Chlorhexidine is an antiseptic that has a broad spectrum effect against both gram-positive and -negative bacteria. Chlorhexidine gluconate oral rinse, which contains glycerol, coloring, flavoring and other compounds, has been studied in patients with cancer for the prevention and treatment of mucositis. (Note: prophylactic use before development of mucositis has a different PEP category than the use of chlorhexidine in patients who already have mucositis symptoms.)
Nashwan, A. J. (2011). Use of chlorhexidine mouthwash in children receiving chemotherapy: A review of literature. Journal of Pediatric Oncology Nursing, 28, 295–299.
To evaluate the effectiveness of chlorhexidine mouthwash in children receiving chemotherapy
Databases searched were PubMed and ScienceDirect.
Search keywords were oral chlorhexidine, chemotherapy-induced mucositis/stomatitis, and pediatrics/children.
Studies were included in the review if they
Studies were excluded if they
Potting, C.M., Uitterhoeve, R., Scholte Op Reimer, W., & Van Achterberg, T. (2006). The effectiveness of commonly used mouthwashes for the prevention of chemotherapy-induced oral mucositis: A systematic review. European Journal of Cancer Care, 15, 431–439.
Databases searched were MEDLINE and CINAHL (1992 to fall 2004).
Search keywords were mucositis, stomatitis, and chemotherapy in combination with prevention, mouthwashes, antiseptic, oral infection, chlorhexidine, chamomile, povidone-iodine, and sodium bicarbonate.
Studies were included in the review if they
Seven studies met the criteria. Five investigated chlorhexidine, one investigated iodine mouthwash, and one investigated chamomile solution. All studies randomly allocated participants to either an intervention or a comparison group. One study assigned patients by stratified block randomization. Most studies used a placebo mouthwash or sterile water as a control.
Povidone-iodine was the only agent to show activity for preventing mucositis. Because of the effects of chlorhexidine (e.g., teeth discoloration, bitter taste, unpleasant sensations), the authors concluded that sterile water, 0.9% saline solution, or sodium bicarbonate all are better alternatives.
Shih, A., Miaskowski, C., Dodd, M. J., Stotts, N.A., & MacPhail, L. (2002). A research review of the current treatments for radiation-induced oral mucositis in patients with head and neck cancer. Oncology Nursing Forum, 29, 1063–1078.
Database searched was MEDLINE (1966–2001). Additional papers were found from reference lists.
Studies were included in the review if they were aimed at prevention, palliation, or reduction of radiation-induced oral mucositis in patients with head and neck cancer.
Studies were excluded if they were not in English.
More than 50 studies were included. Most were randomized, controlled trials; some were pilot or descriptive studies.
Sample sizes ranged from 10 to more than 200.
Based on the findings of studies conducted to date, no conclusions regarding the agents and their ability to decrease the severity of radiation-induced oral mucositis were possible. Results were inconsistent. The most effective measure to treat radiation-induced mucositis was frequent oral rinsing with a bland mouthwash such as saline or sodium bicarbonate. Consistent oral care, dental care, oral assessment, and standardized oral hygiene were the suggested approaches to managing oral mucositis. Sodium bicarbonate reduces the acidity of the oral fluids immediately; it also dilutes accumulating mucus and discourages yeast colonization.
Findings related to benzydamine were inconsistent. In a trial of chlorhexidine versus benzydamine, patients reported more discomfort with benzydamine and were more likely to discontinue participation in the trial. Chlorhexidine was not effective in reducing the severity of mucositis in three double-blind, placebo-controlled trials. Two trials that examined antimicrobial activity failed to show any significant effects on the suppression of any type of oral flora using chlorhexidine.
Dose variations in granulocyte macrophage colony-stimulating factor (subcutaneous) trials make it impossible to determine whether this agent has a role in the radiation setting.
Four studies investigated the effectiveness of using topical antibiotics with a more specific spectrum for gram-negative bacteria and yeast. Two placebo-controlled, randomized clinical trials, both with fewer than 100 patients, and one case-controlled study investigated the efficacy of amphotericin B (polymyxis E, tobramycin, and amphotericin B [PTA] lozenge) to reduce the severity of radiation-induced mucositis. One study examined tetracaine and antibiotics. Additional work is warranted to determine the effects of the PTA lozenge on mucositis severity, pain severity, and dysphagia. Results for the trial were promising; however, conclusions cannot be drawn because only one study examined tetracaine.
Additional investigation of immunoglobulin and povidone-iodine are recommended.
Worthington, H.V., Clarkson, J.E., Bryan, G., Furness, S., Glenny, A.M., Littlewood, A., … Khalid, T. (2011). Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database of Systematic Reviews (Online), 4(4), CD000978.
To evaluate the evidence for prophylactic agents in management of oral mucositis in patients with cancer receiving treatment
Databases searched were MEDLINE, CANCERLIT, Embase, CINAHL, Latin American and Caribbean Health Sciences Literature (LILACS), System for Information on Grey Literature in Europe (SIGLE), and the Cochrane Database.
An extensive list of search terms and strategies used per database was provided in the article.
Studies were included in the review if they
A total of 383 references were retrieved. Risk of bias was evaluated according to the Cochrane Handbook for Systematic Reviews of Interventions. Studies were categorized as low, unclear, or high risk of bias. Studies were labeled using the GRADES system for evaluating quality of evidence.
Findings support the benefits of cryotherapy and keratinocyte growth factor. The low quality of evidence in most of the other interventions points to the need for ongoing, well-designed research in this area. The presentation of findings in many publications made meta-analysis impossible.
The rationale for the authors' summaries of findings was not entirely clear. Similar RR ratio results with similar evidence quality levels were identified differently in terms of potential benefit. Although the review was inclusive and extensive, interpretation of results was inconsistent. High heterogeneity existed in most interventions, and most studies were either at high or unclear risk of bias with low GRADES scoring. Studies did not always differentiate between mucositis and candidiasis, which would affect recommendations.
This article suggests strong support for use of cryotherapy and keratinocyte growth factor for mucositis prevention. It suggests possible benefit from aloe vera, amifostine, IV glutamine, G-CSF, honey, laser, and antibiotic lozenges. Sucralfate may reduce the severity of mucositis. These findings should be interpreted with caution, given the relatively low quality of overall evidence and high heterogeneity across studies included in meta-analysis, as well as the fact that treatments and sample characteristics were highly varied.
Niscola, P., Scaramucci, L., Giovannini, M., Ales, M., Bondanini, F., Cupelli, L., et al. (2009). Palifermin in the management of mucositis in hematological malignancies: Current evidences and future perspectives. Cardiovascular & Hematological Agents in Medicinal Chemistry, 7, 305–312.
To review the role of palifermin and other current and potential treatments for chemotherapy-induced mucositis in the context of pathobiology in hematologic malignancies
Database searched was MEDLINE. Abstracts and published proceedings reporting the role of palifermin in the management of mucositis were reviewed.
Search keywords were MeSH headings for chemotherapy, cyclophosphamide, etoposide, GI mucositis, GVHD, hematology, hematological malignancies, hematopoeietic stem cell transplantation, hemorrhagic cystitis, HSCT, keratinocyte growth factor, KGF, leukemia, lymphoma, melphalan, methotrexate, mucositis, multiple myeloma, oncohematology, oral mucositis, pain, palifermin, radiation, radiotherapy, soreness, and total parenteral nutrition.
Palifermin in standard and high dose chemotherapy
Palifermin in autologous stem cell transplantation
Palfiermin in graft-versus-host disease
Other interventions for management of mucositis
Control of oral mucositis pain and provision of supportive therapy and regular assessment are critical management components.
This article provided information about various approaches in the management and prevention of oral mucositis in patients with hematologic malignancies and outlined the biologic mechanism of action and observed effects from review of the literature. However, it provided little information about the actual strength of evidence and is based on a limited literature search. No clear description of rationale for article inclusion was included.
The authors concluded that evidence supports the use of palifermin, but the article stated elsewhere that evidence in this area is insufficient in some patient groups, and only one nonrandomized study is cited where the duration of high-grade mucositis was shorter in patients who received palifermin, suggesting a biased view of the role of palifermin.
This article can provide useful information regarding the mechanism of action of various treatments, but it is not helpful in determining relative effectiveness of various interventions.
Peterson, D.E., Bensadoun, R.J., Roila, F., & ESMO Guidelines Working Group. (2010). Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines. Annals of Oncology, 21(Suppl. 5), v261–v265.
To summarize the evidence around the use of radiotherapy, standard-dose chemotherapy, and high-dose chemotherapy with or without total body irradiation plus hematopoietic stem cell transplantation (HSCT) for the management of mucositis
The primary author was the principal investigator on the National Institutes of Health (NIH) R13 Conference Grant that provided partial support for the symposium “Oral Complications of Emerging Cancer Therapies,” 14-15 April 2009, Bethesda, MD, USA. Production of a Journal of the National Cancer Institute (JNCI) Monograph for conference publications was supported by an unrestricted educational grant form Biovirum, which owned palifermin at the time of the publication. Peterson also is a member of the Scientific Advisory Board and a paid consultant for the GI Co., Inc, which is responsible for the development of recombinant intestinal trefoil factor, for which the phase II study is cited in the references.
The mucositis guidelines reported contain few changes from the previous two versions of the ESMO Clinical Practice Guidelines. With the 2009 MASCC/ISCO Mucositis Study Group in June 2009, it was decided that no new guidelines were warranted based on the current published literature. Progress has been made in the understanding of molecular basis of mucositis. Evidence-based, cancer-specific identification of risk factors and management of mucositis depend on clinical research so that approval of new drugs and devices will be possible.