title: Taxane-containing regimens for metastatic breast cancer.
abstract: BACKGROUND
  It is generally accepted that taxanes are among the most active chemotherapy agents in the management of metastatic breast cancer. This is an update of a Cochrane review first published in 2003.
  
  
  OBJECTIVE
  The objective of this review was to compare taxane-containing chemotherapy regimens with regimens not containing a taxane in the management of women with metastatic breast cancer.
  
  
  METHODS
  In this review update, we searched the Cochrane Breast Cancer Group Specialised Register, MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP), and ClinicalTrials.gov on 14 February 2013 using keywords such as 'advanced breast cancer' and 'chemotherapy'. We searched reference lists of articles, contacted study authors, and did not apply any language restrictions.
  
  
  METHODS
  Randomised controlled trials comparing taxane-containing chemotherapy regimens to regimens without taxanes in women with metastatic breast cancer. We included published and unpublished studies.
  
  
  METHODS
  Two review authors independently assessed trial quality and extracted data. We derived hazard ratios (HRs) for overall survival, time to progression, and time to treatment failure where possible, and used a fixed-effect model for meta-analysis. We represented objective tumour response rates and toxicity as risk ratios (RRs). We extracted quality of life data where present.
  
  
  RESULTS
  This review included 28 studies. The updated analysis included 6871 randomised women, while the original review had 3643 women. Of the 28 included studies, we considered 19 studies to be at low risk of bias overall; however, some studies failed to report details on allocation concealment and methods of outcome assessment for those outcomes that are more likely to be influenced by a lack of blinding (for example tumour response rate). Studies varied in the taxane-containing chemotherapy backbone, and the comparator arms and were categorised into three groups: Regimen A plus taxane versus Regimen A (2 studies); Regimen A plus taxane versus Regimen B (14 studies); and single-agent taxane versus Regimen C (13 studies). Thirteen studies used paclitaxel, 14 studies used docetaxel, and 1 study allowed the investigator to decide on the type of taxane; the majority of studies delivered a taxane every 3 weeks. Twenty studies administered taxanes as first-line treatment, and 21 studies involved anthracycline naïve women in the metastatic setting. The combined HR for overall survival and time to progression favoured the taxane-containing regimens (HR 0.93, 95% confidence interval (CI) 0.88 to 0.99, P = 0.002, deaths = 4477; and HR 0.92, 95% CI 0.87 to 0.97, P = 0.002, estimated 5122 events, respectively) with moderate to substantial heterogeneity across trials. If the analyses were restricted to studies of first-line chemotherapy, this effect persisted for overall survival (HR 0.93, 95% CI 0.87 to 0.99, P = 0.03) but not for time to progression (HR 0.96, 95% CI 0.90 to 1.02, P = 0.22). Tumour response rates appeared to be better with taxane-containing chemotherapy in assessable women (RR 1.20, 95% CI 1.14 to 1.27, P < 0.00001) with substantial heterogeneity across studies. Taxanes were associated with an increased risk of neurotoxicity (RR 4.84, 95% CI 3.18 to 7.35, P < 0.00001, 24 studies) and hair loss (RR 2.37, 95% CI 1.45 to 3.87, P = 0.0006, 11 studies) but less nausea/vomiting compared to non-taxane-containing regimens (RR 0.62, 95% CI 0.46 to 0.83, P = 0.001, 26 studies). Leukopaenia and treatment-related death did not differ between the two groups (RR 1.07, 95% CI 0.97 to 1.17, P = 0.16, 28 studies; and RR 1.00, 95% CI 0.63 to 1.57, P = 0.99, 23 studies, respectively). For quality of life measures, none of the individual studies reported a difference in overall or any of quality of life subscales between taxane-containing and non-taxane chemotherapy regimens.
  
  
  CONCLUSIONS
  Taxane-containing regimens appear to improve overall survival, time to progression, and tumour response rate in women with metastatic breast cancer. Taxanes are also associated with an increased risk of neurotoxicity but less nausea and vomiting compared to non-taxane-containing regimens. The considerable heterogeneity encountered across studies probably reflects the varying efficacy of the comparator regimens used in these studies and indicates that taxane-containing regimens are more effective than some, but not all, non-taxane-containing regimens.
authors.affiliation: Research Translation Group, National Health and Medical Research Council, 16 Marcus Clarke Street, Canberra, ACT, Australia, 2601.
authors.forename: Davina
authors.initials: D
authors.lastname: Ghersi
authors.forename: Melina L
authors.initials: ML
authors.lastname: Willson
authors.forename: Matthew Ming Ki
authors.initials: MM
authors.lastname: Chan
authors.forename: John
authors.initials: J
authors.lastname: Simes
authors.forename: Emma
authors.initials: E
authors.lastname: Donoghue
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wilcken
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D006801:Humans; D017239:Paclitaxel / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000627:therapeutic use; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D001952:Bridged-Ring Compounds; D043823:Taxoids; D013629:Tamoxifen; D017239:Paclitaxel