Fifty-five articles were of acceptable methodological quality for inclusion, a further 46 papers of lower quality were included in the narrative summary where no better evidence on a topic existed.
Oral care protocols (n=4 controlled trials): At present, there is no convincing experimental evidence that any oral care protocols are effective in preventing or reducing mucositis.
Interventions which reduce the mucosal toxicity of chemotherapy drugs: The use of allopurinol mouthwash (n=3 controlled trials) is supported to prevent mucositis resulting from 5-fluoroucacil, although there was significant heterogeneity between studies (SMD=-0.40 (95% CI: -0.76,-0.04)). Cryotherapy (n=2 high quality trials) is a cheap and effective method of minimising mucositis, but patients may develop an aversion to the ice as a result of concurrent nausea from the chemotherapy.
Mouthwashes with mixed actions: There is no evidence to support the use of chamomile mouthwash (n=1 RCT) to prevent chemotherapy-induced mucositis. There is good evidence that benzydamine hydrochloride mouthwash (n=7 RCTs) is effective in ameliorating the symptoms of radiation-induced mucositis in patients with head and neck cancer. There is limited evidence in favour of corticosteroid mouthwash (no RCTs).
Immunomodulatory agents: One RCT indicated no significant effect of GM-CSF (Granulocyte-macrophage colony stimulating factor) and another small RCT indicated a beneficial effect of G-CSF (Granulocyte colony stimulating factor). Immunoglobin was reported to minimise mucositis in a clinical report and a controlled trial showed statistically significant reductions in mucositis extent and severity was unclear.
Topical anaesthetics: Their effectiveness has either not been evaluated, or the quality of studies was too poor for inclusion.
Antiseptics: This review does not support the use of chlorhexidine (n=9 RCTs) to prevent mucositis. The use of povidone lodine was supported in one uncontrolled study. There is no evidence supporting the use of hydrogen peroxide mouthwash (n=2 RCTs) to prevent radiation-induced mucositis.
Topical antimicrobial agents: Two RCTs showed a lack of effectiveness of combination mouthwashes containing nystatin on mucositis score, there was significant heterogeneity between the two studies. For clotrimazole and other combinations of topical agents including antifungals no studies were found that met the methodological quality criteria for the review. As yet there is no evidence relating to the efficacy of PTA lozenges in chemotherapy-treated patients.
Systemic antifungals: No conclusions about the effectiveness of prophylactic systemic fluconazole can be made.
Antiviral agents: It appears that prophylactic acyclovir (n=2 RCTs) may have some value in reducing oral lesions due to Herpes in susceptible patients, but that the majority of mucositis lesions do not involve a virus and therefore are not affected by this agent.
Mucosal barriers and coating agents: The evidence does not support the use of sucralfate (n=7 RCTs) to prevent or ameliorate mucositis in cancer patients. No comments can be made about the efficacy of other mucosal barriers. Cytoprotectants: More research is required to investigate the effectiveness of beta-carotene. Vitamin E (n=2 RCTs) had no significant effect on the duration of mucositis. Azelastine hydrochloride (n=1 RCT) significantly reduced the duration and severity of mucositis. The evidence does not support the use of prostaglandin E (n=3 RCTs) to prevent chemotherapy-induced mucositis, nor the use of oxpentifylline (n=1 RCT with cross-over design) to prevent mucositis in chemotherapy-patients.
Mucosal cell stimulants: Low energy laser (n=1 RCT) is of benefit in ameliorating the symptoms of mucositis in bone marrow transplant patients, but more research is required for non-transplanted cancer patients. Silver nitrate (n=2 RCTs) is of questionable value in preventing radiation-induced mucositis. There is limited evidence that glutamine (n=1 RCT) may be useful in reducing mucositis severity, but further research is required.
Psychotherapy (n=2 controlled trials) may be useful to minimise perceived oral pain, but does not affect objective mucositis ratings. Further research is required.
Analgesics (n=3 RCTs): The evidence indicates that morphine administration controlled by the patient is safe and effective for managing oral mucositis pain in cancer patients undergoing in bone marrow transplantation, and that a pharmacokinetically based system warrants further investigation.