title: The clinical efficacy of cytotoxic agents in locally advanced or metastatic breast cancer patients pretreated with an anthracycline and a taxane: a systematic review.
abstract: BACKGROUND
  Currently available evidence does not provide definitive guidance regarding the optimal chemotherapy agents and combinations in anthracycline- and taxane-pretreated advanced breast cancer. We performed a systematic review of controlled clinical trials of the cytotoxic agents currently used for this population in Europe: capecitabine, gemcitabine, vinorelbine, docetaxel, paclitaxel and paclitaxel protein-bound particles.
  
  
  METHODS
  A systematic review of randomised (RCT) and non-randomised controlled clinical trials (non-RCTs). The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS); secondary outcomes were duration of response (DR), overall response rate (ORR), adverse events and quality of life (QoL). Six electronic databases and grey literature sources were searched; reference tracking was performed on included publications. A narrative synthesis was conducted: heterogeneity of study design and interventions prevented meta-analysis.
  
  
  RESULTS
  No randomised controlled trial (RCT) found any significant differences between any of the regimens in terms of OS. In terms of PFS, only gemcitabine plus vinorelbine performed significantly better than its comparator, vinorelbine alone. For secondary outcomes, only capecitabine plus bevacizumab had a significantly better outcome than its comparator, capecitabine alone, in terms of ORR. A low quality non-RCT found that both capecitabine monotherapy and a combination of capecitabine plus vinorelbine were significantly more effective than vinorelbine alone in terms of OS and ORR. Across all trials, median OS for these patients typically remained less than 16 months.
  
  
  CONCLUSIONS
  The quantity and quality of the available evidence regarding the efficacy of the particular chemotherapy regimens in patients with advanced breast cancer pretreated with an anthracycline and a taxane is extremely limited. New effective therapies are sorely needed in this population.
authors.affiliation: Department of Oncology and Radiotherapy, Medical University of Gdansk, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.forename: Christopher
authors.initials: C
authors.lastname: Carroll
authors.forename: Sue E
authors.initials: SE
authors.lastname: Ward
authors.forename: Emma
authors.initials: E
authors.lastname: Simpson
authors.forename: Daniel
authors.initials: D
authors.lastname: Hind
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015337:Multicenter Studies as Topic; D009362:Neoplasm Metastasis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D043823:Taxoids