Document Type : Original Article(s)

Authors

1 Department of Oral and Maxillofacial Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

2 Pharmaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

3 Department of Radiation Oncology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Background: Radiation-induced hyposalivation is a common complication of radiotherapy for head and neck cancers. The most commonly prescribed medication for hyposalivation is pilocarpine. However, due to the numerous systemic side-effects associated with pilocarpine, there has been a proposal to use it as a mouthwash. This study aimed to evaluate the impact of 1% pilocarpine mouthwash on salivary flow in patients with radiation-induced xerostomia.
Method: This double-blind, randomized clinical trial involved 63 patients with radiation-induced xerostomia. The patients were randomly allocated into the pilocarpine hydrochloride 1% mouthwash group and the placebo one. Patients were instructed to use these mouthwashes four times a day, with 30 drops each time, for two minutes. Unstimulated saliva production in patients was measured using the spitting method at three stages: two weeks before the commencement of radiotherapy, two weeks after, and four weeks after the completion of radiotherapy. These measurements were then compared between the two groups. Statistical analysis included chi-square, independent t-test, and Analysis of Variance (ANOVA) with repeated measures and the Sidak post hoc test. Statistical analysis was conducted using SPSS 17, and a significance level of P < 0.05 was applied.
Results: A comparison of saliva secretion between the pilocarpine mouthwash group and the control group at various time points after radiotherapy revealed that saliva secretion in the control group significantly decreased compared with the pilocarpine mouthwash group (P < 0.001).
Conclusion: 1% pilocarpine mouthwash is recommended for managing radiationinduced xerostomia.

Highlights

Paria Motahari (Google Scholar)

Katayoun Katebi (Google Scholar)

Keywords

Main Subjects

How to cite this article:

Motahari P, Pakdel F, Hashemzadeh N, Heydari F, Eghdam Zamiri R, Katebi K. The effect of 1% pilocarpine mouthwash on salivary flow rate in patients with radiation-induced xerostomia: a double-blind randomized clinical trial. Middle East J Cancer. 2024;15(2):108-16. doi:10.30476/mejc.2023.98297.1889.

  1. Shaikh T, Handorf EA, Murphy CT, Mehra R, Ridge JA, Galloway TJ. The impact of radiation treatment time on survival in patients with head and neck cancer. Int J Radiat Oncol Biol Phys. 2016;96(5):967-75. doi:10.1016/j.ijrobp.2016.08.046.
  2. Villa A, Connell CL, Abati S. Diagnosis and management of xerostomia and hyposalivation. Ther Clin Risk Manag. 2014;11:45-51. doi:10.2147/TCRM.S76282.
  3. Haddad P, Karimi M. A randomized, double-blind, placebo-controlled trial of concomitant pilocarpine with head and neck irradiation for prevention of radiation-induced xerostomia. Radiother Oncol. 2002;64(1):29-32. doi:10.1016/s0167-8140(02)00104-4.
  4. Wu VW, Leung KY. A review on the assessment of radiation induced salivary gland damage after radiotherapy. Front Oncol. 2019;9:1090. doi:10.3389/fonc.2019.01090.
  5. Millsop JW, Wang EA, Fazel N. Etiology, evaluation, and management of xerostomia. Clin Dermatol. 2017;35(5):468-76. doi:10.1016/j.clindermatol.2017.06.010.
  6. Molek M, Florenly F, Lister INE, Wahab TA, Lister C, Fioni F. Xerostomia and hyposalivation in association with oral candidiasis: a systematic review and meta-analysis. Evid Based Dent. 2022: In press. doi:10.1038/s41432-021-0210-2.
  7. Enoki K, Matsuda KI, Ikebe K, Murai S, Yoshida M, Maeda Y, et al. Influence of xerostomia on oral healthrelated quality of life in the elderly: a 5-year longitudinal study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117(6):716-21. doi:10.1016/j.oooo.2014.03.001.
  8. Feller G, Khammissa RAG, Nemutandani MS, Feller L. Biological consequences of cancer radiotherapy in the context of oral squamous cell carcinoma. Head Face Med. 2021;17(1):35. doi:10.1186/s13005-021-00286-y.
  9. Marin C, Diaz-de-Valdes L, Conejeros C, Martinez R, Niklander S. Interventions for the treatment of xerostomia: A randomized controlled clinical trial. J Clin Exp Dent. 2021;13(2):e104-11. doi:10.4317/jced.57924.
  10. Salum FG, Medella-Junior FD, Figueiredo MA, Cherubini K. Salivary hypofunction: An update on therapeutic strategies. Gerodontology. 2018;35(4):305-16. doi:10.1111/ger.12353.
  11. Farag AM, Holliday C, Cimmino J, Roomian T, Papas A. Comparing the effectiveness and adverse effects of pilocarpine and cevimeline in patients with hyposalivation. Oral Dis. 2019;25(8):1937-44. doi:10.1111/odi.13192.
  12. Davies AN, Thompson J. Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy. Cochrane Database Syst Rev. 2015;2015(10):CD003782. doi:10.1002/14651858.CD003782.pub3.
  13. Sarideechaigul W, Priprem A, Limsitthichaikoon S, Phothipakdee P, Chaijit R, Jorns TP, et al. Efficacy and safety of two artificial saliva-based polymers containing 0.1% pilocarpine for treatment of xerostomia: A randomized clinical pilot trial. J Clin Exp Dent. 2021;13(10):e994-1000. doi:10.4317/jced.58415.
  14. Taweechai Supapong S, Pesee M, Aromdee C, Laopaiboon M, Khunkitti W. Efficacy of pilocarpine lozenge for post-radiation xerostomia in patients with head and neck cancer. Aust Dent J. 2006; 51(4): 333-7. doi:10.1111/j.1834-7819.2006.tb00453.x.
  15. Pereira RMS, Bastos MDR, Ferreira MP, de Freitas O, de Macedo LD, de Oliveira HF, et al. Topical pilocarpine for xerostomia in patients with head and neck cancer treated with radiotherapy. Oral Dis. 2020;26:1209-18. doi:10.1111/odi.13343.
  16. Akhavan Karbasi M, Zarghani H, Akhavan S, Donyadide N, Shamshiry P. Assessment of the preventive effect of pilocarpine on radiotherapyinduced xerostomia in patients with head and neck cancers. Iran J Medical Phys. 2015;12(4):235-41. doi:10.22038/ijmp.2016.6836.
  17. Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 Statement: Updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol. 2010;63(8):834-40. doi:10.1016/j.jclinepi. 2010.02.005.
  18. Motamed B, Alaee A, Azizi A, Jahandar H, Fard MJK, Jafari A. Comparison of the 1 and 2% pilocarpine mouthwash in a xerostomic population: a randomized clinical trial. BMC Oral Health. 2022;22:548. doi:10.1186/s12903-022-02576-6.
  19. Navazesh M, Christensen CM. A comparison of whole mouth resting and stimulated salivary measurement procedures. J Dent Res. 1982;61(10):1158-62. doi:10.1177/00220345820610100901.
  20. Saleh J, Figueiredo MA, Cherubini K, Salum FG. Salivary hypofunction: an update on aetiology, diagnosis and therapeutics. Arch Oral Biol. 2015;60(2):242-55. doi:10.1016/j.archoralbio.2014.10.004.
