title: Effectiveness and safety of pemetrexed-based doublet versus pemetrexed alone as second-line treatment for advanced non-small-cell lung cancer: a systematic review and meta-analysis.
abstract: BACKGROUND
  To compared pemetrexed-based doublet with single-agent pemetrexed as second-line treatment for advanced non-small-cell lung cancer
  
  
  METHODS
  We systematically searched for randomized clinical trials that compared pemetrexed-based doublet with single-agent pemetrexed in patients with histologically proven non-small-cell lung cancer. The primary end point was overall survival. Secondary end points were progression-free survival, overall response rate and grade 3 or 4 toxicity. Data were extracted from the studies by 2 independent reviewers. The meta-analysis was performed by Stata version 10.0 software (Stata Corporation, College Station, Texas, USA).
  
  
  RESULTS
  Five randomized clinical trials (totally 1,186 patients) were eligible. Meta-analysis showed that there was significant improvement in PFS (HR 0.82, 95% CI 0.71-0.95, P = 0.007) and overall response rate (OR 2.39, 95% CI 1.58-3.62, P = 0.000) in pemetrexed-based doublet group, compared with pemetrexed alone, though the pooled HR for overall survival (HR 0.89, 95% CI 0.76-1.04; P = 0.129) showed no significant difference between the two groups. However, there were more incidences of grade 3 or 4 neutropenia (OR 2.3, 95% CI 1.4-3.77, P = 0.001), thrombocytopenia (OR 6.41, 95% CI 2.57-16.0, P = 0.000), and leucopenia (OR 2.45, 95% CI 1.13-5.34, P = 0.024) in pemetrexed-based doublet group. With regard to the risk of grade 3 or 4 anemia (OR 0.71, 95% CI 0.17-2.91, P = 0.629) and fatigue (OR 1.47, 95% CI 0.92-2.35, P = 0.104), there was no significant difference between the two groups.
  
  
  CONCLUSIONS
  Pemetrexed-based doublet therapy didn't gain any benefit in survival but significantly improved PFS and better ORR compared with single-agent pemetrexed as second-line therapy for advanced non-small-cell lung cancer. However, more incidences of grade 3 or 4 neutropenia, thrombocytopenia, and leucopenia were observed in pemetrexed-based doublet group.
authors.affiliation: Department of Oncology, The Sixth People Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Wei-Xiang
authors.initials: WX
authors.lastname: Qi
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Tang
authors.forename: Ai-Na
authors.initials: AN
authors.lastname: He
authors.forename: Zan
authors.initials: Z
authors.lastname: Shen
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
mesh_terms: D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D005971:Glutamates / Q000008:administration & dosage* / Q000009:adverse effects*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000068437:Pemetrexed; D011787:Quality of Health Care; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine