Almenar Cubells, D., Bosch Roig, C., Jimenez Orozco, E., Alvarez, R., Cuervo, J.M., Diaz Fernandez, N., . . . LEARN II Study Group. (2013). Effectiveness of daily versus non-daily granulocyte colony-stimulating factors in patients with solid tumours undergoing chemotherapy: A multivariate analysis of data from current practice. European Journal of Cancer Care, 22, 400–412.

To provide information about patterns of granulocyte colony-stimulating factors (G-CSF) use in Spanish oncology clinical practice and to compare neutropenia-related outcomes in patients treated daily with G-CSF with patients receiving nondaily G-CSF (pegfilgrastim)

Medical records were reviewed for data collection and analysis of outcomes in patients who received pegfilgrastim compared to those who received daily G-CSF.

• N = 391 patients from 34 participating centers 
• AGE: Older than 18 years
• MALES: 46.4% in daily G-CSF group, 31.8% in pegfilgrastim group  
• KEY DISEASE CHARACTERISTICS: Solid tumors excluding breast
• OTHER KEY SAMPLE CHARACTERISTICS: Had chemotherapy with at least one concomitant G-CSF administration more than two months prior; 79.3% had stage 3 or 4 disease

• SITE: Multi-site
• SETTING TYPE: Outpatient
• LOCATION: Spain

• PHASE OF CARE: Active treatment

• Retrospective, multi-center, observational
  • Each investigator reviewed the most recent charts of five patients treated with daily G-CSF and of another five most recently treated with pegfilgrastim.

• Percentage of patients with grade 3 or 4 neutropenia (absolute neutrophil count [ANC], .0 x 10⁹/L) and incidence of febrile neutropenia (FN), defined as ANC 0.5 x 10⁹/L and temperature 38°C or higher during the same day
• Percentage of patients experiencing dose delays (more than three days during any cycle) and dose reductions (less than 84% of planned dose)
• Percentage of patients with dose intensity was 85% or higher (defined as 85% or more of planned dose for all agents in regimen and three days or less of dose delay)
• FN-related hospitalizations and response to chemotherapy—complete, partial, or nonresponse per physician’s criterion

In the multivariate analysis following adjustment for possible confounding factors, a significantly higher risk (OR 1.73, 95% CI 1.004–2.97) of severe neutropenia was associated with daily G-CF versus pegfIlgrastim. The patient group receiving daily G-CSF had a 73% higher probability of grade 3 or 4 neutropenia. Patients receiving daily G-CSF experienced a greater number of dose reductions (38.4% versus 31/6%, p = 0.116) and delays (54.7% versus 41.7%, p = 0.013). Chemotherapy dose intensity of less than 85% also was greater in the daily G-CSF group (39.4% versus 28.9%,p = 0.030). Response rates also were lower in the daily G-CSF group. Complete responses were 17% for daily G-CSF versus 26.4% for the pegfilgrastim group (p = 0.028) and partial response was 41.2% for daily G-CSF versus 52% for the pegfilgrastim group (p = 0.009), again demonstrating better response in the pegfilgrastim group. The two main adverse reactions reported were bone pain and asthenia, with a higher incidence noted in the daily G-CSF group (6.2% versus 1.7%, p = 0.025). Patients receiving at least five days of daily G-CSF, versus those who received fewer than five days, experienced better outcomes.

G-CSF and pegfilgrastim can reduce the incidence and adverse outcomes of treatment-related neutropenia. If G-CSF is stopped prematurely, the efficacy is compromised. This study demonstrates that G-CSF often is initiated later than recommended following chemotherapy, and patients receive fewer days per cycle than required for optimum efficacy.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable

Daily G-CSF and pegfilgrastim are used prophylactically to reduce grade 3 or 4 neutropenia, incidence of FN, dose delays and reductions, and FN-related hospitalizations, and to increase response to chemotherapy, measured as complete, partial, or nonresponse per physician’s criterion. Suboptimal dosing is more prevalent with daily G-CSF because of starting later than recommended following myelosuppressive chemotherapy and stopping too early.