  21. Vissink A, van Luijk P, Langendijk JA, Coppes RP. Current ideas to reduce or salvage radiation damage to salivary glands. Oral Dis. 2015;21(1):e1-0. doi:10.1111/odi.12222.
  22. Likhterov I, Ru M, Ganz C, Urken ML, Chai R, Okay D, et al. Objective and subjective hyposalivation after treatment for head and neck cancer: Long-term outcomes. Laryngoscope. 2018;128(12):2732-9. doi:10.1002/lary.27224.
  23. Germano F, Melone P, Testi D, Arcuri L, Marmiroli L, Petrone A, et al. Oral complications of head and neck radiotherapy: prevalence and management. Minerva Stomatol. 2015;64(4):189-202.
  24. Park JO, Nam IC, Kim CS, Park SJ, Lee DH, Kim HB, et al. Sex differences in the prevalence of head and neck cancers: a 10-year follow-up study of 10 million healthy people. Cancers. 2022;14(10):2521. doi:10.3390/cancers14102521.
  25. Rettig EM, D'Souza G. Epidemiology of head and neck cancer. Surg Oncol Clin N Am. 2015;24(3):379-96. doi:10.1016/j.soc.2015.03.001.
  26. Emadzadeh M, Shahidsales S, Mohammadian Bajgiran A, Salehi M, Massoudi T, Nikfarjam Z, et al. Head and neck cancers in north-east Iran: A 25 year survey. Iran J Otorhinolaryngol. 2017;29(92):137-45.
  27. Taziki MH, Fazel A, Salamat F, Sedaghat SM, Ashaari M, Poustchi H, et al. Epidemiology of head and neck cancers in Northern Iran: A 10-year trend study from Golestan province. Arch Iran Med. 2018;21(9):406-11.
  28. Song JI, Park JE, Kim HK, Kim KS. Dose and timerelated effects of pilocarpine mouthwash on salivation. J Oral Med Pain. 2017;42(3):72-80.doi:10.14476/jomp.2017.42.3.72.
  29. Barazzuol L, Coppes RP, van Luijk P. Prevention and treatment of radiotherapy-induced side effects. Mol Oncol. 2020;14(7):1538-54.doi:10.1002/1878-0261.12750.
  30. Chitapanarux I, Iamaroon A. Salivary glands and dental complications after radiotherapy for nasopharyngeal carcinoma. Ann Nasopharynx Canc. 2020;4:7. doi: 10.21037/anpc-20-17.
  31. Marmary Y, Adar R, Gaska S, Wygoda A, Maly A, Cohen J, et al. Radiation-induced loss of salivary gland function is driven by cellular senescence and prevented by il6 modulation cellular senescence in radiation-induced xerostomia. Cancer Res. 2016;76(5):1170-80. doi: 10.1158/0008-5472.CAN-15-1671.
  32. Yao QT, Wu YH, Liu SH, Song XB, Xu H, Li J, et al. Pilocarpine improves submandibular gland dysfunction in irradiated rats by downregulating the tight junction protein claudin-4. Oral Dis. 2022;28(6):1528-38. doi:10.1111/odi.13870.
  33. Mercadante V, Al Hamad A, Lodi G, Porter S, Fedele S. Interventions for the management of radiotherapyinduced xerostomia and hyposalivation: A systematic review and meta-analysis. Oral oncol. 2017;66:64-74. doi:10.1016/j.oraloncology.2016.12.031.
  34. Cheng CQ, Xu H, Liu L, Wang RN, Liu YT, Li J, et al. Efficacy and safety of pilocarpine for radiationinduced xerostomia in patients with head and neck cancer: a systematic review and meta-analysis. J Am Dent Assoc. 2016;147(4):236-43. doi:10.1016/j.adaj.2015.09.014.
  35. Yang WF, Liao GQ, Hakim SG, Ouyang DQ, Ringash J, Su YX. Is pilocarpine effective in preventing radiation-induced xerostomia? A systematic review and meta-analysis. Int J Radiat Oncol Biol Phys. 2016;94(3):503-11. doi:10.1016/j.ijrobp.2015.11.012.
  36. Al Hamad A, Lodi G, Porter S, Fedele S, Mercadante V. Interventions for dry mouth and hyposalivation in Sjogren’s syndrome: A systematic review and meta?analysis. Oral Dis. 2019;25(4):1027-47. doi:10.1111/odi.12952.
  37. Kapourani A, Kontogiannopoulos KN, Barmpalexis P. A review on the role of pilocarpine on the management of xerostomia and the importance of the topical administration systems development. Pharmaceuticals. 2022;15(6):762. doi:10.3390/ph15060762.
  38. Riley P, Glenny AM, Hua F, Worthington HV. Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy. Cochrane Database Syst Rev. 2017;7(7):CD012744. doi:10.1002/14651858.CD012744.
  39. Yang WF, Liao GQ, Hakim SG, Ouyang DQ, Ringash J, Su YX. Is pilocarpine effective in preventing radiation-induced xerostomia? A systematic review and meta-analysis. Int J Radiat Oncol Biol Phys. 2016;94(3):503-11. doi:10.1016/j.ijrobp.2015.11.012.
  40. Katebi K, Hassanpour S, Eslami H, Salehnia F, Hosseinifard H. The effects of pilocarpine mouthwash on patients with xerostomia: a systematic review and meta-analysis. J Dent (Shiraz). 2023;24(Supplement-March-2023):76-83. doi:10.30476/DENTJODS.2022.94335.1778.