A retrospective study has revealed new potential risk factors for chemotherapy-induced febrile neutropenia in patients with solid tumors and non-Hodgkin lymphoma (NHL).
Dr. Chun Rebecca Chao
Researchers found the timing and duration of corticosteroid use were both associated with febrile neutropenia. The team also observed “marginal” associations between febrile neutropenia and certain dermatologic and mucosal conditions, as well as the use of intravenous antibiotics before chemotherapy.
However, there was no association found between oral antibiotic use and febrile neutropenia or between radiation therapy and febrile neutropenia.
Chun Rebecca Chao, PhD, of the Kaiser Permanente Southern California in Pasadena, and her colleagues reported these findings in the Journal of the National Comprehensive Cancer Network.
“Febrile neutropenia is life threatening and often requires hospitalization,” Dr. Chao said in a statement. “Furthermore, [febrile neutropenia] can lead to chemotherapy dose delay and dose reduction, which, in turn, negatively impacts antitumor efficacy. However, it can be prevented if high-risk individuals are identified and treated prophylactically.”
With this in mind, Dr. Chao and her colleagues set out to identify novel risk factors for febrile neutropenia by analyzing 15,971 patients who were treated with myelosuppressive chemotherapy at Kaiser Permanente Southern California between 2000 and 2009.
Patients had been diagnosed with NHL (n = 1,617) or breast (n = 6,323), lung (n = 3,584), colorectal (n = 3,062), ovarian (n = 924), or gastric (n = 461) cancers. In all, 4.3% of patients developed febrile neutropenia during their first cycle of chemotherapy.
The researchers found that corticosteroid use was associated with an increased risk of febrile neutropenia in a propensity score–adjusted (PSA) model. The hazard ratio was 1.53 (95% confidence interval, 1.17-1.98; P less than .01) for patients who received corticosteroids.
A longer duration of corticosteroid use was associated with a greater risk of febrile neutropenia. The adjusted HR, compared with no corticosteroid use, was 1.78 for corticosteroid treatment lasting less than 15 days and rose to 2.86 for treatment lasting 45-90 days.
“One way to reduce the incidence rate for [febrile neutropenia] could be to schedule prior corticosteroid use and subsequent chemotherapy with at least 2 weeks between them, given the magnitude of the risk increase and prevalence of this risk factor,” Dr. Chao said.
The researchers found a “marginally” increased risk of febrile neutropenia in patients with certain dermatologic conditions (dermatitis, psoriasis, pruritus) and mucosal conditions (gastritis, stomatitis, mucositis). In the PSA model, the HR was 1.40 (95% CI, 0.98-1.93; P = 0.05) for patients with these conditions.
Intravenous antibiotic use was also found to be marginally associated with an increased risk of febrile neutropenia in a restricted analysis covering patients treated in 2008 and 2009. In the PSA model, the HR was 1.35 (95% CI, 0.97-1.87; P = .08).
There was no association found between febrile neutropenia and oral antibiotic use in the restricted analysis. In the PSA model, the HR was 1.07 (95% CI, 0.77-1.48; P = .70) for patients who received oral antibiotics.
Dr. Chao and her colleagues wrote that these results suggest intravenous antibiotics may have a more profound impact than oral antibiotics on the balance of bacterial flora and other immune functions. Another possible explanation is that patients who received intravenous antibiotics were generally sicker and more prone to severe infection than patients who received oral antibiotics.
The researchers also found no association between febrile neutropenia and prior surgery, prior radiation therapy, and concurrent radiation therapy in the PSA model.
The study was funded by Amgen. Three of the authors reported being employees and stockholders of Amgen.
SOURCE: Chao CR et al. J Natl Compr Canc Netw. 2018;16(10):1201-8.