title: A meta-analysis of pemetrexed-based doublet compared with pemetrexed alone for the second-line treatment of advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  This meta-analysis investigated pemetrexed-based doublet compared with pemetrexed alone as second-line therapy for patients with advanced non-small cell lung cancer.
  
  
  METHODS
  Randomized controlled trials which compared pemetrexed-based doublet with single-agent pemetrexed in patients as second-line treatment of advanced non-small cell lung cancer were searched. Overall survival (OS) was the primary end point, while secondary end points included progression-free survival, overall response rate, 1-year survival rate, and grade 3 or 4 toxicity.
  
  
  RESULTS
  Four eligible randomized clinical trials including 1,084 patients were selected. Meta-analysis demonstrated that pemetrexed-based doublet arm significantly improved the overall response rate (OR=2.70, 95% CI: 1.76-4.15, p=0.000), compared with docetaxel alone group, while there were no significant differences in overall survival (HR=0.88, 95% CI: 0.74-1.04, p=0.132), progression-free survival (HR=0.91, 95% CI: 0.73-1.15, p=0.443), and 1-year survival rate (OR=1.43, 95% CI: 0.85-2.40, p=0.178) between the two arms. However, there were more frequencies of grade 3-4 leucopenia (OR=2.86, 95% CI: 1.32-6.20, p=0.008), neutropenia (OR=2.69, 95% CI: 1.55-4.68, p=0.000) and thrombocytopenia (OR=6.92, 95% CI: 2.51-19.07, p=0.000) in pemetrexed-based doublet group. Grade 3-4 anemia (OR=0.62, 95% CI: 0.33-1.18, p=0.144) and fatigue (OR=1.15, 95% CI: 0.73-1.79, p=0.550) had equivalent incidences in the two groups.
  
  
  CONCLUSIONS
  This is the first meta-analysis to compare pemetrexed-based doublet with single-agent pemetrexed in second-line therapy of non-small cell lung cancer. Our meta-analysis suggested that pemetrexed combination chemotherapy was not superior to single-agent arm and was not recommended as the second-line chemotherapy for patients with non-small cell lung cancer (Tab. 2, Fig. 6, Ref. 20).
authors.forename: C T
authors.initials: CT
authors.lastname: Sun
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: W
authors.initials: W
authors.lastname: Sheng
authors.forename: X W
authors.initials: XW
authors.lastname: Wang
authors.forename: S L
authors.initials: SL
authors.lastname: Wen
authors.forename: J Q
authors.initials: JQ
authors.lastname: Han
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018450:Disease Progression; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000068437:Pemetrexed; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine