Mouthwashes used in patients with oral and oropharyngeal mucositis: A systematic review

Mouthwashes used in patients with oral and oropharyngeal mucositis: A systematic review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Mouthwashes used in patients with oral and oropharyngeal mucositis: A systematic review Fernanda Pereira Delgado Costa, Maria Luisa Leandro Souza Dias, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4644677/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose The aim of this study was to conduct a systematic review of randomized clinical trials in order to assess the efficacy of the following mouthwashes recommended for the prevention and treatment of OM and OPM in patients undergoing cancer treatment: chlorhexidine, allopurinol, benzydamine, and propolis. Methods The following research question was formulated based on the PICOS strategy: “Are chlorhexidine, allopurinol, benzydamine and propolis mouthwashes effective in preventing and treating OM and OPM in patients undergoing cancer treatment?” Searches were performed in PubMed, Embase, Scopus, and Web of Science, without publication year or language restrictions. Randomized clinical trials comparing the use of chlorhexidine, allopurinol, benzydamine and propolis with a control group not submitted to any intervention were included. The retrieved articles were analyzed and selected by two reviewers and disagreements were resolved by consultation with a third reviewer. After data extraction, two evaluators independently analyzed the methodological quality of the studies using the Cochrane tool. Results After evaluation of the works, 13 of 1183 articles were selected. mouthwashes containing propolis and benzydamine mouthwashes were promising and effective while chlorhexidine or allopurinol did not provide satisfactory results. Conclusion Mouthwashes could be an alternative for treatment or preventing oral mucositis in cancer patients Services could consider the possibility of incorporating these medications since, in most cases, they are low cost and donot require specialized staff in their use. Antiseptic Mouthrinse Mouthwash Mucositis Systematic Review Figures Figure 1 INTRODUCTION Antineoplastic treatment can compromise the patient's quality of life and nutritional status, in addition to being a limiting factor in the progression of chemotherapy and radiotherapy [ 1 , 2 , 3 , 4 , 5 ]. Oral mucositis (OM) and oropharyngeal mucositis (OPM) are common acute complications in patients undergoing antineoplastic therapy characterized by painful symptoms [ 6 – 8 ]. Diverse resident microorganisms are found in the oral cavity and oral lesions can therefore predispose patients to local and systemic infections, worsening their clinical condition [ 9 , 10 , 11 , 12 , 13 , 14 ]. Furthermore, OPM is frequently associated with pain, dysphagia, dehydration, micronutrient deficiencies, and weight loss [ 15 , 16 , 17 , 18 ]. The prevention and treatment of antineoplastic therapy-induced OM and OPM have been extensively discussed in the literature. Some studies have investigated measures to reduce the severity of these conditions and possible complications; however, there seems to be no consensus regarding a specific protocol to be adopted. Among the methods investigated, photobiomodulation has shown good results in the management of OM [ 19 , 20 , 21 , 22 , 23 ]. However, photobiomodulation requires specialized personnel and equipment and cannot be performed by the patients themselves. Thus, there is a need for new therapies that not only promote symptom relief but also act as a therapeutic alternative. Such therapies are expected to promote the re-epithelialization of tissue lesions and to have a pleasant taste and low toxicity [ 24 , 25 , 26 , 27 , 28 ]. In addition, they can be used safely by the patient and are affordable for most of the population [29.29,30,31,32,33]. In view of the adverse effects of traditional drugs, increasing attention has been given to a range of natural agents because of their anti-inflammatory, antibacterial, antioxidant, immunomodulatory, sedative, and healing activities. These agents may be effective in the prevention and treatment of OM and OPM [34.35,36,37]. The aim of this systematic review was to evaluate the efficacy of chlorhexidine, allopurinol, benzydamine, and propolis mouthwashes in the prevention and treatment of OM and OPM in patients undergoing cancer treatment, as these substances are easily accessible, inexpensive, and do not require specialized technical personnel for daily use and can therefore be easily incorporated by health services. MATERIAL AND METHODS Study design This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [ 38 ], and the protocol was registered on the Open Science Framework (OSF) ( https://osf.io/ ). Research question The following research question was formulated based on the PICOS strategy (Table 1 ): “Are chlorhexidine, allopurinol, benzydamine and propolis mouthwashes effective in preventing and treating OM and OPM in patients undergoing cancer treatment?” Table 1 Description of the PICOS strategy for formulation of the research question Acronym Definition Description P Patients Patients undergoing cancer treatment I Intervention Use of chlorhexidine, allopurinol, benzydamine, and propolis C Comparison Other type of mouthwash; no treatment O Outcome Efficacy in the prevention or treatment of oral and oropharyngeal mucositis S Study design Randomized clinical trial Search strategy Searches were performed in the databases described in Table 2 on 30 October 2023 and updated on 30 January 2024. In addition, the reference list of the included articles was hand searched to identify any references that may have been missed during the electronic database search. The retrieved references were exported to Endnote Online (Clarivate Analytics, London, UK). Duplicates were removed. Table 2 Search strategy Database Keywords used in the search strategy PubMed Embase Scopus Web of Science OpenGrey Google Scholar (mouthwash OR mouthwashes) AND (stomatitides OR stomatitis OR “oral mucositis” OR “oral mucositides” OR “oromucositides”) Inclusion criteria The inclusion criteria were randomized clinical trials that evaluated the use of mouthwashes containing chlorhexidine, allopurinol, benzydamine and propolis for the prevention or treatment of OM or OPM. Exclusion criteria Clinical trials without a control group, studies in which patients had undergone previous interventions, studies in which patients rinsed the mouth and swallowed the mouthwash, in vitro studies, and animal studies were excluded. Study selection and data extraction Two reviewers analyzed and selected each article. In the case of disagreement, a third reviewer was consulted. Article selection was conducted in two steps. First, all titles/abstracts of the records retrieved in the electronic search were evaluated. Records whose title/abstract met the eligibility criteria were directly included in this systematic review. In the case of records whose titles/abstracts contained insufficient information for a decision, the full text was retrieved and evaluated independently by the same two authors in the second step. Records whose full text met the eligibility criteria were also included. Risk of bias in individual studies Risk of bias assessment was performed independently by two authors using the Cochrane tool [ 39 ]. Disagreements were resolved by a third evaluator. The following items were assessed: random sequence generation, allocation concealment, blinding of participants/personnel, blinding of outcome assessors, incomplete data, selective reporting, and other sources of bias. RESULTS Study selection The searches retrieved 1,183 articles. After the removal of duplicate articles, 995 titles/abstracts were evaluated in the first step and 431 records were excluded. The methodology was evaluated in the remaining 564 articles. Screening of titles/abstracts based on the eligibility criteria resulted in the selection of 23 articles for full-text reading. Thirteen of these articles met the eligibility criteria and were included in this systematic review (Fig. 1 ). The studies are described in chronological order in Table 3 . Characteristics of the included studies All studies were published in English and were conducted in eight different countries. The largest number of studies was from Iran (n = 4), followed by India (n = 2). The other countries, including the United States, South Korea, Papua New Guinea, Iraq, Thailand, and Brazil, contributed one study each (n = 6). The total sample of this review consisted of 629 patients who used the mouthwashes evaluated in the included studies. Chlorhexidine was analyzed in five studies (total sample of 230 patients), allopurinol in four (214 patients), benzydamine in three (230 patients), and propolis in one study (40 patients). The sample size of the studies ranged from 83 participants in the largest group analyzed to 23 participants in the smallest group. Table 3 Studies described in chronological order Author and country Years Comparison groups and objective Initial and final sample Treatment Diagnosis Variables analyzed Results of comparisons Loprinzi et al. [ 40 ] United State 1990 TG: allopurinol CG: placebo Prevention 77 (77) Chemotherapy: 5-FU and Leucovorin Colorectal cancer OM degree evaluated using two methods: 1) physician judgment of mucositis severity, graded from 0 to 4 according to NCCTG toxicity guidelines; 2) patient questionnaires to rate their own degree of mucositis There was no significant difference in OM degrees between TG and CG: mean physician-judged toxicity grade was 1.8 for TG and 1.3 for CG (p = 0.07); mean patient-graded toxicity was 1.9 for TG and 1.5 for CG (p = 0.15). Abbasi Nazari et al. [ 41 ] Iran 2007 TG: allopurinol CG: placebo Prevention and treatment 24 (24) Radiotherapy Oral, nasopharyngeal or hypopharyngeal cancer OM degree (WHO) in the first, second, third, fourth, fifth, and sixth week of radiotherapy There was no significant difference in mucositis severity between TG and CG in the first or second week (p = 0.227 and p = 0.121, respectively). TG had lower scores in the third, fourth, fifth and sixth week of treatment (p < 0.05 for each week). Madan et al. [ 42 ] India 2008 Three TG: 1) 0.12% chlorhexidine 2) 1% povidone-iodine 