PMID- 23076939
OWN - NLM
STAT- MEDLINE
DCOM- 20121116
LR  - 20220409
IS  - 1469-493X (Electronic)
IS  - 1361-6137 (Linking)
VI  - 10
DP  - 2012 Oct 17
TI  - Primary prophylactic colony-stimulating factors for the prevention of 
      chemotherapy-induced febrile neutropenia in breast cancer patients.
PG  - CD007913
LID - 10.1002/14651858.CD007913.pub2 [doi]
AB  - BACKGROUND: High-dose or dose-intensive cytotoxic chemotherapy often causes 
      myelosuppression and severe neutropenia among cancer patients. Severe neutropenia 
      accompanied by fever, named febrile neutropenia (FN), is the most serious 
      manifestation of neutropenia usually requiring hospitalization and intravenous 
      antibiotics. FN and neutropenia can lead to chemotherapy treatment delays or dose 
      reductions, which potentially compromises the effectiveness of cancer treatment 
      and prospects for a cure. Granulocyte-macrophage (GM) and granulocyte 
      colony-stimulating factors (G-CSFs) are administered during chemotherapy in order 
      to prevent or reduce the incidence or the duration of FN and neutropenia. 
      OBJECTIVES: To assess the effect of prophylactic colony-stimulating factors 
      (CSFs) in reducing the incidence and duration of FN, and all-cause and 
      infection-related mortality during chemotherapy in patients with breast cancer. 
      SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials 
      (CENTRAL), MEDLINE, EMBASE, HEALTHSTAR, International Health Technology 
      Assessment, SOMED, AMED and BIOSIS up to 8 August 2011. We also searched three 
      Chinese databases (VIP, CNKI, CBM), the metaRegister of Controlled Trials, 
      ClinicalTrials.gov, the World Health Organization's International Clinical Trials 
      Registry Platform (WHO ICTRP) and OpenGrey.eu up to August 2011. SELECTION 
      CRITERIA: Randomized controlled trials (RCTs) comparing CSFs (any dose) with 
      placebo or no treatment in patients with breast cancer at any stage, at risk of 
      developing FN while undergoing any type of chemotherapy. DATA COLLECTION AND 
      ANALYSIS: We used pooled risk ratios (RR) with 95% confidence intervals (CIs) for 
      binary outcomes. At least two review authors independently extracted data and 
      assessed the risk of bias of the included studies. Trial authors were contacted 
      for further details when information was unclear. MAIN RESULTS: We included eight 
      RCTs involving 2156 participants with different stages of breast cancer and 
      chemotherapy regimens. The trials were carried out between 1995 and 2008 and 
      judged as being at least at moderate risk of bias. The strength of the evidence 
      was weak for the majority of outcomes, which was mostly because of the small 
      numbers of evaluable patients, varying definitions, as well as unclear 
      measurements of the trials' outcomes and uncertain influences of supportive 
      treatments on them. In most trials, the chemotherapy regimens had a risk of FN 
      that was below the threshold at which current guidelines recommend routine 
      primary prophylaxis with CSFs. Using CSFs significantly reduced the proportion of 
      patients with FN (RR 0.27; 95% CI 0.11 to 0.70; number needed to treat for an 
      additional beneficial outcome (NNTB) 12) but there was substantial heterogeneity 
      which can be explained by possible differential effects of G-CSFs and GM-CSFs and 
      different definitions of FN. A significant reduction in early mortality was 
      observed in CSF-treated patients compared to placebo or no treatment (RR 0.32; 
      95% CI 0.13 to 0.77; NNTB 79). This finding was based on 23 fatal events in 2143 
      patients; wherein 19 of these 23 events occurred in one study and 17 events were 
      attributed to progression of the disease by the study authors. For 
      infection-related mortality, there were no significant differences between CSF 
      and control groups (RR 0.14; 95% CI 0.02 to 1.29). In CSF-treated patients, the 
      risk for hospitalization was significantly reduced (RR 0.14; 95% CI 0.06 to 0.30; 
      NNTB 13), as well as the use of intravenous antibiotics (RR 0.35; 95% CI 0.22 to 
      0.55; NNTB 18). The risks of severe neutropenia, infection or not maintaining the 
      scheduled dose of chemotherapy did not differ between CSF-treated and control 
      groups. CSFs frequently led to bone pain (RR 5.88; 95% CI 2.54 to 13.60; number 
      needed to treat for an additional harmful outcome (NNTH) 3) and injection-site 
      reactions (RR 3.59; 95% CI 2.33 to 5.53; NNTH 3). AUTHORS' CONCLUSIONS: In 
      patients with breast cancer receiving chemotherapy, CSFs have shown evidence of 
      bene fi t in the prevention of FN. There is evidence, though less reliable, of a 
      decrease of all-cause mortality during chemotherapy and a reduced need for 
      hospital care. No reliable evidence was found for a reduction of 
      infection-related mortality, a higher dose intensity of chemotherapy with CSFs or 
      diminished rates of severe neutropenia and infections. The majority of adverse 
      events reported from CSF use were bone pain and injection-site reactions but no 
      conclusions could be drawn regarding late-term side effects.
FAU - Renner, Peter
AU  - Renner P
AD  - Medizinische Klinik 5-Schwerpunkt Onkologie/Haematologie, Klinikum Nord, 
      Nuernberg, Germany.
FAU - Milazzo, Stefania
AU  - Milazzo S
FAU - Liu, Jian Ping
AU  - Liu JP
FAU - Zwahlen, Marcel
AU  - Zwahlen M
FAU - Birkmann, Josef
AU  - Birkmann J
FAU - Horneber, Markus
AU  - Horneber M
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PT  - Systematic Review
DEP - 20121017
PL  - England
TA  - Cochrane Database Syst Rev
JT  - The Cochrane database of systematic reviews
JID - 100909747
RN  - 0 (Antineoplastic Agents)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Antineoplastic Agents/*adverse effects
MH  - Breast Neoplasms/*drug therapy
MH  - Female
MH  - Fever/etiology/mortality/*prevention & control
MH  - Granulocyte Colony-Stimulating Factor/adverse effects/*therapeutic use
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/adverse effects/*therapeutic use
MH  - Humans
MH  - Neutropenia/chemically induced/mortality/*prevention & control
MH  - Randomized Controlled Trials as Topic
EDAT- 2012/10/19 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/10/19 06:00
PHST- 2012/10/19 06:00 [entrez]
PHST- 2012/10/19 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - 10.1002/14651858.CD007913.pub2 [doi]
PST - epublish
SO  - Cochrane Database Syst Rev. 2012 Oct 17;10:CD007913. doi: 
      10.1002/14651858.CD007913.pub2.