von Minckwitz, G., Schwenkglenks, M., Skacel, T., Lyman, G.H., Pousa, A.L., Bacon, P., . . . Aapro, M.S. (2009). Febrile neutropenia and related complications in breast cancer patients receiving pegfilgrastim primary prophylaxis versus current practice neutropaenia management: Results from an integrated analysis. European Journal of Cancer, 45, 608–617.

The purpose of this systematic review was to compare the efficacy of pegfilgrastim primary prophylaxis (PPP) with current practice (CP [short course of treatment and not beginning in the first cycle]) neutropenia management in breast cancer.

MEDLINE, a clinical trial database at Amgen, and abstracts from the American Society of Clinical Oncology meetings from 2000–2005 were researched.

Key words were taxoids, (pegylated) doxorubicin, adriamycin, epirubicin, docetaxel, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil combined with febrile neutropenia, neutropenia, leucopenia, and infection
 
Inclusion was based on English-language studies (randomized, controlled trials [RCTs], prospective observational studies, retrospective studies) on human subjects who received common breast cancer chemotherapy regimens associated with a febrile neutropenia risk 15% or greater. 

Studies were excluded if they had patients who received two weekly treatment cycles.

513 total references were retrieved.

The proportion of patients with febrile neutropenia across all cycles and the proportion of patients with febrile neutropenia in cycle 1, febrile neutropenia-related hospitalizations, chemotherapy dose delays of three or more days, dose reductions of 15% or greater, and grades 3 and 4 hematologic toxicities. An integrated analysis was conducted on individual patient data. Descriptive summaries of demographic information and disease characteristics for individual and integrated populations within each group (PPP versus CP). G-CSF was characterized by administration. For the comparative analysis homogeneity of patient populations within each group and then between each group was evaluated. A generalized linear mixed model was fitted for the outcome of febrile neutropenia across all cycles and for cycle 1 per type of prophylactic treatment (PPP or CP). Other variables in the model included age, disease stage, and prior chemotherapy/radiation treatment. Variables were adjusted using the least square means. Sensitivity analyses also were conducted. Studies that included G-CSF given within seven days of the last chemotherapy dose in cycle one were removed for the CP group in the analysis.

• 19 studies were included in the final review.
• The sample range across studies was 7–927 participants
• 2,282 total patients were included in this review (1,303 PPP and 979 CP)
• Female patients with breast cancer who received chemotherapy treatments with an associated 15% or greater risk of febrile neutropenia.
• The majority of patients were older than age 50 years, were Caucasian, and had an ECOG status of 0 or 1.
• The majority of patients also had a stage II, III, or IV diagnosis and most had not had prior therapy.
• 981 patients had an unknown estrogen receptor status, 564 were receptor negative, and 737 were receptor positive.
• 338 patients had adenocarcinomas, and the histology was unknown for the remaining patients.
• Chemotherapy regimens varied and included doxorubicin, cyclophosphamide, carboplatin, doecetaxel, epirubicin, and paclitaxel.

Active treatment

The incidence of febrile neutropenia for all cycles and in cycle one were lower in patients who received PPP compared to those who received CP (p < 0.0001). An increased risk of febrile neutropenia was found for older patients and for those with stage IV disease. Hospitalizations associated with febrile neutropenia also were lower for the PPP group compared to the CP group. Grades 3 and 4 neutropenia were lower in the PPP group (47%, 95% CI [9%, 89%]) compared to the CP group (96%, 95% CI [70%, 99%]) adjusted rates and similarly for leucopenia were also lower in the PPP group (47%, 95% CI [15%, 82%]) compared to the CP group (94%, 95% CI [74%, 99%]).

The use pegfilgrastim primary prophylaxis for the prevention of febrile neutropenia, grades 3 and 4 neutropenia, and neutropenia-related hospitalizations is more effective than current practice use of G-CSF (short course of treatment and not beginning in the first cycle) for patients receiving myelosuppressive chemotherapy for treatment of breast cancer.

Oncology nurses can advocate for the use of PPP for this patient population.