oral mucositis among head and neck cancer patients: A triple-blind, pilot randomised controlled trial. Indian J Dent Res. 2020;31(5):718-727. doi: 10.4103/ijdr.IJDR_822_18.
  • 33. Thomas PL, Kang HK, Rishi KS. Randomized Control Study of the Effects of Turmeric Mouthwash on Oral Health Status, Treatment-Induced Mucositis, and Associated Oral Dysfunctions Among Patients With Head and Neck Cancer. Cancer Nurs. 2023;46(1):36-44. doi: 10.1097/NCC.0000000000001149.
There are 33 citations in total.

Details

Primary Language English
Subjects Clinical Oncology
Journal Section Research Article
Authors

Dilek Gümüş 0000-0002-5338-9377

Zeynep Yılmaz 0000-0001-7596-9041

Fuzuli Tuğrul 0000-0001-9724-253X

Early Pub Date May 29, 2025
Publication Date July 4, 2025
Submission Date December 23, 2024
Acceptance Date May 21, 2025
Published in Issue Year 2025 Volume: 11 Issue: 4

Cite

AMA Gümüş D, Yılmaz Z, Tuğrul F. The efficacy of benzydamine on cancer treatment-induced oral mucositis: A systematic review of randomised controlled trials. Eur Res J. July 2025;11(4):809-820. doi:10.18621/eurj.1606165


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