Effectiveness Unlikely

Colony Stimulating Factors By Intravenous Rather Than Subcutaneous Route

for Prevention of Infection: General

Colony-stimulating factors given systemically are generally administered via subcutaneous injection. Administration by an intravenous route was examined for its effects on the prevention of infection compared to subcutaneous administration.

Research Evidence Summaries

Paul, M., Ram, R., Kugler, E., Farbman, L., Peck, A., Leibovici, L., . . . Raanani, P. (2014). Subcutaneous versus intravenous granulocyte colony stimulating factor for the treatment of neutropenia in hospitalized hemato-oncological patients: Randomized controlled trial. American Journal of Hematology, 89, 243–248.

Study Purpose

To examine the effectiveness of intravenous (IV) versus subcutaneous (SC) granulocyte colony-stimulating factor (G-CSF) as related to time to neutropenia resolution and secondarily to assess comparative rates of infection, adverse effects, and patient satisfaction

Intervention Characteristics/Basic Study Process

Randomized, controlled, open-label trial with a 1:1 randomization to SC versus IV filgrastim. Patients were given either IV or SC filgrastim on a prescribed day (day 7 of chemotherapy for patients with acute myeloid leukemia [AML], day 2 after completion of chemotherapy for lymphoma and myeloma, and the day after infusion for patients undergoing hematopoietic stem cell transplantation [HSCT]). On the subsequent chemotherapy course (at least 30 days later), patients were crossed over to the alternative study arm.

Sample Characteristics

  • N = 120 
  • MEAN AGE = 49.2 years
  • MALES: 43.9% (first-course IV); 59% (first-course SC), FEMALES: 56.1% (first-course IV); 41% (first-course SC)
  • KEY DISEASE CHARACTERISTICS: All hematologic malignancies. AML: IV (26.3%) and SC (37.7%). Acute lymphoblastic leukemia (ALL): IV (8.8%) and SC (13.1%). Non-Hodgkin's lymphoma (NHL): IV (36.8%) and SC (19.7%). Myeloma: IV (19.3%) and SC (19.7%). Other: IV (8.8%) and SC (9.8%).
  • OTHER KEY SAMPLE CHARACTERISTICS: Almost 30% of patients in each cohort had a fever episode before randomization. 20%–25% had infection documented before randomization. The total median neutrophil count in the IV group was 0.1; the median neutrophil count in the SC group was 0; the median total leukocyte count in the IV group was 0.29; and the median leukocyte count in the SC group was 0.41.

Setting

  • SITE: Single-site    
  • SETTING TYPE: Inpatient    
  • LOCATION: Hematology/oncology and bone marrow transplantation wards at the Davidoff Cancer Center, Beilinson Hospital, Petah Tikva, Israel

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment

Study Design

Randomized, controlled, open-label trial

Measurement Instruments/Methods

  • Primary outcomes: Time from start of filgrastim to stable neutrophil recovery (> 500 cells/µL for three consecutive days) and a composite clinical outcome of 30-day mortality or infection (clinically or morphologically documented infections, bacteremia or probable/proven invasive fungal infections)
  • Secondary outcomes: Time to stable neutrophil recovery (> 100 cells/µL), any invasive fungal infections (IFIs) including possible IFIs, fever days, thrombocytopenia duration, duration of hospital stay for patients discharged within 30 days, and adverse events
  • Patients’ pain and satisfaction were also assessed by interview.

Results

Primary outcomes: Neutropenia duration was significantly longer with IV versus SC G-CSF (p = 0.001). There were no statistically significant differences in subgroups. Infection or death occurred in 35.1% of IV patients versus 31.3% of SC patients.
 
Secondary outcomes: Time to absolute neutrophil recovery (> 100cells/µL) was longer with IV G-CSF. There were no statistically significant differences in clinical outcomes. There were three proven/probable IFIs, all in the IV treatment arm. There was no difference in fever days, days with severe thrombocytopenia, or hospitalization duration.

Conclusions

Time to neutrophil resolution was longer with an IV bolus G-CSF compared to SC G-CSF with an overall mean difference of 2.5 days. There were no differences in clinical outcomes, including infection rates or adverse events observed.

Limitations

The trial was not powered to examine possible serious complications of SC G-CSF administration and was stopped prematurely due to the observed results.

Nursing Implications

Findings support the continued use of SC G-CSF for limiting the duration of neutropenia. Education about the use of G-CSF in the prevention of neutropenia and managing related side effects is important.

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