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).


OBJECTIVE
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.


METHODS
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: June 2006: CENTRAL (The Cochrane Library 2006, Issue 2).


METHODS
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.


METHODS
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 Collaboration statistical guidelines were followed and risk ratios (RR) calculated using random-effects models.


RESULTS
Two hundred and seventy-seven studies were eligible. One hundred and eighty-eight were excluded for various reasons, usually as there was no useable information on mucositis. Of the 89 useable studies all had data for mucositis comprising 7523 randomised patients. Interventions evaluated were: acyclovir, allopurinol mouthrinse, aloe vera, antibiotic pastille or paste, benzydamine, beta carotene, calcium phosphate, camomile, Chinese medicine, chlorhexidine, etoposide, folinic acid, glutamine, granulocyte/macrophage colony-stimulating factor (GM-CSF), histamine gel, honey, hydrolytic enzymes, ice chips, iseganan, keratinocyte GF, misonidazole, pilocarpine, pentoxifylline, povidone, prednisone, propantheline anticholinergic, prostaglandin, sucralfate, systemic antibiotic clarithromycin, traumeel, zinc sulphate. Of the 33 interventions included in trials, 12 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 mild and moderate mucositis RRs = 0.95 (95% confidence interval (CI) 0.92 to 0.98) and 0.88 (95% CI 0.80 to 0.98); Chinese medicine showed a benefit at all three dichotomies of mucositis with RR values of 0.44 (95% CI 0.20 to 0.96), 0.44 (95% CI 0.33 to 0.59) and 0.16 (95% CI 0.07 to 0.35) for increasing levels of mucositis severity; 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 RRs = 0.64 (95% CI 0.50 to 0.82), 0.38 (95% CI 0.23 to 0.62), and 0.24 (95% CI 0.12 to 0.48). Other interventions showing some benefit with only one study were: benzydamine, calcium phosphate, etoposide bolus, honey, iseganan, oral care, zinc sulphate. The general reporting of RCTs, especially concealment of randomisation, was poor. However, the assessments of the quality of the randomisation improved when the authors provided additional information.


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.
Worthington
H V
HV
School of Dentistry, University of Manchester, MANDEC, Higher Cambridge Street, Manchester, UK, M15 6FH. helen.worthington@manchester.ac.uk
Clarkson
J E
JE
Eden
O B
OB
D000935:Antifungal Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002180:Candidiasis, Oral / Q000209:etiology / Q000517:prevention & control*; D017679:Cryotherapy; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D006801:Humans; D007053:Ice; D009061:Mouth Mucosa; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D016032:Randomized Controlled Trials as Topic; D013280:Stomatitis / Q000209:etiology / Q000517:prevention & control*
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D007053:Ice