title: Assessing the relative effectiveness and tolerability of treatments in small cell lung cancer: a network meta-analysis.
abstract: BACKGROUND
  The combination of Cisplatin plus Etoposide (EP) is currently the standard treatment for small cell lung cancer (SCLC). However, a large number of alternative treatments (monotherapies and combinations) have been studied in randomized controlled trials (RCTs) to identify more effective treatments. Aim of the present study was to assess the relative effectiveness and tolerability of these treatments.
  
  
  METHODS
  PubMed, EMBASE and Cochrane Central Register of Controlled Trials were systematically searched to identify all RCTs that compared treatments for SCLC. Then, effectiveness of the treatments relative to the combination of Cisplatin plus Etoposide, reference treatment) was estimated by performing a network of treatments analysis. The analysis evaluated two efficacy outcomes (complete response - CR and objective response rate - ORR) and two tolerability outcomes (neutropenia and febrile neutropenia). All RCTs that provided data for calculating the odds ratios (OR) for the selected outcomes were considered. The network analysis involved direct and indirect analyses.
  
  
  RESULTS
  We identified 71 articles eligible for inclusion, involving 91 different treatments. In total, 16,026 patients were included in the analysis. In the direct analysis the combination of Cisplatin plus Cyclophosphamide plus Etoposide plus Epirubicin showed better response than EP for the ORR outcome, but with worse tolerability (presence of neutropenia). The indirect analysis revealed that the combination of Cisplatin plus Doxorubicin plus Etoposide (plus Vincrisitine) showed better response that EP for the ORR outcome.
  
  
  CONCLUSIONS
  No therapy shows better response for the two efficacy outcomes (CR and ORR); though, Cisplatin plus Doxorubicin plus Etoposide plus Vincrisitine might be a promising therapy for SCLC. The results should be interpreted with caution because the network was dominated by indirect comparisons. Large scale head-to-head RCTs are needed to confirm the present findings.
authors.affiliation: Evidence-Based Medicine Unit, Department of Biomathematics, University of Thessaly, School of Medicine, Larissa, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Bakalos
authors.forename: Michael
authors.initials: M
authors.lastname: Miligkos
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Doxani
authors.forename: Ioanna
authors.initials: I
authors.lastname: Mpoulimari
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Rodopoulou
authors.forename: Elias
authors.initials: E
authors.lastname: Zintzaras
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic
chemical_list: D015251:Epirubicin; D005047:Etoposide; D003520:Cyclophosphamide; D002945:Cisplatin
keywords: Chemotherapy; Indirect analysis; Network; Randomized control trials; Small cell lung cancer