3) salt/sodium bicarbonate CG: Plain water Prevention and treatment 80(76) Radiotherapy Malignant head and neck neoplasms OM degree (WHO) was assessed at baseline and at weekly intervals during radiation therapy for 6 weeks TG: significant difference between the povidone-iodine group and all other groups No statistically significant difference in mean mucositis scores between TG and CG ShabanloeI et al. [ 43 ] Iran 2009 Two TG: 1) allopurinol 2) chamomile CG: normal saline Prevention 83 (83) Chemotherapy Different malignant diseases OM degree (WHO) for 16 days and self-reporting tools to evaluate pain No significant difference in the variability or total intensity of stomatitis was found between the allopurinol and chamomile groups from the first to the fourth time. Stomatitis pain intensity differed significantly in the allopurinol group compared to the normal saline group. Panahi et al. [ 44 ] Iran 2010 TG: allopurinol CG: placebo Prevention 33 (30) Chemotherapy with 5-FU Different malignant diseases OM degree (WHO) on days 1, 3 and 7 after chemotherapy. The results did not show a significant difference in the occurrence (p = 0.256) or severity (p = 0.386) of mucositis between the two groups. Mehdipour et al. [ 45 ] Iran 2011 TG: 0.2% zinc sulfate CG: 0.2% chlorhexidine gluconate Prevention and treatment 30 (30) Chemotherapy Acute leukemia Spijkervet Scale to grade oral mucositis every week for 8 weeks There was no significant difference between groups in the first week of treatment (p = 0.124). The trend of changes in the OM index assessed during the study was similar in both groups; however, a significant difference was observed in weeks 2 and 3 (p = 0.025), with OM being less severe in patients using zinc sulfate, suggesting efficacy of the product Choi and Kim [ 46 ] South Korea 2012 TG: chlorhexidine (CHX) CG: Sodium bicarbonate (SB) Prevention and treatment 68 (48) Chemotherapy Acute leukemia OM degree (WHO) every day from the day chemotherapy started to the 28th day or to the day of discharge from the hospital No significant differences were noted in the incidence rates of oral mucositis between the two groups. However, the incidence rate of ulcerative oral mucositis was significantly lower in the SB group (25.0%) than in the CHX group (62.5%, p = 0.008). The mean number of days to the onset of oral mucositis after chemotherapy was 13 days in both groups. The onset of ulcerative mucositis was significantly later in the SB group (16.1 days) than in the CHX group (11.4 days, p = 0.013). In this study, the mean duration of oral mucositis was 12 days in both groups. No significant differences were observed in the mean duration of oral mucositis between the SB group (11.8 days) and CHX group (13.7 days). Ahmed [ 47 ] Iraq 2013 TG: benzydamine, olive leaf extract (OLE) CG: placebo Prevention 40 (25) Chemotherapy Acute myeloid leukemia and lymphoblastic leukemia OMAS and WHO scales on days 1, 8, and 15 The lowest mean OMAS scores were recorded in the OLE group, followed by the benzydamine and placebo groups, respectively. Changes in the OMAS scores were highly significant (p < 0.01). The mean OMAS scores were low on day 1 (first day after receiving chemotherapy). On days 8 and 15, the mean OMAS scores increased significantly in the placebo group compared to the OLE and benzydamine groups. According to the WHO oral mucositis grades, the OLE group showed no grade 3 or 4 and grades 2, 3, and 4 were more common in the placebo group compared to the benzydamine group. Akhavan-Karbassi et al. [ 48 ] Iran 2016 TG: propolis CG: placebo (sterile water) Treatment and prevention 40 (40) Chemotherapy with different chemotherapeutic agents Head and neck neoplasms OM degree (WHO) at baseline and on days 3 and 7 In the placebo and propolis groups, mucositis grades were significantly lower on day 7, while on day 3, a significant difference was only observed in the propolis group. There were significant differences in oral mucositis between the propolis and placebo groups (p = 0.007). Gupta et al. [ 49 ] India 2018 TG: benzydamine (0.15%) CG: “candid b lotion (30 ml), cotrimazole (1% w/v), beclomethasone dipropionate (0.025% w/v), tetracycline (500 mg) and glycerin (30 ml). Treatment 60 (60) Radiotherapy Head and neck cancer OM degree (WHO) every week for 2 weeks after the completion of radiotherapy No significant difference between the two groups. Chitapanarux et al. [ 50 ] Thailand 2018 TG: benzydamine hydrochloride (0.15%) CG: sodium bicarbonate (0.15%) Prevention 60 (60) Radiotherapy and platinum-based chemotherapy Head and neck cancer OMAS scale, evaluated weekly during and at the end of radiotherapy The median OMAS scores were significantly lower in the study group every week between the second and eighth week of cancer treatment. The corresponding p values for these weeks in chronological order were 0.003, < 0.001, < 0.001, < 0.001, < 0.001, 0.01, and 0.04. The maximum OMAS score across the whole period in the benzydamine group was 25, substantially lower than the maximum score of 37 in the sodium bicarbonate group. Afrasiabifar et al. [ 51 ] Iran 2020 TG: combined solution of grape vinegar and rose water CG: chlorhexidine Treatment 60 (53) Chemotherapy (any drug) Carcinomas, adenocarcinomas and others OM degree (WHO) at baseline and on days 7, 14, and 21 Comparison between groups using Fisher’s exact test showed no significant differences in the number of patients with treated oral mucositis in either group (p > 0.05). The changes in chemotherapy-induced disease severity after the use of the combined solution of grape vinegar and rose water were similar to those observed for chlorhexidine. Santaella et al. [ 52 ] Brazil 2020 TG: polyhexanide (0.2%) (Prosept®) CG: chlorhexidine Prevention and treatment 40 (23) Chemotherapy (any drug) Radiotherapy plus chemotherapy Different neoplasms OM degree (WHO) evaluated in three stages: immediately before starting radiotherapy and/or chemotherapy sessions; during antineoplastic treatment (radiotherapy: after 15 to 20 sessions; chemotherapy: after 5 to 7 days), and after the end of the antineoplastic treatment cycle There was no significant difference between groups in the assessments regarding the development of mucositis. TG: treatment group; CG: control group; 5-FU: 5-fluorouracil; OM: oral mucositis; NCCTG: North Central Cancer Treatment Group; WHO: World Health Organization; OMAS: Oral Mucositis Assessment Scale. Nine studies evaluated chemotherapy-induced mucositis, three studies analyzed radiotherapy-induced mucositis, and the patients underwent both treatments in one study. Five of the included studies aimed to evaluate interventions for mucositis prevention alone. Another five studies aimed to examine the prevention and treatment of OM, and only three studies the treatment of OM. Among the interventions for prevention, four studies did not report results that would permit to consider the interventions effective. In two studies, the interventions used for treatment proved to be effective. Among the studies that evaluated interventions for simultaneous prevention and treatment, four reported effective interventions for prevention and treatment and one effective interventions for treatment. Regarding the agents used as controls, five studies used placebo. The remaining eight studies used the following products as control: povidone-iodine, sodium bicarbonate, chamomile, normal saline, zinc sulfate, olive leaf extract, magic mouthwash, combined solution of grape vinegar and rose water, and polyhexanide. The severity of OM was assessed using scales that measure the degree of this condition based on specific characteristics. The WHO mucositis grading scale was the most frequently employed instrument, used in 11 of the studies included in the systematic review. Only one study [ 45 ] used the Spijkervet Scale for OM grading and another study [ 40 ] graded OM using the NCCTG toxicity guidelines, and a questionnaire completed by the patients to rate their own symptoms. Risk of bias assessment The high heterogeneity among studies did not allow to perform a meta-analysis; thus, qualitative analysis was carried out (Table 4 ). Regarding random sequence generation and allocation concealment, all studies had a low risk of bias. Two articles had a low risk regarding blinding of participants/personnel and the others had a high risk of bias. Regarding blinding of outcome assessors and incomplete data (losses), nine studies had a low risk of bias and four a high risk. Regarding selective reporting, there was a low risk of bias in seven studies and a high risk in six. Finally, we observed that all studies had a high risk of bias regarding other sources of bias. Table 4 Assessment of risk of bias in the clinical trials Random sequence generation Allocation concealment Blinding of participants/personnel Blinding of outcome assessors Incomplete data (losses) Selective reporting Other sources of bias Loprinzi et al., 1990 [ 40 ] Low risk Low risk Low risk Low risk Low risk High risk High risk Abbasi Nazari et al., 2007 [ 41 ] Low risk Low risk Low risk High risk High risk Low risk High risk Madan et al., 2008 [ 42 ] Low risk Low risk High risk Low risk High risk High risk High risk Shabanloei et al., 2009 [ 43 ] Low risk Low risk High risk High risk Low risk High risk High risk Panahi et al., 2010 [ 44 ] Low risk Low risk High risk Low risk Low risk Low risk High risk Gupta et al., 2018 [ 49 ] Low risk Low risk High risk Low risk Low risk High risk High risk Mehdipour et al., 2011 [ 45 ] Low risk Low risk High risk Low risk Low risk Low risk High risk Choi and Kim, 2012 [ 46 ] Low risk Low risk High risk Low risk Low risk High risk High risk Ahmed, 2013 [ 47 ] Low risk Low risk High risk High risk High risk Low risk High risk Akhavan-Karbassi et al., 2016 [ 48 ] Low risk Low risk High risk High risk Low risk Low risk High risk Chitapanarux et al., 2018 [ 50 ] Low risk Low risk High risk Low risk Low risk Low risk High risk Afrasiabifar et al., 2020 [ 51 ] Low risk Low risk High risk Low risk High risk High risk High risk Santaella et al., 2020 [ 52 ] Low risk Low risk High risk Low risk Low risk Low risk High risk Source: The authors (2024) DISCUSSION The variable number of studies indicates the level of difficulty, complexity, great demand for time, and need