Highlighted review: Interventions for preventing oral mucositis in patients with cancer receiving treatment: cytokines and growth factors

Philip Riley, Anne-Marie Glenny, Helen V Worthington, Anne Littlewood, Luisa M Fernandez Mauleffinch, Jan E Clarkson, Martin G McCabe

Plain language summary: Can cytokines and growth factors help prevent mouth soreness and ulcers (oral mucositis) in patients being treated for cancer?

Review question
This review has been produced to assess whether or not the use of cytokines and growth factors during cancer treatment, can help prevent mouth soreness and ulcers.

Background
Sore mouth and ulcers (oral mucositis) is a side effect of treatment for cancer including chemotherapy, head and neck radiotherapy, and targeted therapy, affecting over 75% of high-risk patients. Ulcers can lead to severe pain and difficulty with eating and drinking. Sufferers may need strong painkillers, possibly have to go into hospital and even be fed through a tube into their stomach or their veins.

These complications may disrupt their cancer therapy, meaning they are not receiving the best treatment, which may reduce survival. Cancer patients have weakened immune systems due to their treatment and are less able to fight infections. An ulcer is an open wound and there is a risk that bacteria can enter the body leading to infection or sepsis (a dangerous inflammatory reaction of the body to infection).

Mouth soreness and ulcers can be costly to healthcare systems, yet there are few preventive interventions or treatments proven to be beneficial. Cytokines and growth factors may help the regeneration of cells lining the mouth, thus preventing or reducing oral mucositis and its negative effects.

Study characteristics
Authors from Cochrane Oral Health carried out this review of existing studies and the evidence is current up to 10 May 2017. It includes 35 studies (published between 1993 and 2017) with 3102 participants, all patients being treated for cancer, aged from 1 to 87 years old.

Review authors included studies comparing cytokines and growth factors for the prevention of oral mucositis. The studies were carried out all over the world and often featured multiple sites, although most took place in high-income countries.

Main results
The main findings were regarding keratinocyte growth factor (KGF). KGF is likely to reduce the risk of oral mucositis in adults who are receiving either radiotherapy to the head and neck with chemotherapy (cisplatin or fluorouracil), or chemotherapy alone for mixed solid and blood cancers.

KGF may also reduce the risk of oral mucositis in adults receiving bone marrow/stem cell transplant after conditioning therapy for blood cancers, but these results are less clear because of multiple complicating factors. KGF appears to be a relatively safe intervention. There did not appear to be any serious adverse effects of any of the interventions assessed in this review.

Due to limited research, review authors are uncertain of any beneficial effects of other cytokines and growth factors. There is currently insufficient evidence to draw any conclusions about the use of cytokines and growth factors in children.

Quality of the evidence
For reducing oral mucositis in adults receiving radiotherapy to the head and neck with chemotherapy, review authors rated the evidence for KGF as moderate to high quality. For reducing oral mucositis in adults receiving chemotherapy alone for mixed solid and blood cancers, they rated the evidence for KGF as low to moderate quality. This evidence was downgraded due to there not being enough data and because some results have not yet been published.

For reducing oral mucositis in adults receiving bone marrow/stem cell transplant after conditioning therapy for blood cancers, they rated the evidence for KGF as low quality because results were not similar across the studies and some results have not yet been published. Evidence on side effects of KGF was poorly reported and inconsistent.

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Citation: Riley P, Glenny AM, Worthington HV, Littlewood A, Fernandez Mauleffinch LM, Clarkson JE, McCabe MG. Interventions for preventing oral mucositis in patients with cancer receiving treatment: cytokines and growth factors. Cochrane Database of Systematic Reviews 2017, Issue 11. Art. No.: CD011990. DOI: 10.1002/14651858.CD011990.pub2.