title: Increased risk of severe infections in non-small-cell lung cancer patients treated with pemetrexed: a meta-analysis of randomized controlled trials.
abstract: Infections related to pemetrexed have been reported in clinical trials. It is not yet clear whether this drug increases infection risk or not. This meta-analysis assessed the overall incidence and risk of severe infections (≥ grade 3) associated with the use of pemetrexed in non-small-cell lung cancer patients.
  
  
  
  The databases of PubMed, Embase, and the Cochrane Library were searched for relevant studies published up to December 2015. Eligible studies included randomized controlled trials (RCTs) of pemetrexed for non-small-cell lung cancer patients that reported grade 3-5 infection and febrile neutropenia. Summary incidence rates, relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using either random-effects or fixed-effects models, according to the heterogeneity of the included studies.
  
  
  
  Seven randomized controlled trials were included, comprising 1848 patients. The incidence of severe infection and febrile neutropenia due to pemetrexed was 5.7% (95% CI: 3.2-8.3%) and 1.3% (95% CI: 0.7-2.0%), respectively. The use of pemetrexed was associated with an increased risk of severe infection (RR 1.61, 95% CI: 1.07-2.44, P = .02) and febrile neutropenia (RR 4.28, 95% CI: 1.08-17.01, P = .04).
  
  
  
  The use of pemetrexed was associated with an increased risk of developing severe infections and febrile neutropenia in non-small-cell lung cancer patients. Frequent clinical monitoring and management of infections should be emphasized during pemetrexed treatment. More studies are needed to reveal the mechanism of the increased risk of severe infections.
authors: a Department of Thoracic Surgery , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors: Song
authors: S
authors: Tong
authors: a Department of Thoracic Surgery , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors: Kai
authors: K
authors: Fan
authors: a Department of Thoracic Surgery , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors: Ke
authors: K
authors: Jiang
authors: a Department of Thoracic Surgery , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors: Wei
authors: W
authors: Zhai
authors: b Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors: Bin
authors: B
authors: Fang
authors: a Department of Thoracic Surgery , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors: Si-Hua
authors: SH
authors: Wang
authors: a Department of Thoracic Surgery , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors: Jian-Jun
authors: JJ
authors: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D000068437:Pemetrexed / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012306:Risk
chemical_list: D000970:Antineoplastic Agents; D000068437:Pemetrexed
keywords: Adverse events; Cancer; Infections; Meta-analysis; Pemetrexed