PMID- 26058962
OWN - NLM
STAT- MEDLINE
DCOM- 20160210
LR  - 20220410
IS  - 1469-493X (Electronic)
IS  - 1361-6137 (Linking)
VI  - 2015
IP  - 6
DP  - 2015 Jun 10
TI  - Taxane-containing regimens for metastatic breast cancer.
PG  - CD003366
LID - 10.1002/14651858.CD003366.pub3 [doi]
LID - CD003366
AB  - 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. OBJECTIVES: 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. 
      SEARCH 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. SELECTION CRITERIA: 
      Randomised controlled trials comparing taxane-containing chemotherapy regimens to 
      regimens without taxanes in women with metastatic breast cancer. We included 
      published and unpublished studies. DATA COLLECTION AND ANALYSIS: 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. MAIN 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 naive 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. 
      AUTHORS' 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.
FAU - Ghersi, Davina
AU  - Ghersi D
AD  - Research Translation Group, National Health and Medical Research Council, 16 
      Marcus Clarke Street, Canberra, ACT, Australia, 2601.
FAU - Willson, Melina L
AU  - Willson ML
FAU - Chan, Matthew Ming Ki
AU  - Chan MM
FAU - Simes, John
AU  - Simes J
FAU - Donoghue, Emma
AU  - Donoghue E
FAU - Wilcken, Nicholas
AU  - Wilcken N
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
PT  - Systematic Review
DEP - 20150610
PL  - England
TA  - Cochrane Database Syst Rev
JT  - The Cochrane database of systematic reviews
JID - 100909747
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Bridged-Ring Compounds)
RN  - 0 (Taxoids)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
UOF - Cochrane Database Syst Rev. 2005;(2):CD003366. PMID: 15846659
MH  - Antineoplastic Agents, Hormonal/*therapeutic use
MH  - Antineoplastic Agents, Phytogenic/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/mortality/pathology
MH  - Bridged-Ring Compounds/therapeutic use
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - Paclitaxel/therapeutic use
MH  - Randomized Controlled Trials as Topic
MH  - Tamoxifen/therapeutic use
MH  - Taxoids/*therapeutic use
PMC - PMC6464903
COIS- DG: none known
 MW: none known
 MC: no relevant conflict of interest
 JS: no 
      relevant conflict of interest
 ED: none known
 NW: has received honoraria from 
      Aventis
EDAT- 2015/06/11 06:00
MHDA- 2016/02/11 06:00
PMCR- 2016/06/10
CRDT- 2015/06/11 06:00
PHST- 2015/06/11 06:00 [entrez]
PHST- 2015/06/11 06:00 [pubmed]
PHST- 2016/02/11 06:00 [medline]
PHST- 2016/06/10 00:00 [pmc-release]
AID - CD003366.pub3 [pii]
AID - 10.1002/14651858.CD003366.pub3 [doi]
PST - epublish
SO  - Cochrane Database Syst Rev. 2015 Jun 10;2015(6):CD003366. doi: 
      10.1002/14651858.CD003366.pub3.