Clarkson, J.E., Worthington, H.V., Furness, S., McCabe, M., Khalid, T., & Meyer, S. (2010). Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochrane Database of Systematic Reviews, 8, CD001973.

DOI Link

Purpose

To assess the effectiveness of interventions for treatment of oral mucositis or its associated pain for patients receiving chemotherapy or radiation therapy

Search Strategy

Databases searched were MEDLINE, CancerLIT, EMBASE, CINAHL, LILACS (Latin American and Caribbean Health Sciences Literature), Cochrane Oral Health Group and PaPaS Trials Registers, Cochrane Central Register of Controlled Trials (CENTRAL), OpenSIGLE, and Current Controlled Trials. Handsearching carried out by the Cochrane Collaboration was included. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information.

Search keywords were (neoplasm* OR leukemia OR leukaemia OR lymphoma* OR plasmacytoma OR “histiocytosis malignant” OR reticuloendotherliosis OR “sarcoma mast cell” OR “LettererSiwe disease” OR “immunoproliferative small intestine disease” OR “Hodkin disease”  OR “bone marrow transplant*” OR cancer* OR tumor* OR malignan* OR netropeni* OR carino* or Adenocarcinoma* OR radioth* OR radiat* OR radiochemo* OR irradiat* OR chemo*) AND (stomatitis OR “Stevnes Johnson syndrome” OR “candidiasis oral” OR mucositis OR (oral AND (cand* OR mucos* OR fung*)) OR mycosis OR mycotic OR thrush. Extensive appendices are provided with specific search strategies used for each database. 

Studies were included in the review if they  

  • Were randomized controlled trials using placebo, no treatment, or another active intervention.
  • Involved patients with cancer receiving chemotherapy or radiotherapy and experiencing oral mucositis.
  • Involved any intervention for the treatment of oral mucositis or its associated pain.
  • Written in any languages. Papers not in English were translated by members of the Cochrane collaboration.

Literature Evaluated

The final assessment incorporated 32 studies. Out of an initial 95 eligible studies, 64 were excluded because of study design issues, protocol violations, lack of useable data, or no relevant outcomes.

Sample Characteristics

  • The final set of studies involved a total of 1,505 patients; 1,023 patients were involved in trials investigating the effectiveness of agents to treat mucositis, and 718 patients were involved in trials evaluating pain relief. 
  • Sample sizes ranged from 6–71 patients per treatment or control group.
  • Twenty-eight trials included only adult patients, and four included only children.
  • Trials included patients treated for a combination of leukemia and solid tumors (n = 14), patients with head and neck cancer (n = 8), and patients who had received bone marrow or stem call transplant (n = 11).

Results

Treatment of mucositis

Summary of data from single trials showed the following interventions to demonstrate statistically significant benefit (p < 0.05).

  • Allopurinal mouthwash resulted in improvement in mucositis, eradication of mucositis in some cases, and reduction in time to healing.
  • Granulocyte macrophage-colony stimulating factor (GM-CSF) demonstrated mixed results, with two trials showing improved time to healing versus use of providone iodine and antimycotic mouthwash and one trial showing improvement in mucositis by the end of radiotherapy.
  • Human placental extract demonstrated improvement in mucositis in one trial.
  • Phenytoin mouthrinse was associated with better quality of life than placebo in one trial, but no benefit for pain was found and healing was not evaluated.
  • Polyvariant intramuscular immunoglobulin was associated with improvement in mucositis versus placebo in one trial.
  • Topical vitamin E was associated with improvement in mucositis and eradication of mucositis compared to systemic vitamin E in one trial.
  • Debridement was associated with fewer days to clinical resolution and decreased severity of mucositis, when compared to no debridement.
  • Laser treatment was beneficial in management of mild to moderate mucositis compared to sham treatment.

Other interventions for treatment of mucositis evaluated included chlorhexadine versus salt and soda, Gelclair verus sucralfate and mucaine,”Magic” mouthwash versus salt and soda, sucralfate versus placebo and versus salt and soda, and tetrachlorodecaoxide.

Management of pain with mucositis

The following interventions demonstrated statistically significant benefit in managing pain (p < 0.05).

  • Opiod use was associated with lower average pain scores when compared to antidepressant use.
  • Morphine pharmacokinetically patient controlled analgesia (PKPCA) was associated with lower average pain score than morphine standard patient controlled analgesia (PCA).
  • When morphine PCA was compared to continuous morphine infusion, meta-analysis showed no difference in mean pain scores; however, mean opiate intake was reduced with PCA, and PCA was associated with fewer days of pain.

Other findings

  • Interventions reviewed that showed no statistical benefit for treatment of mucositis included chlorhexadine, Gelclair, “Magic” mouthwash, and sucralfate.
  • Interventions reviewed for management of associated pain that demonstrated no statistical benefit included hydromorphone PCA versus morphine, Alfentanil versus morphine, Dicofenic versus placebo, PCA versus staff controlled, hypnosis, relaxation, and imagery.
  • Out of 27 different interventions evaluated for treatment of mucositis, only one comparison was significant for one outcome: low level laser treatment reduced the severity of mucositis.
  • No evidence was found to suggest a difference in pain control between continuous infusion and PCA; however, the PCA group required less morphine, and the pain lasted two less days.

Conclusions

  • Some evidence exists that low level laser treatment may help reduce severity of mucositis.
  • No evidence suggests that PCA is more effective than continuous infusion for controlling pain. Weak evidence is available to support that PCA is associated with less opiate used per hour and that the duration of pain may be reduced.
  • No clear benefit appears to be associated with antimicrobial use and GM-CSF for prevention or management of mucositis.
  • This review demonstrated weak and unreliable evidence of benefit for interventions for mucositis.

Limitations

The lack of independent duplication of studies investigating the same intervention limits the strength of evidence and ability to generalize results.

Most studies reviewed had small sample sizes and may have been underpowered to demonstrate significant differences in outcomes.

Different scoring systems for mucositis were used, and, in some studies, the method of scoring was not defined.

Nursing Implications

The need for further well-designed trials to evaluate the effectiveness of interventions continues.

Adoption of standard clinical outcome measures should be considered, including patient-based measures and inclusion of the cost of interventions.

Legacy ID

2255