title: Incidence and risk of treatment-related mortality in cancer patients treated with the mammalian target of rapamycin inhibitors.
abstract: BACKGROUND
  Inhibition of the mammalian target of rapamycin (mTOR) is an established treatment for multiple malignancies. We carried out an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in cancer patients treated with mTOR inhibitors.
  
  
  METHODS
  PubMed, conferences and clinicaltrials.gov databases were searched for articles reported from January 1966 to June 2012. Eligible studies were limited to approved mTOR inhibitors (everolimus and temsirolimus) and reported on patients with cancer, randomized design and adequate safety profiles. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
  
  
  RESULTS
  In all, 3193 patients from eight randomized, controlled trials (RCTs) were included, 2236 from everolimus trials and 957 from temsirolimus trials. The relative risk (RR) of FAEs related to mTOR inhibitors use was 2.20 (95% CI, 1.25-3.90; P = 0.006) compared with control patients. On subgroup analysis, no difference in the rate of FAEs was found between everolimus and temsirolimus or between tumor types [renal cell carcinoma (RCC) versus non-RCC]. No evidence of publication bias was observed.
  
  
  CONCLUSIONS
  The use of mTOR inhibitors is associated with a small but higher risk of FAEs compared to control patients. In the appropriate clinical scenario, the use of these drugs remains justified in their approved indications.
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: T K
authors: TK
authors: Choueiri
authors: Y
authors: Y
authors: Je
authors: G
authors: G
authors: Sonpavde
authors: C J
authors: CJ
authors: Richards
authors: M D
authors: MD
authors: Galsky
authors: P L
authors: PL
authors: Nguyen
authors: F
authors: F
authors: Schutz
authors: D Y
authors: DY
authors: Heng
authors: M D
authors: MD
authors: Kaymakcalan
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000401:mortality; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000401:mortality; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D012306:Risk; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: cancer; fatal adverse events; mTOR inhibitors; meta-analysis; renal cell carcinoma