Allopurinol is a medication that is primarily used to treat gout and reduce uric acid levels. It prevents uric acid production by blocking activity of an enzyme that converts purines to uric acid. Allopurinol is an antagonist of some chemotherapeutic agents, and, as such, may reduce some effects. Allopurinol mouthwash has been evaluated in patients with cancer for its potential local effects in the prevention and management of mucositis.
Clarkson, J.E., Worthington, H.V., Furness, S., McCabe, M., Khalid, T., & Meyer, S. (2010). Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochrane Database of Systematic Reviews, 8, CD001973.
To assess the effectiveness of interventions for treatment of oral mucositis or its associated pain for patients receiving chemotherapy or radiation therapy
Databases searched were MEDLINE, CancerLIT, EMBASE, CINAHL, LILACS (Latin American and Caribbean Health Sciences Literature), Cochrane Oral Health Group and PaPaS Trials Registers, Cochrane Central Register of Controlled Trials (CENTRAL), OpenSIGLE, and Current Controlled Trials. Handsearching carried out by the Cochrane Collaboration was included. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information.
Search keywords were (neoplasm* OR leukemia OR leukaemia OR lymphoma* OR plasmacytoma OR “histiocytosis malignant” OR reticuloendotherliosis OR “sarcoma mast cell” OR “LettererSiwe disease” OR “immunoproliferative small intestine disease” OR “Hodkin disease” OR “bone marrow transplant*” OR cancer* OR tumor* OR malignan* OR netropeni* OR carino* or Adenocarcinoma* OR radioth* OR radiat* OR radiochemo* OR irradiat* OR chemo*) AND (stomatitis OR “Stevnes Johnson syndrome” OR “candidiasis oral” OR mucositis OR (oral AND (cand* OR mucos* OR fung*)) OR mycosis OR mycotic OR thrush. Extensive appendices are provided with specific search strategies used for each database.
Studies were included in the review if they
The final assessment incorporated 32 studies. Out of an initial 95 eligible studies, 64 were excluded because of study design issues, protocol violations, lack of useable data, or no relevant outcomes.
Treatment of mucositis
Summary of data from single trials showed the following interventions to demonstrate statistically significant benefit (p < 0.05).
Other interventions for treatment of mucositis evaluated included chlorhexadine versus salt and soda, Gelclair verus sucralfate and mucaine,”Magic” mouthwash versus salt and soda, sucralfate versus placebo and versus salt and soda, and tetrachlorodecaoxide.
Management of pain with mucositis
The following interventions demonstrated statistically significant benefit in managing pain (p < 0.05).
The lack of independent duplication of studies investigating the same intervention limits the strength of evidence and ability to generalize results.
Most studies reviewed had small sample sizes and may have been underpowered to demonstrate significant differences in outcomes.
Different scoring systems for mucositis were used, and, in some studies, the method of scoring was not defined.
The need for further well-designed trials to evaluate the effectiveness of interventions continues.
Adoption of standard clinical outcome measures should be considered, including patient-based measures and inclusion of the cost of interventions.
Kwong, K.K. (2004). Prevention and treatment of oropharyngeal mucositis following cancer therapy: Are there new approaches? Cancer Nursing, 27(3), 183–205.
Database searched was MEDLINE (1993–2003) for randomized, controlled trials evaluating mucositis interventions.
A total of 50 randomized controlled trials were presented. Other trials and papers were referenced.
The author concluded that most agents require more study.
The author noted the problem of variation in study protocols, insufficient sample sizes, and a lack of consensus regarding the scoring system for mucositis.
The author noted the need to include psychotherapeutic interventions and management and pointed out the lack of a quality-of-life tool for mucositis.
Stokman, M.A., Spijkervet, F.K., Boezen, H.M., Schouten, J.P., Roodenburg, J.L., & deVries, E. G. (2006). Preventive intervention possibilities in radiotherapy and chemotherapy-induced oral mucositis: Results of meta-analysis. Journal of Dental Research, 85, 690–700.
Databases searched were MEDLINE, EMBASE, and CINAHL (1966–2004).
Search keywords were [neoplasms] AND [(mucositis OR stomatitis)] AND [limit to (clinical trial OR randomized-controlled trials)].
