title: Risk of oral and gastrointestinal mucosal injury in patients with solid tumors treated with everolimus, temsirolimus or ridaforolimus: a comparative systematic review and meta-analysis.
abstract: BACKGROUND
  The authors performed a systematic review and meta-analysis of diarrhea and stomatitis associated with the use of everolimus, temsirolimus or ridaforolimus in patients with solid tumors.
  
  
  METHODS
  Eligible studies included randomized trials of patients with solid tumors on everolimus, temsirolimus or ridaforolimus, describing the events of diarrhea and stomatitis.
  
  
  RESULTS
  After exclusion of ineligible studies, a total of 18 clinical trials including 8143 patients were considered eligible for the meta-analysis. The relative risk ratios of all-grade diarrhea and stomatitis were 1.94 (95% CI: 1.6-2.36; p < 0.00001) and 3.54 (95% CI: 2.59-4.84; p < 0.00001), respectively, while the relative risk ratios of high-grade diarrhea and stomatitis were 3.49 (95% CI: 2.39-5.09; p < 0.00001) and 6.98 (95% CI: 4.76-10.26; p < 0.00001), respectively. On subgroup analysis, there was no statistically significant difference between everolimus and temsirolimus in the risk of relevant adverse events.
  
  
  CONCLUSIONS
  This meta-analysis demonstrated that regimens containing everolimus, temsirolimus or ridaforolimus for the treatment of solid tumors are associated with a significantly increased risk of all-grade and high-grade diarrhea and stomatitis. Close clinical monitoring is required when administering these drugs.
authors.affiliation: Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Omar
authors.initials: O
authors.lastname: Abdel-Rahman
authors.forename: Mona
authors.initials: M
authors.lastname: Fouad
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D000068338:Everolimus / Q000009:adverse effects*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D009061:Mouth Mucosa / Q000187:drug effects* / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives*; D013280:Stomatitis / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; C515074:ridaforolimus; C401859:temsirolimus; D000068338:Everolimus; D020123:Sirolimus
keywords: diarrhea; everolimus; ridaforolimus; stomatitis; temsirolimus