title: Duration of chemotherapy for advanced non-small-cell lung cancer: a systematic review and meta-analysis of randomized trials.
abstract: OBJECTIVE
  To determine if it is preferable to extend chemotherapy beyond a standard number of cycles in patients receiving first-line chemotherapy for advanced non-small-cell lung cancer.
  
  
  METHODS
  We searched biomedical literature databases and conference proceedings for randomized controlled trials (RCTs) comparing a defined number of cycles with continuation of the same chemotherapy until disease progression, a larger defined number of cycles of identical chemotherapy, and a defined number of cycles of identical initial chemotherapy followed by additional cycles of an alternative chemotherapy. Meta-analysis was performed using the fixed effect model. The primary outcome was overall survival (OS); secondary outcomes included progression-free survival (PFS), adverse events (AE), and health-related quality of life (HRQL).
  
  
  RESULTS
  We found 13 RCTs including 3,027 patients. Extending chemotherapy improved PFS substantially (hazard ratio [HR], 0.75; 95% CI, 0.69 to 0.81; P < .00001) and OS modestly (HR, 0.92; 95% CI, 0.86 to 0.99; P = .03). Subgroup analysis revealed that effects on PFS were greater for trials extending chemotherapy with third-generation regimens rather than older regimens (HR, 0.70 interaction v 0.92 interaction; P = .003). Extending chemotherapy was associated with more frequent AE in all trials where it was reported and impaired HRQL in two of seven trials.
  
  
  CONCLUSIONS
  Extending chemotherapy, particularly with a third-generation regimen, improved PFS substantially, but OS less so. Future trials should test extending treatment with more effective and/or better-tolerated agents.
authors.affiliation: Sydney Cancer Center, Royal Prince Alfred Hospital, National Health and Medical Research Council Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: Yu Yang
authors.initials: YY
authors.lastname: Soon
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stockler
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Askie
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Boyer
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004334:Drug Administration Schedule; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010146:Pain / Q000139:chemically induced; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome