Interventions for treating oral mucositis for patients with cancer receiving treatment

Treatment of cancer is increasingly effective but associated with short and long-term side effects. Oral side effects, including oral mucositis (mouth ulceration), remain a major source of illness despite the use of a variety of agents to treat them.

To assess the effectiveness of interventions for treating oral mucositis or its associated pain in patients with cancer receiving chemotherapy and/or radiotherapy.

Computerised searches of Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE and EMBASE were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information. Date of the most recent searches August 2003: (CENTRAL) (The Cochrane Library Issue 3, 2003).

All randomised controlled trials comparing agents prescribed to treat oral mucositis in people receiving chemotherapy and/or radiotherapy. Outcomes were oral mucositis, time to heal mucositis, oral pain, duration of pain control, dysphagia, systemic infection, amount of analgesia, length of hospitalisation, cost and quality of life.

Data were independently extracted, in duplicate, by two reviewers. Authors were contacted for details of randomisation, blindness and withdrawals. Quality assessment was carried out on these three criteria. The Cochrane Oral Health Group statistical guidelines were followed and relative risk values calculated using fixed effect models.

Twenty-five trials involving 1292 patients satisfied the inclusion criteria. Three agents, each in single trials, were found to be effective for improving (allopurinol RR 3.33, 95% CI 1.06 to 10.49; immunoglobulin RR 1.81, 95% CI 1.24 to 2.65; human placentral extract RR 4.50, 95% CI 2.29 to 8.86) or eradicating mucositis (allopurinol RR 19.00, 95% CI 1.17 to 307.63). Two of these trials were rated as at moderate risk of bias and one as at high risk of bias. The following agents were not found to be effective: benzydamine HCl, sucralfate, tetrachlorodecaoxide, chlorhexidine and 'magic' (lidocaine solution, diphenhydramine hydrochloride and aluminum hydroxide suspension). Six trials compared the time to heal and mucositis was found to heal more quickly with two interventions: Granulocyte Macrophage-Colony Stimulating Factor when compared to povidone iodine, with mean difference -3.5 days (95% CI -4.1 to -2.9) and allopurinol compared to placebo, with mean difference -4.5 days (95% CI -5.8 to -3.2). Three trials compared patient controlled analgesia (PCA) to the continuous infusion method for controlling pain. There was no evidence of a difference, however, less opiate was used per hour for PCA, and the duration of pain was shorter. One trial demonstrated that pharmacokinetically based analgesia (PKPCA) reduced pain compared with PCA, however more opiate was used with PKPCA.

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 (PCA) is better than continuous infusion method for controlling pain, however, less opiate was used per hour, and duration of pain was shorter, for PCA. 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.