title: Role of Gemcitabine and Pemetrexed as Maintenance Therapy in Advanced NSCLC: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
abstract: BACKGROUND
  Gemcitabine and pemetrexed have been used as maintenance therapy. However, few systematic reviews and meta-analyses have assessed their effects in the newest studies. This systematic review and meta-analysis were conducted to assess the role of gemcitabine and pemetrexed in the maintenance treatment of non-small-cell lung carcinoma (NSCLC).
  
  
  METHODS
  We performed a literature search using PubMed, EMBASE and Cochrane library databases from their inceptions to September 16, 2015. We also searched the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and National Comprehensive Cancer Network (NCCN) databases from 2008 to 2015. Two authors independently extracted the data. The Cochrane Collaboration's risk of bias graph was used to assess the risk of bias. The GRADE system was used to assess the grading of evidence, and a meta-analysis was conducted using Stata 11.0 software.
  
  
  RESULTS
  Eleven randomized controlled trial (RCT) studies were collected. Ten studies were included in the meta-analysis and divided into the following 4 groups: gemcitabine vs. best supportive care (BSC)/observation, pemetrexed vs. BSC/placebo, pemetrexed + bevacizumab vs. bevacizumab and pemetrexed vs. bevacizumab. Gemcitabine exhibited significantly improved progression-free survival (PFS) compared with BSC (hazard ratio (HR) = 0.62, p = 0.000). Pemetrexed exhibited significantly improved PFS (HR = 0.54, p = 0.000) and OS (HR = 0.75, p = 0.000) compared with BSC. Pemetrexed + bevacizumab almost exhibited significantly improved PFS (HR = 0.71, p = 0.051) compared with bevacizumab. Pemetrexed exhibited no improvement in PFS or overall survival (OS) compared with bevacizumab. Regarding the grade, the GRADE system indicated that the gemcitabine group was "MODERATE", the pemetrexed group was "HIGH", and both the pemetrexed + bevacizumab vs. bevacizumab groups and pemetrexed vs. B groups were "LOW".
  
  
  CONCLUSIONS
  Gemcitabine or pemetrexed compared with BSC/observation/placebo significantly improved PFS or OS. Whether pemetrexed + bevacizumab compared with bevacizumab alone significantly improves PFS requires further investigation.
authors.affiliation: Department of Oncology, Nanchong Central Hospital (The Second Clinical College of North Sichuan Medical College), Nanchong, China.
authors.forename: Xingsheng
authors.initials: X
authors.lastname: Hu
authors.affiliation: DaZhou College of Chinese Medicine, DaZhou, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Pu
authors.affiliation: Department of Oncology, Nanchong Central Hospital (The Second Clinical College of North Sichuan Medical College), Nanchong, China.
authors.forename: Xuqin
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Oncology, Nanchong Central Hospital (The Second Clinical College of North Sichuan Medical College), Nanchong, China.
authors.forename: Shimin
authors.initials: S
authors.lastname: Wen
authors.affiliation: Department of Oncology, Nanchong Central Hospital (The Second Clinical College of North Sichuan Medical College), Nanchong, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Oncology, Nanchong Central Hospital (The Second Clinical College of North Sichuan Medical College), Nanchong, China.
authors.forename: Cuihua
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Cardiothoracic Surgery, Nanchong Central Hospital, Nanchong, China.
authors.forename: Wenwu
authors.initials: W
authors.lastname: He
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D000068437:Pemetrexed / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D000068437:Pemetrexed; D003841:Deoxycytidine; D000093542:Gemcitabine