Oral mucositis as a complication of chemotherapy: approaches to treatment and prevention

Relevance. Oral mucositis is one of the earliest and most common complications of chemotherapy. It adversely affects patients’ quality of life and may limit the delivery of anticancer treatment. The reported incidence of oral mucositis is 30-40%. Any cytotoxic agent may potentially induce mucositis. Patients with oral mucositis may experience severe pain, dysphagia, altered taste perception, weight loss, and secondary infections. In severe cases, oral mucositis may lead to poor adherence to treatment or become a dose-limiting toxicity requiring modification or interruption of therapy. Objective. To review current approaches to the treatment and prevention of chemotherapy-induced oral mucositis based on published evidence.

Materials and methods. To achieve this objective, a targeted literature review was conducted using the following search terms: oral mucositis, chemotherapy side effects, oral mucositis treatment, and oral mucositis prevention. A total of 2,999 records were identified through searches of PubMed, MEDLINE, NCBI, eLIBRARY.RU, CyberLeninka, Google Scholar, and Crossref. Based on the eligibility criteria, 60 publications reporting on the treatment and prevention of chemotherapy-induced oral mucositis were included in the analysis. The review methodology was consistent with PRISMA standards for systematic reviews and meta-analyses.

Results. In 2020, MASCC/ISOO published clinical practice guidelines for the management of mucositis, grouping interventions into the following categories: basic oral care, anti-inflammatory agents, photobiomodulation, cryotherapy, antimicrobial and analgesic agents, growth factors and cytokines, and natural agents. However, despite the broad range of available interventions, existing treatment protocols do not consistently demonstrate sufficient clinical effectiveness.

Conclusion. Further research is needed to improve the effectiveness of oral mucositis treatment, develop innovative therapeutic approaches, and improve interdisciplinary collaboration.

1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263. https://doi.org/10.3322/caac.21834

2. Qods P, Arkat J, Batmani Y. Optimal administration strategy in chemotherapy regimens using multi-drug cell-cycle specific tumor growth models. Biomedical Signal Processing and Control. 2023;86(1):105221. https://doi.org/10.1016/j.bspc.2023.105221

3. Juthani R, Punatar S, Mittra I. New light on chemotherapy toxicity and its prevention. BJC Rep. 2024;41(2):1-6. https://doi.org/10.1038/s44276-024-00064-8

4. Nagaeva MO, Ryabinina MA, Shestel AI, Akopdzhanyan RV. Risk factors for the development of medicamentous oral mucositis against the background of cytostatic therapy of oncological diseases. Actual problems in dentistry. 2025;21(3):10-15. (in Russ.). https://doi.org/10.18481/2077-7566-2025-21-3-10-15

5. Shatokhina E.A., Logacheva N.S., Konova Z.V., Kuzmina L.A. Oral mucositis as an adverse event of antitumor therapy: modern concepts on pathogenesis, prevention and approaches to treatment. Effektivnaya farmakoterapiya. 2023;19(19):92–100 (In Russ.). https://doi.org/10.33978/2307-3586-2023-19-19-92-100

6. Gvozdikova E.N., Avanesov K.A., Khalil' E.F., Kandakova E.YU., Avanesov K.A. Personalized or unified approach in the prevention and treatment of oral mucositis in patients with malignant neoplasms of the head and neck organs: the choice of the optimal solution. Head and Neck Tumors. 2022;12(3):44-52 (In Russ.). https://doi.org/10.17650/2222-1468-2022-12-3-44-52

7. Semiglazova T.YU., Belyak N.P., Vladimirova L.Yu., Kornieckaya A.L., Koroleva I.A., Nechaeva M.N., et al. Practical recommendations for the treatment and prevention of mucositis. Malignant tumors. 2021;11(3):224–232 (In Russ.). https://doi.org/10.18027/2224-5057-2021-11-3s2-51

8. Yang J, Liu Y, Yao H, Sun M, Tong Y, Ma G, et al. Effect of Dendrobium Officinale on Radioactive Oral Mucositis of Nasopharyngeal Carcinoma and Changes of Oral Microecology. Integr Cancer Ther. 2025;24:e15347354251313524. https://doi.org/10.1177/15347354251313524

9. Köstler WJ, Hejna M, Wenzel C, Zielinski CC. Oral mucositis complicating chemotherapy and/or radiotherapy: options for prevention and treatment. CA Cancer J Clin. 2001;51(5):290–315. https://doi.org/10.3322/canjclin.51.5.290

10. Elad S, Fong-Cheng KF, Lalla RV. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2020;126(19):4423–4431. https://doi.org/10.1002/cncr.33100

11. Mubaraki S, Fong-Cheng SC, Alseraihy A, Abed H, Alkhayal Z. The efficacy of two different oral hygiene regimens on the incidence and severity of oral mucositis in pediatric patients receiving hematopoietic stem cell transplantation: A prospective interventional study. Spec Care Dentist. 2020;40(6):566–573. https://doi.org/10.1111/scd.12525

12. Yokota T, Tachibana H, Konishi T, Yurikusa T, Hamauchi S, Sakai K, et al. Multicenter phase II study of an oral care program for patients with head and neck cancer receiving chemoradiotherapy. Support Care Cancer. 2016;24:3029–3036. https://doi.org/10.1007/s00520-016-3122-5

13. Lima Martins JO, Carlos ACAM, Costa GAJ, Ribeiro RS, Malta CEN, Borges MMF, et al. Oral hygiene protocols reduce the severity and incidence of oral mucositis during antineoplastic treatment: a systematic review and meta-analysis of randomized and non-randomized clinical trials. Support Care Cancer. 2023;31(8):480. https://doi.org/10.1007/s00520-023-07858-5

14. Elsaadany B, Anayb SM, Mashhour K, Yossif M, Zahran F. Rebamipide gargle and benzydamine gargle in prevention and management of chemo-radiotherapy and radiotherapy-induced oral mucositis in head and neck cancer patients (randomized clinical trial). BMC Oral Health. 2024;24(1):645. https://doi.org/10.1186/s12903-024-04379-3

15. Rastogi M, Khurana R, Revannasiddaiah S, Jaiswal I, Nanda SS, Gupta P, 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. https://doi.org/10.1007/s00520-016-3548-9

16. Hata H, Takada S, Sato J, Yoshikawa K, Imamachi K, Edo M, et al. Analgesic effects of indomethacin spray on drug-induced oral mucositis pain in patients with cancer: A single-arm cross-sectional study. Spec Care Dentist. 2021;41(4):498–504. https://doi.org/10.1111/scd.12587

17. Nagaoka H, Momo K, Hamano J, Miyaji T, Oyamada S, Kawaguchi T, et al. Effects of an indomethacin oral spray on pain due to oral mucositis in cancer patients treated with radiotherapy and chemotherapy: a double-blind, randomized, placebo-controlled trial. J Pain Symptom Manage. 2021;62(3):537–544. https://doi.org/10.1016/j.jpainsymman.2021.01.123

18. Ruddy KJ, Zahrieh D, He J, Waechter B, Holleran JL, Lewis LD, et al. Dexamethasone to prevent everolimusinduced stomatitis (Alliance MIST Trial: A221701). Semin Oncol. 2023;50(1–2):7–10. https://doi.org/10.1053/j.seminoncol.2023.01.001

19. Kauark-Fontes E, Migliorati CA, Epstein JB, Treister NS, Alves CGB, Faria KM, et al. Extraoral photobiomodulation for prevention of oral and oropharyngeal mucositis in head and neck cancer patients: interim analysis of a randomized, double-blind, clinical trial. Support Care Cancer. 2022;30(3):2225–2236. https://doi.org/10.1007/s00520-021-06625-8

20. Vianna-Camolesi GC, Prado-Pena IB, GómezCaamaño A, Victoria-Fernández C, Blanco-Carrión A, García-García A, et al. Photobiomodulation for the prevention of oral side effects secondary to head and neck cancer therapy: results of a randomised, single-blind clinical trial. Oral Oncol. 2025;164:e107266. https://doi.org/10.1016/j.oraloncology.2025.107266

21. Askarifar M, Lakdizaji S, Ramzi M, Rahmani A, Jabbarzadeh F. The effects of oral cryotherapy on chemotherapy induced oral mucositis in patients undergoing autologous transplantation of blood stem cells: a clinical trial. Iran Red Crescent Med J. 2016;18(4):e24775. https://doi.org/10.5812/ircmj.24775

22. Rodrigues AB, Aguiar MIF, Oliveira PP, Alves NP, Silva RA, Vitorino WO, Lopes TSS. Effect of cryotherapy in preventing mucositis associated with the use of 5 fluorouracil. Rev Lat Am Enfermagem. 2020;19(28):33–63. https://doi.org/10.1590/1518-8345.3953.3363

23. Walladbegi J, Henriksson R, Tavelin B, Svanberg A, Larfors G, Jädersten M, et al. Efficacy of a novel device for cryoprevention of oral mucositis: a randomized, blinded, multicenter, parallel group, phase 3 trial. Bone Marrow Transplant. 2022;57(2):191–197. https://doi.org/10.1038/s41409-021-01512-6

24. Eslami H, Pouralibaba F, Falsafi P, Bohluli S, Najati B, Negahdari R, Ghanizadeh M. Efficacy of Hypozalix spray and propolis mouthwash for prevention of chemotherapy induced oral mucositis in leukemic patients: a double blind randomized clinical trial. J Dent Res Dent Clin Dent Prospects. 2016;10(4):226–233. https://doi.org/10.15171/joddd.2016.036

25. Cardona A, Balouch A, Abdul MM, Sedghizadeh PP, Enciso R. Efficacy of chlorhexidine for the prevention and treatment of oral mucositis in cancer patients: a systematic review with meta analyses. J Oral Pathol Med. 2017;46(9):680–688. https://doi.org/10.1111/jop.12549

26. Nuchit S, Lam Ubol A, Paemuang W, Talungchit S, Chokchaitam O, Mungkung OO, et al. Alleviation of dry mouth by saliva substitutes improved swallowing ability and clinical nutritional status of post radiotherapy head and neck cancer patients: a randomized controlled trial. Support Care Cancer. 2020;28(6):2817–2828. https://doi.org/10.1007/s00520-019-05132-1

27. Marimuthu D, Han KM, Mohamad MSF, Azman M. Saliva substitute mouthwash in nasopharyngeal cancer survivors with xerostomia: a randomized controlled trial. Clin Oral Investig. 2021;25(5):3105–3115. https://doi.org/10.1007/s00784-020-03634-5

28. Kaur H, Singh Banipal RP, Singh H, Sonik YA, Sandhu SK. Safety and efficacy of oral pilocarpine in radiation induced xerostomia in oropharyngeal carcinoma patients. J Cancer Res Ther. 2023;19(3):788–792. https://doi.org/10.4103/jcrt.jcrt_2346_21

29. Li K, Ren X, Xie R. Radiation induced mucositis: a retrospective study of dexamethasone lidocaine vitamin B12 mouth rinse versus compound chlorhexidine mouthwash in nasopharyngeal carcinoma. Heliyon. 2023;9(5):e15955. https://doi.org/10.1016/j.heliyon.2023.e15955

30. Schaller AKCS, Peterson A, Bäckryd E. Pain management in patients undergoing radiation therapy for head and neck cancer – a descriptive study. Scand J Pain. 2020;21(2):256–265. https://doi.org/10.1515/sjpain-2020-0067

31. Scarborough BM, Smith CB. Optimal pain management for patients with cancer in the modern era. CA Cancer J Clin. 2018;68(3):182–196. https://doi.org/10.3322/caac.21453

32. Zembillas AS, Thomas SM, Rotz SJ, Buhtoiarov IN, Hanna R. Palifermin as primary mucositis prophylaxis in patients with B cell Non Hodgkin lymphoma: a case series. Pediatr Hematol Oncol. 2022;39(1):80–82. https://doi.org/10.1080/08880018.2021.1927271

33. Bradstock KF, Link E, Collins M, Di Iulio J, Lewis ID, Schwarer A, et al. A randomized trial of prophylactic palifermin on gastrointestinal toxicity after intensive induction therapy for acute myeloid leukaemia. Br J Haematol. 2014;167:618–625. https://doi.org/10.1111/bjh.13086

34. Blijlevens N, de Château M, Krivan G, Rabitsch W, Szomor A, Pytlik Rб et al. In a high dose melphalan setting, palifermin compared with placebo had no effect on oral mucositis or related patient’s burden. Bone Marrow Transplant. 2013;48:966–971. https://doi.org/10.1038/bmt.2012.257

35. Zhang Y, Li Y, He A, Wang J, Zhang P, Lei Bб et al. Efficacy of recombinant human interleukin 11 in preventing and treating oral mucositis after chemotherapy for patients with acute leukemia. BMC Oral Health. 2023;23(1):476. https://doi.org/10.1186/s12903-023-03118-4

36. Wei H, Wei J, Dong X. A prospective interventional study of recombinant human interleukin 11 mouthwash in chemotherapy induced oral mucositis. BMC Oral Health. 2022;22(1):313. https://doi.org/10.1186/s12903-022-02348-2

37. Mutluay Yayla E, Izgu N, Ozdemir L, Aslan Erdem S, Kartal M. Sage tea thyme peppermint hydrosol oral rinse reduces chemotherapy induced oral mucositis: a randomized controlled pilot study. Complement Ther Med. 2016;27:58–64. https://doi.org/10.1016/j.ctim.2016.05.010

38. Kim DR, Kim J, Oh JY, Kim HY, Kim YJ, Chang MS. Protective effect of Salvia miltiorrhiza Bunge on 5 fluorouracil induced oral mucositis. Int J Mol Med. 2017;40(1):39–46. https://doi.org/10.3892/ijmm.2017.2999

39. Guberti M, Botti S, Caffarri C, Cavuto S, Savoldi L, Fusco A, et al. Efficacy and safety of a colostrum and Aloe vera based oral care protocol to prevent and treat severe oral mucositis in patients undergoing hematopoietic stem cell transplantation: a single arm phase II study. Ann Hematol. 2022;101(10):2325-2336. https://doi.org/10.1007/s00277-022-04934-4

40. Su CK, Mehta V, Ravikumar L, Shah R, Pinto H, Halpern J, et al. Phase II double blind randomized study comparing oral aloe vera versus placebo to prevent radiation related mucositis in patients with head and neck neoplasms. Int J Radiat Oncol Biol Phys. 2004;60(1):171–177. https://doi.org/10.1016/j.ijrobp.2004.02.012

41. Xia C, Jiang C, Li W, Wei J, Hong H, Li J, et al. A Phase II randomized clinical trial and mechanistic studies using improved probiotics to prevent oral mucositis induced by concurrent radiotherapy and chemotherapy in nasopharyngeal carcinoma. Front Immunol. 2021;12:e618150. https://doi.org/10.3389/fimmu.2021.618150

42. Peng X, Li Z, Pei Y, Zheng S, Liu J, Wang J, et al. Streptococcus salivarius K12 alleviates oral mucositis in patients undergoing radiotherapy for malignant head and neck tumors: a randomized controlled trial. J Clin Oncol. 2024;42(12):1426–1435. https://doi.org/10.1200/JCO.23.00837

43. Sanctis V, Belgioia L, Cante D, Porta MR, Caspiani O, Guarnaccia R, et al. Lactobacillus brevis CD2 for prevention of oral mucositis in patients with head and neck tumors: a multicentric randomized study. Anticancer Res. 2019;39(4):1935–1942. https://doi.org/10.21873/anticanres.13303

44. Padure A, Horhat R, Talpos Niculescu IC, Scheusan R, Anghel MD, Rusu LC, Lungeanu D. Oral mucositis in adult cancer patients undergoing chemotherapy: six month on treatment follow up. J Clin Med. 2024;13(19):e13195723. https://doi.org/10.3390/jcm13195723

45. Oliveira FM, Borges MM, Malta CE, Moura JF, Forte CP, Barbosa JV, et al. Comparison of a daily and alternate day photobiomodulation protocol in the prevention of oral mucositis in patients undergoing radiochemotherapy for oral cancer: a triple blind, controlled clinical trial. Med Oral Patol Oral Cir Bucal. 2024;29(3):e430–e440. https://doi.org/10.4317/medoral.26436