Studies were included in the review if they were
The search yielded 109 publications. Of these, five were not aimed at prevention, 13 were nonrandomized, and 29 did not contain data in a comprehensive form. Seventeen articles stood alone in terms of intervention, and 45 articles included meta-analyses. Studies with zero or infinite odds ratios were omitted because variances could not be calculated with accuracy. Sample sizes ranged from 14–502.
Patients with various cancer diagnoses receiving chemotherapy, radiation therapy, or combination chemoradiotherapy.
Of the 27 interventions identified for the prevention of oral mucositis, meta-analysis could be performed on eight. Four interventions showed a preventive effect on the development or severity of oral mucositis: PTA (polymyxin E, tobramycine, and amphotericin B) lozenges or paste, systemic administration of granulocyte macrophage–colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF), oral cooling, and amifostine.
Of 14 studies (each on a different intervention type), nine showed some positive results; however, methodological flaws (e.g., small sample sizes, lack of double-blind or placebo-controlled designs) prevented those studies from demonstrating effectiveness. One study of benzydamine (Epstein et al., 2001) showed an improved ulcer-free rate and decreased incidence of ulcer and erythema.
Palifermin demonstrated positive results for the prevention of mucositis in patients with hematologic malignancies undergoing autologous stem cell transplantation.
Worthington, H.V., Clarkson, J.E., & Eden, O.B. (2004). Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochrane Database of Systematic Reviews (Online), 2, CD001973.
Database searched were Cochrane Oral Health Group's Trial Register, CENTRAL, MEDLINE, and EMBASE. Reference lists from relevant articles were searched, and the authors of eligible trials were contacted to identify trials and obtain additional information. Most recent search was conducted in August 2003.
A total of 25 randomized, controlled trials comparing agents prescribed to treat oral mucositis were evaluated.
In one trial of 44 patients, a mouthwash of 300 mg allopurinol dissolved in water was compared to placebo. Patients rinsed with the mouthwash for one minute, four to six times per day. The study showed improvement but had a moderate risk of bias and weak evidence.
In another study of 80 patients with head and neck cancer and radiation-induced mucositis, patients were given immunoglobulin (10 mL on day 0, 5 mL on day 2, 5 mL on day 4) or placebo of 10% human albumin given at the same dosages and times. Both groups received nystatin. Patients who received immunoglobulin showed improvement; however, evidence was weak.
According to the authors, “There is weak and unreliable evidence that allopurinol mouthwash, vitamin E, immunoglobulin, or human placental extract improve or eradicate mucositis. There is no evidence that patient-controlled analgesia is better than the continuous infusion method for controlling pain; however, less opiate was used per hour, and duration of pain was shorter for patient-controlled analgesia. Further, well-designed, placebo-controlled trials assessing the effectiveness of allopurinol mouthwash, immunoglobulin, human placental extract, other interventions investigated in this review and new interventions for treating mucositis are needed.”
Panahi, Y., Ala, S., Saeedi, M., Okhovatian, A., Bazzaz, N., & Naghizadeh, M. (2010). Allopurinol mouth rinse for prophylaxis of fluorouracil-induced mucositis. European Journal of Cancer Care, 19(3), 308–312.
To prepare and evaluate an allopurinol mouth rinse for prophylaxis of fluorouracil-induced mucositis
Allopurinol mouthwash (1 mg/ml) or placebo was administered 1, 2, and 3 hours after chemotherapy and three consecutive nights for 30 seconds. Patients were instructed to neither wash their mouths nor to eat and drink for 15 minutes afterward.
This was a single-site, outpatient study conducted in a clinic in Sari, Iran.
This was a placebo-controlled, double-blinded, randomized clinical trial.
An independent physician completed questionnaires consisting of demographic parameters, medical status, quality-of-life survey, and mucosal injury scoring table (based on World Health Organization [WHO] scales for mucositis).
No significant differences were found between the groups with regard to occurrence and severity of mucositis.
Because of compliance issues with the mouth rinse regimen, low concentration of the allopurinol in the rinse, and a small sample size, the treatment was deemed ineffective in prevention and severity of mucositis. Further studies are needed once the limitations are removed.