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

BACKGROUND: Oral mucositis is a side effect of chemotherapy, head and neck radiotherapy, and targeted therapy, affecting over 75% of high-risk patients. Ulceration can lead to severe pain and difficulty with eating and drinking, which may necessitate opioid analgesics, hospitalisation and supplemental nutrition. These complications may disrupt cancer therapy, which may reduce survival. There is also a risk of death from sepsis if pathogens enter the ulcers of immunocompromised patients. Ulcerative oral mucositis can be costly to healthcare systems, yet there are few preventive interventions proven to be beneficial. Cytokines and growth factors may help the regeneration of cells lining of the mouth, thus preventing or reducing oral mucositis and its negative effects. OBJECTIVES: To assess the effects of cytokines and growth factors for preventing oral mucositis in patients with cancer who are receiving treatment. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (searched 10 May 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 4) in the Cochrane Library (searched 10 May 2017); MEDLINE Ovid (1946 to 10 May 2017); Embase Ovid (7 December 2015 to 10 May 2017); CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 10 May 2017); and CANCERLIT PubMed (1950 to 10 May 2017). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. SELECTION CRITERIA: We included parallel-design randomised controlled trials (RCTs) assessing the effects of cytokines and growth factors in patients with cancer receiving treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of electronic searches, extracted data and assessed risk of bias. For dichotomous outcomes, we reported risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, we reported mean differences (MD) and 95% CIs. We pooled similar studies in random-effects meta-analyses. We reported adverse effects in a narrative format. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer.

BACKGROUND: Treatment of cancer is increasingly effective, but associated with oral complications such as mucositis, fungal infections, bacterial infections and viral infections such as the herpes simplex virus (HSV). OBJECTIVES: To examine the effects of interventions for the prevention or treatment or both, of herpes simplex virus in patients receiving treatment for cancer. SEARCH STRATEGY: We searched the following databases: Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, CANCERLIT, SIGLE and LILACS. The reference list of all related review articles and articles considered to be potentially relevant were checked for further trials. Authors of identified trials and known specialists in the field were also contacted in an attempt to identify any additional published or unpublished trials. Date of most recent search: November 2008. SELECTION CRITERIA: All randomised controlled trials comparing interventions for the prevention or treatment or both of HSV infection in people being treated for cancer. Outcomes were presence/absence of clinical/culture positive HSV infections (prevention), time to complete healing of lesions (treatment), duration of viral shedding, recurrence of lesions, relief of pain, amount of analgesia, duration of hospital stay, cost of oral care, patient quality of life and adverse effects. DATA COLLECTION AND ANALYSIS: Data were independently extracted, in duplicate, by two review authors. Authors were contacted for details of randomisation, blindness and sample demographics where necessary. Quality assessment was carried out on randomisation, blindness, withdrawals and selective reporting. The Cochrane Collaboration's statistical guidelines were followed and risk ratio (RR) values were calculated using random-effects models. MAIN RESULTS: Seventeen trials satisfied the inclusion criteria. Four trials evaluated preventative interventions for HSV lesions, three trials for viral isolates, and eight trials evaluated both outcome measures. A single trial reported on the cost of prophylaxis for HSV. Two trials evaluating treatment reported on time to healing, duration of viral shedding and relief of pain. No trials reported on duration of hospital stay, amount of analgesia or patient quality of life.In placebo controlled trials, aciclovir was found to be effective for the prevention of HSV infections as measured by oral lesions or viral isolates (RR = 0.16, 95% confidence interval (CI) 0.08 to 0.31 nine trials; RR = 0.17, 95% CI 0.07 to 0.37 nine trials). There is no evidence that valaciclovir is more efficacious than aciclovir, or that higher doses of valaciclovir are more effective than lower doses. Placebo was found to be more effective than prostaglandin E for prevention of viral isolates (RR = 1.87, 95% CI 1.12 to 3.14 one trial).Aciclovir was also found to be effective for the treatment of HSV in terms of duration of viral shedding (median of 2.5 days versus 17.0 days, P = 0.0002; 2 days compared to more than 9, P = 0.0008), time to first decrease in pain (median 3 days compared to 16, P = 0.04), complete resolution of pain (9.9 days compared to 13.6 days, P = 0.01; median of 6 days compared to 16, P = 0.05), 50% healing (median of 6 days compared to 11, P = 0.01) and total healing (median 13.9 days compared to 20.7 days, P = 0.08; median of 8 days compared to 21, P = 0.0). AUTHORS' CONCLUSIONS: There is evidence that aciclovir is efficacious in the prevention and treatment of herpes simplex virus infections. There is no evidence that valaciclovir is more efficacious than aciclovir, or that a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence that as a prophylaxis, placebo is more efficacious than prostaglandin E. However, in all included trials, risk of bias is unclear.