Corticosteroid, IV Antibiotic Use May Increase Risk of Chemo-Induced Febrile Neutropenia

The timing and length of use for certain immunosuppressive drugs, such as corticosteroids, in patients with cancer may affect the risk of chemotherapy-induced febrile neutropenia (FN), according to a new study published in the Journal of the National Comprehensive Cancer Network (JNCCN).

FN, a dangerously low white blood cell count, can increase the risk of serious infection and fever in patients treated with chemotherapy. For prophylactic management of FN, it is important for providers to understand the key risk factors, the researchers wrote.

According to the study, the risk of developing chemotherapy-induced FN can depend on patient-, treatment-, and disease-related characteristics. Factors such as bone marrow suppression, impaired neutrophil function, or disturbance of barrier function have been previously identified as potential contributors to FN. The study authors aimed to determine additional clinical characteristics related to these mechanisms that may contribute to FN risk.

For the study, the researchers examined 15,971 patients who were diagnosed with non-Hodgkin lymphoma, breast, lung, colorectal, ovarian, or gastric cancer and treated with myelosuppressive chemotherapy at Kaiser Permanente Southern California over a 9-year period. Of the patients enrolled in the study, 4.3% developed FN in the first chemotherapy cycle.

Overall, the study showed that use of corticosteroids was significantly associated with increased risk of FN (adjusted hazard ratio [aHR], 1.53; 95% CI, 1.17—1.98). Longer term and more recent use appeared to increase the risk of FN the most. According to the data, the researchers observed a positive relationship for the duration of corticosteroid use and FN risk, with the adjusted hazard ratio (aHR) increasing from 1.78 (95% CI, 1.50–2.11) for use of <15 days to 2.86 (95% CI, 1.74–4.47) for use of 45 to 90 days.

Additionally, selected dermatologic/mucosal conditions and intravenous antibiotic use were also associated with increased risk (aHR, 1.40; 95% CI, 0.98—1.93, and 1.35; 95% CI, 0.97–1.87, respectively). The researchers did not find a statistically significant association with surgery, radiation therapy, and oral antibiotic use.

“One way to reduce the incidence rate for FN 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,” lead study author Chun Rebecca Chao, PhD, from Kaiser Permanente Southern California Department of Research & Evaluation, said in a press release. “Physicians should also consider which patients are at higher risk of FN, as identified by this study, when making decisions about using prophylactic treatments like granulocyte-colony stimulating factor (G-CSF).”

Although there was no association between prior and concurrent radiation therapy and FN, the researchers noted that they did not account for radiation field or dose, and indicated the need for more comprehensive studies to confirm their findings.

Overall, the researchers concluded that conditions affecting the skin/mucosal barrier, corticosteroid use, and intravenous antibiotic use should be considered when making prophylaxis and patient monitoring decisions.

References

Family L, Li Y, Chen LH, Page JH, et al. A study of novel febrile neutropenia risk factors related to bone marrow or immune suppression, barrier function, and bacterial flora. Journal of the National Comprehensive Cancer Network. 2018. Doi: 10.6004/jnccn.2018.7051

Study in JNCCN Identifies Significant Factors for Reducing the Risk of Immunosuppression and Fever in People Being Treated with Chemotherapy [news release]. NCCN’s website. https://www.nccn.org/about/news/newsinfo.aspx?NewsID=1268. Accessed October 31, 2018.