for knowledge, among other factors, that are necessary for the successful design of studies. In the studies analyzed, propolis and benzydamine hydrochloride mouthwashes were effective in reducing OM and OPM, while allopurinol mouthwash with did not show significant results. It is important to note that each patient is unique and may respond differently to treatment. Thus, further studies are needed to develop definitive protocols for the management of OM and OPM in cancer patients. Allopurinol is a drug commonly used to treat gout, a condition characterized by painful episodes of inflammation in different joints as a result of excess uric acid in the body [ 21 , 53 , 54 ]. The drug acts by inhibiting xanthine oxidase, an enzyme that plays a crucial role in the production of uric acid, causing a decrease in uric acid levels in blood and the consequent relief of pain and inflammation [ 55 ]. Allopurinol was evaluated in four articles; three of these studies analyzed patients undergoing chemotherapy and one study evaluated patients undergoing radiotherapy. The randomized, double-blind, placebo-controlled clinical trial 41 investigating patients submitted to radiotherapy found no differences in the severity of OM between the group treated with allopurinol and the control group over the first 2 weeks of treatment. However, there were significant differences between groups from weeks 3 to 6, with significant improvement of mucositis in the allopurinol group. In contrast, the other studies involving patients submitted to chemotherapy found no significant difference between the group that used allopurinol and the other compounds analyzed [ 21 , 53 ]. Benzydamine is a local analgesic and anti-inflammatory agent that is used to treat a variety of painful and inflammatory conditions, particularly those affecting the mouth and throat. The mechanism of action of benzydamine consists of the inhibition of prostaglandin synthesis, contributing to the reduction in pain and swelling (anti-inflammatory and analgesic) [ 54 , 56 ]. Three studies evaluated the activity of benzydamine, two including patients undergoing chemotherapy and one including patients undergoing radiotherapy. Only one study [ 50 ] found benzydamine hydrochloride to be superior in the prevention and treatment of OM in patients undergoing chemotherapy. Chlorhexidine is a potent antiseptic agent that acts against a broad spectrum of bacteria, both gram-positive and gram-negative. The compound is often incorporated in oral health products because of its effectiveness in reducing plaque formation and in treating gingivitis [ 57 ]. Due to its bactericidal and bacteriostatic activity, chlorhexidine is frequently used in hospital environments for skin disinfection before surgical procedures [ 58 , 59 ]. Chlorhexidine is the most widely used and recommended mouthwash for patients undergoing cancer treatment because of its bactericidal, fungicidal, and virucidal properties. Six studies analyzed chlorhexidine; of these, one study investigated patients undergoing radiotherapy, one study examined patients undergoing chemotherapy and radiotherapy, and four studies investigated patients undergoing chemotherapy. However, chlorhexidine was not superior in any of these studies when compared to other compounds [ 60 , 61 , 62 ]. It is important to note that one study [ 46 ] comparing the efficacy of sodium bicarbonate solution and chlorhexidine in the oral care of patients during induction chemotherapy found the former to be more effective than chlorhexidine mouthwash, reinforcing that the indication of mouthwashes must be well assessed by the patient’s care team. Propolis is a resin collected by bees from different plants to protect the hive. This resin has antimicrobial, anti-inflammatory, antioxidant, and anticarcinogenic properties; it is therefore a product with different therapeutic applications [ 63 , 64 , 65 ]. The history of propolis use extends into traditional medicine, where it is used to boost immunity and to treat different infections and inflammatory conditions. Only one study evaluated the effectiveness of propolis [ 48 ] and found that it reduced chemotherapy-induced OM. The results showed that the use of propolis as a mouthwash was effective in reducing OM and in improving the oral health of patients. The methods used in the studies varied widely in terms of study design, active ingredients in the mouthwashes, and substances used for comparison. It is important to note that most studies observed a reduction in OM in patients with different types of cancer despite the wide variety of chemotherapy drugs and doses administered. In some studies, the authors included patients with diverse diseases that required different antineoplastic treatments, a fact that may interfere with the development and severity of OM and OPM (Table 5 ). Table 5 Efficacy of medications in the studies analyzed Benzydamine (3 articles) Chemotherapy (2) Chitapanarux et al. [ 50 ] Ahmed [ 47 ] Showed efficacy Radiotherapy (1) Gupta et al. [ 49 ] Showed efficacy – no severe mucositis Propolis (1 article) Chemotherapy (1) Akhaven-Karbassi et al. [ 48 ] Showed efficacy Chlorhexidine (5 articles) Chemotherapy (3) Afrasiabifar et al. [ 51 ] Mehdipour et al. [ 45 ] Choi and Kim [ 46 ] Did not show efficacy Radiotherapy (1) Madan et al. [ 42 ] Santaella et al. [ 52 ] Did not show efficacy Chemotherapy and radiotherapy (1) Gupta et al. [ 49 ] Did not show efficacy Allopurinol (4 articles) Chemotherapy (3) Loprinzi et al. [ 40 ] Shabanloei et al. [ 43 ] Panahi et al. [ 44 ] Did not show efficacy Radiotherapy (1) Abassi-Nazari et al. [ 41 ] Efficacy after 3 weeks Source: The authors (2024) Benzydamine was shown to be superior to sodium bicarbonate in preventing chemo/radiotherapy-induced OM [ 50 ]. On the other hand, sodium bicarbonate mouthwash was more effective than chlorhexidine in the oral care of patients with acute leukemia during induction chemotherapy [ 46 ]. The diversity of interventions explored reflects the complexity of mucositis and highlights the importance of multifaceted approaches to the treatment and prevention of OM in cancer patients. Regarding the results obtained, most studies provided qualitative data on the improvement of OM with the use of mouthwashes. However, the lack of standardization impairs the direct comparison of studies and the determination of the relative efficacy of mouthwashes. It is noteworthy that the studies evaluated did not identify important adverse effects of the interventions implemented for the prevention or treatment of OM and OPM. Regarding limitations, all studies provided incomplete information, including a lack of details about randomization, possible conflicts of interest, and a clear description of the study design. These limitations can affect the interpretation of the results and the risk of bias in the studies. There is also the possibility that studies reporting negative results, especially small ones, have not been published. The studies provided valuable information on different strategies to prevent and treat OM in cancer patients and thus contribute to the development of more effective approaches using the substances described that can improve the quality of life of patients undergoing antineoplastic treatment. These substances are easily accessible at public or private hospitals and do not require the recruitment of additional technical staff for their use. Limitations must be considered when interpreting and comparing the results of the studies. Further studies with a robust design that provide more detailed information about the results are needed to obtain stronger scientific evidence. Conclusion Mouthwashes containing chlorhexidine or allopurinol were not effective in preventing and treating OM. Benzydamine and propolis show promising results in the prevention and treatment of OM in patients undergoing cancer treatment. The use of benzydamine and propolis can contribute to improving the patient’s quality of life and to reducing the negative impacts of mucositis during antineoplastic treatment. Services should consider the possibility of incorporating these medications since, in most cases, they are low cost and do not require specialized staff in their use. Some studies did not find significant differences between intervention groups, indicating the complexity of OM and the need of multifaceted assessment for its management. The complexity of this condition and the diversity of studies highlight the importance of further comprehensive and standardized investigations to provide more consistent evidence and to support clinical decisions. There is continued need to improve mucositis prevention and treatment strategies, including the development of personalized and effective approaches to improve the well-being of cancer patients. Declarations Author Contribution Fernanda Pereira Delgado Costa and Maria Luisa Leandro de Souza Dias participated in the data collection, literature review, methodology, analysis and discussion of the data and drafting the article.Karla Emília Rodrigues participated in the analysis and discussion of data, drafting and correction of the article.Lucas Guimarães Abreu participated Study conception and design , acquisition of data , drafting of manuscript and correction of the article.Tarcília Aparecida Silva and Denise Vieira Travassos devised directed and coordinated the study, participated in the analysis and discussion of data, drafting and correcting the article.All authors critically revised the manuscript, approved the final version to be published, and agree to be accountable for all aspects of the work. References Pulito C, Cristaudo A, Porta CL, Zapperi S, Blandino G, Morrone A, Strano S (2020) Oral mucositis: the hidden side of cancer therapy. 