Interventions for preventing oral mucositis for patients with cancer receiving treatment.

Background: Treatment of cancer is increasingly more effective but is associated with short and long-term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. One of these side effects is oral mucositis (mouth ulcers).

Objectives: To evaluate the effectiveness of prophylactic agents for oral mucositis in patients with cancer receiving treatment, compared with other potentially active interventions, placebo or no treatment.

Search Strategy: The Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched. Reference lists from relevant articles were scanned and the authors of eligible studies were contacted to identify trials and obtain additional information. Date of most recent searches: April 2004.

Selection Criteria: Trials were selected if they met the following criteria: design - random allocation of participants; participants - anyone with cancer receiving chemotherapy or radiotherapy treatment for cancer; interventions - agents prescribed to prevent oral mucositis; outcomes - prevention of mucositis, pain, amount of analgesia, dysphagia, systemic infection, length of hospitalisation, cost and patient quality of life.

Data Collection And Analysis: Information regarding methods, participants, interventions and outcome measures and results were independently extracted, in duplicate, by two review authors. Authors were contacted for details of randomisation and withdrawals and a quality assessment was carried out. The Cochrane Oral Health Group statistical guidelines were followed and risk ratios (RR) calculated using random-effects models.

Main Results: Two hundred and two studies were eligible. One hundred and thirty two were excluded for various reasons, usually as there was no useable information on mucositis. Of the 71 useable studies all had data for mucositis comprising 5217 randomised patients. Interventions evaluated were: acyclovir, allopurinol mouthrinse, aloe vera, amifostine, antibiotic pastille or paste, benzydamine, beta carotene, calcium phosphate, camomile, chlorhexidine, clarithromycin, folinic acid, glutamine, GM-CSF, honey, hydrolytic enzymes, ice chips, iseganan, keratinocyte GF, misonidazole, oral care, pentoxifylline, povidone, prednisone, propantheline, prostaglandin, sucralfate, traumeel and zinc sulphate. Of the 29 interventions included in trials, 10 showed some evidence of a benefit (albeit sometimes weak) for either preventing or reducing the severity of mucositis. Interventions where there was more than one trial in the meta-analysis finding a significant difference when compared with a placebo or no treatment were: amifostine which provided minimal benefit in preventing moderate and severe mucositis RR = 0.84 (95% confidence interval (CI) 0.75 to 0.95) and 0.60 (95% CI 0.37 to 0.97), antibiotic paste or pastille demonstrated a moderate benefit in preventing mucositis RR = 0.87 (95% CI 0.79 to 0.97), hydrolytic enzymes reduced moderate and severe mucositis with RRs = 0.52 (95% CI 0.36 to 0.74) and 0.17 (95% CI 0.06 to 0.52), and ice chips prevented mucositis at all levels RR = 0.63 (95% CI 0.44 to 0.91), 0.43 (95% CI 0.23 to 0.81), 0.27 (95% CI 0.11 to 0.68). Other interventions showing some benefit with only one study were: benzydamine, calcium phosphate, honey, oral care protocols, povidone and zinc sulphate. The number needed to treat (NNT) to prevent one patient experiencing moderate or severe mucositis over a baseline incidence of 60% for amifostine is 10 (95% CI 7 to 33), antibiotic paste or pastille 13 (95% CI 8 to 56), hydrolytic enzyme 4 (95% CI 3 to 6) and ice chips 5 (95% CI 3 to 19). When the baseline incidence is 40%/90% the NNTs for amifostine are 16/7, for antibiotic paste or pastille 19/7, for hydrolytic enzyme 5/3 and for ice chips 7/3. The general reporting of RCTs was poor. However, the assessments of the quality of the randomisation improved when the authors provided additional information.

Authors' Conclusions: Several of the interventions were found to have some benefit at preventing or reducing the severity of mucositis associated with cancer treatment. The strength of the evidence was variable and implications for practice include consideration that benefits may be specific for certain cancer types and treatment. There is a need for well designed and conducted trials with sufficient numbers of participants to perform subgroup analyses by type of disease and chemotherapeutic agent.