Howard Ozer, MD, PhD

Grade 3 and 4 neutropenia as well as febrile neutropenia have been demonstrated to occur in all tumor types and are clearly associated with major morbidity and significant mortality; this is particularly true when myelosuppressive regimens are used with curative intent as is the case in most breast cancer and non-Hodgkin's lymphoma regimens. Myeloid colony-stimulating factors (CSFs) substantially decrease the risk of severe and febrile neutropenia. Although the white cell growth factors might not be cost-effective at lower risks of febrile neutropenia, they clearly benefit other outcomes such as the incidence of severe neutropenia and febrile neutropenia, hospitalization, and mortality. Updated guidelines from the American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the European Organisation for Research and Treatment of Cancer now recommend primary prophylaxis or first-cycle use of white cell growth factors with regimens where the occurrence of febrile neutropenia is approximately 20% (as well as when other risk factors are present). This article briefly describes the rationale for the development of several of the guideline changes as well as highlights some of the ongoing issues related to the use of CSFs.

Chemotherapy-induced neutropenia (CIN) and its complications exact a substantial toll on patients with cancer. Febrile neutropenia (FN), a sign of life-threatening infections, is associated with lengthy hospitalizations, early mortality, and high medical costs. In addition, neutropenia is the primary cause of dose reductions and dose delays, limiting the delivery of the chemotherapy at full dose and on schedule and thus compromising long-term survival in patients with potentially curable malignancies. Many recent studies in several major tumor types have documented that the greatest risk of neutropenia and its complications is in the first cycle of chemotherapy, with more than 50% of the first episodes of neutropenia and FN occurring in the first cycle. In addition to their other negative effects, these first-cycle events are also associated with early termination of the chemotherapy. The disproportionately high risk of neutropenia in the first cycle has important implications for managing CIN, as well as for the development and use of guidelines for supportive care. It highlights the importance of determining which patients are at high risk for neutropenia and its complications before the chemotherapy is initiated and implementing interventions, such as prophylactic growth factor support in the first and subsequent cycles, to reduce that risk.