von Minckwitz, G., Kummel, S., du Bois, A., Eiermann, W., Eidtmann, H., Gerber, B., . . . German Breast Group. (2008). Pegfilgrastim +/- ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study. Annals of Oncology, 19, 292–298.

The purpose of the study was to compare rates of febrile neutropenia between four treatments: (a) ciprofloxacin 500 mg PO BID on days 5–14, (b) G-CSF (filgrastim 5 mg/kg per day or lenograstim 150 mg/m² per day) on days 5–10, (c) pegfilgratim 6 mg on day 2, and (d) pegfilgrastim plus ciprofloxacin.

A secondary aim was to compare the incidence of neutropenia and other hematologic toxic effects, infection, nonhematologic toxic effects, and hospitalization.

Patients enrolled in the German GeparTrio study from April 2001 and June 2005 who received one of the four neutropenia prophylactic regimens were analyzed. Patients analyzed had completed at least one cycle of TAC and were not randomized to no treatment.

• 1,256 participants were enrolled.
• All were aged 18 years or older
• All were female
• All were diagnosed with breast cancer

89 outpatient sites in Germany

Active treatment

Retrospective cohort study of women with breast cancer enrolled in the Germany GeparTrio study.

• Febrile neutropenia
• Grade 4 neutropenia
• Hematologic toxicities (leukopenia, anemia [hemoglobin lower than 10 g/dl], thrombocytopenia)
• Hospitalizations
• Non-hematologic toxicities (infection without neutropenia, stomatitis, dysphagia/esophagitis, diarrhea)
   

Among the 1,256 patients in the analyses, 1,057 completed all planned cycles of treatment (six cycles, n = 793; eight cycles, n = 264). The combination of pegfilgrastim and ciprofloxacin was statistically significantly better than other regimens for the prevention of overall febrile neutropenia (p < 0.001), febrile neutropenia during the first chemotherapy cycle (p < 0.001), lower incidences of grade 4 neutropenia, prevention of leukopenia and anemia (p < 0.001), fewer hospitalizations (p < 0.001), and for the reduction of stomatitis/mucositis, dysphagia/esophagitis, and diarrhea. Pegfilgrastim alone was as effective as pegfilgrastim and cipro for overall febrile neutropenia (p < 0.001) and for the reduction of grade 4 neutropenia, leukopenia, and anemia (p < 0.01). Daily G-CSF was better than cipro alone for the reduction of grade 4 neutropenia. Thrombocytopenia was lowest for cipro alone (p < 0.001). Infection with neutropenia was not statistically different between groups.

The use of pegfilgratim, especially in combination with ciprofloxacin, is superior to ciprofloxacin alone or daily G-CSF for the reduction of febrile neutropenia, grade 4 neutropenia, and related hospitalizations. No regimen proved superior over others for the prevention of infection with neutropenia.

The administration of daily G-CSF was not given according to protocol of beginning 24 hours after the last dose of chemotherapy with continuation until absolute neutrophil count (ANC) has returned to normal range or for a maximum of 14 days. G-CSF was started at a later time in the cohorts who received G-CSF which could have skewed the results in favor of pegfilgrastim, which was given according to protocol.

The use of pegfilgratim, especially with ciprofloxacin, for the prevention of febrile neutropenia, grade 4 neutropenia, and neutropenic-related hospitalizations appears beneficial for women with stage T2–T4 primary breast cancer. Oncology nurses can advocate for use of this regimen for their patients.