Wang, L., Baser, O., Kutikova, L., Page, J.H., & Barron, R. (2015). The impact of primary prophylaxis with granulocyte colony-stimulating factors on febrile neutropenia during chemotherapy: A systematic review and meta-analysis of randomized controlled trials. Supportive Care in Cancer, 23, 3131–3140. 

DOI Link

Purpose

STUDY PURPOSE: To assess the relative efficacy of granulocyte-colony stimulating factor (G-CSF) administered as a primary prophylaxis to patients with cancer receiving myelosuppressive chemotherapy
 
TYPE OF STUDY: Meta-analysis and systematic review

Search Strategy

DATABASES USED: PubMed, EMBASE, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane central register of controlled clinical trials, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, and the NHS Economic Evaluation Database plus manual searches of original publications (The search included publications from January 1990 to September 2013.)
 
KEYWORDS: Febrile neutropenia, filgrastim, G-CSF, lipegfilgrastim, meta-analysis, and pegfilgrastim
 
INCLUSION CRITERIA: Randomized, controlled trials that compared primary prophylaxis (PP) with filgrastim, pegfilgrastim, lenograstim, or lipegfilgrastim with a placebo, no G-CSF PP, or PP with a different G-CSF in adult patients receiving myelosuppressive chemotherapy for solid tumors or non-Hodgkin lymphoma
 
EXCLUSION CRITERIA: If patients had received G-CSF for established ​febrile neutropenia (FN), or different doses of the same G-CSF in each treatment arm, and if patients had leukemia or multiple myeloma, or bone marrow or peripheral-blood stem cell transplantation; studies also excluded if they were economic analyses, evaluated investigational or unapproved drugs, or were published in languages other than English

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 4,790
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two independent reviewers evaluated publications identified in the search and compared them to the search criteria for relevance. Disagreements were resolved by consensus (this process was not detailed). The data of interest were then extracted – these included protocol designs and patient, disease, and treatment characteristics. Statistic analyses included using an OR for febrile neutropenia incidence. For treatment effects, direct and indirect comparisons were made using mixed treatment comparisons (MTC) and ORs, and pairwise meta-analyses were calculated for conventional random effects. In addition, Bayesian statistics were applied for treatment effects as a posterior distribution. Finally, a full metaregression analysis and treatment effect with adjustment for relative dose intensity (RDI) was intended to be conducted; however, there weren’t enough data by group because of too much heterogeneity between studies for the RDI adjustment.

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 27 (evaluated 30 trials in total)
  • TOTAL PATIENTS INCLUDED IN REVIEW = 6,037
    • Primary lipegfilgrastim compared to primary pegfilgrastim (two studies n = 306) 
    • Primary lipegfilgrastim compared to no primary G-CSF/placebo (one study n = 375) 
    • Primary lenograstim compared to no primary G-CSF/placebo (five studies n = 467)
    • Primary filgrastim compared to no primary G-CSF/placebo (11 studies n = 2,181) 
    • Primary pegfilgrastim compared to no primary G-CSF/placebo (five studies n = 2,060) 
    • Primary pegfilgrastim compared to primary filgrastim (six studies n = 647)
  • KEY SAMPLE CHARACTERISTICS: Adult patients who received myelosuppressive chemotherapy for solid tumors or non-Hodgkin lymphoma

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Results

Overall Findings
  • Primary prophylaxis using filgrastim, pegfilgrastim, lenograstim, and lipegfilgrastim were statistically significantly better than not using G-CSF or placebo for the reduction of FN risk. Across all chemotherapy cycles, pegfilgrastim was slightly better than lipegfilgrastim for reducing NF risk, but this finding was not significant.
Detailed findings
  • Using direct comparison, FN risk was significantly reduced following PP with pegfilgrastim, filgrastim, or lenograstim compared to no G-CSF PP or a placebo. 
  • Using indirect comparison, PP with pegfilgrastim or filgrastim significantly reduced FN risk compared to no G-CSF PP or a placebo.  
  • Using mixed-treatment comparison, PP with pegfilgrastim, filgrastim or lenograstim, significantly reduced FN risk compared to no G-CSF PP or a placebo. PP with pegfilgrastim significantly reduced FN risk compared to filgrastim PP. PP with lipegfilgrastim significantly reduced FN risk compared to no G-CSF or a placebo.
  • Using mixed-treatment comparison, PP with pegfilgrastim, filgrastim, and lipegfilgrastim significantly reduced FN risk in the first cycle and across all cycles of chemotherapy compared to no G-CSF or a placebo. PP with pegfilgrastim significantly reduced FN compared to filgrastim PP. No significant difference was found in FN risk during first cycle of chemotherapy using PP with either pegfilgrastim or lipegfilgrastim.
  • A meta-analysis of all cycles with adjustment of RDI could not be evaluated.

Conclusions

Prophylaxis with G-CSF reduces the risk for NF during myelosuppressive chemotherapy.

Limitations

  • More information could be obtained if the RDI adjustment could have been conducted.
  • There was some heterogeneity between studies, limiting the ability to evaluate relative dose intensities, number of chemotherapy cycles, and dose delays.
  • Detailed study characteristics were lacking.
  • The Bayesian method was appropriate to use as a prediction model but may not accurately capture true events.
  • Publication bias: No specific data comparing G-CSF effect and type of myelosuppressive regimen

Nursing Implications

Patients with cancer undergoing myelosuppressive chemotherapy are at risk for FN. Prophylaxis with G-CSF can reduce this risk for improved patient outcomes.

Legacy ID

5226