Primary G-CSF Prophylaxis During the First Two Cycles Only or Throughout All Chemotherapy Cycles in Breast Cancer Patients at Risk of Febrile Neutropenia

1. Febrile neutropenia Febrile neutropenia is a serious side effect of cancer treatment. Febrile neutropenia predisposes to serious and sometimes life-threatening infections. Given the seriousness, the majority of febrile neutropenia patients are admitted to hospital for treatment with intravenous antibiotics. Thus, chemotherapy-induced febrile neutropenia can result in death, increased hospitalisations and intravenous antibiotic use. In addition, it can lead to significant chemotherapy dose modifications, which may theoretically be of concern for treatments with curative intent. Clearly, prevention of chemotherapy-induced febrile neutropenia is a medical priority.

2 Prophylaxis of febrile neutropenia To prevent chemotherapy-related febrile neutropenia, prophylaxis with antibiotics and granulocyte colony-stimulating factor (G-CSF) have proven efficacious [1-3]. The use of the G-CSF was shown to shorten the duration of neutropenia, resulting in reduction of the incidence of febrile neutropenia, hospitalisation and use of intravenous therapeutic antibiotics by approximately 50%. .Antibiotics may, however, lead to emergence of microbial resistance. G-CSF has only few side effects, but is expensive. Previous guidelines recommended primary G-CSF prophylaxis to prevent febrile neutropenia, but only for patients at substantial risk of febrile neutropenia (more than 40%). In 2006, updated G-CSF guidelines conclude that primary G-CSF prophylaxis has clinical benefits for and should be offered to patients at a more than 20% risk of febrile neutropenia.

Most of the recent EORTC-reviewed evidence indicate that primary and secondary G-CSF prophylaxis had no significant impact on survival, despite the fact that G-CSF prophylaxis enabled to maintain chemotherapy dose and dose intensity. In the GEICAM 9805 study, primary G-CSF support did not lead to improved median dose intensity or cumulative dose when compared to secondary G-CSF prophylaxis, although the percentage of patients who completed six cycles of therapy increased significantly.

3. Developments in the adjuvant treatment of breast cancer After the introduction of taxanes in the treatment of advanced breast cancer in the late nineties, these agents have now also been introduced in the (neo) adjuvant setting. Many adjuvant trials with a positive outcome have recently been reported.

Based on the available data with many positive and few negative trials, one can consider the use of taxanes as standard of care in the adjuvant setting in node-positive breast cancer, although the preferred schedule, concurrent or sequential, with or without dose-densification, needs to be clarified from ongoing trials.