Both the chemotherapy regimen selected and therapeutic dose intensity used in treatment factor into the calculation of neutropenia risk.
Cancer treatment–induced neutropenia is a decrease in neutrophil counts as a result of myelosuppressive therapy, and is defined as an absolute neutrophil count (ANC) less than 500 neutrophils/µL or an anticipated ANC of less than or equal to 500 neutrophils/µL according to the National Comprehensive Cancer Network (NCCN) standards, or less than 1000 neutrophils/µL according to parameters from the American Society of Clinical Oncology (ASCO) and the Infectious Diseases Society of America (IDSA).1,2 Progression of neutropenia to febrile neutropenia, in which an individual develops a temperature of 38.3°C/101°F or higher or 38.0°C/100.4°F or higher for at least 1 hour, is considered a major dose-limiting toxicity.
The prevention and treatment of neutropenia and febrile neutropenia are important because they are associated with morbidity and mortality. The mortality rate of patients hospitalized with febrile neutropenia ranges from 10% to more than 20% depending on comorbidities.3 In addition, neutropenia may require a decrease in chemotherapy dose intensity, dose delays, or the use of alternative regimens that may be less efficacious. Reductions in chemotherapy dose intensity have been associated with shorter disease-free and overall survival across different tumor types.
Both the chemotherapy regimen selected and the therapeutic dose intensity used in treatment factor into the calculation of neutropenia risk. Although there is currently no consensus algorithm for determining an individual's risk for neutropenia, distinct risk levels are assigned to different chemotherapy regimens based on the reported rates of neutropenia during their respective clinical trials. Regimens associated with a neutropenia rate of more than 20% are considered high risk, a rate of 10% to 20% is considered intermediate risk, and a rate below 10% is considered low risk.1 However, neutropenia rates are believed to be underreported. Observational studies report higher rates of neutropenia than randomized controlled trials (RCTs).4
For example, a meta-analysis of patients who received adjuvant fluorouracil, epirubicin, cyclophosphamide (FEC)-docetaxel in the community stetting showed a febrile neutropenia rate of 30.6%, which is in contrast to the 11.2% reported in the RCT that evaluated FEC-docetaxel.4 Similarly, a meta-analysis of 65 observational studies and 110 RCTs found that the febrile neutropenia rate was significantly higher in observational cohorts at 11.7% compared with 7.9% in randomized controlled cohorts (odds ratio, 1.58; 95% CI, 1.09-2.28; P = .017).4 Therefore, some myelosuppressive therapies may carry a higher risk of inducing neutropenia than has been identified during clinical trials.
Individual patient factors also affect neutropenia risk. Some important factors that are known to increase the risk of neutropenia are being aged 65 years or older; previous exposure to chemotherapy or radiation; prior history of neutropenia; tumor involvement in the bone marrow; poor performance status or nutritional status; comorbidities such as renal or liver impairment, cardiovascular disease, HIV infection, and other conditions; advanced cancer; and, open wounds, recent surgery, or infection.5