PURPOSE Standard practice in protecting against chemotherapy-associated infection has been chemotherapy dose modification or dose delay, administration of progenitor-cell support, or selective use of prophylactic antibiotics. Therapy of chemotherapy-associated neutropenic fever or infection has customarily involved treatment with intravenous antibiotics, usually accompanied by hospitalization. The hematopoietic colony-stimulating factors (CSFs) have been introduced into clinical practice as additional supportive measures that can reduce the likelihood of neutropenic complications due to chemotherapy. Clinical benefit has been shown, but the high cost of CSFs has led to concern about their appropriate use. The American Society of Clinical Oncology (ASCO) wishes to establish evidence-based, clinical practice guidelines for the use of CSFs in patients who are not enrolled on clinical trials. METHODS An expert multidisciplinary panel reviewed the clinical data documenting the activity of CSFs. For each common clinical situation, the Panel formulated a guideline to encourage reasonable use of CSFs to preserve effectiveness but discourage excess use when little marginal benefit is anticipated. Consensus was reached after critically appraising the available evidence. Guidelines were validated by comparing them with recommendations for CSF use developed in other countries and by several academic institutions. Outcomes considered in evaluating CSF benefit included duration of neutropenia, incidence of febrile neutropenia, incidence and duration of antibiotic use, frequency and duration of hospitalization, infectious mortality, chemotherapy dose-intensity, chemotherapy efficacy, quality of life, CSF toxicity, and economic impact. To the extent that these data were available, the Panel placed greatest value on survival benefit, reduction in rates of febrile neutropenia, decreased hospitalization, and reduced costs. Lesser value was placed on alterations in absolute neutrophil counts (ANC). CONCLUSIONS CSFs are recommended in some situations, eg, to reduce the likelihood of febrile neutropenia when the expected incidence is > or = 40%; after documented febrile neutropenia in a prior chemotherapy cycle to avoid infectious complications and maintain dose-intensity in subsequent treatment cycles when chemotherapy dose-reduction is not appropriate; and after high-dose chemotherapy with autologous progenitor-cell transplantation. CSFs are also effective in the mobilization of peripheral-blood progenitor cells. Therapeutic initiation of CSFs in addition to antibiotics at the onset of febrile neutropenia should be reserved for patients at high risk for septic complications. CSF use in patients with myelodysplastic syndromes may be reasonable if they are experiencing neutropenic infections. Administration of CSFs after initial chemotherapy for acute myeloid leukemia does not appear to be detrimental, but clinical benefit has been variable and caution is advised. Available data support use of CSFs in pediatric cancer patients similar to that recommended for adult patients. Outside of clinical trials, CSFs should not be used concurrently with chemotherapy and radiation, or to support increasing chemotherapy dose-intensity. Further research is warranted as a means to improve the cost-effective administration of the CSFs and identify clinical predictors of infectious complications that may direct their use.
Recommendations for Obesity Clinical Trials in Cancer Survivors: American Society of Clinical Oncology Statement
