Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis
The purpose of the study is to compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemoradiation-induced oral mucositis in head and neck cancer patients.
Sixty locally advanced head and neck cancer patients treated with high-dose radiotherapy concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to 2 weeks after the completion of treatment. The total score for mucositis, based on the Oral Mucositis Assessment Scale (OMAS), was used for the assessment, conducted weekly during the treatment period and at the fourth week of the follow-up. Pain score, all prescribed medications, and tube feeding needs were also recorded and compared.
The median of total OMAS score was statistically significant lower in patients who received benzydamine HCl during concurrent chemo-radiotherapy (CCRT) than in those who received sodium bicarbonate, (p value < 0.001). There was no difference in median pain score, (p value = 0.52). Nineteen percent of patients in sodium bicarbonate arm needed oral antifungal agents whereas none in the benzydamine HCl arm required such medications, (p value = 0.06). Tube feeding needs and the compliance of CCRT were not different between the two study arms.
For patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy, using benzydamine HCl mouthwash as a preventive approach was superior to basic oral care using sodium bicarbonate mouthwash in terms of reducing the severity of oral mucositis and encouraging trend for the less need of oral antifungal drugs.
KeywordsBenzydamine HCl Sodium bicarbonate Concurrent chemoradiation Mucositis
Compliance with ethical standards
It was conducted in compliance with principles of good clinical practice and all subjects provided the institutional approved informed consents.
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Baujat B, Audry H, Bourhis J, Chan AT, Onat H, Chua DT, Kwong DL, Al-Sarraf M, Chi KH, Hareyama M, Leung SF, Thephamongkhol K, Pignon JP, Group M-NC (2006) Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys 64(1):47–56. https://doi.org/10.1016/j.ijrobp.2005.06.037 CrossRefPubMedGoogle Scholar
- 2.Bourhis J, Sire C, Graff P, Gregoire V, Maingon P, Calais G, Gery B, Martin L, Alfonsi M, Desprez P, Pignon T, Bardet E, Rives M, Geoffrois L, Daly-Schveitzer N, Sen S, Tuchais C, Dupuis O, Guerif S, Lapeyre M, Favrel V, Hamoir M, Lusinchi A, Temam S, Pinna A, Tao YG, Blanchard P, Auperin A (2012) Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial. Lancet Oncol 13(2):145–153. https://doi.org/10.1016/S1470-2045(11)70346-1 CrossRefPubMedGoogle Scholar
- 4.Calais G, Alfonsi M, Bardet E, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Oudinot P, Bertrand P (1999) Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst 91(24):2081–2086CrossRefPubMedGoogle Scholar
- 5.Hansen O, Overgaard J, Hansen HS, Overgaard M, Hoyer M, Jorgensen KE, Bastholt L, Berthelsen A (1997) Importance of overall treatment time for the outcome of radiotherapy of advanced head and neck carcinoma: dependency on tumor differentiation. Radiother Oncol 43(1):47–51CrossRefPubMedGoogle Scholar
- 6.Sonis ST (2009) Mucositis: the impact, biology and therapeutic opportunities of oral mucositis. Oral Oncol 45(12):1015–1020. https://doi.org/10.1016/j.oraloncology.2009.08.006 CrossRefPubMedGoogle Scholar
- 7.Narayan S, Lehmann J, Coleman MA, Vaughan A, Yang CC, Enepekides D, Farwell G, Purdy JA, Laredo G, Nolan K, Pearson FS, Vijayakumar S (2008) Prospective evaluation to establish a dose response for clinical oral mucositis in patients undergoing head-and-neck conformal radiotherapy. Int J Radiat Oncol Biol Phys 72(3):756–762. https://doi.org/10.1016/j.ijrobp.2008.01.060 CrossRefPubMedGoogle Scholar
- 8.Fu KK, Pajak TF, Trotti A, Jones CU, Spencer SA, Phillips TL, Garden AS, Ridge JA, Cooper JS, Ang KK (2000) A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys 48(1):7–16CrossRefPubMedGoogle Scholar
- 9.Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A, van Glabbeke M, European Organization for R, Treatment of Cancer T (2004) Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350(19):1945–1952. https://doi.org/10.1056/NEJMoa032641 CrossRefPubMedGoogle Scholar
- 10.Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK, Radiation Therapy Oncology Group I (2004) Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350(19):1937–1944. https://doi.org/10.1056/NEJMoa032646 CrossRefPubMedGoogle Scholar
- 12.Epstein JB, Silverman S Jr, Paggiarino DA, Crockett S, Schubert MM, Senzer NN, Lockhart PB, Gallagher MJ, Peterson DE, Leveque FG (2001) Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: results from a multicenter, randomized, double-blind, placebo-controlled clinical trial. Cancer 92(4):875–885CrossRefPubMedGoogle Scholar
- 13.Keefe DM, Schubert MM, Elting LS, Sonis ST, Epstein JB, Raber-Durlacher JE, Migliorati CA, DB MG, Hutchins RD, Peterson DE, Mucositis Study Section of the Multinational Association of Supportive Care in C, the International Society for Oral O (2007) Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer 109(5):820–831. https://doi.org/10.1002/cncr.22484 CrossRefPubMedGoogle Scholar
- 17.Kazemian A, Kamian S, Aghili M, Hashemi FA, Haddad P (2009) Benzydamine for prophylaxis of radiation-induced oral mucositis in head and neck cancers: a double-blind placebo-controlled randomized clinical trial. Eur J Cancer Care (Engl) 18(2):174–178. https://doi.org/10.1111/j.1365-2354.2008.00943.x CrossRefGoogle Scholar
- 18.Sonis ST, Eilers JP, Epstein JB, LeVeque FG, Liggett WH Jr, Mulagha MT, Peterson DE, Rose AH, Schubert MM, Spijkervet FK, Wittes JP (1999) Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy. Mucositis Study Group. Cancer 85(10):2103–2113CrossRefPubMedGoogle Scholar
- 20.Rastogi M, Khurana R, Revannasiddaiah S, Jaiswal I, Nanda SS, Gupta P, Chufal KS, Bhatt ML (2017) 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 25(5):1439–1443. https://doi.org/10.1007/s00520-016-3548-9 CrossRefPubMedGoogle Scholar
- 21.Roopashri G, Jayanthi K, Guruprasad R (2011) Efficacy of benzydamine hydrochloride, chlorhexidine, and povidone iodine in the treatment of oral mucositis among patients undergoing radiotherapy in head and neck malignancies: a drug trail. Contemp Clin Dent 2(1):8–12. https://doi.org/10.4103/0976-237X.79292 CrossRefPubMedPubMedCentralGoogle Scholar