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A controlled evaluation of an allopurinol mouthwash as prophylaxis against 5-fluorouracil‐induced stomatitis. Cancer, 65 (8):1879–1882. https://doi.org/10.1002/1097-0142(19900415)65 :8%3C1879::AID-CNCR2820650834%3E3.0.CO;2-8 Abbasi Nazari M. et al (2007) Allopurinol mouthwash may prevent mucositis in patients undergoing 5-fluorouracil chemotherapy. Journal of Clinical Oncology 25(24): 3886–3890. Madan PDK. et al (2008) The effect of three mouthwashes on radiation-induced oral mucositis in patients with head and neck malignancies: a randomized control trial. Journal of Cancer Research and Therapeutics 4(4):194–198. https://doi.org/10.4103/0973-1482.39597 ShabanloeI R, Ahmadi F, Vaez J, Ansarin K, Hajizadeh E, Javadzadeh Y, et al (2009) Alloporinol, chamomile and normal saline mouthwashesfor the prevention of chemotherapy-induced stomatitis. Journal of Clinical and Diagnostic Research 3:1537–1542. Panahi Y, Ala S, Saeedi M, Okhovatian A, Bazzaz N, Naghizadeh MM (2010) Allopurinol mouth rinse for prophylaxis of fluorouracil-induced mucositis. European Journal of Cancer Care 19(3):308–312. https://doi.org/10.1111/j.1365-2354.2008.01042.x Mehdipour M, Taghavi Zenoz A, Asvadi Kermani I, Hosseinpour A (2011) A comparison between zinc sulfate and chlorhexidine gluconate mouthwashes in the prevention of chemotherapy-induced oral mucositis. Daru 19(1):71–73 Choi SE, Kim HS (2012) Sodium bicarbonate solution versus chlorhexidine mouthwash in oral care of acute leukemia patients undergoing induction chemotherapy: a randomized controlled trial. Asian Nursing Research 6(2):60–66. https://doi.org/10.1016/j.anr.2012.05.004 Ahmed KM (2013) 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, The Saudi Dental Journal 25(4):41–147. https://doi.org/10.1016/j.sdentj.2013.09.001 . Akhavan-Karbassi MH, Yazdi MF, Ahadian H, SadrAbad MJ (2016). Randomized doubleblind placebo-controlled trial of propolis for oral mucositis in patients receiving chemotherapy for head and neck cancer. Asian Pacific Journal of Cancer Prevention 17 (7):3611–3614. https://doi.org/10.14456/apjcp.2016.142/APJCP.2016.17.7.3611 Gupta, Y. et al (2018) Magic mouth wash v/s benzydamine mouth wash in prophylaxis and treatment of radiation induced oral mucositis in patients with head and neck cancers: A prospective study. Indian Journal of Cancer Education and Research 6(1): 52–57. http://dx.doi.org/10.21088/ijcer.2321.9815.6118.6 Chitapanarux I, Tungkasamit T, Petsuksiri J, et al (2018) Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis. Support Care Cancer 26: 879–886. https://doi.org/10.1007/s00520-017-3904-4 . Afrasiabifar A, et al (2020) Grape vinegar and rose water solution versus chlorhexidine mouthwash for chemotherapy-induced oral mucositis: a randomized controlled trial. Complementary Therapies in Medicine 50:102–107. https://doi.org/10.1188/20.CJON.E71-E78 Santaella NG, Gonçales MG, Martins LJO, Brondino BM, Manzano BR, da Silva Santos PS (2020) Perception and acceptance of the use of 0.2% polyhexanide versus 0.12% chlorhexidine digluconate in patients at a risk of developing oral mucositis. J Oral Res 9(3):187–194. https://doi.org/10.17126/joralres.2020 . Dalbeth N, Gosling AL, Gaffo A, Abhishek A (2021) Gout. The Lancet 397 (10287):1843–1855. https://doi.org/10.1016/S0140-6736(21)00569-9 Oshiro-Sembokuya M, Uchida S, Kashiwagura Y, Ashihara M, Tanaka S, Hashimoto T, et al (2021) Evaluation of Disappearance Time and Palatability of Foams in the Oral Cavities of Healthy Volunteers, and Preparation of Drug-Containing Foam Formulations for Use in the Treatment of Oral Mucositis. Chemical and Pharmaceutical Bulletin 69 (4): 400–406. https://doi.org/10.1248/cpb.c21-00035 Kwan KR, Skokan S, Blesh-Boren T, Vogel J, Harter N, Ford JB (2024) Chemotherapeutic metabolism presenting as a recalcitrant case of hand–foot syndrome and mucositis. Journal of Oncology Pharmacy Practice 30(3):584–588. doi: 10.1177/10781552241226595 Kannarunimit D, Chotirut A, Prayongrat A, Pakvisal N, Sitthideatphaiboon P, Lertbutsayanukul C, et al (2023) 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 9 (4). https://doi.org/10.1016/j.heliyon.2023.e15437 Jones CG (1997) Chlorhexidine: is it still the gold standard? Periodontology 2000 15: 55–62. https://doi.org/10.1111/j.1600-0757.1997.tb00105.x Pitten FA, Kramer A (1999) Antimicrobial efficacy of antiseptic mouthrinse solutions. E J Clin Pharmacol 55:95–100. https://doi.org/10.1007/s002280050601 Fardad F, Ghasemi K, Ansarinejad N, Khodakarim N, Nasiripour S, Farasatinasab M (2023) A comparative study to assess the effectiveness of curcumin, mucosamin, and chlorhexidine in chemotherapy-induced oral mucositis. Explore 19(1):65–70. https://doi.org/10.1016/j.explore.2022.04.009 Alzoman H, Alojaym TG, Chalikkandy SN, Mehmood A, Rashed F, Divakar DD (2020) Comparison of an Herbal-and a 0.12% chlorhexidine-based oral rinse as adjuncts to nonsurgical mechanical debridement in the management of peri-implant mucositis: a randomised controlled trial. Oral Health Prev Dent, 18(1):52–645. Dumitriu AS, Păunică S, Nicolae XA, Bodnar DC, Albu ȘD, Suciu I, Ciongaru DN, Giurgiu MC (2023) The Effectiveness of the Association of Chlorhexidine with Mechanical Treatment of Peri-Implant Mucositis. Healthcare 11(13):1918. https://doi.org/10.3390/healthcare11131918 Bahrololoomi Z, Sadat-Hashemi A, Hassan-Akhavan-Karbassi M, Khaksar Y (2020) Evaluating the additive effect of Persica and chlorhexidine mouthwashes on oral health status of children receiving chemotherapy for their hematomalignancy: A randomized clinical trial. J Clin Exp Dent. 12(6):e574-e580. https://doi.org/10.4317/jced.56104 . Bankova V (2005) Chemical diversity of propolis and the problem of standardization. Journal of Ethnopharmacology 100:114–117. https://doi.org/10.1016/j.jep.2005.05.004 Münstedt K, Männle H (2019) Using Bee Products for the Prevention and Treatment of Oral Mucositis Induced by Cancer Treatment. Molecules 24(17):3023. https://doi.org/10.3390/molecules24173023 . Dastan F, Ameri A, Dodge S, Shishvan HH, Pirsalehi A, Abbasinazari M (2020) Efficacy and safety of propolis mouthwash in management of radiotherapy induced oral mucositis, A randomized, double blind clinical trial. Reports of Practical Oncology & Radiotherapy 25(6):969–973. https://doi.org/10.1016/j.rpor.2020.09.012 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4644677","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":321945632,"identity":"4e694d0a-adf4-4186-a89e-240754e8b8ee","order_by":0,"name":"Fernanda Pereira Delgado Costa","email":"","orcid":"","institution":"Universidade Federal de Minas Gerais, Minas Gerais (UFMG)","correspondingAuthor":false,"prefix":"","firstName":"Fernanda","middleName":"Pereira Delgado","lastName":"Costa","suffix":""},{"id":321945635,"identity":"fd2e0241-cc4b-4f8a-ba89-1aac24b571b6","order_by":1,"name":"Maria Luisa Leandro Souza Dias","email":"","orcid":"","institution":"Universidade Federal de Minas Gerais, Minas Gerais (UFMG)","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"Luisa Leandro Souza","lastName":"Dias","suffix":""},{"id":321945636,"identity":"cd11a87d-7ef2-432c-be09-5d6097e5ec6c","order_by":2,"name":"Karla Emília Rodrigues","email":"","orcid":"","institution":"Hospital de Câncer de Barretos","correspondingAuthor":false,"prefix":"","firstName":"Karla","middleName":"Emília","lastName":"Rodrigues","suffix":""},{"id":321945638,"identity":"9e5cc090-4f35-42e3-9aca-1d663594ae8e","order_by":3,"name":"Lucas Guimarães Abreu","email":"","orcid":"","institution":"Federal University of Minas Gerais (UFMG)","correspondingAuthor":false,"prefix":"","firstName":"Lucas","middleName":"Guimarães","lastName":"Abreu","suffix":""},{"id":321945640,"identity":"9e33be2f-0858-433b-8ab7-ecb47b3b6edc","order_by":4,"name":"Tarcília Aparecida Silva","email":"","orcid":"","institution":"Universidade Federal de Minas Gerais (UFMG), Minas Gerais","correspondingAuthor":false,"prefix":"","firstName":"Tarcília","middleName":"Aparecida","lastName":"Silva","suffix":""},{"id":321945642,"identity":"3e6f2eb9-39e2-430c-a2a8-9211a6ca705e","order_by":5,"name":"Denise Vieira Travassos","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA40lEQVRIiWNgGAWjYDCCAwgm4wMgwcNHWAsznMlsANLCRooWNgkwSUgH3/H+Yx9+ttnZy7e3P6v8mmMnw8bA/PDRDTxaJM8cZp7Z25acuOHMGbPbstuSgQ5jMzbOwaPF4EYyMwPPGeYEA4kcttuS25iBWnjYpPFquf+YmfHPmXp7+Rnpz4olt9UToeUGMzMzT8VhxoYbCWaMH7cdJqxF8kyyMbNMxXGQX4ylGbcd52FjJuAXvuMHHzO+MagGhdjDjz+3Vdvzszc/fIxPCwpg5gGTxCoHAcYfpKgeBaNgFIyCEQMA6dpFC9nMWvIAAAAASUVORK5CYII=","orcid":"","institution":"Universidade Federal de Minas Gerais (UFMG), Minas Gerais","correspondingAuthor":true,"prefix":"","firstName":"Denise","middleName":"Vieira","lastName":"Travassos","suffix":""}],"badges":[],"createdAt":"2024-06-26 19:46:41","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4644677/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4644677/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":61181999,"identity":"7222511b-da4f-493e-ad8e-f45f38eaa8d3","added_by":"auto","created_at":"2024-07-26 16:53:25","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":214018,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flow diagram of the article selection process.\u003c/p\u003e\n\u003cp\u003eSource: The authors (2024)\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4644677/v1/5b6a93652bc23105c7b99f0c.jpeg"},{"id":62820128,"identity":"9a6061ed-0021-4ef2-89d6-aaaf21711fe9","added_by":"auto","created_at":"2024-08-20 00:03:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1116024,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4644677/v1/4b345bd7-3d04-4c8f-a0e7-e5caaa4d90b7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mouthwashes used in patients with oral and oropharyngeal mucositis: A systematic review","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAntineoplastic treatment can compromise the patient's quality of life and nutritional status, in addition to being a limiting factor in the progression of chemotherapy and radiotherapy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Oral mucositis (OM) and oropharyngeal mucositis (OPM) are common acute complications in patients undergoing antineoplastic therapy characterized by painful symptoms [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDiverse resident microorganisms are found in the oral cavity and oral lesions can therefore predispose patients to local and systemic infections, worsening their clinical condition [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Furthermore, OPM is frequently associated with pain, dysphagia, dehydration, micronutrient deficiencies, and weight loss [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe prevention and treatment of antineoplastic therapy-induced OM and OPM have been extensively discussed in the literature. Some studies have investigated measures to reduce the severity of these conditions and possible complications; however, there seems to be no consensus regarding a specific protocol to be adopted. Among the methods investigated, photobiomodulation has shown good results in the management of OM [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, photobiomodulation requires specialized personnel and equipment and cannot be performed by the patients themselves. Thus, there is a need for new therapies that not only promote symptom relief but also act as a therapeutic alternative. Such therapies are expected to promote the re-epithelialization of tissue lesions and to have a pleasant taste and low toxicity [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In addition, they can be used safely by the patient and are affordable for most of the population [29.29,30,31,32,33].\u003c/p\u003e \u003cp\u003eIn view of the adverse effects of traditional drugs, increasing attention has been given to a range of natural agents because of their anti-inflammatory, antibacterial, antioxidant, immunomodulatory, sedative, and healing activities. These agents may be effective in the prevention and treatment of OM and OPM [34.35,36,37].\u003c/p\u003e \u003cp\u003eThe aim of this systematic review was to evaluate the efficacy of chlorhexidine, allopurinol, benzydamine, and propolis mouthwashes in the prevention and treatment of OM and OPM in patients undergoing cancer treatment, as these substances are easily accessible, inexpensive, and do not require specialized technical personnel for daily use and can therefore be easily incorporated by health services.\u003c/p\u003e"},{"header":"MATERIAL AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e], and the protocol was registered on the Open Science Framework (OSF) (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://osf.io/\u003c/span\u003e\u003cspan address=\"https://osf.io/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eResearch question\u003c/h2\u003e \u003cp\u003eThe following research question was formulated based on the PICOS strategy (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e): \u0026ldquo;Are chlorhexidine, allopurinol, benzydamine and propolis mouthwashes effective in preventing and treating OM and OPM in patients undergoing cancer treatment?\u0026rdquo;\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDescription of the PICOS strategy for formulation of the research question\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcronym\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDefinition\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDescription\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients undergoing cancer treatment\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUse of chlorhexidine, allopurinol, benzydamine, and propolis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComparison\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOther type of mouthwash; no treatment\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEfficacy in the prevention or treatment of oral and oropharyngeal mucositis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStudy design\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRandomized clinical trial\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSearch strategy\u003c/h2\u003e \u003cp\u003eSearches were performed in the databases described in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e on 30 October 2023 and updated on 30 January 2024. In addition, the reference list of the included articles was hand searched to identify any references that may have been missed during the electronic database search. The retrieved references were exported to Endnote Online (Clarivate Analytics, London, UK). Duplicates were removed.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSearch strategy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDatabase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKeywords used in the search strategy\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePubMed\u003c/p\u003e \u003cp\u003eEmbase\u003c/p\u003e \u003cp\u003eScopus\u003c/p\u003e \u003cp\u003eWeb of Science\u003c/p\u003e \u003cp\u003eOpenGrey\u003c/p\u003e \u003cp\u003eGoogle Scholar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(mouthwash OR mouthwashes) AND (stomatitides OR stomatitis OR \u0026ldquo;oral mucositis\u0026rdquo; OR \u0026ldquo;oral mucositides\u0026rdquo; OR \u0026ldquo;oromucositides\u0026rdquo;)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eInclusion criteria\u003c/h2\u003e \u003cp\u003eThe inclusion criteria were randomized clinical trials that evaluated the use of mouthwashes containing chlorhexidine, allopurinol, benzydamine and propolis for the prevention or treatment of OM or OPM.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eExclusion criteria\u003c/h2\u003e \u003cp\u003eClinical trials without a control group, studies in which patients had undergone previous interventions, studies in which patients rinsed the mouth and swallowed the mouthwash, \u003cem\u003ein vitro\u003c/em\u003e studies, and animal studies were excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStudy selection and data extraction\u003c/h2\u003e \u003cp\u003eTwo reviewers analyzed and selected each article. In the case of disagreement, a third reviewer was consulted. Article selection was conducted in two steps. First, all titles/abstracts of the records retrieved in the electronic search were evaluated. Records whose title/abstract met the eligibility criteria were directly included in this systematic review. In the case of records whose titles/abstracts contained insufficient information for a decision, the full text was retrieved and evaluated independently by the same two authors in the second step. Records whose full text met the eligibility criteria were also included.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eRisk of bias in individual studies\u003c/h2\u003e \u003cp\u003eRisk of bias assessment was performed independently by two authors using the Cochrane tool [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Disagreements were resolved by a third evaluator. The following items were assessed: random sequence generation, allocation concealment, blinding of participants/personnel, blinding of outcome assessors, incomplete data, selective reporting, and other sources of bias.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStudy selection\u003c/h2\u003e \u003cp\u003eThe searches retrieved 1,183 articles. After the removal of duplicate articles, 995 titles/abstracts were evaluated in the first step and 431 records were excluded. The methodology was evaluated in the remaining 564 articles. Screening of titles/abstracts based on the eligibility criteria resulted in the selection of 23 articles for full-text reading. Thirteen of these articles met the eligibility criteria and were included in this systematic review (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The studies are described in chronological order in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of the included studies\u003c/h2\u003e \u003cp\u003eAll studies were published in English and were conducted in eight different countries. The largest number of studies was from Iran (n\u0026thinsp;=\u0026thinsp;4), followed by India (n\u0026thinsp;=\u0026thinsp;2). The other countries, including the United States, South Korea, Papua New Guinea, Iraq, Thailand, and Brazil, contributed one study each (n\u0026thinsp;=\u0026thinsp;6).\u003c/p\u003e \u003cp\u003e The total sample of this review consisted of 629 patients who used the mouthwashes evaluated in the included studies. Chlorhexidine was analyzed in five studies (total sample of 230 patients), allopurinol in four (214 patients), benzydamine in three (230 patients), and propolis in one study (40 patients).\u003c/p\u003e \u003cp\u003eThe sample size of the studies ranged from 83 participants in the largest group analyzed to 23 participants in the smallest group.\u003c/p\u003e\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStudies described in chronological order\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAuthor and country\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYears\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eComparison groups and objective\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eInitial and final sample\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eVariables analyzed\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eResults of comparisons\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLoprinzi et al. [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eUnited State\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1990\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTG: allopurinol \u003c/p\u003e \u003cp\u003eCG: placebo\u003c/p\u003e \u003cp\u003ePrevention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e77 (77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChemotherapy: \u003c/p\u003e \u003cp\u003e5-FU and Leucovorin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eColorectal cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOM degree evaluated using two methods: 1) physician judgment of mucositis severity, graded from 0 to 4 according to NCCTG toxicity guidelines; 2) patient questionnaires to rate their own degree of mucositis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eThere was no significant difference in OM degrees between TG and CG: mean physician-judged toxicity grade was 1.8 for TG and 1.3 for CG (p\u0026thinsp;=\u0026thinsp;0.07); mean patient-graded toxicity was 1.9 for TG and 1.5 for CG (p\u0026thinsp;=\u0026thinsp;0.15).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbbasi Nazari et al. [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTG: allopurinol\u003c/p\u003e \u003cp\u003eCG: placebo\u003c/p\u003e \u003cp\u003ePrevention and treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOral, nasopharyngeal or hypopharyngeal cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOM degree (WHO) in the first, second, third, fourth, fifth, and sixth week of radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eThere was no significant difference in mucositis severity between TG and CG in the first or second week (p\u0026thinsp;=\u0026thinsp;0.227 and p\u0026thinsp;=\u0026thinsp;0.121, respectively). TG had lower scores in the third, fourth, fifth and sixth week of treatment (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 for each week).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMadan et al. [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThree TG:\u003c/p\u003e \u003cp\u003e1) 0.12% chlorhexidine\u003c/p\u003e \u003cp\u003e2) 1% povidone-iodine\u003c/p\u003e \u003cp\u003e3) salt/sodium bicarbonate\u003c/p\u003e \u003cp\u003eCG: Plain water\u003c/p\u003e \u003cp\u003ePrevention and treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80(76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMalignant head and neck neoplasms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOM degree (WHO) was assessed at baseline and at weekly intervals during radiation therapy for 6 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eTG: significant difference between the povidone-iodine group and all other groups\u003c/p\u003e \u003cp\u003eNo statistically significant difference in mean mucositis scores between TG and CG\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShabanloeI et al. [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTwo TG:\u003c/p\u003e \u003cp\u003e1) allopurinol\u003c/p\u003e \u003cp\u003e2) chamomile\u003c/p\u003e \u003cp\u003eCG: normal saline\u003c/p\u003e \u003cp\u003ePrevention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83 (83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDifferent malignant diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOM degree (WHO) for 16 days and self-reporting tools to evaluate pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo significant difference in the variability or total intensity of stomatitis was found between the allopurinol and chamomile groups from the first to the fourth time. Stomatitis pain intensity differed significantly in the allopurinol group compared to the normal saline group.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePanahi et al. [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTG: allopurinol\u003c/p\u003e \u003cp\u003eCG: placebo\u003c/p\u003e \u003cp\u003ePrevention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChemotherapy with 5-FU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDifferent malignant diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOM degree (WHO) on days 1, 3 and 7 after chemotherapy.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eThe results did not show a significant difference in the occurrence (p\u0026thinsp;=\u0026thinsp;0.256) or severity (p\u0026thinsp;=\u0026thinsp;0.386) of mucositis between the two groups.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMehdipour et al. [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTG: 0.2% zinc sulfate\u003c/p\u003e \u003cp\u003eCG: 0.2% chlorhexidine gluconate\u003c/p\u003e \u003cp\u003ePrevention and treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAcute leukemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSpijkervet Scale to grade oral mucositis every week for 8 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eThere was no significant difference between groups in the first week of treatment (p\u0026thinsp;=\u0026thinsp;0.124). The trend of changes in the OM index assessed during the study was similar in both groups; however, a significant difference was observed in weeks 2 and 3 (p\u0026thinsp;=\u0026thinsp;0.025), with OM being less severe in patients using zinc sulfate, suggesting efficacy of the product\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChoi and Kim [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eSouth Korea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTG: chlorhexidine (CHX)\u003c/p\u003e \u003cp\u003eCG: Sodium bicarbonate (SB)\u003c/p\u003e \u003cp\u003ePrevention and treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68 (48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAcute leukemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOM degree (WHO) every day from the day chemotherapy started to the 28th day or to the day of discharge from the hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo significant differences were noted in the incidence rates of oral mucositis between the two groups. However, the incidence rate of ulcerative oral mucositis was significantly lower in the SB group (25.0%) than in the CHX group (62.5%, p\u0026thinsp;=\u0026thinsp;0.008). The mean number of days to the onset of oral mucositis after chemotherapy was 13 days in both groups. The onset of ulcerative mucositis was significantly later in the SB group (16.1 days) than in the CHX group (11.4 days, p\u0026thinsp;=\u0026thinsp;0.013). In this study, the mean duration of oral mucositis was 12 days in both groups. No significant differences were observed in the mean duration of oral mucositis between the SB group (11.8 days) and CHX group (13.7 days).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAhmed [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIraq\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTG: benzydamine, olive leaf extract (OLE)\u003c/p\u003e \u003cp\u003eCG: placebo\u003c/p\u003e \u003cp\u003ePrevention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAcute myeloid leukemia and lymphoblastic leukemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOMAS and WHO scales on days 1, 8, and 15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eThe lowest mean OMAS scores were recorded in the OLE group, followed by the benzydamine and placebo groups, respectively. Changes in the OMAS scores were highly significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). The mean OMAS scores were low on day 1 (first day after receiving chemotherapy). On days 8 and 15, the mean OMAS scores increased significantly in the placebo group compared to the OLE and benzydamine groups. According to the WHO oral mucositis grades, the OLE group showed no grade 3 or 4 and grades 2, 3, and 4 were more common in the placebo group compared to the benzydamine group.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAkhavan-Karbassi et al. [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTG: propolis\u003c/p\u003e \u003cp\u003eCG: placebo (sterile water)\u003c/p\u003e \u003cp\u003eTreatment and prevention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChemotherapy with different chemotherapeutic agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHead and neck neoplasms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOM degree (WHO) at baseline and on days 3 and 7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eIn the placebo and propolis groups, mucositis grades were significantly lower on day 7, while on day 3, a significant difference was only observed in the propolis group. There were significant differences in oral mucositis between the propolis and placebo groups (p\u0026thinsp;=\u0026thinsp;0.007).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGupta et al. [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTG: benzydamine (0.15%)\u003c/p\u003e \u003cp\u003eCG: \u0026ldquo;candid b lotion (30 ml), cotrimazole (1% w/v), beclomethasone dipropionate (0.025% w/v), tetracycline (500 mg) and glycerin (30 ml).\u003c/p\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHead and neck cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOM degree (WHO) every week for 2 weeks after the completion of radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo significant difference between the two groups.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChitapanarux \u003cem\u003eet al.\u003c/em\u003e [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThailand\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTG: benzydamine hydrochloride (0.15%)\u003c/p\u003e \u003cp\u003eCG: sodium bicarbonate (0.15%)\u003c/p\u003e \u003cp\u003ePrevention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRadiotherapy and platinum-based chemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHead and neck cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOMAS scale, evaluated weekly during and at the end of radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eThe median OMAS scores were significantly lower in the study group every week between the second and eighth week of cancer treatment. The corresponding p values for these weeks in chronological order were 0.003, \u0026lt;\u0026thinsp;0.001, \u0026lt;\u0026thinsp;0.001, \u0026lt;\u0026thinsp;0.001, \u0026lt;\u0026thinsp;0.001, 0.01, and 0.04. The maximum OMAS score across the whole period in the benzydamine group was 25, substantially lower than the maximum score of 37 in the sodium bicarbonate group.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfrasiabifar et al. [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTG: combined solution of grape vinegar and rose water\u003c/p\u003e \u003cp\u003eCG: chlorhexidine\u003c/p\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 (53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChemotherapy (any drug)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCarcinomas, adenocarcinomas and others\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOM degree (WHO) at baseline and on days 7, 14, and 21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eComparison between groups using Fisher\u0026rsquo;s exact test showed no significant differences in the number of patients with treated oral mucositis in either group (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The changes in chemotherapy-induced disease severity after the use of the combined solution of grape vinegar and rose water were similar to those observed for chlorhexidine.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSantaella et al. [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eBrazil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTG: polyhexanide (0.2%) (Prosept\u0026reg;)\u003c/p\u003e \u003cp\u003eCG: chlorhexidine\u003c/p\u003e \u003cp\u003ePrevention and treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChemotherapy (any drug)\u003c/p\u003e \u003cp\u003eRadiotherapy plus chemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDifferent neoplasms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOM degree (WHO) evaluated in three stages: immediately before starting radiotherapy and/or chemotherapy sessions; during antineoplastic treatment (radiotherapy: after 15 to 20 sessions; chemotherapy: after 5 to 7 days), and after the end of the antineoplastic treatment cycle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eThere was no significant difference between groups in the assessments regarding the development of mucositis.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTG: treatment group; CG: control group; 5-FU: 5-fluorouracil; OM: oral mucositis; NCCTG: North Central Cancer Treatment Group; WHO: World Health Organization; OMAS: Oral Mucositis Assessment Scale.\u003c/p\u003e \u003cp\u003eNine studies evaluated chemotherapy-induced mucositis, three studies analyzed radiotherapy-induced mucositis, and the patients underwent both treatments in one study.\u003c/p\u003e \u003cp\u003eFive of the included studies aimed to evaluate interventions for mucositis prevention alone. Another five studies aimed to examine the prevention and treatment of OM, and only three studies the treatment of OM. Among the interventions for prevention, four studies did not report results that would permit to consider the interventions effective. In two studies, the interventions used for treatment proved to be effective. Among the studies that evaluated interventions for simultaneous prevention and treatment, four reported effective interventions for prevention and treatment and one effective interventions for treatment.\u003c/p\u003e \u003cp\u003eRegarding the agents used as controls, five studies used placebo. The remaining eight studies used the following products as control: povidone-iodine, sodium bicarbonate, chamomile, normal saline, zinc sulfate, olive leaf extract, magic mouthwash, combined solution of grape vinegar and rose water, and polyhexanide.\u003c/p\u003e \u003cp\u003eThe severity of OM was assessed using scales that measure the degree of this condition based on specific characteristics. The WHO mucositis grading scale was the most frequently employed instrument, used in 11 of the studies included in the systematic review. Only one study [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e] used the Spijkervet Scale for OM grading and another study [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e] graded OM using the NCCTG toxicity guidelines, and a questionnaire completed by the patients to rate their own symptoms.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eRisk of bias assessment\u003c/h2\u003e \u003cp\u003eThe high heterogeneity among studies did not allow to perform a meta-analysis; thus, qualitative analysis was carried out (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Regarding random sequence generation and allocation concealment, all studies had a low risk of bias. Two articles had a low risk regarding blinding of participants/personnel and the others had a high risk of bias. Regarding blinding of outcome assessors and incomplete data (losses), nine studies had a low risk of bias and four a high risk. Regarding selective reporting, there was a low risk of bias in seven studies and a high risk in six. Finally, we observed that all studies had a high risk of bias regarding other sources of bias.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssessment of risk of bias in the clinical trials\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRandom sequence generation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAllocation concealment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBlinding of participants/personnel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBlinding of outcome assessors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIncomplete data (losses)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSelective reporting\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOther sources of bias\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLoprinzi et al., 1990 [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbbasi Nazari et al., 2007 [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMadan et al., 2008 [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShabanloei et al., 2009 [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePanahi et al., 2010 [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGupta et al., 2018 [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMehdipour et al., 2011 [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChoi and Kim, 2012 [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAhmed, 2013 [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAkhavan-Karbassi et al., 2016 [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChitapanarux et al., 2018 [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfrasiabifar et al., 2020 [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSantaella et al., 2020 [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSource: The authors (2024)\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe variable number of studies indicates the level of difficulty, complexity, great demand for time, and need for knowledge, among other factors, that are necessary for the successful design of studies.\u003c/p\u003e \u003cp\u003eIn the studies analyzed, propolis and benzydamine hydrochloride mouthwashes were effective in reducing OM and OPM, while allopurinol mouthwash with did not show significant results. It is important to note that each patient is unique and may respond differently to treatment. Thus, further studies are needed to develop definitive protocols for the management of OM and OPM in cancer patients.\u003c/p\u003e \u003cp\u003eAllopurinol is a drug commonly used to treat gout, a condition characterized by painful episodes of inflammation in different joints as a result of excess uric acid in the body [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. The drug acts by inhibiting xanthine oxidase, an enzyme that plays a crucial role in the production of uric acid, causing a decrease in uric acid levels in blood and the consequent relief of pain and inflammation [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAllopurinol was evaluated in four articles; three of these studies analyzed patients undergoing chemotherapy and one study evaluated patients undergoing radiotherapy. The randomized, double-blind, placebo-controlled clinical trial \u003csup\u003e41\u003c/sup\u003e investigating patients submitted to radiotherapy found no differences in the severity of OM between the group treated with allopurinol and the control group over the first 2 weeks of treatment. However, there were significant differences between groups from weeks 3 to 6, with significant improvement of mucositis in the allopurinol group. In contrast, the other studies involving patients submitted to chemotherapy found no significant difference between the group that used allopurinol and the other compounds analyzed [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBenzydamine is a local analgesic and anti-inflammatory agent that is used to treat a variety of painful and inflammatory conditions, particularly those affecting the mouth and throat. The mechanism of action of benzydamine consists of the inhibition of prostaglandin synthesis, contributing to the reduction in pain and swelling (anti-inflammatory and analgesic) [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThree studies evaluated the activity of benzydamine, two including patients undergoing chemotherapy and one including patients undergoing radiotherapy. Only one study [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e] found benzydamine hydrochloride to be superior in the prevention and treatment of OM in patients undergoing chemotherapy.\u003c/p\u003e \u003cp\u003eChlorhexidine is a potent antiseptic agent that acts against a broad spectrum of bacteria, both gram-positive and gram-negative. The compound is often incorporated in oral health products because of its effectiveness in reducing plaque formation and in treating gingivitis [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. Due to its bactericidal and bacteriostatic activity, chlorhexidine is frequently used in hospital environments for skin disinfection before surgical procedures [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eChlorhexidine is the most widely used and recommended mouthwash for patients undergoing cancer treatment because of its bactericidal, fungicidal, and virucidal properties. Six studies analyzed chlorhexidine; of these, one study investigated patients undergoing radiotherapy, one study examined patients undergoing chemotherapy and radiotherapy, and four studies investigated patients undergoing chemotherapy. However, chlorhexidine was not superior in any of these studies when compared to other compounds [\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e, \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e, \u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e]. It is important to note that one study [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e] comparing the efficacy of sodium bicarbonate solution and chlorhexidine in the oral care of patients during induction chemotherapy found the former to be more effective than chlorhexidine mouthwash, reinforcing that the indication of mouthwashes must be well assessed by the patient\u0026rsquo;s care team.\u003c/p\u003e \u003cp\u003ePropolis is a resin collected by bees from different plants to protect the hive. This resin has antimicrobial, anti-inflammatory, antioxidant, and anticarcinogenic properties; it is therefore a product with different therapeutic applications [\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e, \u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e, \u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e]. The history of propolis use extends into traditional medicine, where it is used to boost immunity and to treat different infections and inflammatory conditions.\u003c/p\u003e \u003cp\u003eOnly one study evaluated the effectiveness of propolis [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e] and found that it reduced chemotherapy-induced OM. The results showed that the use of propolis as a mouthwash was effective in reducing OM and in improving the oral health of patients.