title: The efficacy and safety of probiotics in people with cancer: a systematic review.
abstract: BACKGROUND
  Probiotics are living microorganisms that are generally thought of as being beneficial to the recipient. They have been shown to be effective in people with acute infectious diarrhoea, and cost-effective in antibiotic-associated diarrhoea. Probiotics may have a role in people with cancer, as various cancer treatments often lead to diarrhoea. However, as people with cancer are often immunocompromised, it is important to assess for adverse events (AEs) such as infection, which could potentially be a consequence of deliberate ingestion of living microorganisms.
  
  
  METHODS
  A systematic review was carried out to collect, analyse and synthesise all available data on the efficacy and safety of probiotics in people with cancer (PROSPERO registration: CRD42012003454). Randomised, controlled trials, identified through screening multiple databases and grey literature, were included for analysing efficacy, while all studies were included for the analysis of safety of probiotics. Primary outcomes were the reduction in duration, severity and incidence of antibiotic-associated diarrhoea and chemotherapy-associated diarrhoea, and AEs, especially probiotic-associated infection. Where possible, data were combined for meta-analysis by a random-effects model, assessing causes of heterogeneity, including differences in strains, dosage and patient characteristics.
  
  
  RESULTS
  Eleven studies (N = 1557 participants) were included for assessing efficacy. Results show that probiotics may reduce the severity and frequency of diarrhoea in patients with cancer and may reduce the requirement for anti-diarrhoeal medication, but more studies are needed to assess the true effect. For example comparing probiotic use to control 25 groups on effect on Common Toxicity Criteria ≥2 grade diarrhoea, odds ratio (OR) = 0.32 [95% confidence interval (CI) of 0.13-0.79; P = 0.01]. Seventeen studies (N = 1530) were included in the safety analysis. Five case reports showed probiotic-related bacteraemia/fungaemia/positive blood cultures.
  
  
  CONCLUSIONS
  Probiotics may be a rare cause of sepsis. Further evidence needs to be collated to determine whether probiotics provide a significant overall benefit for people with cancer.
authors.affiliation: Hull York Medical School, York; Centre for Reviews and Dissemination, York. Electronic address: melody.redman@hyms.ac.uk.
authors.forename: M G
authors.initials: MG
authors.lastname: Redman
authors.affiliation: Department of Paediatric Oncology and Haematology, Leeds General Infirmary, Leeds; Paediatric Dietetic Department, Leeds General Infirmary, Leeds, UK.
authors.forename: E J
authors.initials: EJ
authors.lastname: Ward
authors.affiliation: Centre for Reviews and Dissemination, York; Department of Paediatric Oncology and Haematology, Leeds General Infirmary, Leeds.
authors.forename: R S
authors.initials: RS
authors.lastname: Phillips
mesh_terms: D003362:Cost-Benefit Analysis; D003967:Diarrhea / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D019936:Probiotics / Q000009:adverse effects* / Q000627:therapeutic use; D018805:Sepsis / Q000139:chemically induced* / Q000453:epidemiology
keywords: cancer; diarrhoea; health care-associated infection; probiotics; systematic review