title: Risk of infections in renal cell carcinoma (RCC) and non-RCC patients treated with mammalian target of rapamycin inhibitors.
abstract: BACKGROUND
  Mammalian target of rapamycin (mTOR) inhibitors are used in a variety of malignancies. Infections have been reported with these drugs. We performed an up-to-date meta-analysis to further characterise the risk of infections in cancer patients treated with these agents.
  
  
  METHODS
  Pubmed and oncology conferences' proceedings were searched for studies from January 1966 to June 2012. Studies were limited to phase II and III randomised controlled trials (RCTs) of everolimus or temsirolimus reporting on cancer patients with adequate safety profiles. Summary incidences, relative risks (RRs), and 95% confidence intervals (CIs) were calculated.
  
  
  RESULTS
  A total of 3180 patients were included. The incidence of all-grade and high-grade infections due to mTOR inhibitors was 33.1% (95% CI, 24.5-43.0%) and 5.6% (95% CI, 3.8-8.3%), respectively. Compared with controls, the RR of all-grade and high-grade infections due to mTOR inhibitors was 2.00 (95% CI, 1.76-2.28, P<0.001) and 2.60 (95% CI, 1.54-4.41, P<0.001), respectively. Subgroup analysis found no difference in incidences or risks between everolimus and temsirolimus or between different tumour types (renal cell carcinoma (RCC) vs non-RCC). Infections included respiratory tract (61.7%), genitourinary (29.4%), skin/soft tissue (4.2%), and others (4.9%).
  
  
  CONCLUSIONS
  Treatment with mTOR inhibitors is associated with a significant increase in risk of infections. Close monitoring for any signs of infections is warranted.
authors.affiliation: Department of Pharmacy, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Kaymakcalan
authors.forename: Y
authors.initials: Y
authors.lastname: Je
authors.forename: G
authors.initials: G
authors.lastname: Sonpavde
authors.forename: M
authors.initials: M
authors.lastname: Galsky
authors.forename: P L
authors.initials: PL
authors.lastname: Nguyen
authors.forename: D Y C
authors.initials: DY
authors.lastname: Heng
authors.forename: C J
authors.initials: CJ
authors.lastname: Richards
authors.forename: T K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000453:epidemiology; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D006801:Humans; D007239:Infections / Q000139:chemically induced* / Q000453:epidemiology* / Q000209:etiology; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012307:Risk Factors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases