Abstract: We included 35 RCTs analysing 3102 participants. Thirteen studies were at low risk of bias, 12 studies were at unclear risk of bias, and 10 studies were at high risk of bias. Our main findings were regarding keratinocyte growth factor (KGF) and are summarised as follows. There might be a reduction in the risk of moderate to severe oral mucositis in adults receiving bone marrow/stem cell transplantation after conditioning therapy for haematological cancers (RR 0.89, 95% CI 0.80 to 0.99; 6 studies; 852 participants; low-quality evidence). We would need to treat 11 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 6 to 112). There might be a reduction in the risk of severe oral mucositis in this population, but there is also some possibility of an increase in risk (RR 0.85, 95% CI 0.65 to 1.11; 6 studies; 852 participants; low-quality evidence). We would need to treat 10 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 5 to prevent the outcome to 14 to cause the outcome). There is probably a reduction in the risk of moderate to severe oral mucositis in adults receiving radiotherapy to the head and neck with cisplatin or fluorouracil (RR 0.91, 95% CI 0.83 to 1.00; 3 studies; 471 participants; moderate-quality evidence). We would need to treat 12 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 7 to infinity). It is very likely that there is a reduction in the risk of severe oral mucositis in this population (RR 0.79, 95% CI 0.69 to 0.90; 3 studies; 471 participants; high-quality evidence). We would need to treat 7 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 5 to 15). It is likely that there is a reduction in the risk of moderate to severe oral mucositis in adults receiving chemotherapy alone for mixed solid and haematological cancers (RR 0.56, 95% CI 0.45 to 0.70; 4 studies; 344 participants; moderate-quality evidence). We would need to treat 4 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 3 to 6). There might be a reduction in the risk of severe oral mucositis in this population (RR 0.30, 95% CI 0.14 to 0.65; 3 studies; 263 participants; low -quality evidence). We would need to treat 10 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 8 to 19). Due to the low volume of evidence, single-study comparisons and insufficient sample sizes, we found no compelling evidence of a benefit for any other cytokines or growth factors and there was no evidence on children. There did not appear to be any serious adverse effects of any of the interventions assessed in this review. We are confident that KGF is beneficial in the prevention of oral mucositis in adults who are receiving: a) radiotherapy to the head and neck with cisplatin or fluorouracil; or b) chemotherapy alone for mixed solid and haematological cancers. We are less confident about a benefit for KGF in adults receiving bone marrow/stem cell transplant after conditioning therapy for haematological cancers because of multiple factors involved in that population, such as whether or not they received total body irradiation (TBI) and whether the transplant was autologous (the patients' own cells) or allogeneic (cells from a donor). KGF appears to be a relatively safe intervention. Due to limited research, we are not confident that there are 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.

Plain-language summary: 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. 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. 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.