Predicting Individual Risk of Neutropenic Complications in Patients Receiving Cancer Chemotherapy

Myelosuppression represents a major toxicity of systemic cancer chemotherapy associated with considerable morbidity, mortality, and costs.1 Such complications also result in dose reductions or treatment delays, which may compromise clinical outcomes.2–6 Previous studies have demonstrated that the risk of an initial episode of febrile neutropenia is greatest during the first cycle of treatment when most patients are receiving full dose intensity often without prophylactic measures.7–9 The risk of febrile neutropenia in cancer patients who are receiving systemic chemotherapy is generally based on reported rates in randomized controlled clinical trials (RCTs).10 However, studies have suggested that the risk of chemotherapy-induced neutropenia and its complications are considerably underreported in RCTs.11 Reported rates vary greatly for the same chemotherapy regimen, making it difficult to estimate the actual risk for neutropenic complications for common chemotherapy regimens.11 Variation in reported rates may relate to differences in study populations as well as to the chemotherapy dose intensity delivered, which is also frequently underreported.11 In addition, the selected patient populations eligible for such trials may not be representative of the majority of cancer patients treated in the general cancer population. Recognized risk factors for chemotherapy-induced neutropenia and its complications can be classified on the basis of patient characteristics, cancer type, or type of treatment.12 Although older age has been identified as a risk factor for neutropenic complications potentially compromising cancer treatment in the elderly, age is less relevant than major in Wiley Online Library (wileyonlinelibrary.com) comorbidities that accompany increasing age.1–3,6,13,14 Low baseline white blood cell and neutrophil counts and hemoglobin levels appear to be predictors for febrile neutropenia.7,8 The intensity of the specific chemotherapy regimen used also represents a major determinant of the risk of chemotherapy-induced neutropenia.4 Risk assessment models for neutropenia developed to date have largely been based on retrospective data with several important methodologic limitations including small sample size, adjustment for different risk factors, and little, if any, validation.12 A prospective cohort study of cancer patients treated at oncology practices throughout the United States was undertaken to further study the incidence of and risk factors for neutropenic events in cancer patients who were receiving systemic chemotherapy. Preliminary observations with this population have confirmed that half to two-thirds of initial febrile neutropenia episodes occur during the first chemotherapy cycle across a broad range of malignancies.9 The primary goal of this investigation was to prospectively develop and validate a clinical risk model for the occurrence of severe or febrile neutropenia. The development of a valid risk model for neutropenic complications in patients receiving cancer chemotherapy should enable the identification of patients at greatest risk, facilitating more targeted application of available supportive care.