Oral mucositis in cancer patients: no benefit from chlorhexidine mouthwash

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Chlorhexidine (CHX) is a topical antiseptic with bactericidal, fungicidal, and virucidal activities. In 2014 the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO)  advised against the use of CHX mouthwash for  oral mucositis (OM) prevention in patients having head and neck radiotherapy.  However evidence for CHX use in patients receiving chemotherapy or hematopoietic stem cell transplant was unclear.

This systematic review was to evaluate the effect of CHX in preventing and reducing the severity of OM in patients with cancer undergoing radiation therapy, chemotherapy, or both, to provide a meta-analysis of the evidence to the OM community, particularly for chemotherapy or hematopoietic stem cell transplant patients.


Searches were conducted in the Medline, Cochrane Library and Web of Science databases. Randomised controlled trials (RCTs) on the efficacy of CHX compared to placebo group for treating oral mucositis in cancer patients treated with chemotherapy, radiotherapy, or both, and at least one oral mucositis outcome reported by trial authors (severity of mucositis and/or incidence of mucositis) were considered.

3 reviewers independently selected studies abstracted data and assessed study quality using the Cochrane risk of bias tool. The primary outcome was the incidence of oral mucositis. Meta-analyses were conducted for incidence of mucositis (Risk ratios [RR] with 95% CIs) and severity of mucositis (Standardized differences in means [SDM] with 95% confidence intervals).


  • 12 RCTs were included
  • 8 studies were considered to have a high risk of bias
  • 9 studies contributed to the meta-analysis
  • Meta-analysis found
    •  CHX did not significantly reduce incidence of mucositis compared to the placebo  RR = 0.655 (95%CI; 0.379–1.131) P = 0.129 ( 5 studies)
    • CHX did significantly reduce the severity of mucositis SDM = 0.358 (95%CI;0.818 to 0.101) P = 0.127  8 studies)


The authors concluded

CHX is not significantly effective in reducing the severity of mucositis (moderate quality of evidence) nor significantly effective in preventing oral mucositis (low quality of evidence). However, more studies are needed in patients receiving chemotherapy only, as a positive trend toward significance was found (P = 0.054). Reversible side effects reported included teeth and tongue staining, and alteration in taste perception. In conclusion, although clinically CHX is a therapy that may be routinely used or recommended in cancer patients with OM, the current evidence does not support the routine prescription and cost of CHX for the prevention or treatment of OM until further studies are performed.


This question has been addressed by two Cochrane reviews (Clarkson et al 2010, and Worthington et al 2011) which focused more broadly on interventions to prevent and treat oral mucositis. The Worthington review addressed prevention finding that no evidence of benefit for CHX compared to either placebo or no treatment based on 9 RCTS involving more than 650 patients.  The treatment review (Clarkson et al 2010) only included 1 trial comparing chlorhexidine versus salt and soda and finding no statistically significant difference.

It is worth noting that none of the trials included in this current review were published after these Cochrane reviews and that the Cochrane reviews are being updated in in liaison with the Mucositis Study Group (MSG) of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO).  The first one of these reviews (Dental Elf – 11th Jan 2016 )  has demonstrated that oral cryotherapy leads to large reductions in oral mucositis of all severities in adults receiving fluorouracil-based (5FU) chemotherapy


Primary paper

Cardona A, Balouch A, Abdul MM, Sedghizadeh PP, Enciso R. Efficacy of chlorhexidine for the prevention and treatment of oral mucositis in cancer patients: a systematic review with meta-analyses. J Oral Pathol Med. 2017 Jan 11.doi: 10.1111/jop.12549. [Epub ahead of print] Review. PubMed PMID: 28075506.

Other references

Clarkson JE, Worthington HV, Furness S, McCabe M, Khalid T, Meyer S. Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochrane Database of Systematic Reviews 2010, Issue 8. Art. No.: CD001973. DOI: 10.1002/14651858.CD001973.pub4.

Worthington HV, Clarkson JE, Bryan G, Furness S, Glenny AM, Littlewood A, McCabe MG, Meyer S, Khalid T. Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database of Systematic Reviews 2011, Issue 4. Art. No.: CD000978. DOI: 10.1002/14651858.CD000978.pub5.

Dental Elf – 11th Jan 2016

Oral cryotherapy reduces oral mucositis in patients receiving 5FU-based treatment for solid cancers

Dental Elf – 25th Sep 2014

Low level laser therapy: review suggests it reduces mucositis in patients undergoing cancer treatment

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