Mitchell, S., Li, X., Woods, M., Garcia, J., Hebard-Massey, K., Barron, R., & Samuel, M. (2016). Comparative effectiveness of granulocyte colony-stimulating factors to prevent febrile neutropenia and related complications in cancer patients in clinical practice: A systematic review. Journal of Oncology Pharmacy Practice. Advance online publication. 

DOI Link

Purpose

STUDY PURPOSE: To synthesize evidence to compare effectiveness of prophylaxis with a long-acting versus short-acting colony-stimulating factor (CSF)
 
TYPE OF STUDY: Systematic review

Search Strategy

DATABASES USED:  MEDLINE, CINAHL, BIOSIS, EMBASE, Cochrane Library, ASCO, ESMO, and MASCC congress databases, and Google Scholar
 
KEYWORDS: Full search terms are provided in a supplemental table
 
INCLUSION CRITERIA: Varied study types, adult patients receiving granulocyte–colony-stimulating factor (G-CSF) prophylaxis, comparative studies of pegfilgrastim versus filgrastim, lenograstim, or short-acting biosimilars, reporting FN and related outcomes
 
EXCLUSION CRITERIA: Randomized controlled trials, children or adolescents, single treatment studies with no comparator

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 1,494
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Large studies used data from pharmacy databases. Four studies were prospective, and the rest were retrospective. The GRADES method was to evaluate studies. Most were of low quality.

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 18; 3 were conference abstracts 
  • TOTAL PATIENTS INCLUDED IN REVIEW = 22,882
  • SAMPLE RANGE ACROSS STUDIES: 20–32,072
  • KEY SAMPLE CHARACTERISTICS: Multiple tumor types

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Results

Febrile neutropenia (FN) and FN-associated hospitalization: In seven studies comparing pegfilgrastim with short-acting CSF, the risk of FN was significantly lower in three studies, and numerically lower in three studies for those on pegfilgrastim. Those receiving pegfilgrastim had a lower risk of FN-related hospitalization. Duration of short-acting CSF use varied. Fewer FN-related deaths, severe neutropenia episodes, dose reductions, and antimicrobial use were seen with pegfilgrastim.

Conclusions

Findings suggest that the use of long-acting CSFs was associated with a lower risk of FN, FN hospitalizations, and other related adverse patient outcomes.

Limitations

  • Tumor types varied. Those with hematologic cancers were included, but there was no subgroup analysis to differentiate from those with lower-risk solid tumor types.
  • Variability of chemotherapy regimens involved
  • Variation in the timing and duration of short-acting CSF interventions and dose differences that were not captured in the data
  • Known potential inaccuracies of medical claims data from which most cases were obtained
  • There is no single diagnosis code for FN, and the algorithms used to define FN can vary.
  • Low GRADES quality rating of studies included.
  • Some data was provided per patient, and some was provided per cycle.
  • In some studies, patients had received both filgrastim and pegfilgrastim.

Nursing Implications

Findings suggest that use of long-acting CSF may provide better prophylaxis for FN and FN-related events, but data and limitations of this review were insufficient to draw firm conclusions. Because of the variety of new biosimilar alternatives, additional work to determine comparative effectiveness and cost-benefit analysis of various formulations is increasingly important. This study does raise the question of what denominator is best used in outcomes measurement, whether outcomes should be viewed per patient, per cycle, or per patient-cycle.

Legacy ID

5801