title: Platinum rechallenge in patients with advanced NSCLC: a pooled analysis.
abstract: BACKGROUND
  The sole agents pemetrexed (PEM), docetaxel and anti-EGFR agents are approved second-line therapies for non-small cell lung cancer (NSCLC) after failure with cisplatin-based doublets. The potential usefulness of platinum-based doublets as rechallenge for second-line chemotherapy has not yet been established.
  
  
  METHODS
  Studies that enrolled NSCLC platinum pre-treated patients were identified using electronic databases (MEDLINE and EMBASE). Pemetrexed and taxanes (TAXs)-based platinum combinations were considered. A systematic review was conducted using Comprehensive Meta-Analysis (version 2.2.064) software to calculate the event rate of response and 95% confidence interval. Median weighted progression-free survival (PFS) and overall survival (OS) time for PEM and TAXs-based doublets were compared by two-sided Student's t test. We tested for significant heterogeneity by Cochran's chi-square test and I(2) index.
  
  
  RESULTS
  Eleven studies published between 1999 and 2012 were included in this analysis with a total of 607 patients enrolled; 468 were treated with PEM-doublets and 139 with TAXs-doublets. The overall response rate was 27.5% with a higher response rate of 37.8% (range, 29.7-46.7%) for TAXs-based treatment vs. 22% (range, 13.4-34.1%) for PEM-based combinations; (p < 0.0001). Median PFS and OS were 3.9 and 8.7 months with weighted PFS of 3.9 vs. 5.3 months (p < 0.0001) and similar OS for PEM vs. TAXs-based doublets.
  
  
  CONCLUSIONS
  With the limitations of small and not randomised trials included, this pooled analysis shows that NSCLC patients who relapsed after a first-line platinum-based chemotherapy obtain a tumour response of 27% from a platinum rechallenge containing PEM or TAXs. Response rate and median PFS appear better with TAXs-than with PEM-doublets.
authors.affiliation: Azienda Ospedaliera di Treviglio, Oncology Department, Medical Oncology Unit, Piazzale Ospedale 1, 24047 Treviglio, BG, Italy. Electronic address: faupe@libero.it.
authors.forename: Fausto
authors.initials: F
authors.lastname: Petrelli
authors.affiliation: Azienda Ospedaliera di Treviglio, Oncology Department, Medical Oncology Unit, Piazzale Ospedale 1, 24047 Treviglio, BG, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Coinu
authors.affiliation: Azienda Ospedaliera di Treviglio, Oncology Department, Medical Oncology Unit, Piazzale Ospedale 1, 24047 Treviglio, BG, Italy.
authors.forename: Mary
authors.initials: M
authors.lastname: Cabiddu
authors.affiliation: Azienda Ospedaliera di Treviglio, Oncology Department, Medical Oncology Unit, Piazzale Ospedale 1, 24047 Treviglio, BG, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Ghilardi
authors.affiliation: Azienda Ospedaliera di Treviglio, Oncology Department, Medical Oncology Unit, Piazzale Ospedale 1, 24047 Treviglio, BG, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Ardine
authors.affiliation: Azienda Ospedaliera di Treviglio, Oncology Department, Medical Oncology Unit, Piazzale Ospedale 1, 24047 Treviglio, BG, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Barni
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*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D016017:Odds Ratio; D010984:Platinum / Q000008:administration & dosage; D017594:Publication Bias; D019233:Retreatment; D016896:Treatment Outcome
chemical_list: D010984:Platinum
keywords: Metastatic; NSCLC; Platinum-based doublets; Rechallenge; Second line