Middle East Journal of Cancer

Pentoxifylline Mouthwash: A Novel Approach to Managing Chemotherapy-Induced Oral Mucositis, a Randomized, Double blind, and Placebo-controlled Clinical Trial

Document Type : Original Article(s)

Authors

Azadeh Moghaddas 1, 2
Ali Rismanbaf 1
Ali Dargahi 1
Alireza Sadeghi 3
Mehran Sharifi 2, 3
Mahboubeh Rezazadeh 4
Faezeh Khozeimeh 5

1 Department of Clinical Pharmacy and Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

2 Cancer Prevention Center, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Internal Medicine, Oncology and Hematology Section, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Pharmaceutics, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

5 Department of Oral Medicine and diagnosis, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran

https://doi.org/10.30476/mejc.2026.104892.2213
Abstract
Background: Chemotherapy-induced oral mucositis (CIOM) is a prevalent inflammatory condition among cancer patients. Pentoxifylline (PTX), a phosphodiesterase inhibitor with established anti-inflammatory properties, has shown potential in CIOM management. The present study investigated the efficacy and safety of PTX mouthwash as a therapeutic intervention.
Method: A randomized, double-blind, placebo-controlled clinical trial was conducted at Omid Hospital, Isfahan, Iran. Participants diagnosed with CIOM were randomly assigned to receive either PTX mouthwash or placebo for seven days, in addition to standard care. Pain severity was measured using the numerical rating scale. Mucositis severity, xerostomia, and quality of life were assessed via the visual analogue scale and a modified oral mucositis daily questionnaire (OMDQ), respectively, at the baseline and after seven-day follow-ups. Data analysis was conducted using statistical package for the social sciences (SPSS) software, employing a per-protocol approach. P < 0.05 was considered to be statistically significant.
Results: Of the participants, 33 in the intervention group and 32 in the control group completed follow-up. There were no statistically significant differences in patients’ demographic and clinical characteristics between the groups at the study's outset.
The PTX group demonstrated significant improvements in mucositis grade (P = 0.02), pain score (P = 0.02), xerostomia (P = 0.03), and multiple OMDQ parameters, including overall health status, drinking ability, speech, and oral discomfort in comparison with the placebo group. No significant adverse effects were reported.
Conclusion: The findings suggest that PTX mouthwash may serve as a promising adjunctive therapy for reducing the severity of oral mucositis, alleviating pain, and addressing xerostomia in patients with CIOM, warranting further exploration in larger clinical trials.

Highlights

Azadeh Moghaddas (google scholar)

Mahboubeh Rezazadeh (google scholar)

Keywords

Oral mucositis
Xerostomia
Pentoxifylline
Chemotherapy
Mouthwash
Subjects

How to cite this article:

Moghaddas A, Rismanbaf A, Dargahi A, Sadeghi A, Sharifi M, Rezazadeh M, et al. Pentoxifylline mouthwash: A novel approach to managing chemotherapy-induced oral mucositis, a randomized, double blind, and placebo-controlled clinical trial. Middle East J Cancer. 2026; 17(3): 219-33. doi: 10.30476/mejc.2026.104892.2213.

  1. Shetty SS, Maruthi M, Dhara V, de Arruda JAA, Abreu LG, Mesquita RA, et al. Oral mucositis: Current knowledge and future directions. Dis Mon. 2022;68(5):101300. doi: 10.1016/j.disamonth.2021.101300. PMID: 34758917.
  2. Kwon Y. Mechanism-based management for mucositis: option for treating side effects without compromising the efficacy of cancer therapy. Onco Targets Ther. 2016;9:2007-16. doi: 10.2147/OTT.S96899. PMID: 27103826; PMCID: PMC4827894.
  3. Al-Dasooqi N, Sonis ST, Bowen JM, Bateman E, Blijlevens N, Gibson RJ, et al. Emerging evidence on the pathobiology of mucositis. Support Care Cancer. 2013;21(7):2075-83. doi: 10.1007/s00520-013-1810-y. PMID: 23604521.
  4. Sultani M, Stringer AM, Bowen JM, Gibson RJ. Anti-inflammatory cytokines: important immunoregulatory factors contributing to chemotherapy-induced gastrointestinal mucositis. Chemother Res Pract. 2012;2012:490804. doi: 10.1155/2012/490804. PMID: 22973511; PMCID: PMC3437608.
  5. Blijlevens N, de Château M, Krivan G, Rabitsch W, Szomor A, Pytlik R, 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(7):966-71. doi: 10.1038/bmt.2012.257. PMID: 23241739.
  6. Luo Y, Feng M, Fan Z, Zhu X, Jin F, Li R, et al. Effect of Kangfuxin solution on chemo/radiotherapy-induced mucositis in nasopharyngeal carcinoma patients: A multicenter, prospective randomized phase III clinical study. Evid Based Complement Alternat Med. 2016;2016:8692343. doi: 10.1155/2016/8692343. PMID: 27375766; PMCID: PMC4914730.
  7. Wong KH, Kuciejewska A, Sharabiani MT, Ng-Cheng-Hin B, Hoy S, Hurley T, et al. A randomised controlled trial of Caphosol mouthwash in management of radiation-induced mucositis in head and neck cancer. Radiother Oncol. 2017;122(2):207-11. doi: 10.1016/j.radonc.2016.06.015. PMID: 27393218.
  8. Wu SX, Cui TT, Zhao C, Pan JJ, Xu BY, Tian Y, et al. A prospective, randomized, multi-center trial to investigate Actovegin in prevention and treatment of acute oral mucositis caused by chemoradiotherapy for nasopharyngeal carcinoma. Radiother Oncol. 2010;97(1):113-8. doi: 10.1016/j.radonc.2010.08.003. PMID: 20826029.
  9. Daugėlaitė G, Užkuraitytė K, Jagelavičienė E, Filipauskas A. Prevention and treatment of chemotherapy and radiotherapy induced oral mucositis. Med. 2019;55(2):25. doi: 10.3390/medicina55020025. PMID: 30678228.
  10. Sunil VR, Vayas KN, Cervelli JA, Malaviya R, Hall L, Massa CB, et al. Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation. Exp Mol Pathol. 2014;97(1):89-98. doi: 10.1016/j.yexmp.2014.05.009. PMID: 24886962.
  11. Garcia FAdO, Rebouças JF, Balbino TQ, da Silva TG, de Carvalho-Júnior CHR, Cerqueira GS, et al. Pentoxifylline reduces the inflammatory process in diabetic rats: relationship with decreases of pro-inflammatory cytokines and inducible nitric oxide synthase. J Inflamm. 2015;12(1):1-10. doi: 10.1186/s12950-015-0080-5. PMID: 25922592.
  12. Gruber S, Bozsaky E, Roitinger E, Schwarz K, Schmidt M, Dörr W. Early inflammatory changes in radiation-induced oral mucositis. Strahlenther Onkol. 2017;193(6):499-507. doi: 10.1007/s00066-017-1119-8. PMID: 28258409.
  13. Brie D, Sahebkar A, Penson PE, Dinca M, Ursoniu S, Serban MC, et al. Effects of pentoxifylline on inflammatory markers and blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2016;34(12):2318-29. doi: 10.1097/HJH.0000000000001086. PMID: 27512972.
  14. Rezadoost L, Khosroshahi HT, Farnood F, Sarbakhsh P, Behzad H, Gharakhani A. Effects of Pentoxifylline on inflammatory factors and quality of life in maintenance hemodialysis patients. Pharm Sci. 2024;30(3):304-11. doi:10.34172/PS.2024.3.
  15. Da Cruz Campos MI, Campos CN, Corrêa JOA, Aarestrup FM, Aarestrup BJV. Induced oral mucositis in Wistar rats treated with different drugs: Preventive potential in cytokine production. Mol Clin Oncol. 2021;14(6):1-10. doi: 10.3892/mco.2021.2289. PMID: 33981431.
  16. Sayed R, El Wakeel L, Saad AS, Kelany M, El-Hamamsy M. Pentoxifylline and vitamin E reduce the severity of radiotherapy-induced oral mucositis and dysphagia in head and neck cancer patients: a randomized, controlled study. Med Oncol. 2020;37(1):1-8. doi: 10.1007/s12032-019-1334-5. PMID: 31748905.
  17. Common Terminology Criteria for Adverse Events (CTCAE). [accessed at: 2.1.2025] Available from https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_40
  18. Kim J, Shin W. How to do random allocation (randomization). Clin Orthop Surg. 2014;6(1):103. doi: 10.4055/cios.2014.6.1.103. PMID: 24605197.
  19. Pai S, Ghezzi EM, Ship JA. Development of a Visual Analogue Scale questionnaire for subjective assessment of salivary dysfunction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91(3):311-6. doi: 10.1067/moe.2001.111551. PMID: 11250628.
  20. Sonis ST, Eilers JP, Epstein JB, LeVeque FG, Liggett Jr WH, Mulagha MT, et al. Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy. Cancer. 1999;85(10):2103-13. doi: 10.1002/(sici)1097-0142(19990515)85:10<2103::aid-cncr2>3.0.co;2-0. PMID: 10326686.
  21. Kim KI, Kim JW, Lee HJ, Kim BS, Bang SM, Kim I, et al. Recombinant human epidermal growth factor on oral mucositis induced by intensive chemotherapy with stem cell transplantation. Am J Hematol. 2013;88(2):107-12. doi: 10.1002/ajh.23359. PMID: 23225026.
  22. Wang C, Wang P, Ouyang H, Wang J, Sun L, Li Y, et al. Efficacy of traditional Chinese medicine in treatment and prophylaxis of radiation-induced oral mucositis in patients receiving radiotherapy: a randomized controlled trial. Integr Cancer Ther. 2018;17(2):444-50. doi: 10.1177/1534735417725578. PMID: 28870095.
  23. Wilairat P, Kengkla K, Kaewpanan T, Kaewthong J, Ruankon S, Subthaweesin C, et al. Comparative efficacy and safety of interventions for preventing chemotherapy-induced oral mucositis in adult cancer patients: a systematic review and network meta-analysis. Eur J Hosp Pharm. 2020;27(2):103-10. doi: 10.1136/ejhpharm-2018-001649. PMID: 32133137.
  24. Hamzi H, Binhassan A, Najmeldin A, Alhariri E, Elhussein B, Althibani N, et al. Efficacy of palifermin in the treatment of oral mucositis in non-hematopoietic stem cell transplant pediatric patients: experience of a single tertiary hospital. J Egypt Natl Canc Inst. 2024;36(1):38. doi: 10.1186/s43046-024-00247-x. PMID: 39617846.
  25. Baskar K, Patil A, Ramya K, Yadav TB. A comprehensive review of oral mucositis and its management. Cross Current Int J Med Biosci. 2025;7(2):9-23. doi:10.36344/ccijmb.2025.v07i02.002.
  26. Al-Rudayni AH, Gopinath D, Maharajan MK, Veettil SK, Menon RK. Efficacy of oral cryotherapy in the prevention of oral mucositis associated with cancer chemotherapy: systematic review with meta-analysis and trial sequential analysis. Curr Oncol. 2021;28(4):2852-67. doi: 10.3390/curroncol28040250. PMID: 34436016.
  27. Gruber S, Hamedinger D, Bozsaky E, Schmidt M, Wolfram K, Haagen J, et al. Local hypoxia in oral mucosa (mouse) during daily fractionated irradiation–effect of pentoxifylline. Radiother Oncol. 2015;116(3):404-8. doi: 10.1016/j.radonc.2015.03.024. PMID: 25890574.
  28. Khairy MH, Kamel MA, Mohammed HH, Zagzoug A. Pharmacological studies on Pentoxifylline and Silymarin in male albino rats. Zagazig Vet J. 2023;51(1):1-3. doi: 10.21608/zvjz.2023.174032.1192.
  29. Lima V, Brito GA, Cunha FQ, Rebouças CG, Falcão BA, Augusto RF, et al. Effects of the tumour necrosis factor-alpha inhibitors pentoxifylline and thalidomide in short-term experimental oral mucositis in hamsters. Eur J Oral Sci. 2005;113(3):210-7. doi: 10.1111/j.1600-0722.2005.00216.x. PMID: 15953245.
  30. Yang KM, Suh HS. The effects of diltiazem and pentoxifylline on apoptosis of irradiated rat salivary gland. Radiat Oncol J. 1998;16(4):367-75.
  31. Bianco J, Appelbaum F, Nemunaitis J, Almgren J, Andrews F, Kettner P, et al. Phase I-II trial of pentoxifylline for the prevention of transplant-related toxicities following bone marrow transplantation. Blood. 1991;78(5):1205-11. Erratum in: Blood. 1992;79(12):3397. doi.org/10.1182/blood.V78.5.1205.1205. PMID: 1878587.
  32. Verdi CJ, Garewal HS, Koenig LM, Vaughn B, Burkhead T. A double-blind, randomized, placebo-controlled, crossover trial of pentoxifylline for the prevention of chemotherapy-induced oral mucositis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995;80(1):36-42. doi: 10.1016/s1079-2104(95)80014-x. PMID: 7552860.

Home

Guide for Authors

Submit Manuscript

Guide for Reviewers

Contact Us