\u003c/p\u003e \u003cp\u003eThe methods used in the studies varied widely in terms of study design, active ingredients in the mouthwashes, and substances used for comparison. It is important to note that most studies observed a reduction in OM in patients with different types of cancer despite the wide variety of chemotherapy drugs and doses administered. In some studies, the authors included patients with diverse diseases that required different antineoplastic treatments, a fact that may interfere with the development and severity of OM and OPM (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEfficacy of medications in the studies analyzed\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBenzydamine (3 articles)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChitapanarux et al. [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAhmed [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eShowed efficacy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGupta et al. [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eShowed efficacy \u0026ndash; \u003c/p\u003e \u003cp\u003eno severe mucositis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003ePropolis (1 article)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAkhaven-Karbassi et al. [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eShowed efficacy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eChlorhexidine (5 articles)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAfrasiabifar et al. [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eMehdipour et al. [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eChoi and Kim [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDid not show efficacy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMadan et al. [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eSantaella et al. [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDid not show efficacy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy and radiotherapy (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGupta et al. [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDid not show efficacy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAllopurinol (4 articles)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLoprinzi et al. [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eShabanloei et al. [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/p\u003e \u003cp\u003ePanahi et al. [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDid not show efficacy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbassi-Nazari et al. [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEfficacy after 3 weeks\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eSource: The authors (2024)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBenzydamine was shown to be superior to sodium bicarbonate in preventing chemo/radiotherapy-induced OM [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. On the other hand, sodium bicarbonate mouthwash was more effective than chlorhexidine in the oral care of patients with acute leukemia during induction chemotherapy [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe diversity of interventions explored reflects the complexity of mucositis and highlights the importance of multifaceted approaches to the treatment and prevention of OM in cancer patients. Regarding the results obtained, most studies provided qualitative data on the improvement of OM with the use of mouthwashes. However, the lack of standardization impairs the direct comparison of studies and the determination of the relative efficacy of mouthwashes. It is noteworthy that the studies evaluated did not identify important adverse effects of the interventions implemented for the prevention or treatment of OM and OPM.\u003c/p\u003e \u003cp\u003eRegarding limitations, all studies provided incomplete information, including a lack of details about randomization, possible conflicts of interest, and a clear description of the study design. These limitations can affect the interpretation of the results and the risk of bias in the studies. There is also the possibility that studies reporting negative results, especially small ones, have not been published.\u003c/p\u003e \u003cp\u003eThe studies provided valuable information on different strategies to prevent and treat OM in cancer patients and thus contribute to the development of more effective approaches using the substances described that can improve the quality of life of patients undergoing antineoplastic treatment. These substances are easily accessible at public or private hospitals and do not require the recruitment of additional technical staff for their use.\u003c/p\u003e \u003cp\u003eLimitations must be considered when interpreting and comparing the results of the studies. Further studies with a robust design that provide more detailed information about the results are needed to obtain stronger scientific evidence.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eMouthwashes containing chlorhexidine or allopurinol were not effective in preventing and treating OM. Benzydamine and propolis show promising results in the prevention and treatment of OM in patients undergoing cancer treatment. The use of benzydamine and propolis can contribute to improving the patient\u0026rsquo;s quality of life and to reducing the negative impacts of mucositis during antineoplastic treatment. Services should consider the possibility of incorporating these medications since, in most cases, they are low cost and do not require specialized staff in their use.\u003c/p\u003e \u003cp\u003eSome studies did not find significant differences between intervention groups, indicating the complexity of OM and the need of multifaceted assessment for its management. The complexity of this condition and the diversity of studies highlight the importance of further comprehensive and standardized investigations to provide more consistent evidence and to support clinical decisions. There is continued need to improve mucositis prevention and treatment strategies, including the development of personalized and effective approaches to improve the well-being of cancer patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eFernanda Pereira Delgado Costa and Maria Luisa Leandro de Souza Dias participated in the data collection, literature review, methodology, analysis and discussion of the data and drafting the article.Karla Em\u0026iacute;lia Rodrigues participated in the analysis and discussion of data, drafting and correction of the article.Lucas Guimar\u0026atilde;es Abreu participated Study conception and design , acquisition of data , drafting of manuscript and correction of the article.Tarc\u0026iacute;lia Aparecida Silva and Denise Vieira Travassos devised directed and coordinated the study, participated in the analysis and discussion of data, drafting and correcting the article.All authors critically revised the manuscript, approved the final version to be published, and agree to be accountable for all aspects of the work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePulito C, Cristaudo A, Porta CL, Zapperi S, Blandino G, Morrone A, Strano S (2020) Oral mucositis: the hidden side of cancer therapy. 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Reports of Practical Oncology \u0026amp; Radiotherapy 25(6):969\u0026ndash;973. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.rpor.2020.09.012\u003c/span\u003e\u003cspan address=\"10.1016/j.rpor.2020.09.012\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Antiseptic Mouthrinse, Mouthwash, Mucositis, Systematic Review","lastPublishedDoi":"10.21203/rs.3.rs-4644677/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4644677/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe aim of this study was to conduct a systematic review of randomized clinical trials in order to assess the efficacy of the following mouthwashes recommended for the prevention and treatment of OM and OPM in patients undergoing cancer treatment: chlorhexidine, allopurinol, benzydamine, and propolis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe following research question was formulated based on the PICOS strategy: \u0026ldquo;Are chlorhexidine, allopurinol, benzydamine and propolis mouthwashes effective in preventing and treating OM and OPM in patients undergoing cancer treatment?\u0026rdquo; Searches were performed in PubMed, Embase, Scopus, and Web of Science, without publication year or language restrictions. Randomized clinical trials comparing the use of chlorhexidine, allopurinol, benzydamine and propolis with a control group not submitted to any intervention were included. The retrieved articles were analyzed and selected by two reviewers and disagreements were resolved by consultation with a third reviewer. After data extraction, two evaluators independently analyzed the methodological quality of the studies using the Cochrane tool.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAfter evaluation of the works, 13 of 1183 articles were selected. mouthwashes containing propolis and benzydamine mouthwashes were promising and effective while chlorhexidine or allopurinol did not provide satisfactory results.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eMouthwashes could be an alternative for treatment or preventing oral mucositis in cancer patients Services could consider the possibility of incorporating these medications since, in most cases, they are low cost and donot require specialized staff in their use.\u003c/p\u003e","manuscriptTitle":"Mouthwashes used in patients with oral and oropharyngeal mucositis: A systematic review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-26 16:53:20","doi":"10.21203/rs.3.rs-4644677/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"42ee2b7b-0fb9-460f-b60f-180450cc856b","owner":[],"postedDate":"July 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-19T23:55:22+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-26 16:53:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4644677","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4644677","identity":"rs-4644677","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}