46. Khalil M, Hamadah O, Saifo M. Photobiomodulation preconditioning for oral mucositis prevention and quality of life improvement in chemotherapy patients: a randomized clinical trial. BMC Oral Health. 2025;25(1):190. https://doi.org/10.1186/s12903-025-05579-1

47. Kamsvag T, Svanberg A, Legert KG, Arvidson J, von Essen L, Mellgren K, et al. Prevention of oral mucositis with cryotherapy in children undergoing hematopoietic stem cell transplantations – a feasibility study and randomized controlled trial. Support Care Cancer. 2020;28(10):4869–4879. https://doi.org/10.1007/s00520-019-05258-2

48. Mahdi A, Stübner J, Bergling M, Jontell M, Walladbegi J. Can cryoprevention of oral mucositis be obtained at a higher temperature? Clin Oral Investig. 2021;25(7):4519–4526. https://doi.org/10.1007/s00784-020-03765-9

49. Raber-Durlacher JE, Zadik Y, Treister NS, Stempler N, Bruno JS, Epstein JB, Elad S. MASCC/ISOO clinical practice statement: current understanding on controversies in basic oral care in hemato oncology and hematopoietic cell transplantation. Support Care Cancer. 2024;32(8):520–550. https://doi.org/10.1007/s00520-024-08690-1

50. Bahar E, Yoon H. Lidocaine: a local anesthetic, its adverse effects and management. Medicina (Kaunas). 2021;57(8):782. https://doi.org/10.3390/medicina57080782

51. Silva FC, Marto JM, Salgado A, Machado P, Silva AN, Almeida AJ. Nystatin and lidocaine pastilles for the local treatment of oral mucositis. Pharmaceut Dev Technol. 2017;22(2):266–274. https://doi.org/10.1080/10837450.2016.1221424

52. Aldalhin K, Wedian F, Al Mazaideh GM, Ayyal Salman H, Al Rimawi F, Alakhras F, et al. Comparative analysis of phytochemical composition of ethanolic extract of Jordanian Silvia officinalis. Pak J Biol Sci. 2020;23(8):989–994. https://doi.org/10.3923/pjbs.2020.989.994

53. Abbasi F, Rasoulzadeh Z, Yavari A. The effect of sage (Salvizan gel) compared to triamcinolone acetonide on the treatment of recurrent aphthous stomatitis: a double blinded randomized clinical trial. BMC Oral Health. 2023;23(1):157. https://doi.org/10.1186/s12903-023-02861-y

54. Radha MH, Laxmipriya NP. Evaluation of biological properties and clinical effectiveness of Aloe vera: a systematic review. J Tradit Complement Med. 2014;5(1):21–26. https://doi.org/10.1016/j.jtcme.2014.10.006

55. Gok Metin Z, Helvaci A, Gulbahar Eren M. Effects of Aloe vera in adults with mucocutaneous problems: a systematic review and meta analysis. J Adv Nurs. 2021;77(3):1105–1126. https://doi.org/10.1111/jan.14653

56. 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 randomized controlled trial. Indian J Dent Res. 2020;31(5):718–727. https://doi.org/10.4103/ijdr.IJDR_822_18

57. Ramezani V, Ghadirian S, Shabani M, Boroumand MA, Daneshvar R, Saghafi F. Efficacy of curcumin for amelioration of radiotherapy induced oral mucositis: a preliminary randomized controlled clinical trial. BMC Cancer. 2023;23(1):354. https://doi.org/10.1186/s12885-023-10730-8

58. Fan C, Sun X, Wang X, Yu H. Therapeutic potential of the chemical composition of Dendrobium nobile Lindl. Front Pharmacol. 2023;14:e1163830. https://doi.org/10.3389/fphar.2023.1163830

59. Li Y, Li Z, Zheng S, Xu X. Probiotics in the management of radiation induced oral mucositis. Front Cell Infect Microbiol. 2024;14:e1477143. https://doi.org/10.3389/fcimb.2024.1477143

60. Lin Y, Li S, Mo C, Liu H, Bi J, Xu S, et al. Oral microbial changes and oral disease management before and after the treatment of hematological malignancies: a narrative review. Clin Oral Investig. 2023;27(8):4083–4106. https://doi.org/10.1007/s00784-023-05021-2